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Ye B, Wu Y, Cao M, Xu C, Zhou C, Zhang X. Altered patterns of dynamic functional connectivity of brain networks in deficit and non-deficit schizophrenia. Eur Arch Psychiatry Clin Neurosci 2025; 275:743-753. [PMID: 38662092 DOI: 10.1007/s00406-024-01803-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 03/19/2024] [Indexed: 04/26/2024]
Abstract
This study aims to investigate the altered patterns of dynamic functional network connectivity (dFNC) between deficit schizophrenia (DS) and non-deficit schizophrenia (NDS), and further explore the associations with cognitive impairments. 70 DS, 91 NDS, and 120 matched healthy controls (HCs) were enrolled. The independent component analysis was used to segment the whole brain. The fMRI brain atlas was used to identify functional networks, and the dynamic functional connectivity (FC) of each network was detected. Correlation analysis was used to explore the associations between altered dFNC and cognitive functions. Four dynamic states were identified. Compared to NDS, DS showed increased FC between sensorimotor network and default mode network in state 1 and decreased FC within auditory network in state 4. Additionally, DS had a longer mean dwell time of state 2 and a shorter one in state 3 compared to NDS. Correlation analysis showed that fraction time and mean dwell time of states were correlated with cognitive impairments in DS. This study demonstrates the distinctive altered patterns of dFNC between DS and NDS patients. The associations with impaired cognition provide specific neuroimaging evidence for the pathogenesis of DS.
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Affiliation(s)
- Biying Ye
- Department of Fourth Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Yiqiao Wu
- Department of Fourth Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Mingjun Cao
- Department of Fourth Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Chanhuan Xu
- Department of Fourth Clinical Medical College, Nanjing Medical University, Nanjing, China
| | - Chao Zhou
- Department of Geriatric Psychiatry, Affiliated Nanjing Brain Hospital, Nanjing Medical University, No.264 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
| | - Xiangrong Zhang
- Department of Geriatric Psychiatry, Affiliated Nanjing Brain Hospital, Nanjing Medical University, No.264 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
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Executive Functions and Psychopathology Dimensions in Deficit and Non-Deficit Schizophrenia. J Clin Med 2023; 12:jcm12051998. [PMID: 36902784 PMCID: PMC10003976 DOI: 10.3390/jcm12051998] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 02/24/2023] [Accepted: 02/27/2023] [Indexed: 03/06/2023] Open
Abstract
This study: (a) compared executive functions between deficit (DS) and non-deficit schizophrenia (NDS) patients and healthy controls (HC), controlling premorbid IQ and level of education; (b) compared executive functions in DS and NDS patients, controlling premorbid IQ and psychopathological symptoms; and (c) estimated relationships between clinical factors, psychopathological symptoms, and executive functions using structural equation modelling. Participants were 29 DS patients, 44 NDS patients, and 39 HC. Executive functions were measured with the Mazes Subtest, Spatial Span Subtest, Letter Number Span Test, Color Trail Test, and Berg Card Sorting Test. Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale, Brief Negative Symptom Scale, and Self-evaluation of Negative Symptoms. Compared to HC, both clinical groups performed poorer on cognitive flexibility, DS patients on verbal working memory, and NDS patients on planning. DS and NDS patients did not differ in executive functions, except planning, after controlling premorbid IQ and negative psychopathological symptoms. In DS patients, exacerbation had an effect on verbal working memory and cognitive planning; in NDS patients, positive symptoms had an effect on cognitive flexibility. Both DS and NDS patients presented deficits, affecting the former to a greater extent. Nonetheless, clinical variables appeared to significantly affect these deficits.
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Gerritsen CJ, Goldberg JO, Kiang M, Remington G, Foussias G, Eastwood JD. Distinct profiles of psychological and neuropsychological functions underlying goal-directed pursuit in schizophrenia. Aust N Z J Psychiatry 2022; 56:1628-1641. [PMID: 35191327 DOI: 10.1177/00048674221077031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Several components are known to underlie goal-directed pursuit, including executive, motivational and volitional functions. These were explored in schizophrenia spectrum disorders in order to identify subgroups with distinct profiles. METHODS Multiple executive, motivational and volitional tests were administered to a sample of outpatients with schizophrenia spectrum diagnoses (n = 59) and controls (n = 63). Research questions included whether distinct profiles exist and whether some functions are impacted disproportionately. These questions were addressed via cluster analysis and profile analysis, respectively. RESULTS Some such functions were significantly altered in schizophrenia while others were unaffected. Two distinct profiles emerged, one characterized by energizing deficits, reduced reward sensitivity and few subjective complaints; while another was characterized by markedly increased punishment sensitivity, intact reward sensitivity and substantial subjective reporting of avolitional symptoms and boredom susceptibility. CONCLUSION These findings highlight the importance of considering distinct patterns of strengths and deficits in functions governing goal-directed pursuit in schizophrenia that demarcate identifiable subtypes. These distinctions have implications for treatment, assessment and research.
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Affiliation(s)
- Cory J Gerritsen
- Campbell Family Mental Health Research Institute, Forensic Early Intervention Service, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada.,Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Joel O Goldberg
- Department of Psychology, York University, Toronto, ON, Canada
| | - Michael Kiang
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada.,Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
| | - Gary Remington
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada.,Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
| | - George Foussias
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada.,Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada
| | - John D Eastwood
- Department of Psychology, York University, Toronto, ON, Canada
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Llorca PM, Nuss P, Fakra É, Alamome I, Drapier D, Hage WE, Jardri R, Mouchabac S, Rabbani M, Simon N, Vacheron MN, Azorin JM. Place of the partial dopamine receptor agonist aripiprazole in the management of schizophrenia in adults: a Delphi consensus study. BMC Psychiatry 2022; 22:364. [PMID: 35643542 PMCID: PMC9142729 DOI: 10.1186/s12888-022-04008-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 05/16/2022] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Aripiprazole is a second-generation antipsychotic, efficacious in patients with schizophrenia during acute episodes. Due to its pharmacological profile, aripiprazole may be of interest in patients with specific clinical profiles who have not been studied extensively in randomised clinical trials. OBJECTIVES To capture experience with aripiprazole in everyday psychiatric practice using the Delphi method in order to inform decision-making on the use of aripiprazole for the treatment of patients with schizophrenia in clinical situations where robust evidence from clinical trials is lacking. METHODS The scope of the survey was defined as the management of schizophrenia in adults. A systematic literature review was performed to identify the different clinical situations in which aripiprazole has been studied, and to describe the level of clinical evidence. Clinical profiles to include in the Delphi survey were selected if there was a clear interest in terms of medical need but uncertainty over the efficacy of aripiprazole. For each clinical profile retained, five to seven specific statements were generated and included in a questionnaire. The final 41-item questionnaire was proposed to a panel of 406 French psychiatrists with experience in the treatment of schizophrenia. Panellists rated their level of agreement using a Likert scale. A second round of voting on eleven items was organised to clarify points for which a consensus was not obtained in the first round. RESULTS Five clinical profiles were identified in the literature review (persistent negative symptoms, pregnancy, cognitive dysfunction, addictive comorbidity and clozapine resistance). Sixty-two psychiatrists participated in the first round of the Delphi survey and 33 in the second round. A consensus was obtained for 11 out of 41 items in the first round and for 9/11 items in the second round. According to the panellists' clinical experience, aripiprazole can be used as maintenance treatment for pregnant women, is relevant to preserve cognitive function and can be considered an option in patients with a comorbid addictive disorder or with persistent negative symptoms. CONCLUSION These findings may help physicians in choosing relevant ways to use aripiprazole and highlight areas where more research is needed to widen the evidence base.
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Affiliation(s)
- Pierre-Michel Llorca
- Department of Psychiatry, Clermont-Ferrand University Hospital, Clermont Auvergne University, Clermont-Ferrand, France.
| | - Philippe Nuss
- grid.412370.30000 0004 1937 1100Psychiatry and Medical Psychology Department, Saint-Antoine Hospital, Paris Sorbonne University, Paris, France
| | - Éric Fakra
- grid.412954.f0000 0004 1765 1491University Hospital Psychiatry Group, Saint-Étienne University Hospital, Saint-Étienne, France
| | - Isabelle Alamome
- Department of Psychiatry, Polyclinic of Limoges, Limoges, France
| | - Dominique Drapier
- grid.410368.80000 0001 2191 9284University Hospital Adult Psychiatry Group, Guillaume-Régnier Hospital, University of Rennes 1, Rennes, France
| | - Wissam El Hage
- grid.12366.300000 0001 2182 6141UMR 1253, iBrain, Tours University, Inserm, Tours, France
| | - Renaud Jardri
- grid.410463.40000 0004 0471 8845Lille Neuroscience & Cognition Centre, INSERM U1172, Fontan Hospital, Lille University Hospital, Lille, France
| | - Stéphane Mouchabac
- grid.412370.30000 0004 1937 1100Psychiatry and Medical Psychology Department, Saint-Antoine Hospital, Paris Sorbonne University, Paris, France
| | - Marc Rabbani
- Medical Affairs Department, Lundbeck SAS, Puteaux, France
| | - Nicolas Simon
- grid.464064.40000 0004 0467 0503Department of Clinical Pharmacology, Aix Marseille University, INSERM, SESSTIM, Hospital Sainte Marguerite, CAP, Marseille, IRD France
| | | | - Jean-Michel Azorin
- grid.414438.e0000 0000 9834 707XDepartment of Psychiatry, Sainte Marguerite Hospital, Marseille, France
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Navalón P, Sahuquillo-Leal R, Moreno-Giménez A, Salmerón L, Benavent P, Sierra P, Cañada Y, Cañada-Martínez A, Berk M, García-Blanco A. Attentional engagement and inhibitory control according to positive and negative symptoms in schizophrenia: An emotional antisaccade task. Schizophr Res 2022; 239:142-150. [PMID: 34891078 DOI: 10.1016/j.schres.2021.11.044] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Revised: 10/18/2021] [Accepted: 11/27/2021] [Indexed: 11/18/2022]
Abstract
Despite schizophrenia (SZ) is characterized by a high psychopathological heterogeneity, the underlying psychological mechanisms that result in different clinical profiles are unclear. This study examined the cognitive processing of emotional faces (angry, happy, neutral, and sad) by means of assessing inhibitory control (antisaccade task) and attentional engagement (prosaccade task) with the eye-tracking paradigm. Firstly, two clinical SZ subgroups classified according to the predominance of positive (PSZ; n = 20) or negative symptoms (NSZ; n = 34) and a control group of 32 individuals were compared. Secondly, the association between prosaccade and antisaccade measurements and the severity of positive and negative symptoms were analyzed. The PSZ group showed slower antisaccades when angry faces were displayed, and higher positive symptoms were associated with slower prosaccade latencies to ones. Conversely, the NSZ group made overall slower prosaccades with an emotional advantage for angry faces, and higher negative symptoms were associated with faster antisaccade latencies to ones. Hence, whereas positive SZ profile is related to a lack of attentional engagement and an impaired inhibitory control to threatening information; negative SZ profile is linked to a lack of attentional engagement to faces, mainly with non-threat ones, and with an advantage to ignore distracting threatening stimuli. These findings support affective information-processing theories suggesting a hypersensitivity to threat for positive SZ profiles, and a desensitization to socio-emotional information for negative ones. Consequently, characterizing psychological mechanisms of SZ may allow improving current treatments to threat management when positive symptoms are predominant, or emotion sensitization when negative symptoms prevail.
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Affiliation(s)
- Pablo Navalón
- Department of Psychiatry and Clinical Psychology, La Fe University and Polytechnic Hospital, Valencia, Spain; Neonatal Research Group, La Fe Health Research Institute, Valencia, Spain
| | - Rosa Sahuquillo-Leal
- Department of Personality, Evaluation, and Psychological Treatment, University of Valencia, Valencia, Spain
| | | | | | - Pilar Benavent
- Department of Psychiatry and Clinical Psychology, La Fe University and Polytechnic Hospital, Valencia, Spain; Mental Health Research Group, La Fe Health Research Institute, Valencia, Spain
| | - Pilar Sierra
- Department of Psychiatry and Clinical Psychology, La Fe University and Polytechnic Hospital, Valencia, Spain; Mental Health Research Group, La Fe Health Research Institute, Valencia, Spain; Department of Medicine, University of Valencia, Valencia, Spain
| | - Yolanda Cañada
- Department of Psychiatry and Clinical Psychology, La Fe University and Polytechnic Hospital, Valencia, Spain; Mental Health Research Group, La Fe Health Research Institute, Valencia, Spain
| | - Antonio Cañada-Martínez
- Data Science, Biostatistics, and Bioinformatics, La Fe Health Research Institute, Valencia, Spain
| | - Michael Berk
- Deakin University, IMPACT Strategic Research Centre, School of Medicine, Geelong, Australia; Orygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, Florey Institute for Neuroscience and Mental Health, Department of Psychiatry, The University of Melbourne, Melbourne, Australia
| | - Ana García-Blanco
- Department of Psychiatry and Clinical Psychology, La Fe University and Polytechnic Hospital, Valencia, Spain; Neonatal Research Group, La Fe Health Research Institute, Valencia, Spain; Department of Personality, Evaluation, and Psychological Treatment, University of Valencia, Valencia, Spain.
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Brunelin J, Mondino M, Haesebaert J, Attal J, Benoit M, Chupin M, Dollfus S, El-Hage W, Galvao F, Jardri R, Llorca PM, Magaud L, Plaze M, Schott-Pethelaz AM, Suaud-Chagny MF, Szekely D, Fakra E, Poulet E. Examining transcranial random noise stimulation as an add-on treatment for persistent symptoms in schizophrenia (STIM'Zo): a study protocol for a multicentre, double-blind, randomized sham-controlled clinical trial. Trials 2021; 22:964. [PMID: 34963486 PMCID: PMC8715588 DOI: 10.1186/s13063-021-05928-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Accepted: 12/08/2021] [Indexed: 12/26/2022] Open
Abstract
Background One out of three patients with schizophrenia failed to respond adequately to antipsychotics and continue to experience debilitating symptoms such as auditory hallucinations and negative symptoms. The development of additional therapeutic approaches for these persistent symptoms constitutes a major goal for patients. Here, we develop a randomized-controlled trial testing the efficacy of high-frequency transcranial random noise stimulation (hf-tRNS) for the treatment of resistant/persistent symptoms of schizophrenia in patients with various profiles of symptoms, cognitive deficits and illness duration. We also aim to investigate the biological and cognitive effects of hf-tRNS and to identify the predictors of clinical response. Methods In a randomized, double-blind, 2-arm parallel-group, controlled, multicentre study, 144 patients with schizophrenia and persistent symptoms despite the prescription of at least one antipsychotic treatment will be randomly allocated to receive either active (n = 72) or sham (n = 72) hf-tRNS. hf-tRNS (100–500 Hz) will be delivered for 20 min with a current intensity of 2 mA and a 1-mA offset twice a day on 5 consecutive weekdays. The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left temporoparietal junction. Patients’ symptoms will be assessed prior to hf-tRNS (baseline), after the 10 sessions, and at 1-, 3- and 6-month follow-up. The primary outcome will be the number of responders defined as a reduction of at least 25% from the baseline scores on the Positive and Negative Syndrome Scale (PANSS) after the 10 sessions. Secondary outcomes will include brain activity and connectivity, source monitoring performances, social cognition, other clinical (including auditory hallucinations) and biological variables, and attitude toward treatment. Discussion The results of this trial will constitute a first step toward establishing the usefulness of hf-tRNS in schizophrenia whatever the stage of the illness and the level of treatment resistance. We hypothesize a long-lasting effect of active hf-tRNS on the severity of schizophrenia symptoms as compared to sham. This trial will also have implications for the use of hf-tRNS as a preventive intervention of relapse in patients with schizophrenia. Trial registration ClinicalTrials.gov NCT02744989. Prospectively registered on 20 April 2016
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Affiliation(s)
- Jerome Brunelin
- Centre Hospitalier Le Vinatier, PSYR2 team, Bat 416 - 1st floor; 95 boulevard Pinel, 69678, F-69500, Bron cedex, France. .,INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center, PSYR2 Team, F-69000, Lyon, France. .,Lyon 1 University, F-69000, Villeurbanne, France. .,Université Jean Monnet Saint Etienne, F-42000, Saint Etienne, France.
| | - Marine Mondino
- Centre Hospitalier Le Vinatier, PSYR2 team, Bat 416 - 1st floor; 95 boulevard Pinel, 69678, F-69500, Bron cedex, France.,INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center, PSYR2 Team, F-69000, Lyon, France.,Lyon 1 University, F-69000, Villeurbanne, France.,Université Jean Monnet Saint Etienne, F-42000, Saint Etienne, France
| | - Julie Haesebaert
- Hospices Civils de Lyon, Pôle Santé Publique, Service Recherche et Epidémiologie Cliniques, F-69003, Lyon, France.,Research on Healthcare Performance RESHAPE, INSERM U1290, Université Claude Bernard Lyon 1, Villeurbanne, France
| | | | | | - Marie Chupin
- Paris Brain Institute - Institut du Cerveau (ICM), Inserm U 1127, CNRS UMR 7225, Sorbonne Université, F-75013, Paris, France.,CATI Multicenter Neuroimaging Platform, F-75000, Paris, France
| | | | - Wissam El-Hage
- CHRU de Tours, CIC 1415, INSERM, Tours; UMR 1253, iBrain, Université de Tours, INSERM, F-37044, Tours, France
| | - Filipe Galvao
- Centre Hospitalier Le Vinatier, PSYR2 team, Bat 416 - 1st floor; 95 boulevard Pinel, 69678, F-69500, Bron cedex, France
| | - Renaud Jardri
- University in Lille, INSERM U1172, CHU Lille, Lille Neuroscience & Cognition Research Centre, Plasticity & SubjectivitY (PSY) team, CURE Platform, Lille, France
| | | | - Laurent Magaud
- Hospices Civils de Lyon, Pôle Santé Publique, Service Recherche et Epidémiologie Cliniques, F-69003, Lyon, France
| | - Marion Plaze
- GHU PARIS Psychiatrie & Neurosciences, site Sainte-Anne, Service Hospitalo-Universitaire, F-75014, Paris, France.,Université de Paris, F-75005, Paris, France
| | - Anne Marie Schott-Pethelaz
- Hospices Civils de Lyon, Pôle Santé Publique, Service Recherche et Epidémiologie Cliniques, F-69003, Lyon, France.,Research on Healthcare Performance RESHAPE, INSERM U1290, Université Claude Bernard Lyon 1, Villeurbanne, France
| | - Marie-Françoise Suaud-Chagny
- INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center, PSYR2 Team, F-69000, Lyon, France.,Lyon 1 University, F-69000, Villeurbanne, France.,Université Jean Monnet Saint Etienne, F-42000, Saint Etienne, France
| | | | - Eric Fakra
- INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center, PSYR2 Team, F-69000, Lyon, France.,Lyon 1 University, F-69000, Villeurbanne, France.,Université Jean Monnet Saint Etienne, F-42000, Saint Etienne, France.,CHU de Saint Etienne, F-42000, Saint Etienne, France
| | - Emmanuel Poulet
- Centre Hospitalier Le Vinatier, PSYR2 team, Bat 416 - 1st floor; 95 boulevard Pinel, 69678, F-69500, Bron cedex, France.,INSERM, U1028; CNRS, UMR5292; Lyon Neuroscience Research Center, PSYR2 Team, F-69000, Lyon, France.,Lyon 1 University, F-69000, Villeurbanne, France.,Université Jean Monnet Saint Etienne, F-42000, Saint Etienne, France.,Psychiatric emergency service, Hospices civils de Lyon, F-69005, Lyon, France
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Türk Y, Ercan I, Sahin I, Erdemli Gursel B, Uzunoglu A, Öge C, Beyazyüz E, Albayrak Y. Corpus callosum in schizophrenia with deficit and non-deficit syndrome: a statistical shape analysis. Gen Psychiatr 2021; 34:e100635. [PMID: 34950854 PMCID: PMC8638449 DOI: 10.1136/gpsych-2021-100635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 10/27/2021] [Indexed: 11/09/2022] Open
Abstract
Background The corpus callosum (CC) is the most targeted region in the cerebrum that integrates cognitive data between homologous areas in the right and left hemispheres. Aims Our study used statistical analysis to determine whether there was a correlation between shape changes in the CC in patients with schizophrenia (SZ) (deficit syndrome (DS) and non-deficit syndrome (NDS)) and healthy control (HC) subjects. Methods This study consisted of 27 HC subjects and 50 schizophrenic patients (20 with DS and 30 with NDS). 3 patients with DS and 4 patients with NDS were excluded. Three-dimensional, sagittal, T1-spoiled, gradient-echo imaging was used. Standard anatomical landmarks were selected and marked on each image using specific software. Results As to comparing the Procrustes mean shapes of the CC, statistically significant differences were observed between HC and SZ (DS+NDS) (p=0.017, James’s Fj=73.732), HC and DS (p<0.001, James’s Fj=140.843), HC and NDS (p=0.006, James’s Fj=89.178) and also DS and NDS (p<0.001, James’s Fj=152.967). Shape variability in the form of CC was 0.131, 0.085, 0.082 and 0.086 in the HC, SZ (DS+NDS), DS and NDS groups, respectively. Conclusions This study reveals callosal shape variations in patients with SZ and their DS and NDS subgroups that take into account the CC’s topographic distribution.
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Affiliation(s)
- Yaşar Türk
- Department of Radiology, Medical Faculty of Bülent Ecevit University, Kozlu, Zonguldak, Turkey
| | - Ilker Ercan
- Department of Biostatistics, Bursa Uludag University Faculty of Medicine, Bursa, Turkey
| | - Ibrahim Sahin
- Department of Biostatistics, Bursa Uludag University Faculty of Medicine, Bursa, Turkey
| | - Basak Erdemli Gursel
- Department of Radiology, Bursa Uludag University Faculty of Medicine, Bursa, Turkey
| | - Arda Uzunoglu
- Department of Biostatistics, Bursa Uludag University Faculty of Medicine, Bursa, Turkey
| | - Cem Öge
- Department of Psychiatry, Çorlu State Hospital, Çorlu, Turkey
| | - Elmas Beyazyüz
- Department of Psychiatry, Medical Faculty of Tekirdag Namık Kemal University, Tekirdag, Turkey
| | - Yakup Albayrak
- Department of Psychiatry, Medical Faculty of Tekirdag Namık Kemal University, Tekirdag, Turkey
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8
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Relationship Between Symptomatic Dimensions and Global Functioning of Non-Help-Seeking Individuals at Risk for Psychosis. J Nerv Ment Dis 2020; 208:953-957. [PMID: 32925694 DOI: 10.1097/nmd.0000000000001237] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
This study aims to analyze the relationship between the symptomatic dimensions of psychosis and functioning of individuals at risk for psychosis (ultrahigh risk [UHR]) in a non-help-seeking UHR sample from the general population. The sample is the same as the one used in the Brazilian Subclinical Symptoms and Prodromal Psychosis cohort study. We applied questionnaires of functioning (Global Assessment of Functioning Scale) and symptomatic dimensions (Scale of Prodromal Symptoms). Next, we correlated the symptomatic dimensions with functioning. We found a significant relationship between avolition and uncommon thought content with poor functioning, whereas the remaining symptoms were not as relevant. Poor functioning was most related to avolition, a negative symptom, followed by unusual thought content, a positive symptom.
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Neuroanatomy of Patients with Deficit Schizophrenia: An Exploratory Quantitative Meta-Analysis of Structural Neuroimaging Studies. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17176227. [PMID: 32867189 PMCID: PMC7503710 DOI: 10.3390/ijerph17176227] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 08/17/2020] [Accepted: 08/19/2020] [Indexed: 11/29/2022]
Abstract
Little is known regarding the neuroanatomical correlates of patients with deficit schizophrenia or persistent negative symptoms. In this meta-analysis, we aimed to determine whether patients with deficit schizophrenia have characteristic brain abnormalities. We searched PubMed, CINAHL and Ovid to identify studies that examined the various regions of interest amongst patients with deficit schizophrenia, patients with non-deficit schizophrenia and healthy controls. A total of 24 studies met our inclusion criteria. A random-effects model was used to calculate a combination of outcome measures, and heterogeneity was assessed by the I2 statistic and Cochran’s Q statistic. Our findings suggested that there was statistically significant reduction in grey matter volume (−0.433, 95% confidence interval (CI): −0.853 to −0.014, p = 0.043) and white matter volume (−0.319, 95% CI: −0.619 to −0.018, p = 0.038) in patients with deficit schizophrenia compared to healthy controls. There is also statistically significant reduction in total brain volume (−0.212, 95% CI: −0.384 to −0.041, p = 0.015) and white matter volume (−0.283, 95% CI: −0.546 to −0.021, p = 0.034) in patients with non-deficit schizophrenia compared to healthy controls. Between patients with deficit and non-deficit schizophrenia, there were no statistically significant differences in volumetric findings across the various regions of interest.
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10
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López-Díaz Á, Menéndez-Sampil C, Pérez-Romero A, Palermo-Zeballos FJ, Valdés-Florido MJ. Characterization of deficit schizophrenia and reliability of the bidimensional model of its negative symptomatology. Nord J Psychiatry 2020; 74:400-406. [PMID: 32149549 DOI: 10.1080/08039488.2020.1736151] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Background: Cumulative evidence has demonstrated important differences between deficit (DS) and non-deficit (NDS) schizophrenia, suggesting that DS may be a separate disease. However, most data come from the same research groups and more replication is needed to validate this hypothesis.Aims: Our study aimed to examine the distribution of DS, to compare their characteristics with NDS patients and to analyze the reliability of the two-factor structure of its negative symptomatology in a Spanish clinical sample.Methods: Sixty clinically stabilized patients with schizophrenia were evaluated. The Schedule for the Deficit Syndrome was used for DS/NDS categorization. Patient characteristics included age, gender, education, age at onset of psychosis, duration of illness, family history of psychosis, type of antipsychotic regimen, schizophrenia subtype and severity of the disease.Results: DS prevalence was 28.3%. Bivariate analysis revealed statistical differences between DS and NDS in terms of years of education and schizophrenia subtype. Factor analysis replicated the two-factor solution consisting of the 'Expressive deficit' and 'Avolition-apathy' domains reported in previous studies.Conclusions: Our results were consistent with the published data and indicated that the DS profile in the Spanish population is similar to that in other populations, which would corroborate the homogeneity of DS within the schizophrenia spectrum and contribute to the hypothesis that DS constitutes a separate disease.
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Affiliation(s)
- Álvaro López-Díaz
- UGC Salud Mental, Hospital Universitario Virgen Macarena, Seville, Spain.,Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain
| | | | - Ana Pérez-Romero
- UGC Salud Mental, Hospital Universitario Virgen Macarena, Seville, Spain
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11
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Delamillieure P, Ochoa-Torres D, Vasse T, Brazo P, Gourevitch R, Langlois S, Assouly-Besse F, Van Der Elst A, Morello R, Guelfi J, Petit M, Dollfus S. The subjective quality of life in deficit and nondeficit schizophrenic patients. Eur Psychiatry 2020; 20:346-8. [PMID: 16018928 DOI: 10.1016/j.eurpsy.2005.04.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2003] [Revised: 01/18/2005] [Accepted: 04/20/2005] [Indexed: 10/25/2022] Open
Abstract
AbstractWe assessed the subjective quality of life (QOL) of 30 deficit schizophrenic patients compared to 112 nondeficit schizophrenic patients. The deficit patients did not differ in term of QOL, total score of positive symptoms, general psychopathology from the nondeficit patients. This result suggested an absence of impact of primary negative symptoms on the subjective QOL in schizophrenic patients.
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Affiliation(s)
- Pascal Delamillieure
- Centre Esquirol, Centre Hospitalier et Universitaire, avenue côte de nacre, 14000 Caen, France
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12
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Association between DRD2 and ANKK1 polymorphisms with the deficit syndrome in schizophrenia. Ann Gen Psychiatry 2020; 19:39. [PMID: 32565876 PMCID: PMC7302002 DOI: 10.1186/s12991-020-00289-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 06/11/2020] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND The clinical course of schizophrenia varies among patients and is difficult to predict. Some patient populations present persistent negative symptoms, referred to as the deficit syndrome. Compared to relatives of non-deficit schizophrenia patients, family members of this patient population are at an increased risk of developing schizophrenia. Therefore, the aim of this study was to search for genetic underpinnings of the deficit syndrome in schizophrenia. METHODS Three SNPs, i.e., rs1799732 and rs6276 located within DRD2, and rs1800497 within ANKK1, were identified in the DNA samples of 198 schizophrenia probands, including 103 patients with deficit (DS) and 95 patients with non-deficit schizophrenia (NDS). Results: No significant differences concerning any of the analyzed polymorphisms were found between DS and NDS patients. However, significant links were observed between family history of schizophrenia and the deficit syndrome, G/G genotype and rs6276 G allele. In a separate analysis, we identified significant differences in frequencies of rs6276 G allele between DS and NDS patients with family history of schizophrenia. No significant associations were found between DRD2 and ANKK1 SNPs and the age of onset or schizophrenia symptom severity. CONCLUSIONS The results of our preliminary study fail to provide evidence of associations between DRD2 and ANKK1 polymorphisms with the deficit syndrome or schizophrenia symptom severity, but suggest potential links between rs6276 in DRD2 and the deficit syndrome in patients with hereditary susceptibility to schizophrenia. However, further studies are necessary to confirm this observation.
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13
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Gerritsen C, Bagby RM, Sanches M, Kiang M, Maheandiran M, Prce I, Mizrahi R. Stress precedes negative symptom exacerbations in clinical high risk and early psychosis: A time-lagged experience sampling study. Schizophr Res 2019; 210:52-58. [PMID: 31248749 DOI: 10.1016/j.schres.2019.06.015] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Revised: 03/15/2019] [Accepted: 06/17/2019] [Indexed: 12/18/2022]
Abstract
The experience sampling method (ESM) has revealed associations between fluctuations in stress and positive symptoms in psychosis. It is unknown, however, how negative symptoms including anhedonia respond to stress. Stress is divided according to its source: event-related stress stemming from negative events, and activity-related stress stemming from engaging in tasks beyond one's skill or control. Anhedonia is divided into consummatory and anticipatory anhedonia, reflecting a lack of pleasure in current and expected activities. This study uses ESM to determine whether each form of anhedonia increases in response to stress. Antipsychotic-naïve individuals with first episode psychosis (n = 39), clinical high-risk states for psychosis (n = 44), and healthy controls (n = 34) responded to daily prompts on a palmtop computer for up to ten days by indicating levels of stress and anhedonia. Time-lagged multilevel modelling was employed to explore increases in anhedonia following increases in stress while controlling for prior levels of anhedonia. Mean levels of anhedonia were also compared across groups. Only activity-related stress produced increases in anhedonia. This effect did not vary between groups. Clinical groups showed greater overall levels of anhedonia than healthy controls, but did not differ from each other. Anhedonia responds only to activity-related stressors, suggesting that this form of stress has a specific causal role in anhedonia. The results also provide further evidence for global increases in anhedonia in antipsychotic-naïve psychosis spectrum individuals.
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Affiliation(s)
- Cory Gerritsen
- Centre for Addiction and Mental Health, 250 College St, Toronto, Ontario M5T 1R8, Canada; University of Toronto, 27 King's College Circle, Toronto, Ontario M5S 1A1, Canada.
| | - R Michael Bagby
- Centre for Addiction and Mental Health, 250 College St, Toronto, Ontario M5T 1R8, Canada; University of Toronto, 27 King's College Circle, Toronto, Ontario M5S 1A1, Canada.
| | - Marcos Sanches
- Centre for Addiction and Mental Health, 250 College St, Toronto, Ontario M5T 1R8, Canada.
| | - Michael Kiang
- Centre for Addiction and Mental Health, 250 College St, Toronto, Ontario M5T 1R8, Canada; University of Toronto, 27 King's College Circle, Toronto, Ontario M5S 1A1, Canada.
| | - Margaret Maheandiran
- Centre for Addiction and Mental Health, 250 College St, Toronto, Ontario M5T 1R8, Canada.
| | - Ivana Prce
- Sunnybrook Research Institute, 2075 Bayview Ave, Toronto, Ontario M4N 3M5, Canada.
| | - Romina Mizrahi
- Centre for Addiction and Mental Health, 250 College St, Toronto, Ontario M5T 1R8, Canada; University of Toronto, 27 King's College Circle, Toronto, Ontario M5S 1A1, Canada.
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14
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Lei W, Kirkpatrick B, Wang Q, Deng W, Li M, Guo W, Liang S, Li Y, Zhang C, Li X, Zhang P, Li Z, Xiang B, Chen J, Hu X, Zhang N, Li T. Progressive brain structural changes after the first year of treatment in first-episode treatment-naive patients with deficit or nondeficit schizophrenia. Psychiatry Res Neuroimaging 2019; 288:12-20. [PMID: 31059954 DOI: 10.1016/j.pscychresns.2019.04.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 04/27/2019] [Accepted: 04/28/2019] [Indexed: 02/05/2023]
Abstract
Progressive brain volume atrophy has been reported in patients with schizophrenia. However, whether this progress differs between patients with primary negative symptoms (deficit schizophrenia; DS) and those without such symptoms (nondeficit schizophrenia; NDS) is unknown. Here, we examined grey matter volume (GMV) and white matter volume (WMV) changes over 12 months in 34 first-episode treatment-naive patients with schizophrenia (14 DS and 20 NDS) and 32 healthy controls (HCs) using structural magnetic resonance imaging and voxel-based morphometry. At baseline, compared to HCs, patients with DS but not NDS had less WMV in bilateral posterior limb of the internal capsule (PLIC) and cerebellar tonsil (P < 0.05, FDR corrected) and smaller GMV in the cerebellar culmen (P < 0.05, FWE corrected). At follow-up, NDS group showed WMV reduction in bilateral PLIC (P < 0.05, FDR corrected), while DS group showed no progressive WMV changes. While both patient groups exhibited GMV reduction in the hippocampus and insular cortex, patients with NDS showed additional GMV loss in the frontal and cingulate cortex and a selective increase in GMV in the left thalamus (P < 0.05 FWE corrected). Our study revealed double dissociations in developmental brain volume changes in the first year after clinical contact for psychosis in DS versus NDS patients.
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Affiliation(s)
- Wei Lei
- Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China; Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China; Department of Psychiatry, The Affiliated Hospital of Southwest Medical University, Luzhou, China; Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
| | - Brian Kirkpatrick
- Department of Psychiatry & Behavioral Sciences, University of Nevada, Reno School of Medicine, Reno, NV, USA
| | - Qiang Wang
- Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China; Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Wei Deng
- Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China; Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Mingli Li
- Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China; Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Wanjun Guo
- Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China; Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Sugai Liang
- Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China; Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Yinfei Li
- Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China; Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Chengcheng Zhang
- Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China; Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Xiaojing Li
- Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China; Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Pingping Zhang
- Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China; Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Zhe Li
- Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China; Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China
| | - Bo Xiang
- Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China; Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China; Department of Psychiatry, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Jing Chen
- Department of Psychiatry, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Xun Hu
- Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China; Huaxi Biobank, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Nanyin Zhang
- Department of Biomedical Engineering, The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA, USA
| | - Tao Li
- Mental Health Center and Psychiatric Laboratory, The State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China; Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, China.
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15
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Takayanagi Y, Sasabayashi D, Takahashi T, Komori Y, Furuichi A, Kido M, Nishikawa Y, Nakamura M, Noguchi K, Suzuki M. Altered brain gyrification in deficit and non-deficit schizophrenia. Psychol Med 2019; 49:573-580. [PMID: 29739476 DOI: 10.1017/s0033291718001228] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Patients with the deficit form of schizophrenia (D-SZ) are characterized by severe primary negative symptoms and differ from patients with the non-deficit form of schizophrenia (ND-SZ) in several aspects. No study has measured brain gyrification, which is a potential marker of neurodevelopment, in D-SZ and ND-SZ. METHODS We obtained magnetic resonance scans from 135 schizophrenia patients and 50 healthy controls. The proxy scale for deficit syndrome (PDS) was used for the classification of D-SZ and ND-SZ. The local gyrification index (LGI) of the entire cortex was measured using FreeSurfer. Thirty-seven D-SZ and 36 ND-SZ patients were included in the LGI analyses. We compared LGI across the groups. RESULTS SZ patients exhibited hyper-gyral patterns in the bilateral dorsal medial prefrontal and ventromedial prefrontal cortices, bilateral anterior cingulate gyri and right lateral parietal/occipital cortices as compared with HCs. Although patients with D-SZ or ND-SZ had higher LGI in similar regions compared with HC, the hyper-gyral patterns were broader in ND-SZ. ND-SZ patients exhibited a significantly higher LGI in the left inferior parietal lobule relative to D-SZ patients. Duration of illness inversely associated with LGI in broad regions only among ND-SZ patients. CONCLUSIONS The common hyper-gyral patterns among D-SZ and ND-SZ suggest that D-SZ and ND-SZ may share neurodevelopmental abnormalities. The different degrees of cortical gyrification seen in the left parietal regions, and the distinct correlation between illness chronicity and LGI observed in the prefrontal and insular cortices may be related to the differences in the clinical manifestations among D-SZ and ND-SZ.
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Affiliation(s)
- Yoichiro Takayanagi
- Department of Neuropsychiatry,University of Toyama Graduate School of Medicine and Pharmaceutical Sciences,Toyama,Japan
| | - Daiki Sasabayashi
- Department of Neuropsychiatry,University of Toyama Graduate School of Medicine and Pharmaceutical Sciences,Toyama,Japan
| | - Tsutomu Takahashi
- Department of Neuropsychiatry,University of Toyama Graduate School of Medicine and Pharmaceutical Sciences,Toyama,Japan
| | - Yuko Komori
- Department of Neuropsychiatry,University of Toyama Graduate School of Medicine and Pharmaceutical Sciences,Toyama,Japan
| | - Atsushi Furuichi
- Department of Neuropsychiatry,University of Toyama Graduate School of Medicine and Pharmaceutical Sciences,Toyama,Japan
| | - Mikio Kido
- Department of Neuropsychiatry,University of Toyama Graduate School of Medicine and Pharmaceutical Sciences,Toyama,Japan
| | - Yumiko Nishikawa
- Department of Neuropsychiatry,University of Toyama Graduate School of Medicine and Pharmaceutical Sciences,Toyama,Japan
| | - Mihoko Nakamura
- Department of Neuropsychiatry,University of Toyama Graduate School of Medicine and Pharmaceutical Sciences,Toyama,Japan
| | - Kyo Noguchi
- Department of Radiology,University of Toyama Graduate School of Medicine and Pharmaceutical Sciences,Toyama,Japan
| | - Michio Suzuki
- Department of Neuropsychiatry,University of Toyama Graduate School of Medicine and Pharmaceutical Sciences,Toyama,Japan
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16
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Affective modulation of target detection in deficit and non-deficit schizophrenia. Schizophr Res 2019; 204:138-145. [PMID: 30126815 PMCID: PMC6378118 DOI: 10.1016/j.schres.2018.08.023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Revised: 07/20/2018] [Accepted: 08/13/2018] [Indexed: 11/22/2022]
Abstract
Emotional deficits are an integral feature of schizophrenia (SZ), but our understanding of these deficits is limited. In the present study, we examined whether the severity of emotional deficits reflects difficulty in the cognitive processing of affectively valenced stimuli. Healthy controls (HC; N = 170) and stable outpatients with SZ (N = 245), characterized as either deficit syndrome (DS; N = 62) or non-deficit syndrome (NDS; N = 183), completed an Affective Go/NoGo task requiring discrimination of positively, negatively or neutrally valenced words. Accuracy (d') and response bias (c) were calculated for each of the three conditions, and a series of ANOVAs were carried out to examine group differences. Examination of accuracy revealed significant main effects of group and valence and a significant valence × group interaction, indicating that while affective valence impacted accuracy for the HC and NDS groups, the DS group maintained the same low level of accuracy across all levels of affective valence. Examination of response bias also revealed significant main effects of group and valence and a significant valence × group interaction. Specifically, within the HC and NDS groups, response bias did not differ between negatively and positively valenced words while response bias in the DS group was lowest for neutral, higher for negatively valenced and higher still for positively valenced words. These results suggest that emotional deficits in DS may be directly related to deficits in processing affective information. Moreover, although this deficit is observed across both positively and negatively valenced stimuli, it is most pronounced for positively valenced material.
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17
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Aleman A, Enriquez-Geppert S, Knegtering H, Dlabac-de Lange JJ. Moderate effects of noninvasive brain stimulation of the frontal cortex for improving negative symptoms in schizophrenia: Meta-analysis of controlled trials. Neurosci Biobehav Rev 2018; 89:111-118. [DOI: 10.1016/j.neubiorev.2018.02.009] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Revised: 01/24/2018] [Accepted: 02/12/2018] [Indexed: 01/28/2023]
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18
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Sum MY, Tay KH, Sengupta S, Sim K. Neurocognitive functioning and quality of life in patients with and without deficit syndrome of schizophrenia. Psychiatry Res 2018; 263:54-60. [PMID: 29499447 DOI: 10.1016/j.psychres.2018.02.025] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Revised: 02/02/2018] [Accepted: 02/12/2018] [Indexed: 11/15/2022]
Abstract
Deficit syndrome of schizophrenia is a subtype of schizophrenia characterized by primary and enduring negative symptoms. This study examined the differences in neurocognitive functioning and quality of life (QOL) between deficit and non-deficit patients, and specific predictors of both clinical measures. Overall, 344 subjects (175 patients with non-deficit schizophrenia (NDSZ), 58 patients with deficit schizophrenia (DSZ) and 111 healthy controls) were evaluated on severity of psychopathology, QOL and a smaller subset of 198 subjects (104 NDSZ, 27 DSZ, 67 healthy controls) underwent neurocognitive assessments. Multivariate analyses were used to determine differences in outcomes between subject groups and predictors of clinical measures. Both DSZ and NDSZ had significantly worse QOL compared with healthy controls. DSZ had more extensive cognitive deficits compared with healthy controls and performed worse on semantic fluency task compared to NDSZ. Multiple linear regression analysis found that DSZ, shorter duration of illness were associated with poorer QOL whereas fewer years of education, lower premorbid intelligence were associated with poorer overall neurocognitive functioning. The poorer QOL, greater extent of neurocognitive deficits especially semantic fluency associated with DSZ behoves the need for greater attention during clinical evaluation and treatment planning of this subgroup of individuals with schizophrenia.
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Affiliation(s)
- Min Yi Sum
- Research Division, Institute of Mental Health, 10 Buangkok View, Buangkok Green Medical Park, 539747, Singapore
| | - Kai Hong Tay
- Department of General Psychiatry, Institute of Mental Health, 10 Buangkok View, Buangkok Green Medical Park, 539747, Singapore
| | - Somnath Sengupta
- Department of General Psychiatry, Institute of Mental Health, 10 Buangkok View, Buangkok Green Medical Park, 539747, Singapore
| | - Kang Sim
- Research Division, Institute of Mental Health, 10 Buangkok View, Buangkok Green Medical Park, 539747, Singapore; Department of General Psychiatry, Institute of Mental Health, 10 Buangkok View, Buangkok Green Medical Park, 539747, Singapore.
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19
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Quality of Life-a Goal for Schizophrenia's Therapy. CURRENT HEALTH SCIENCES JOURNAL 2018; 44:122-128. [PMID: 30746158 PMCID: PMC6320457 DOI: 10.12865/chsj.44.02.05] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/04/2017] [Accepted: 03/27/2018] [Indexed: 12/03/2022]
Abstract
Quality of Life (QOL) assessment represents a good instrument to monitor the evolution of schizophrenia and the treatment’s outcomes. The present study has evaluated the relationship between the level of the QOL and different socio-demographical and clinical factors. Lower QOL for schizophrenic persons was influenced by the severity of symptoms and cognitive deficits, while same low level of QOL could be considered an indicator for suicidal behavior. The correct therapeutically management of individuals with schizophrenia could lead to better outcomes in terms of life satisfaction of patients and response to the treatment’s strategies.
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20
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Mak M, Misiak B, Frydecka D, Pełka-Wysiecka J, Kucharska-Mazur J, Samochowiec A, Bieńkowski P, Pawlak-Adamska E, Karabon L, Szmida E, Skiba P, Kotowicz K, Piotrowski P, Beszłej JA, Samochowiec J. Polymorphisms in immune-inflammatory response genes and the risk of deficit schizophrenia. Schizophr Res 2018; 193:359-363. [PMID: 28673752 DOI: 10.1016/j.schres.2017.06.050] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Revised: 06/24/2017] [Accepted: 06/25/2017] [Indexed: 01/06/2023]
Abstract
Polymorphisms in immune-inflammatory response genes are believed to impact schizophrenia susceptibility. However, it remains unknown whether immunogenetic factors play a role in the etiology of deficit schizophrenia (D-SCZ). Therefore, we genotyped four polymorphisms in genes encoding two immune system regulatory proteins (CTLA-4 rs231775 and CD28 rs3116496), interleukin-6 (IL6 rs1800795) and transforming growth factor-β (TGFB1 rs1800470) in 513 schizophrenia patients and 374 controls. The CD28 rs3116496-CC genotype and C-allele were significantly more frequent in the whole group of patients and D-SCZ patients compared to controls. Our results indicate that the CD28 rs3116496 polymorphism might impact the risk of schizophrenia, especially D-SCZ.
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Affiliation(s)
- Monika Mak
- Department of Psychiatry, Pomeranian Medical University, 26 Broniewski Street, 71-460 Szczecin, Poland
| | - Błażej Misiak
- Department of Genetics, Wroclaw Medical University, 1 Marcinkowski Street, 50-368 Wroclaw, Poland.
| | - Dorota Frydecka
- Department of Psychiatry, Wroclaw Medical University, 10 Pasteur Street, 50-367 Wroclaw, Poland
| | - Justyna Pełka-Wysiecka
- Department of Psychiatry, Pomeranian Medical University, 26 Broniewski Street, 71-460 Szczecin, Poland
| | - Jolanta Kucharska-Mazur
- Department of Psychiatry, Pomeranian Medical University, 26 Broniewski Street, 71-460 Szczecin, Poland
| | - Agnieszka Samochowiec
- Institute of Psychology, Department of Clinical Psychology, University of Szczecin, 69 Krakowska Street, 71-017 Szczecin, Poland
| | - Przemysław Bieńkowski
- Department of Psychiatry, Medical University of Warsaw, 27 Nowowiejska Street, 00-665 Warsaw, Poland
| | - Edyta Pawlak-Adamska
- Department of Experimental Therapy, Laboratory of Immunopathology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Weigla Street, 51-114 Wroclaw, Poland
| | - Lidia Karabon
- Department of Experimental Therapy, Laboratory of Immunopathology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Weigla Street, 51-114 Wroclaw, Poland
| | - Elżbieta Szmida
- Department of Genetics, Wroclaw Medical University, 1 Marcinkowski Street, 50-368 Wroclaw, Poland
| | - Paweł Skiba
- Department of Genetics, Wroclaw Medical University, 1 Marcinkowski Street, 50-368 Wroclaw, Poland
| | - Kamila Kotowicz
- Department of Psychiatry, Wroclaw Medical University, 10 Pasteur Street, 50-367 Wroclaw, Poland
| | - Patryk Piotrowski
- Department of Psychiatry, Wroclaw Medical University, 10 Pasteur Street, 50-367 Wroclaw, Poland
| | - Jan Aleksander Beszłej
- Department of Psychiatry, Wroclaw Medical University, 10 Pasteur Street, 50-367 Wroclaw, Poland
| | - Jerzy Samochowiec
- Department of Psychiatry, Pomeranian Medical University, 26 Broniewski Street, 71-460 Szczecin, Poland
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21
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Ahmed AO, Strauss GP, Buchanan RW, Kirkpatrick B, Carpenter WT. Schizophrenia heterogeneity revisited: Clinical, cognitive, and psychosocial correlates of statistically-derived negative symptoms subgroups. J Psychiatr Res 2018; 97:8-15. [PMID: 29156414 DOI: 10.1016/j.jpsychires.2017.11.004] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2017] [Revised: 11/07/2017] [Accepted: 11/10/2017] [Indexed: 10/18/2022]
Abstract
Traditional efforts to delineate the clinical heterogeneity of schizophrenia have been unsuccessful because of the absence of a valid, stable, and meaningful subtyping scheme. A clinically-informed nosology supported by multivariate statistical classification methods may provide a better approach for classifying schizophrenia. The goals of the current study were to 1) use multivariate classification methods to validate a clinical subtyping scheme based on the profile of negative symptoms; and 2) following validation to contrast the statistically-derived subgroups to ascertain distinguishing demographic, clinical, cognitive, and functional characteristics. In the current study, 706 people with schizophrenia completed measures of positive and negative symptoms, premorbid adjustment, cognition, and psychosocial functioning. Latent class analysis served to identify the number of negative symptom subgroups in schizophrenia. Next, statistical classification methods-Bayes Theorem and the Base Rate Classification Technique-were used to assign participants into the identified subgroups. Subgroups were compared on external validation variables not used in the classification process via logistic regression and discriminant function analysis. Latent class analysis supported a three-class model of schizophrenia that included deficit, persistent, and transient negative symptom subgroups. Posthoc comparisons showed that demographic characteristics, positive symptoms, premorbid adjustment, and cognitive profiles can distinguish the schizophrenia subgroups with moderate accuracy. The deficit subgroup had the greatest impairments in psychosocial functioning and quality of life variables. Findings suggest that schizophrenia encapsulates qualitatively distinct negative symptom subgroups that differ in their demographic, symptomatic, neuropsychological, and functional profiles. Schizophrenia heterogeneity reflects a combination of non-arbitrary subgroups and severity-based differences in negative symptoms.
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Affiliation(s)
| | | | - Robert W Buchanan
- Department of Psychiatry, University of Maryland School of Medicine, Maryland Psychiatric Research Center, USA
| | - Brian Kirkpatrick
- Department of Psychiatry, University of Nevada School of Medicine, USA
| | - William T Carpenter
- Department of Psychiatry, University of Maryland School of Medicine, Maryland Psychiatric Research Center, USA
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22
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Dickinson D, Pratt DN, Giangrande EJ, Grunnagle M, Orel J, Weinberger DR, Callicott JH, Berman KF. Attacking Heterogeneity in Schizophrenia by Deriving Clinical Subgroups From Widely Available Symptom Data. Schizophr Bull 2018; 44:101-113. [PMID: 28369611 PMCID: PMC5768050 DOI: 10.1093/schbul/sbx039] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Previous research has identified (1) a "deficit" subtype of schizophrenia characterized by enduring negative symptoms and diminished emotionality and (2) a "distress" subtype associated with high emotionality-including anxiety, depression, and stress sensitivity. Individuals in deficit and distress categories differ sharply in development, clinical course and behavior, and show distinct biological markers, perhaps signaling different etiologies. We tested whether deficit and distress subtypes would emerge from a simple but novel data-driven subgrouping analysis, based on Positive and Negative Syndrome Scale (PANSS) negative and distress symptom dimensions, and whether subgrouping was informative regarding other facets of behavior and brain function. PANSS data, and other assessments, were available for 549 people with schizophrenia diagnoses. Negative and distress symptom composite scores were used as indicators in 2-step cluster analyses, which divided the sample into low symptom (n = 301), distress (n = 121), and deficit (n = 127) subgroups. Relative to the low-symptom group, the deficit and distress subgroups had comparably higher total PANSS symptoms (Ps < .001) and were similarly functionally impaired (eg, global functioning [GAF] Ps < .001), but showed markedly different patterns on symptom, cognitive and personality variables, among others. Initial analyses of functional magnetic resonance imaging (fMRI) data from a 182-participant subset of the full sample also suggested distinct patterns of neural recruitment during working memory. The field seeks more neuroscience-based systems for classifying psychiatric conditions, but these are inescapably behavioral disorders. More effective parsing of clinical and behavioral traits could identify homogeneous target groups for further neural system and molecular studies, helping to integrate clinical and neuroscience approaches.
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Affiliation(s)
- Dwight Dickinson
- Clinical and Translational Neuroscience Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD,To whom correspondence should be addressed; 10 Center Drive, Building 10, Room 3c-115, Bethesda, MD 20814, US; tel: 301-451-2123, fax: 301-480-7795, e-mail:
| | - Danielle N Pratt
- Clinical and Translational Neuroscience Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD
| | - Evan J Giangrande
- Clinical and Translational Neuroscience Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD
| | - MeiLin Grunnagle
- Clinical and Translational Neuroscience Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD
| | - Jennifer Orel
- Clinical and Translational Neuroscience Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD
| | - Daniel R Weinberger
- The Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD
| | - Joseph H Callicott
- Clinical and Translational Neuroscience Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD
| | - Karen F Berman
- Clinical and Translational Neuroscience Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD
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23
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Yu M, Dai Z, Tang X, Wang X, Zhang X, Sha W, Yao S, Shu N, Wang X, Yang J, Zhang X, Zhang X, He Y, Zhang Z. Convergence and Divergence of Brain Network Dysfunction in Deficit and Non-deficit Schizophrenia. Schizophr Bull 2017; 43:1315-1328. [PMID: 29036672 PMCID: PMC5737538 DOI: 10.1093/schbul/sbx014] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Deficit schizophrenia (DS), characterized by primary and enduring negative symptoms, has been considered as a pathophysiologically distinct schizophrenic subgroup. Neuroimaging characteristics of DS, especially functional brain network architecture, remain largely unknown. Resting-state functional magnetic resonance imaging and graph theory approaches were employed to investigate the topological organization of whole-brain functional networks of 114 male participants including 33 DS, 41 non-deficit schizophrenia (NDS) and 40 healthy controls (HCs). At the whole-brain level, both the NDS and DS group exhibited lower local efficiency (Eloc) than the HC group, implying the reduction of local specialization of brain information processing (reduced functional segregation). The DS, but not NDS group, exhibited enhanced parallel information transfer (enhanced functional integration) as determined by smaller characteristic path length (Lp) and higher global efficiency (Eglob). The Lp and Eglob presented significant correlations with Brief Psychiatric Rating Scale (BPRS) total score in the DS group. At the nodal level, both the NDS and DS groups showed higher functional connectivity in the inferior frontal gyrus and hippocampus, and lower connectivity in the visual areas and striatum than the controls. The DS group exhibited higher nodal connectivity in the right inferior temporal gyrus than the NDS and HC group. The diminished expression of Scale for the Assessment of Negative Symptoms (SANS) subfactors negatively correlated with nodal connectivity of right putamen, while asociality/amotivation positively correlated with right hippocampus across whole patients. We highlighted the convergence and divergence of brain functional network dysfunctions in patients with DS and NDS, which provides crucial insights into pathophysiological mechanisms of the 2 schizophrenic subtypes.
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Affiliation(s)
- Miao Yu
- Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Zhengjia Dai
- Department of Psychology, Sun Yat-sen University, Guangzhou, China,State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China
| | - Xiaowei Tang
- Department of Psychiatry, Wutaishan Hospital of Yangzhou, Yangzhou, China
| | - Xiang Wang
- Medical Psychological Institute of the Second Xiangya Hospital, Central South University, Changsha, China
| | - Xiaobin Zhang
- Department of Psychiatry, Wutaishan Hospital of Yangzhou, Yangzhou, China
| | - Weiwei Sha
- Department of Psychiatry, Wutaishan Hospital of Yangzhou, Yangzhou, China
| | - Shuqiao Yao
- Medical Psychological Institute of the Second Xiangya Hospital, Central South University, Changsha, China
| | - Ni Shu
- State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China
| | - Xindi Wang
- State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China
| | - Jiaying Yang
- Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing, China
| | - Xiangyang Zhang
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX
| | - Xiangrong Zhang
- Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China,Department of Geriatric Psychiatry, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, China,To whom correspondence should be addressed; Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, No.87 DingJiaQiao Road, Nanjing 210009, China; tel: 0086-25-822906586, fax:0086-25-83719457, e-mail:
| | - Yong He
- State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China
| | - Zhijun Zhang
- Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China,Beijing Institute for Brain Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
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24
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Tyburski E, Pełka-Wysiecka J, Mak M, Samochowiec A, Bieńkowski P, Samochowiec J. Neuropsychological Profile of Specific Executive Dysfunctions in Patients with Deficit and Non-deficit Schizophrenia. Front Psychol 2017; 8:1459. [PMID: 28912737 PMCID: PMC5582382 DOI: 10.3389/fpsyg.2017.01459] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Accepted: 08/14/2017] [Indexed: 11/13/2022] Open
Abstract
Objectives: Although it has been shown that there are more profound deficits present in deficit schizophrenia (DS) patients than in non-deficit schizophrenia (NDS) patients, there still remain some matters requiring further investigation. In this context, we formulated three research aims: (1) to compare executive functions between the investigated groups, (2) to determine the relationship between particular aspects of executive functions within the groups, and (3) to draw up a neuropsychological profile for executive functions. Methods: The study involved 148 schizophrenia patients divided into two groups on the basis of the Schedule for the Deficit Syndrome: DS (n = 70) and NDS (n = 78). Patients were matched for sex, age, years of education, and overall cognitive functioning. For assessing executive functions we used the Wisconsin Card Sorting Test (WCST), the Trail Making Test (TMT), the Phonemic Verbal Fluency Test (VFT P), the Stroop Color and Word Test (SCWT), and the Go/No Go task (GNG). Results: Deficit schizophrenia patients scored lower on the WCST and TMT (relative flexibility) than did the NDS patients. There were no inter-group differences in the VFT P, SCWT (relative inhibition), or GNG. There were significant correlations between WCST and TMT scores in both groups. The general neuropsychological profiles were similar in both groups. Conclusion: Deficit schizophrenia patients exhibited slightly greater interference with concept formation and non-verbal cognitive flexibility. Therefore, such problems may be specific to this particular type of schizophrenia. These results may be useful for the development of neuropsychological diagnostic methods for patients with schizophrenia.
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Affiliation(s)
- Ernest Tyburski
- Department of Clinical Psychology, Institute of Psychology, University of SzczecinSzczecin, Poland
| | | | - Monika Mak
- Independent Clinical Psychology Unit, Department of Psychiatry, Pomeranian Medical UniversitySzczecin, Poland
| | - Agnieszka Samochowiec
- Department of Clinical Psychology, Institute of Psychology, University of SzczecinSzczecin, Poland
| | | | - Jerzy Samochowiec
- Department of Psychiatry, Pomeranian Medical UniversitySzczecin, Poland
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25
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Mucci A, Merlotti E, Üçok A, Aleman A, Galderisi S. Primary and persistent negative symptoms: Concepts, assessments and neurobiological bases. Schizophr Res 2017; 186:19-28. [PMID: 27242069 DOI: 10.1016/j.schres.2016.05.014] [Citation(s) in RCA: 99] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Revised: 05/10/2016] [Accepted: 05/17/2016] [Indexed: 02/01/2023]
Abstract
Primary and persistent negative symptoms (PPNS) represent an unmet need in the care of people with schizophrenia. They have an unfavourable impact on real-life functioning and do not respond to available treatments. Underlying etiopathogenetic mechanisms of PPNS are still unknown. The presence of primary and enduring negative symptoms characterizes deficit schizophrenia (DS), proposed as a separate disease entity with respect to non-deficit schizophrenia (NDS). More recently, to reduce the heterogeneity of negative symptoms by using criteria easily applicable in the context of clinical trials, the concept of persistent negative symptoms (PNS) was developed. Both PNS and DS constructs include enduring negative symptoms (at least 6months for PNS and 12months for DS) that do not respond to available treatments. PNS exclude secondary negative symptoms based on a cross-sectional evaluation of severity thresholds on commonly used rating scales for positive symptoms, depression and extrapyramidal side effects; the DS diagnosis, instead, excludes all potential sources of secondary negative symptoms based on a clinical longitudinal assessment. In this paper we review the evolution of concepts and assessment modalities relevant to PPNS, data on prevalence of DS and PNS, as well as studies on clinical, neuropsychological, brain imaging electrophysiological and psychosocial functioning aspects of DS and PNS.
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Affiliation(s)
- Armida Mucci
- Department of Psychiatry, University of Naples SUN, Naples, Italy.
| | | | - Alp Üçok
- Department of Psychiatry, Psychotic Disorders Research Program, Istanbul Faculty of Medicine, Istanbul, Turkey
| | - André Aleman
- University of Groningen, University Medical Center Groningen, Department of Neuroscience and Department of Psychology, Groningen, The Netherlands
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26
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Anxiety does not contribute to social withdrawal in the subchronic phencyclidine rat model of schizophrenia. Behav Pharmacol 2017; 28:512-520. [PMID: 28704273 DOI: 10.1097/fbp.0000000000000325] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Social withdrawal should not be considered a direct measure of the negative symptoms of schizophrenia as it may result not only from asociality (primary negative symptom) but also from other altered processes such as anxiety. To understand the contribution of these two factors to social deficit, we investigated whether the social withdrawal observed in the subchronic phencyclidine (PCP) rat model of schizophrenia could be attributed to increased anxiety. Compared to saline controls, PCP-treated rats (5 mg/kg, twice daily for 7 days, followed by a washout period) spent significantly less time in social interaction, but did not show anxiety-like behaviors in different relevant behavioral paradigms. In addition, their social deficit was not affected by a behavioral procedure known to reduce anxiety-like behavior (repeated exposure to the same partner) nor by systemic administration of the classical anxiolytic diazepam. In contrast, PCP-induced social withdrawal was reversed by the cannabinoid agonist CP55,940, a drug with known anxiogenic properties. Furthermore, when using the social approach task, PCP-treated animals performed similarly to control animals treated with diazepam, but not to those treated with the anxiogenic compound pentylenetetrazole. Taken together, our results indicate that PCP-induced social withdrawal cannot be attributed to increased anxiety. These data are discussed in the context of primary versus secondary negative symptoms and the deficit syndrome of schizophrenia.
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27
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Abstract
PURPOSE OF REVIEW To provide a review on studies published in the last year relevant to the categorization and assessment of negative symptoms. RECENT FINDINGS Recent research supported the validity of the 'deficit/non-deficit schizophrenia' categorization. Few studies confirmed the validity of the category 'persistent negative symptoms', whereas no recent study explored the validity of the category 'predominant negative symptoms'. The two-factor structure of the negative dimension is supported by studies reporting different correlates for the two subdomains: diminished expression and avolition/apathy. The need to further split avolition/apathy in two distinct components, that is anhedonia and amotivation, is confirmed in recent papers. Additional approaches to the assessment of negative symptoms have been proposed, including the self-assessment of negative symptoms, and the evaluation of negative symptoms in daily life and their assessment by means of computerized analyses. SUMMARY Negative symptoms represent an unmet need in the care of schizophrenia, as they are associated to poor response to available treatments and to poor functional outcome. Their accurate categorization and assessment represent a major challenge for research on neurobiological substrates and new treatment strategies.
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28
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Stewart P, Craik C. Occupation, Mental Illness and Medium Security: Exploring Time-Use in Forensic Regional Secure Units. Br J Occup Ther 2016. [DOI: 10.1177/030802260707001002] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Research investigating occupational experience among people with mental illness has highlighted their difficulties in selecting, organising, valuing, enjoying and competently performing occupations. Although occupational therapy literature consistently identifies environmental factors as key in facilitating successful and valued engagement, few authors have studied the implications of detention in secure mental health settings for this population. This study investigated the occupational experiences of five people with schizophrenia in two forensic regional secure units. Quantitative and qualitative methodologies were used, with semi-structured interviews adding depth and subjectivity to Occupational Questionnaire (Smith et al 1986) responses. The quantitative data were analysed using non-parametric analysis, with content analysis applied to the qualitative data. Time-use was characterised predominantly by engagement in passive leisure and rest occupations. This reflects the findings of both inpatient and community-based studies elsewhere and suggests that mental illness is a common factor influencing time-use. The participants chose occupations based on expectations of enjoyment and success, and associations with independence and normality. Significant correlations were found between perceived competence, value and enjoyment (p<0.01), and the participants were more likely to enjoy self-chosen occupations (p<0.05). Forensic occupational therapists must use evidence to optimise resources and deliver interventions that facilitate choice and autonomy and reflect individual needs. Further research with larger samples and longitudinal methodologies will facilitate generalisation and establish temporal perspectives.
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Affiliation(s)
- Paul Stewart
- South West London and St George's Mental Health NHS Trust
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29
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De Rossi P, Dacquino C, Piras F, Caltagirone C, Spalletta G. Left nucleus accumbens atrophy in deficit schizophrenia: A preliminary study. Psychiatry Res Neuroimaging 2016; 254:48-55. [PMID: 27322868 DOI: 10.1016/j.pscychresns.2016.06.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Revised: 06/02/2016] [Accepted: 06/04/2016] [Indexed: 01/21/2023]
Abstract
A question that remains to be answered is whether schizophrenia can be characterized by a single etiopathophysiology or whether separate sub-syndromes should be differentiated to define specific mechanisms for each sub-type. Individuals affected by the deficit subtype of schizophrenia (DSZ) display avolitional/amotivational features that respond poorly to conventional treatments. Characterizing DSZ from a neuroanatomical point of view may help clarify this issue and develop new treatment strategies. To determine if DSZ is associated with structural alterations in specific deep grey matter structures linked to its key clinical features, 22 DSZ patients, 22 non-deficit schizophrenia (NDSZ) patients and 22 healthy controls (HC) were recruited for a case-control cross-sectional study. High-resolution magnetic resonance imaging was performed in all subjects and volumes of deep grey matter structures were measured using FreeSurfer. DSZ patients displayed smaller left accumbens volumes compared to both NDSZ patients and HC. Moreover, age and duration of illness were significantly associated with lower volume of the left accumbens in DSZ but not in NDSZ. Findings indicate that DSZ is associated with lower volume of the nucleus accumbens in the dominant hemisphere. This is consistent with the psychopathological features and functional impairments present in DSZ and thus indicates a potential mechanism.
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Affiliation(s)
- Pietro De Rossi
- Department of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, 00179, Rome, Italy; Department NESMOS, Faculty of Medicine and Psychology, University "Sapienza" of Rome, Rome, Italy; Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
| | - Claudia Dacquino
- Department of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, 00179, Rome, Italy; Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Italy
| | - Fabrizio Piras
- Department of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, 00179, Rome, Italy
| | - Carlo Caltagirone
- Department of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, 00179, Rome, Italy; Department of Neuroscience, "Tor Vergata" University, 00173, Rome, Italy
| | - Gianfranco Spalletta
- Department of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, 00179, Rome, Italy; Beth K. and Stuart C. Yudofsky Division of Neuropsychiatry, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
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30
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Sarkar S, Hillner K, Velligan DI. Conceptualization and treatment of negative symptoms in schizophrenia. World J Psychiatry 2015; 5:352-361. [PMID: 26740926 PMCID: PMC4694548 DOI: 10.5498/wjp.v5.i4.352] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2015] [Revised: 07/07/2015] [Accepted: 10/13/2015] [Indexed: 02/05/2023] Open
Abstract
Negative symptoms of schizophrenia including social withdrawal, diminished affective response, lack of interest, poor social drive, and decreased sense of purpose or goal directed activity predict poor functional outcomes for patients with schizophrenia. They may develop and be maintained as a result of structural and functional brain abnormalities, particularly associated with dopamine reward pathways and by environmental and psychosocial factors such as self-defeating cognitions and the relief from overstimulation that accompanies withdrawal from social and role functioning. Negative symptoms are more difficult to treat than the positive symptoms of schizophrenia and represent an unmet therapeutic need for large numbers of patients with schizophrenia. While antipsychotic medications to treat the symptoms of schizophrenia have been around for decades, they have done little to address the significant functional impairments in the disorder that are associated with negative symptoms. Negative symptoms and the resulting loss in productivity are responsible for much of the world-wide personal and economic burden of schizophrenia. Pharmacologic treatments may be somewhat successful in treating secondary causes of negative symptoms, such as antipsychotic side effects and depression. However, in the United States there are no currently approved treatments for severe and persistent negative symptoms (PNS) that are not responsive to treatments for secondary causes. Pharmacotherapy and psychosocial treatments are currently being developed and tested with severe and PNS as their primary targets. Academia, clinicians, the pharmaceutical industry, research funders, payers and regulators will need to work together to pursue novel treatments to address this major public health issue.
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31
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Lei W, Deng W, Li M, He Z, Han Y, Huang C, Ma X, Wang Q, Guo W, Li Y, Jiang L, Gong Q, Hu X, Zhang N, Li T. Gray matter volume alterations in first-episode drug-naïve patients with deficit and nondeficit schizophrenia. Psychiatry Res 2015; 234:219-226. [PMID: 26409573 PMCID: PMC4859347 DOI: 10.1016/j.pscychresns.2015.09.015] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2014] [Revised: 06/16/2015] [Accepted: 09/02/2015] [Indexed: 02/05/2023]
Abstract
Different patterns of gray matter volume (GMV) abnormalities have been reported between chronic patients with deficit schizophrenia (DS), relative to nondeficit schizophrenia (NDS) patients. However, it is not clear whether these differences are characteristic to the pathophysiology of DS or due to the effects of medications or illness durations. To address this issue, GMV in 88 first-episode, drug-naive patients with schizophrenia (44 DS and 44 NDS), 67 of their first-degree relatives and 84 healthy controls were assessed using voxel- based morphometry (VBM) and compared between groups. Correlations between GMV and clinical symptoms in patients were also assessed. Compared to controls, DS patients displayed more severe GMV reduction in the cerebellar culmen than NDS patients. GMV reduction in culmen was also observed in the first-degree relatives of DS (but not NDS) patients, suggesting possible different genetic risk in DS and NDS. The left insula was significantly smaller in DS patients than both NDS patients and controls, and smaller GMV of this region was associated with more severe negative symptoms in patients. Our results collectively indicate that DS might represent a distinct subtype of schizophrenia from NDS and the GMV change in left insula may be a morphological signature of DS.
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Affiliation(s)
- Wei Lei
- The Mental Health Center & Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Wei Deng
- The Mental Health Center & Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Mingli Li
- The Mental Health Center & Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Zongling He
- The Mental Health Center & Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Yuanyuan Han
- The Mental Health Center & Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Chaohua Huang
- The Mental Health Center & Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Xiaohong Ma
- The Mental Health Center & Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Qiang Wang
- The Mental Health Center & Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Wanjun Guo
- The Mental Health Center & Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Yinfei Li
- The Mental Health Center & Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Lijun Jiang
- The Mental Health Center & Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Qiyong Gong
- Huaxi MRI center, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Xun Hu
- Department of Clinical Neuroscience, King's College London, Medical Research Council (MRC) Centre for Neurodegeneration Research, Institute of Psychiatry, London, UK
| | - Nanyin Zhang
- Department of Biomedical Engineering, The Huck Institutes of the Life Sciences,The Pennsylvania State University, W-341 Millennium Science Complex, University Park, PA 16802, USA, Correspondence Authors: Tao Li. No. 28 South Dianxin Street, Wuhou District, Chengdu, Sichuan Province, 610041, P. R. China. Phone: 86-028-85423561/Fax: 00-86-2885422632. , Nanyin Zhang. W-341 Millenium Science Complex, University Park, PA 16802, USA. Phone: 814-867-4791.
| | - Tao Li
- The Mental Health Center & Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China, Correspondence Authors: Tao Li. No. 28 South Dianxin Street, Wuhou District, Chengdu, Sichuan Province, 610041, P. R. China. Phone: 86-028-85423561/Fax: 00-86-2885422632. , Nanyin Zhang. W-341 Millenium Science Complex, University Park, PA 16802, USA. Phone: 814-867-4791.
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32
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Yu M, Tang X, Wang X, Zhang X, Zhang X, Sha W, Yao S, Shu N, Zhang X, Zhang Z. Neurocognitive Impairments in Deficit and Non-Deficit Schizophrenia and Their Relationships with Symptom Dimensions and Other Clinical Variables. PLoS One 2015; 10:e0138357. [PMID: 26381645 PMCID: PMC4575183 DOI: 10.1371/journal.pone.0138357] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2015] [Accepted: 08/28/2015] [Indexed: 11/18/2022] Open
Abstract
Background Deficit schizophrenia (DS) has been proposed as a pathophysiologically distinct subgroup within schizophrenia. Earlier studies focusing on neurocognitive function of DS patients have yielded inconsistent findings ranging from substantial deficits to no significant difference relative to non-deficit schizophrenia patients (NDS). The present study investigated the severity and characteristic patterns of neurocognitive impairments in DS and NDS patients and their relationships with clinical variables. Methods Attention, ideation fluency, cognitive flexibility and visuospatial memory function were assessed in 40 DS patients, 57 NDS patients, and 52 healthy controls by a comprehensive neuropsychological battery. Results Both schizophrenia subgroups had overall more severe cognitive impairments than controls while DS performed worse on every neuropsychological measure except the Stroop interference than the NDS patients with age and education as the covariates. Profile analysis found significantly different patterns of cognitive profiles between two patients group mainly due to their differences in attention and cognitive flexibility functions. Age, education, illness duration and negative symptoms were found to have the correlations with cognitive impairments in the NDS group, while only age and the negative symptoms were correlated with the cognitive impairments in the DS group. Multiple regression analyses revealed that sustained attention and cognitive flexibility were the core impaired cognitive domains mediating other cognitive functions in DS and NDS patients respectively. Conclusions DS patients exemplified worse in almost all cognitive domains than NDS patients. Sustained attention and cognitive flexibility might be the key impaired cognitive domains for DS and NDS patients respectively. The present study suggested the DS as a specific subgroup of schizophrenia.
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Affiliation(s)
- Miao Yu
- Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China
| | - XiaoWei Tang
- Department of Psychiatry, Wutaishan Hospital of Yangzhou, Yangzhou, Jiangsu, China
| | - Xiang Wang
- Medical Psychological Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - XiangRong Zhang
- Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China
- Department of Geriatric Psychiatry, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, China
- * E-mail: (XRZ); (ZJZ)
| | - XiaoBin Zhang
- Department of Psychiatry, Wutaishan Hospital of Yangzhou, Yangzhou, Jiangsu, China
| | - WeiWei Sha
- Department of Psychiatry, Wutaishan Hospital of Yangzhou, Yangzhou, Jiangsu, China
| | - ShuQiao Yao
- Medical Psychological Institute of the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Ni Shu
- State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China
| | - XiangYang Zhang
- Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas, United States of America
| | - ZhiJun Zhang
- Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China
- * E-mail: (XRZ); (ZJZ)
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Lei W, Li N, Deng W, Li M, Huang C, Ma X, Wang Q, Guo W, Li Y, Jiang L, Zhou Y, Hu X, McAlonan GM, Li T. White matter alterations in first episode treatment-naïve patients with deficit schizophrenia: a combined VBM and DTI study. Sci Rep 2015; 5:12994. [PMID: 26257373 PMCID: PMC4530339 DOI: 10.1038/srep12994] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2015] [Accepted: 07/06/2015] [Indexed: 02/05/2023] Open
Abstract
Categorizing ‘deficit schizophrenia’ (DS) as distinct from ‘non-deficit’ schizophrenia (NDS) may help reduce heterogeneity within schizophrenia. However, it is unknown if DS has a discrete white matter signature. Here we used MRI to compare white matter volume (voxel-based morphometry) and microstructural integrity (fractional anisotropy, FA) in first-episode treatment-naïve patients with DS and NDS and their unaffected relatives to control groups of similar age. We found that white matter disruption was prominent in DS compared to controls; the DS group had lower volumes in the cerebellum, bilateral extra-nuclear and bilateral frontoparietal regions, and lower FA in the body of corpus callosum, posterior superior longitudinal fasciculus and uncinate fasciculus. The DS group also had lower volume in bilateral extra-nuclear regions compared to NDS, and the volume of these clusters was negatively correlated with deficit symptom ratings. NDS patients however, had no significant volume alterations and limited disruption of microstructural integrity compared to controls. Finally, first-degree relatives of those with DS shared volume abnormalities in right extra-nuclear white matter. Thus, white matter pathology in schizophrenia is most evident in the deficit condition, and lower extra-nuclear white matter volumes in both DS patients and their relatives may represent a brain structural ‘endophenotype’ for DS.
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Affiliation(s)
- Wei Lei
- The Mental Health Center &Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Na Li
- The Mental Health Center &Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Wei Deng
- The Mental Health Center &Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Mingli Li
- The Mental Health Center &Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Chaohua Huang
- The Mental Health Center &Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Xiaohong Ma
- The Mental Health Center &Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Qiang Wang
- The Mental Health Center &Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Wanjun Guo
- The Mental Health Center &Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Yinfei Li
- The Mental Health Center &Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Lijun Jiang
- The Mental Health Center &Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Yi Zhou
- Department of Radiology, Hospital of Chengdu Office of People's Government of Tibetan autonomous Region, Branch Hospital of West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Xun Hu
- Huaxi Biobank, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
| | - Grainne Mary McAlonan
- Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK
| | - Tao Li
- The Mental Health Center &Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu City, Sichuan Province, China
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34
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White matter alterations in first episode treatment-naïve patients with deficit schizophrenia: a combined VBM and DTI study. Sci Rep 2015. [PMID: 26257373 DOI: 10.1038/srep12994.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Categorizing 'deficit schizophrenia' (DS) as distinct from 'non-deficit' schizophrenia (NDS) may help reduce heterogeneity within schizophrenia. However, it is unknown if DS has a discrete white matter signature. Here we used MRI to compare white matter volume (voxel-based morphometry) and microstructural integrity (fractional anisotropy, FA) in first-episode treatment-naïve patients with DS and NDS and their unaffected relatives to control groups of similar age. We found that white matter disruption was prominent in DS compared to controls; the DS group had lower volumes in the cerebellum, bilateral extra-nuclear and bilateral frontoparietal regions, and lower FA in the body of corpus callosum, posterior superior longitudinal fasciculus and uncinate fasciculus. The DS group also had lower volume in bilateral extra-nuclear regions compared to NDS, and the volume of these clusters was negatively correlated with deficit symptom ratings. NDS patients however, had no significant volume alterations and limited disruption of microstructural integrity compared to controls. Finally, first-degree relatives of those with DS shared volume abnormalities in right extra-nuclear white matter. Thus, white matter pathology in schizophrenia is most evident in the deficit condition, and lower extra-nuclear white matter volumes in both DS patients and their relatives may represent a brain structural 'endophenotype' for DS.
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Ahmed AO, Strauss GP, Buchanan RW, Kirkpatrick B, Carpenter WT. Are Negative Symptoms Dimensional or Categorical? Detection and Validation of Deficit Schizophrenia With Taxometric and Latent Variable Mixture Models. Schizophr Bull 2015; 41:879-91. [PMID: 25399026 PMCID: PMC4466177 DOI: 10.1093/schbul/sbu163] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Studies have supported the validity of the deficit form of schizophrenia (ie, people with primary and enduring negative symptoms). A test of whether that group is a true taxon-that is, a distinct, discontinuous group-has yet to be conducted and the underlying structure of negative symptoms as categorical or dimensional remains undetermined. The present study examined the latent structure of negative and deficit symptoms to determine if a nonarbitrary boundary distinguishes deficit from nondeficit forms of schizophrenia (ie, whether these symptoms reflect a continuous or categorical variable). Schedule for the Deficit Syndrome ratings of 789 individuals with a psychotic disorder were submitted to taxometric and latent variable mixture analyses to test categorical vs dimensional hypotheses of negative symptoms and deficit schizophrenia. Analytic models favored a taxonic structure of negative symptoms and the validity of the deficit/nondeficit classification scheme. Taxometric classification outperformed clinician-based deficit/nondeficit classification in its association with summer birth, male sex, premorbid adjustment, neurocognition, and psychosocial functioning. Within taxon and complement classes, severity scores remained significant predictors of premorbid adjustment, neurocognition, and psychosocial functioning. Thus, although a categorical approach is validated, a hybrid categorical-dimensional conceptualization of negative symptoms also has validity for the prediction of external variables.
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Affiliation(s)
- Anthony O. Ahmed
- Department of Psychiatry, Weill Cornell Medical College, White Plains, NY;,Department of Psychiatry and Health Behavior, Medical College of Georgia, Georgia Regents University, Augusta, GA;,*To whom correspondence should be addressed; Department of Psychiatry, Weill Cornell Medical College, 21 Bloomingdale Road, White Plains, NY 10605, US; tel: 914-997-5251, fax: 914-682-6906, e-mail:
| | | | - Robert W. Buchanan
- Department of Psychiatry;,Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD
| | - Brian Kirkpatrick
- Department of Psychiatry, University of Nevada School of Medicine, Reno, NV
| | - William T. Carpenter
- Department of Psychiatry;,Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD
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Suzuki T, Kanahara N, Yamanaka H, Takase M, Kimura H, Watanabe H, Iyo M. Dopamine supersensitivity psychosis as a pivotal factor in treatment-resistant schizophrenia. Psychiatry Res 2015; 227:278-82. [PMID: 25863824 DOI: 10.1016/j.psychres.2015.02.021] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2014] [Revised: 01/09/2015] [Accepted: 02/18/2015] [Indexed: 12/26/2022]
Abstract
There may be subtypes in treatment-resistant schizophrenia (TRS), and one of the subtypes may be related to dopamine supersensitivity psychosis (DSP). In developing strategies for prevention and treatment TRS, it is important to clarify the role of DSP in TRS. TRS patients were recruited from 3 hospitals for the present study. Through chart reviews, all patients were judged as either TRS or not, and then possible TRS patients were investigated about their past/present histories of DSP episode(s) by direct interviews. We then compared each factor between the groups with and without DSP episode(s). Out of 611 patients screened, 147 patients met the criteria for TRS and were included in the present analysis. These were divided into groups with and without DSP, comprising 106 (72.1%) and 41 patients (27.9%), respectively. Clinical characteristics in the two groups were similar, except for drug-induced movement disorders (DIMDs), which were significantly more important in DSP patients. Of the DSP patients, 42% and 56% experienced rebound psychosis and tolerance to antipsychotic effects, respectively. The present study revealed that approximately 70% of TRS patients experienced one or more DSP episodes, which may have a strong impact on the long-term prognosis of patients with schizophrenia.
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Affiliation(s)
- Tomotaka Suzuki
- Department of Psychiatry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba 260-8670, Japan; Department of Psychiatry, Koutoku-kai Sato Hospital, 948-1 Kunugizuka, Nanyo City, Yamagata 999-2221, Japan
| | - Nobuhisa Kanahara
- Department of Psychiatry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba 260-8670, Japan; Division of Medical Treatment and Rehabilitation, Center for Forensic Mental Health, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba 260-8670, Japan.
| | - Hiroshi Yamanaka
- Department of Psychiatry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba 260-8670, Japan; Department of Psychiatry, Chiba Psychiatric Medical Center, 5 Toyosuna, Mihama-ku, Chiba 261-0024, Japan
| | - Masayuki Takase
- Department of Psychiatry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba 260-8670, Japan
| | - Hiroshi Kimura
- Department of Psychiatry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba 260-8670, Japan
| | - Hiroyuki Watanabe
- Department of Psychiatry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba 260-8670, Japan; Division of Medical Treatment and Rehabilitation, Center for Forensic Mental Health, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba 260-8670, Japan
| | - Masaomi Iyo
- Department of Psychiatry, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba 260-8670, Japan; Division of Medical Treatment and Rehabilitation, Center for Forensic Mental Health, Chiba University, 1-8-1 Inohana, Chuou-ku, Chiba 260-8670, Japan
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Spalletta G, De Rossi P, Piras F, Iorio M, Dacquino C, Scanu F, Girardi P, Caltagirone C, Kirkpatrick B, Chiapponi C. Brain white matter microstructure in deficit and non-deficit subtypes of schizophrenia. Psychiatry Res 2015; 231:252-261. [PMID: 25649975 DOI: 10.1016/j.pscychresns.2014.12.006] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Revised: 11/05/2014] [Accepted: 12/23/2014] [Indexed: 01/20/2023]
Abstract
Dividing schizophrenia into its deficit (SZD) and nondeficit (SZND) subtypes may help to identify specific and more homogeneous pathophysiological characteristics. Our aim was to define a whole brain voxelwise map specifically characterizing white matter tracts of schizophrenia patients with and without the deficit syndrome. We compared microstructural diffusion-related parameters as measured by diffusion tensor imaging in 21 SZD patients, 21 SZND patients, and 21 healthy controls, age- and gender-matched. Results showed that fractional anisotropy was reduced in the right precentral area in SZND patients, and in the left corona radiata of the schizophrenia group as a whole. Axial diffusivity was reduced in the left postcentral area of SZD patients and in the left cerebellum of the whole schizophrenia group. Radial diffusivity was increased in the left forceps minor of SZD patients, in the left internal capsule of SZND patients, and in the right inferior fronto-occipital fasciculus in the whole schizophrenia group. Mean diffusivity was increased from healthy controls to SZD patients to SZND patients in the right occipital lobe. In conclusion, SZD patients are not simply at the extreme end of a severity continuum of white matter disruption. Rather, the SZD and SZND subtypes are associated with distinct and specific brain microstructural anomalies that are consistent with their peculiar psychopathological dimensions.
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Affiliation(s)
- Gianfranco Spalletta
- Laboratory of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
| | - Pietro De Rossi
- Laboratory of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Italy; NESMOS Department, Faculty of Medicine and Psychology, "Sapienza" University of Rome, Rome, Italy
| | - Fabrizio Piras
- Laboratory of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Italy
| | - Mariangela Iorio
- Laboratory of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Italy
| | - Claudia Dacquino
- Laboratory of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Italy
| | - Francesca Scanu
- Laboratory of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Italy; Department of Neurology and Psychiatry, Faculty of Medicine, "Sapienza" University of Rome, Rome, Italy
| | - Paolo Girardi
- NESMOS Department, Faculty of Medicine and Psychology, "Sapienza" University of Rome, Rome, Italy
| | - Carlo Caltagirone
- Laboratory of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Italy; Department of Neuroscience, "Tor Vergata" University, Rome, Italy
| | - Brian Kirkpatrick
- Department of Psychiatry and Behavioral Science, University of Nevada School of Medicine, Reno, NV, USA
| | - Chiara Chiapponi
- Laboratory of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Italy
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Shibre T, Medhin G, Alem A, Kebede D, Teferra S, Jacobsson L, Kullgren G, Hanlon C, Fekadu A. Long-term clinical course and outcome of schizophrenia in rural Ethiopia: 10-year follow-up of a population-based cohort. Schizophr Res 2015; 161:414-20. [PMID: 25468171 DOI: 10.1016/j.schres.2014.10.053] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2014] [Revised: 10/27/2014] [Accepted: 10/27/2014] [Indexed: 10/24/2022]
Abstract
BACKGROUND Although the few available studies from LMICs report favorable outcome, the course of schizophrenia is more complex than has been indicated so far. METHODS A sample of 361 people with a standardized clinical diagnosis of schizophrenia were recruited from a predominantly rural community in Ethiopia and followed up regularly for an average of 10years. Psychiatrists used the Longitudinal Interval Follow-up Evaluation chart to carry out assessment of illness course. Duration of time in clinical remission was the primary outcome. RESULT About 61.0% of the patients remained under active follow-up, while 18.1% (n=65) were deceased. The mean percentage of follow-up time in complete remission was 28.4% (SD=33.0). Female patients were significantly more likely to have episodic illness course with no inter-episode residual or negative symptoms (χ(2)=6.28, P=0.012). Nearly 14.0% had continuous psychotic symptoms for over 75% of their follow-up time. Only 18.1% achieved complete remission for over 75% of their follow-up time. Later onset of illness was the only significant predictor of achieving full remission for over 50% of follow-up time in a fully adjusted model. Conventional antipsychotic medications were fairly well tolerated in 80% of the patients and 4.2% (n=15) experienced tardive dyskinesia. CONCLUSION This population-based study is one of the very few long-term outcome studies of schizophrenia in LMICs. The study demonstrated clearly a differential and more favorable course and outcome for female patients but overall course and outcome of schizophrenia appeared less favorable in this setting than has been reported from other LMICs.
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Affiliation(s)
- Teshome Shibre
- Addis Ababa University, Ethiopia; University of Toronto, Ontario Shores Centre for Mental Health Sciences, Canada.
| | - Girmay Medhin
- Addis Ababa University, Aklilu-Lemma Institute of Pathobiology, Ethiopia
| | | | - Derege Kebede
- Addis Ababa University, School of Public Health, Addis Ababa, Ethiopia; WHO Regional Office for Africa, Brazzaville, Congo
| | | | | | | | - Charlotte Hanlon
- Addis Ababa University, Ethiopia; King's College London, Institute of Psychiatry, Health Services and Population Research Department, Centre for Global Mental Health, London, UK
| | - Abebaw Fekadu
- Addis Ababa University, Ethiopia; King's College London, Institute of Psychiatry, Department of Psychological Medicine, London, UK
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White RG, Lysaker P, Gumley AI, McLeod H, McCleery M, O'Neill D, MacBeth A, Giurgi-Oncu C, Mulholland CC. Plasma cortisol levels and illness appraisal in deficit syndrome schizophrenia. Psychiatry Res 2014; 220:765-71. [PMID: 25262562 DOI: 10.1016/j.psychres.2014.08.043] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2013] [Revised: 08/21/2014] [Accepted: 08/24/2014] [Indexed: 12/01/2022]
Abstract
Research investigating the association between negative symptoms and plasma cortisol levels in individuals with schizophrenia has produced inconsistent findings. This study investigated whether deficit syndrome schizophrenia (characterized by high levels of primary negative symptoms) is associated with comparatively high morning plasma cortisol levels, more negative appraisals about illness and higher levels of depression. Participants were 85 individuals diagnosed with schizophrenia and 85 individuals with no history of contact with psychiatric services matched for age and gender. All participants provided fasting 9.00a.m. plasma cortisol samples. There were no significant differences between the schizophrenia and control participants in plasma cortisol levels. The Proximal Deficit Syndrome method was used to identify individuals with deficit syndrome schizophrenia. Contrary to what had been hypothesized, participants with deficit syndrome schizophrenia had significantly lower plasma cortisol levels than both non-deficit syndrome participants and control participants. Participants with the deficit syndrome reported significantly less negative appraisals about illness (assessed by PBIQ) and lower levels of depression (assessed by BDI-II). Differences in cortisol levels continued to trend toward significance when levels of depression were controlled for. The patterns of illness-related appraisals and plasma cortisol levels raise the possibility that the deficit syndrome could be a form of adaptation syndrome.
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Affiliation(s)
- Ross G White
- Institute of Health and Well-being, The University of Glasgow, Glasgow G12 0XH, UK.
| | - Paul Lysaker
- Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Psychiatry, Roudebush VA Medical Center, Indianapolis, IN, USA
| | - Andrew I Gumley
- Institute of Health and Well-being, The University of Glasgow, Glasgow G12 0XH, UK
| | - Hamish McLeod
- Institute of Health and Well-being, The University of Glasgow, Glasgow G12 0XH, UK
| | - Muriel McCleery
- Department of Psychiatry, The Queen's University of Belfast, Belfast BT7 1NN, Ireland
| | - Donnacha O'Neill
- Department of Psychiatry, The Queen's University of Belfast, Belfast BT7 1NN, Ireland
| | - Angus MacBeth
- Centre for Rural Health, University of Aberdeen, Aberdeen AB24 3FX, UK
| | - Catalina Giurgi-Oncu
- The Victor Babeș University of Medicine and Pharmacy of Timișoara, 300041, Romania
| | - Ciaran C Mulholland
- Department of Psychiatry, The Queen's University of Belfast, Belfast BT7 1NN, Ireland
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40
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Üçok A, Ergül C. Persistent negative symptoms after first episode schizophrenia: A 2-year follow-up study. Schizophr Res 2014; 158:241-6. [PMID: 25107850 DOI: 10.1016/j.schres.2014.07.021] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2014] [Revised: 07/13/2014] [Accepted: 07/14/2014] [Indexed: 10/24/2022]
Abstract
BACKGROUND The aim of this study is to determine the rate of persistent negative symptoms according to different criteria during two years of follow-up after first-episode schizophrenia. METHODS The study sample consisted of 105 patients with first-episode schizophrenia who completed at least 12 months of follow-up period. We used 6 different definitions of persistent negative symptoms (PNS) based on the Scale for the Assessment of Negative Symptoms subscale scores at seven time points throughout the follow-up. In some definitions of PNS, patients with suprathreshold depressive symptoms were excluded. Premorbid adjustment and baseline cognitive performances of the patients were assessed. RESULTS The PNS rates were between 14.2 and 27.9% in the first year and 11.1 and 25.8% in the second year. Seventy-eight percent of the patients who met the strictest PNS criteria during the first 12 months met the same criteria also during the second 12-month-period. Those with PNS had earlier onset, lower premorbid functioning, worse executive functioning and attention at baseline, and lower rates of working/studying during the 2-year follow-up. Duration of education and untreated psychosis are the independent variables that contribute to the PNS status at the first year of follow-up in logistic regression analysis. CONCLUSION Our findings suggest that PNS has specific predictors and effect on the course of illness after first-episode schizophrenia.
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Affiliation(s)
- Alp Üçok
- Department of Psychiatry, Istanbul Faculty of Medicine, Istanbul University, Millet Street, Çapa, Fatih, Istanbul, Turkey.
| | - Ceylan Ergül
- Department of Psychiatry, Istanbul Faculty of Medicine, Istanbul University, Millet Street, Çapa, Fatih, Istanbul, Turkey
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41
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Pełka-Wysiecka J, Wroński M, Jasiewicz A, Grzywacz A, Tybura P, Kucharska-Mazur J, Bieńkowski P, Samochowiec J. BDNF rs 6265 polymorphism and COMT rs 4680 polymorphism in deficit schizophrenia in Polish sample. Pharmacol Rep 2014; 65:1185-93. [PMID: 24399714 DOI: 10.1016/s1734-1140(13)71476-2] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2013] [Revised: 04/10/2013] [Indexed: 12/19/2022]
Abstract
BACKGROUND Deficit schizophrenia (DS) is distinguished from the group of schizophrenic psychoses based on the presence of primary negative symptoms. It differs from nondeficit (NDS) forms of schizophrenia in dimensions such as risk factors, family history, course of illness and neurobiological differences. The aim of the study was assessment of a potential association of the investigated polymorphisms of the brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT) genes with the deficit syndrome in schizophrenia. METHODS A cohort of 200 patients with schizophrenia (81 DS and 119 NDS subjects) and a group of 100 control subjects matched for ethnicity, sex and age were recruited. Somatic and psychometric assessment were conducted as well as structured interview about the influence of adverse biological, family and social factors. Genetic analysis of the BDNF (Val66Met) rs6265 and the COMT (Val158Met) rs4680 polymorphisms was performed. RESULTS We found significant differences between DS and NDS in rs4680 COMT genotype distribution: more homozygous Val/Val were found (31 vs. 17%) in the NDS compared to the DS subgroup. No associations were found between the investigated polymorphisms of the BDNF gene and the presence of schizophrenia either in DS and NDS subgroups. CONCLUSION The analysis of the COMT rs4680 polymorphism in the present DS and NDS study shows that some genetic factors may be relevant in analyzing the reasons for the differentiation of schizophrenic subtypes.
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Affiliation(s)
- Justyna Pełka-Wysiecka
- Department of Psychiatry, Pomeranian Medical University, Broniewskiego 26, PL 71-460 Szczecin, Poland.
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42
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Troisi A. Functional Classification of Psychiatric Disorders: A Luminous Future? PSYCHOLOGICAL INQUIRY 2014. [DOI: 10.1080/1047840x.2014.916192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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43
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Bahorik AL, Newhill CE, Eack SM. Neurocognitive functioning of individuals with schizophrenia: using and not using drugs. Schizophr Bull 2014; 40:856-67. [PMID: 23884348 PMCID: PMC4059433 DOI: 10.1093/schbul/sbt099] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
OBJECTIVES Research on neurocognition in schizophrenia, using modest samples and self-rated assessments, reports drug use contributes to improved rather than impaired cognitive function. We have sought to replicate these findings in a large sample of patients that had their drug-use status confirmed by laboratory assays and evaluated the potential differences in cognitive function between patients with positive and negative results. METHODS Nine hundred and seventy four schizophrenia patients completed neuropsychological and laboratory tests at screening/baseline of the Clinical Antipsychotic Trials of Intervention Effectiveness study. Radioimmunoassay (RIA) of hair tested for cannabis, cocaine and methamphetamine. RESULTS Many patients screened positive for drug use (n = 262; 27%), and there were no differences between patients with positive and negative results in terms of cognitive function after adjusting for multiple inference testing, except patients with positive RIA for methamphetamine demonstrated increased processing speed (corrected, P = .024). Moderator models were employed to explore potential subgroup differences in this pattern of results. At low medication dosages, patients with positive RIA for cocaine demonstrated decreased processing speed compared with patients with negative RIA for cocaine (uncorrected, P = .008). And for any other drugs with low psychopathology, patients with positive RIA demonstrated decreased working memory compared with patients with negative RIA (uncorrected, P = .006). CONCLUSIONS No positive effects of cannabis on cognitive function were observed, and drug use was not associated with improved neurocognition across most of the subgroup characteristics explored in this sample of schizophrenia patients.
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Affiliation(s)
- Amber L. Bahorik
- School of Social Work, University of Pittsburgh, Pittsburgh, PA;,Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, PA,*To whom correspondence should be addressed; School of Social Work, University of Pittsburgh, 2117 Cathedral of Learning, 4200 Fifth Avenue, Pittsburgh, PA 15260, US; tel: 814-659-5713; e-mail:
| | | | - Shaun M. Eack
- School of Social Work, University of Pittsburgh, Pittsburgh, PA;,Western Psychiatric Institute and Clinic, University of Pittsburgh, Pittsburgh, PA
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44
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Marder SR, Kirkpatrick B. Defining and measuring negative symptoms of schizophrenia in clinical trials. Eur Neuropsychopharmacol 2014; 24:737-43. [PMID: 24275698 DOI: 10.1016/j.euroneuro.2013.10.016] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2013] [Revised: 10/09/2013] [Accepted: 10/31/2013] [Indexed: 11/30/2022]
Abstract
Recent attention has focused on negative symptoms as a target for new therapeutic approaches including pharmacological agents, medical devices, and psychosocial treatments. Each of these approaches requires an instrument for measuring the severity of negative symptoms as well as changes in severity over time. The instrument selected should provide coverage for the domains of negative symptoms; it should be sensitive to change; it should be reliable and relatively brief; and it should be useful for large international trials. These criteria were used to evaluate a number of older instruments including the Schedule for the Assessment of Negative Symptoms (SANS), the Positive and Negative Symptoms Scale (PANSS), and the Negative Symptom Assessment Scale (NSA). Two newer scales, the Brief Negative Symptom Scale (BNSS) and the Clinical Assessment Interview for Negative Symptoms (CAINS) were developed following a National Institute of Mental Health consensus meeting and addressed some of the shortcomings of earlier instruments.
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Affiliation(s)
- Stephen R Marder
- Semel Institute for Neuroscience at UCLA and VA Desert Pacific Mental Illness Research, Education, and Clinical Center, Los Angeles, USA.
| | - Brian Kirkpatrick
- Department of Psychiatry, School of Medicine, University of Nevada, Reno, NV, USA
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Executive functioning and psychopathological profile in relatives of individuals with deficit v. non-deficit schizophrenia: a pilot study. Epidemiol Psychiatr Sci 2014; 23:85-97. [PMID: 23545096 PMCID: PMC6998377 DOI: 10.1017/s2045796013000140] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Aims. Heterogeneity of schizophrenia is known to be reflected in neuropsychological functioning of patients, but its expression in relatives is understudied. This study aims at exploring relationship between executive functioning and clinical profiles of first-degree relatives of patients who are classified as having or not having the deficit subtype of schizophrenia (DSRELs v. non-DSRELs), with the prediction of greater executive impairment in DSRELs. Methods. DSRELs (n = 15) and non-DSRELs (n = 40) were compared with community controls (CCs, n = 55) on executive functioning measured by the Wisconsin Card Sorting Test (WCST) and the phonemic verbal fluency (PVF), and clinical measures. Effects of psychopathology and intelligence quotient (IQ) measures were investigated to determine their association with executive performance. Results. DSRELs showed more executive dysfunction on WCST and poorer social functioning than CCs and more severe negative symptoms than non-DSRELs. Differences on WCST-categories achieved (WCST-CA) remained significant after adjustment for clinical confounders and IQ. WCST-CA was associated with apathy and paranoid ideation only within the DSREL subgroup. Conclusions. Executive functioning and negative symptoms are severely impaired in first-degree relatives of deficit syndrome patients, thus suggesting that some neurocognitive deficits in patients may be transmitted within families according to the pathophysiology of the probands.
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Abstract
A selective review of the negative symptoms of schizophrenia is an appropriate article to result from the festschrift honoring William T. Carpenter Jr, as he has made substantial contributions in this area. This review assesses progress in 3 areas in which he has been an important investigator: the distinction between primary vs secondary negative symptoms; the appropriate design for treatment trials; and the nosology of negative symptoms.
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Affiliation(s)
- Brian Kirkpatrick
- *To whom correspondence should be addressed; Department of Psychiatry and Behavioral Sciences, University of Nevada School of Medicine,1664 North Virginia Street, Mail Stop 0354, Reno, NV 89557-0354, US; tel: 775-682-8449, fax: 775-784-1428, e-mail:
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Csukly G, Polgár P, Tombor L, Benkovits J, Réthelyi J. Theory of mind impairments in patients with deficit schizophrenia. Compr Psychiatry 2014; 55:349-56. [PMID: 24262115 DOI: 10.1016/j.comppsych.2013.08.025] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2013] [Revised: 07/04/2013] [Accepted: 08/04/2013] [Indexed: 11/25/2022] Open
Abstract
The deficit syndrome, a subgroup within schizophrenia, is characterized by enduring, idiopathic negative symptoms. Theory of mind (ToM), a domain of social cognition, is the ability of attributing mental states to ourselves and other people. ToM impairments have not been investigated earlier in deficit schizophrenia. The aim of the present study was to examine ToM differences between patients with deficit (SZ-D) and non-deficit schizophrenia (SZ-ND). Gender differences were also investigated, and based on the literature a better ToM performance was expected in female patients. The participants were 28 patients with SZ-ND, 30 patients with SZ-D, and 29 healthy control volunteers. The "Reading the Mind in the Eyes Test" was used to asses ToM deficits. Control subjects outperformed both patient groups, while there were no significant differences between the two schizophrenia subgroups. In female subjects, both controls and patients with SZ-ND performed significantly better than the SZ-D subgroup. In male subjects, controls performed significantly better than both patient groups. The "diminished emotional range" and the "curbing of interest" items of the Schedule for the Deficit Syndrome showed significant negative relationship with the ToM score. Our main finding is that female subjects with SZ-ND performed significantly better than female subjects with SZ-D.
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Affiliation(s)
- Gábor Csukly
- Department of Psychiatry Psychotherapy, Semmelweis University, 1083 Budapest, Hungary.
| | - Patrícia Polgár
- Department of Psychiatry Psychotherapy, Semmelweis University, 1083 Budapest, Hungary
| | - László Tombor
- Department of Psychiatry Psychotherapy, Semmelweis University, 1083 Budapest, Hungary
| | - Judit Benkovits
- Department of Psychiatry Psychotherapy, Semmelweis University, 1083 Budapest, Hungary
| | - János Réthelyi
- Department of Psychiatry Psychotherapy, Semmelweis University, 1083 Budapest, Hungary
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Chue P, Lalonde JK. Addressing the unmet needs of patients with persistent negative symptoms of schizophrenia: emerging pharmacological treatment options. Neuropsychiatr Dis Treat 2014; 10:777-89. [PMID: 24855363 PMCID: PMC4020880 DOI: 10.2147/ndt.s43404] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
The negative symptoms of schizophrenia represent an impairment of normal emotional responses, thought processes and behaviors, and include blunting or flattening of affect, alogia/aprosody, avolition/apathy, anhedonia, and asociality. Negative symptoms contribute to a reduced quality of life, increased functional disability, increased burden of illness, and poorer long-term outcomes, to a greater degree than positive symptoms. Primary negative symptoms are prominent and persistent in up to 26% of patients with schizophrenia, and they are estimated to occur in up to 58% of outpatients at any given time. Negative symptoms respond less well to medications than positive symptoms, and to date treatment options for negative symptoms have been limited, with no accepted standard treatment. Modest benefits have been reported with a variety of different agents, including second-generation antipsychotics and add-on therapy with antidepressants and other pharmacological classes. Recent clinical research focusing on negative symptoms target novel biological systems, such as glutamatergic neurotransmission. Different approaches include: enhancing N-methyl-D-aspartate receptor function with agents that bind directly to the glycine ligand site or with glycine reuptake inhibitors; influencing the metabotropic glutamate receptor (mGluR2/3) with positive allosteric modulators; and stimulating nicotinic acetylcholine receptors. In conclusion, the lack of clearly efficacious pharmacological treatments for the management of negative symptoms represents a significant unmet need, especially considering the importance of these symptoms on patient outcomes. Hence, further research to identify and characterize novel pharmacological treatments for negative symptoms is greatly needed.
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Affiliation(s)
- Pierre Chue
- Department of Psychiatry, University of Alberta, Edmonton, AB, Canada
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Smyth AM, Lawrie SM. The neuroimmunology of schizophrenia. CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE : THE OFFICIAL SCIENTIFIC JOURNAL OF THE KOREAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY 2013; 11:107-17. [PMID: 24465246 PMCID: PMC3897758 DOI: 10.9758/cpn.2013.11.3.107] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Revised: 11/22/2013] [Accepted: 11/25/2013] [Indexed: 01/16/2023]
Abstract
Schizophrenia (SCZ) is a polygenic, multi-factorial disorder and a definitive understanding of its pathophysiology has been lacking since it was first described more than a century ago. The predominant pharmacological approach used to treat SCZ is the use of dopamine receptor antagonists. The fact that many patients remain symptomatic, despite complying with medication regimens, emphasises the need for a more encompassing explanation for both the causes and treatment of SCZ. Recent neuroanatomical, neurobiological, environmental and genetic studies have revived the idea that inflammatory pathways are involved in the pathogenesis of SCZ. These new insights have emerged from multiple lines of evidence, including the levels of inflammatory proteins in the central nervous system of patients with SCZ and animal models. This review focuses on aberrant inflammatory mechanisms present both before and during the onset of the psychotic symptoms that characterise SCZ and discusses recent research into adjunctive immune system modulating therapies for its more effective treatment.
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Affiliation(s)
- Annya M. Smyth
- Department of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, United Kingdom
| | - Stephen M. Lawrie
- Department of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh, United Kingdom
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Takayanagi M, Wentz J, Takayanagi Y, Schretlen DJ, Ceyhan EL, Wang L, Suzuki M, Sawa A, Barta PE, Ratnanather JT, Cascella NG. Reduced anterior cingulate gray matter volume and thickness in subjects with deficit schizophrenia. Schizophr Res 2013; 150:484-90. [PMID: 24035178 PMCID: PMC4076020 DOI: 10.1016/j.schres.2013.07.036] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2013] [Revised: 07/12/2013] [Accepted: 07/17/2013] [Indexed: 12/15/2022]
Abstract
BACKGROUND Patients with deficit schizophrenia (D-SZ) differ from patients with the non-deficit form of schizophrenia (ND-SZ) in several aspects such as risk factors, neurobiological correlates, treatment response and clinical outcome. It has been debated if brain morphology could differentiate D-SZ from ND-SZ. Anterior cingulate gyrus (ACG) region regulates cognitive and emotional processing and past studies reported structural changes in this region in patients with SZ. METHODS 1.5-T 3D MRI scans were obtained from 18 D-SZ patients, 30 ND-SZ patients and 82 healthy controls (HCs). We used FreeSurfer-initalized labeled cortical distance mapping (FSLCDM) to measure ACG gray matter volume, cortical thickness, and area of the gray/white interface. Furthermore, cortical thickness was compared among the 3 groups using the pooled labeled cortical distance mapping (LCDM) method. RESULTS The ACG cortex of the D-SZ group was thinner than the ND-SZ group. Pooled LCDM demonstrated that the ACG cortex was bilaterally thinner in both the ND-SZ group and the D-SZ group compared with the control group. The right ACG gray matter volume was significantly reduced in D-SZ patients as compared with healthy controls (p=0.005 CONCLUSION: Our data suggest that qualitative, categorical differences in neuroanatomy may distinguish between deficit and non-deficit subtypes of schizophrenia.
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Affiliation(s)
- Mizuho Takayanagi
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States,Department of Neuropsychiatry, University of Toyama, Toyama, Japan
| | - Jacqueline Wentz
- Center for Imaging Science and Institute for Computational Medicine, The Whitaker Biomedical Engineering Institute, Johns Hopkins University, Baltimore, MD, United States
| | - Yoichiro Takayanagi
- Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
| | - David J. Schretlen
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | | | - Lei Wang
- Department of Psychiatry and Behavioral Sciences, Northwestern University School of Medicine, Chicago, IL, United States
| | - Michio Suzuki
- Department of Neuropsychiatry, University of Toyama, Toyama, Japan
| | - Akira Sawa
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Patrick E. Barta
- Center for Imaging Science and Institute for Computational Medicine, The Whitaker Biomedical Engineering Institute, Johns Hopkins University, Baltimore, MD, United States
| | - J. Tilak Ratnanather
- Center for Imaging Science and Institute for Computational Medicine, The Whitaker Biomedical Engineering Institute, Johns Hopkins University, Baltimore, MD, United States
| | - Nicola G. Cascella
- Department of Psychiatry and Behavioral Sciences, Northwestern University School of Medicine, Chicago, IL, United States
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