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Isaacs DA, Xue A, Conley AC, Key AP. Auditory gating and its clinical correlates in adults with chronic tic disorder and neurotypical adults. Clin Neurophysiol 2024; 168:72-82. [PMID: 39476471 PMCID: PMC11647855 DOI: 10.1016/j.clinph.2024.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Revised: 09/22/2024] [Accepted: 10/11/2024] [Indexed: 11/06/2024]
Abstract
BACKGROUND Over 80% of adults with chronic tic disorder (CTD) experience sensory over-responsivity (SOR), defined as heightened awareness of and/or behavioral reactivity to commonplace environmental stimuli. One potential mechanism underpinning SOR is sensory gating impairment. Sensory gating is the physiologic process whereby redundant stimuli are filtered out in early perceptual stages. In this study, we compared sensory gating between neurotypical and CTD adults and determined if gating indices associated with SOR. METHODS Neurotypical (n = 31) and CTD adults (n = 26) completed a clinical assessment, including two SOR measures (Sensory Gating Inventory, SGI; Sensory Perception Quotient, SPQ), and an auditory gating paradigm while monitored on EEG. RESULTS CTD adults exhibited greater SOR. Neurotypical and CTD adults did not differ in P50, N100, or P200 gating ratios. In regression analyses, N100 gating ratio was significantly associated with SGI score; the magnitude of this association was greater for neurotypical than CTD adults. No other significant associations emerged between gating ratios and SOR measures. CONCLUSION Findings do not support sensory gating impairment as a mechanism underpinning SOR in CTD. The relationship between N100 gating and SOR warrants further investigation. SIGNIFICANCE This is the first study to examine auditory gating in individuals with CTD.
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Affiliation(s)
- David A Isaacs
- Department of Neurology, Vanderbilt University Medical Center, 1161 21st Ave S, Nashville, TN 37232, USA.
| | - Andrew Xue
- Department of Neuroscience, Vanderbilt University, 2201 West End Ave, Nashville, TN 37235, USA.
| | - Alexander C Conley
- Center for Cognitive Medicine, Vanderbilt University Medical Center, 1601 23rd Ave S, Nashville, TN 37212, USA.
| | - Alexandra P Key
- Department of Pediatrics, Marcus Autism Center, Emory University School of Medicine, 1920 Briarcliff Rd, NE, Atlanta, GA 30329, USA.
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2
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Schulz SE, Luszawski M, Hannah KE, Stevenson RA. Sensory Gating in Neurodevelopmental Disorders: A Scoping Review. Res Child Adolesc Psychopathol 2023; 51:1005-1019. [PMID: 37014483 DOI: 10.1007/s10802-023-01058-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/16/2023] [Indexed: 04/05/2023]
Abstract
This review aimed to explore the current understanding of sensory gating in neurodevelopmental disorders as a possible transdiagnostic mechanism. We applied methods according to the Joanna Briggs Institute Manual for Evidence Synthesis, following the population, concept, and context scoping review eligibility criteria. Using a comprehensive search strategy in five relevant research databases (Medline, EMBASE, CINAHL, PsychInfo, and Scopus), we searched for relevant peer-reviewed, primary research articles and unpublished data. Two independent reviewers screened the titles and abstracts, full-texts, and completed data extraction. We identified a total of 81 relevant articles and used descriptive analyses to summarize the characteristics and outcomes of all identified studies. Literature regarding sensory gating was most common in autistic populations with relatively fewer studies examining attention-deficit/hyperactivity disorder, tic disorders, and childhood-onset fluency disorder (COFD). The methods to assess sensory gating varied widely both within and between groups and included measures such as habituation, prepulse inhibition, affect-modulated inhibition, medication and other intervention trials. Most consistently, when participants complete questionnaires about their sensory experiences, those who have neurodevelopmental disorders report differences in their sensory gating. Affect-modulated inhibition appears to be discrepant between samples with and without neurodevelopmental disorder diagnoses. Habituation was the most commonly reported phenomenon and many differences in habituation have been found in autistic individuals and individuals with tic disorders whereas concerns with inhibition seemed more common in COFD. Overall, the evidence is inconsistent within and between disorders suggesting there is still much to learn about sensory gating in neurodevelopmental disorders.
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Affiliation(s)
- Samantha E Schulz
- Department of Psychology, University of Western Ontario, London, Canada
- Brain and Mind Institute, University of Western Ontario, London, Canada
- Western Institute for Neuroscience, University of Western Ontario, London, ON, Canada
| | - Michelle Luszawski
- Department of Psychology, University of Western Ontario, London, Canada
- Brain and Mind Institute, University of Western Ontario, London, Canada
- Western Institute for Neuroscience, University of Western Ontario, London, ON, Canada
| | - Kara E Hannah
- Department of Psychology, University of Western Ontario, London, Canada
- Brain and Mind Institute, University of Western Ontario, London, Canada
- Western Institute for Neuroscience, University of Western Ontario, London, ON, Canada
| | - Ryan A Stevenson
- Department of Psychology, University of Western Ontario, London, Canada.
- Brain and Mind Institute, University of Western Ontario, London, Canada.
- Western Institute for Neuroscience, University of Western Ontario, London, ON, Canada.
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le Sommer J, Low AM, Møllegaard Jepsen JR, Fagerlund B, Vangkilde S, Habekost T, Glenthøj B, Oranje B. Effects of methylphenidate on mismatch negativity and P3a amplitude of initially psychostimulant-naïve, adult ADHD patients. Psychol Med 2023; 53:957-965. [PMID: 34218835 DOI: 10.1017/s0033291721002373] [Citation(s) in RCA: 2] [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] [Indexed: 11/05/2022]
Abstract
BACKGROUND Deficient information processing in ADHD theoretically results in sensory overload and may underlie the symptoms of the disorder. Mismatch negativity (MMN) and P3a amplitude reflect an individual's detection and subsequent change in attention to stimulus change in their environment. Our primary aim was to explore MMN and P3a amplitude in adult ADHD patients and to examine the effects of methylphenidate (MPH) on these measures. METHODS Forty initially psychostimulant-naïve, adult ADHD patients without comorbid ASD and 42 matched healthy controls (HC) were assessed with an MMN paradigm at baseline. Both groups were retested after 6 weeks, in which patients were treated with MPH. RESULTS Neither significant group differences in MMN nor P3a amplitude were found at baseline. Although 6-week MPH treatment significantly reduced symptomatology and improved daily functioning of the patients, it did not significantly affect MMN amplitude; however, it did significantly reduce P3a amplitude compared to the HC. Furthermore, more severe ADHD symptoms were significantly associated with larger MMN amplitudes in the patients, both at baseline and follow-up. CONCLUSION We found no evidence for early information processing deficits in patients with ADHD, as measured with MMN and P3a amplitude. Six-week treatment with MPH decreased P3a but not MMN amplitude, although more severe ADHD-symptoms were associated with larger MMN amplitudes in the patients. Given that P3a amplitude represents an important attentional process and that glutamate has been linked to both ADHD and MMN amplitude, future research should investigate augmenting MPH treatment of less responsive adults with ADHD with glutamatergic antagonists.
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Affiliation(s)
- Julijana le Sommer
- Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark
- Department of Psychology, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Ann-Marie Low
- Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark
- Department of Psychology, University of Copenhagen, Copenhagen, Denmark
| | - Jens Richardt Møllegaard Jepsen
- Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark
- Child and Adolescent Mental Health Centre, Mental Health Services, Copenhagen, Denmark
| | - Birgitte Fagerlund
- Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark
| | - Signe Vangkilde
- Department of Psychology, University of Copenhagen, Copenhagen, Denmark
- Child and Adolescent Mental Health Centre, Mental Health Services, Copenhagen, Denmark
| | - Thomas Habekost
- Department of Psychology, University of Copenhagen, Copenhagen, Denmark
| | - Birte Glenthøj
- Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Bob Oranje
- Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark
- Department of Psychiatry, University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands
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Ptukha M, Fesenko Z, Belskaya A, Gromova A, Pelevin A, Kurzina N, Gainetdinov RR, Volnova A. Effects of Atomoxetine on Motor and Cognitive Behaviors and Brain Electrophysiological Activity of Dopamine Transporter Knockout Rats. Biomolecules 2022; 12:biom12101484. [PMID: 36291693 PMCID: PMC9599468 DOI: 10.3390/biom12101484] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 10/03/2022] [Accepted: 10/12/2022] [Indexed: 11/16/2022] Open
Abstract
Changes in dopaminergic and noradrenergic transmission are considered to be the underlying cause of attention deficit and hyperactivity disorder (ADHD). Atomoxetine (ATX) is a selective norepinephrine transporter (NET) inhibitor that is currently used for ADHD treatment. In this study, we aimed to evaluate the effect of atomoxetine on the behavior and brain activity of dopamine transporter knockout (DAT-KO) rats, which are characterized by an ADHD-like behavioral phenotype. Prepulse inhibition (PPI) was assessed in DAT-KO and wild type rats after saline and ATX injections, as well as behavioral parameters in the Hebb-Williams maze and power spectra and coherence of electrophysiological activity. DAT-KO rats demonstrated a pronounced behavioral and electrophysiological phenotype, characterized by hyperactivity, increased number of errors in the maze, repetitive behaviors and disrupted PPI, changes in cortical and striatal power spectra and interareal coherence. Atomoxetine significantly improved PPI and decreased repetitive behaviors in DAT-KO rats and influenced behavior of wild-type rats. ATX also led to significant changes in power spectra and coherence of DAT-KO and wild type rats. Assessment of noradrenergic modulation effects in DAT-KO provides insight into the intricate interplay of monoaminergic systems, although further research is still required to fully understand the complexity of this interaction.
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Affiliation(s)
- Maria Ptukha
- Institute of Translational Biomedicine, Saint Petersburg State University, 199034 Saint Petersburg, Russia
- Correspondence: (M.P.); (A.V.)
| | - Zoia Fesenko
- Institute of Translational Biomedicine, Saint Petersburg State University, 199034 Saint Petersburg, Russia
| | - Anastasia Belskaya
- Institute of Translational Biomedicine, Saint Petersburg State University, 199034 Saint Petersburg, Russia
| | - Arina Gromova
- Faculty of Biology, Saint Petersburg State University, 199034 Saint Petersburg, Russia
| | - Arseniy Pelevin
- Faculty of Biology, Saint Petersburg State University, 199034 Saint Petersburg, Russia
| | - Natalia Kurzina
- Institute of Translational Biomedicine, Saint Petersburg State University, 199034 Saint Petersburg, Russia
| | - Raul R. Gainetdinov
- Institute of Translational Biomedicine, Saint Petersburg State University, 199034 Saint Petersburg, Russia
- Saint Petersburg State University Hospital, Saint Petersburg State University, 199034 Saint Petersburg, Russia
| | - Anna Volnova
- Institute of Translational Biomedicine, Saint Petersburg State University, 199034 Saint Petersburg, Russia
- Faculty of Biology, Saint Petersburg State University, 199034 Saint Petersburg, Russia
- Correspondence: (M.P.); (A.V.)
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Stolte M, Oranje B, Van Luit JEH, Kroesbergen EH. Prepulse Inhibition and P50 Suppression in Relation to Creativity and Attention: Dispersed Attention Beneficial to Quantitative but Not Qualitative Measures of Divergent Thinking. Front Psychiatry 2022; 13:875398. [PMID: 35757214 PMCID: PMC9218263 DOI: 10.3389/fpsyt.2022.875398] [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: 02/14/2022] [Accepted: 05/16/2022] [Indexed: 11/13/2022] Open
Abstract
The current study investigated whether lower sensory and sensorimotor gating were related to higher levels of creativity and/or attentional difficulties in a natural population of primary school children (9- to 13-year-old). Gating abilities were measured with P50 suppression and prepulse inhibition of the startle reflex (PPI). The final sample included 65 participants in the P50 analyses and 37 participants in the PPI analyses. Our results showed that children with a high P50 amplitude to testing stimuli scored significantly higher on the divergent outcome measures of fluency and flexibility but not originality compared to children with a lower amplitude. No significant differences were found on any of the creativity measures when the sample was split on average PPI parameters. No significant differences in attention, as measured with a parent questionnaire, were found between children with low or high levels of sensory or sensorimotor gating. The data suggest that quantitative, but not qualitative measures of divergent thinking benefit from lower psychophysiological gating and that attentional difficulties stem from specific instead of general gating deficits. Future studies should take the effect of controlled attention into consideration.
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Affiliation(s)
- Marije Stolte
- Department of Orthopedagogics: Cognitive and Motor Disabilities, Utrecht University, Utrecht, Netherlands
| | - Bob Oranje
- Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Center Glostrup, Glostrup, Denmark
| | - Johannes E H Van Luit
- Department of Orthopedagogics: Cognitive and Motor Disabilities, Utrecht University, Utrecht, Netherlands
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6
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Leshem R, Icht M, Ben-David BM. Processing of Spoken Emotions in Schizophrenia: Forensic and Non-forensic Patients Differ in Emotional Identification and Integration but Not in Selective Attention. Front Psychiatry 2022; 13:847455. [PMID: 35386523 PMCID: PMC8977511 DOI: 10.3389/fpsyt.2022.847455] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Accepted: 02/22/2022] [Indexed: 11/13/2022] Open
Abstract
Patients with schizophrenia (PwS) typically demonstrate deficits in visual processing of emotions. Less is known about auditory processing of spoken-emotions, as conveyed by the prosodic (tone) and semantics (words) channels. In a previous study, forensic PwS (who committed violent offenses) identified spoken-emotions and integrated the emotional information from both channels similarly to controls. However, their performance indicated larger failures of selective-attention, and lower discrimination between spoken-emotions, than controls. Given that forensic schizophrenia represents a special subgroup, the current study compared forensic and non-forensic PwS. Forty-five PwS listened to sentences conveying four basic emotions presented in semantic or prosodic channels, in different combinations. They were asked to rate how much they agreed that the sentences conveyed a predefined emotion, focusing on one channel or on the sentence as a whole. Their performance was compared to that of 21 forensic PwS (previous study). The two groups did not differ in selective-attention. However, better emotional identification and discrimination, as well as better channel integration were found for the forensic PwS. Results have several clinical implications: difficulties in spoken-emotions processing might not necessarily relate to schizophrenia; attentional deficits might not be a risk factor for aggression in schizophrenia; and forensic schizophrenia might have unique characteristics as related to spoken-emotions processing (motivation, stimulation).
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Affiliation(s)
- Rotem Leshem
- Department of Criminology, Bar-Ilan University, Ramat Gan, Israel
| | - Michal Icht
- Department of Communication Disorders, Ariel University, Ariel, Israel
| | - Boaz M Ben-David
- Baruch Ivcher School of Psychology, Reichman University (IDC), Herzliya, Israel.,Department of Speech-Language Pathology, University of Toronto, Toronto, ON, Canada.,Toronto Rehabilitation Institute, University Health Networks, Toronto, ON, Canada
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7
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Sommer JL, Low AM, Jepsen JRM, Fagerlund B, Vangkilde S, Habekost T, Glenthøj B, Oranje B. Effects of methylphenidate on sensory and sensorimotor gating of initially psychostimulant-naïve adult ADHD patients. Eur Neuropsychopharmacol 2021; 46:83-92. [PMID: 33663902 DOI: 10.1016/j.euroneuro.2021.02.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 01/15/2021] [Accepted: 02/09/2021] [Indexed: 11/16/2022]
Abstract
Deficient information processing in ADHD theoretically results in sensory overload, which in turn may underlie its symptoms. If this sensory overload is caused by deficient filtering of environmental stimuli, then one would expect finding deficits in P50 gating and prepulse inhibition of the startle reflex (PPI). Previous reports on these measures in ADHD have shown inconsistent findings, which may have been caused by either medication use or comorbidity (e.g. ASD). The primary aim of this study was therefore to explore P50 suppression and PPI in adult, psychostimulant-naïve patients with ADHD without major comorbidity, and to examine the effects of 6 weeks treatment with methylphenidate (MPH) on these measures. A total of 42 initially psychostimulant-naive, adult ADHD patients without major comorbidity and 42 matched healthy controls, were assessed for their P50 gating, PPI, and habituation/sensitization abilities at baseline and after 6 weeks of treatment with methylphenidate. Although six weeks of treatment with MPH significantly reduced symptomatology as well as improved daily life functioning in our patients, it neither significantly affected PPI, P50 suppression nor sensitization, but habituation unexpectedly decreased. The absence of PPI and P50 suppression deficits in our patients in the psychostimulant-naïve state indicates no gating deficits. In turn, this suggests that the difficulties to inhibit distraction of attention by irrelevant stimuli that many patients with (adult) ADHD report, have a different origin than the theoretical causes of sensory overload frequently reported in studies on patients with schizophrenia.
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Affiliation(s)
- Julijana le Sommer
- Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, Glostrup, Denmark; Department of Psychology, University of Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Faculty of Health and Medical Sciences, Denmark
| | - Ann-Marie Low
- Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, Glostrup, Denmark; Department of Psychology, University of Copenhagen, Denmark
| | - Jens Richardt Møllegaard Jepsen
- Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, Glostrup, Denmark; Child and Adolescent Mental Health Center, Mental Health Services, Copenhagen, Denmark
| | - Birgitte Fagerlund
- Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, Glostrup, Denmark
| | | | | | - Birte Glenthøj
- Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, Glostrup, Denmark; Department of Clinical Medicine, University of Copenhagen, Faculty of Health and Medical Sciences, Denmark
| | - Bob Oranje
- Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, Glostrup, Denmark; Department of Psychiatry, UMC-Utrecht Brain Center, Utrecht University, Utrecht, the Netherlands.
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Adra N, Cao A, Makris N, Valera EM. Sensory Modulation Disorder and its Neural Circuitry in Adults with ADHD: A Pilot Study. Brain Imaging Behav 2021; 15:930-940. [PMID: 32770315 PMCID: PMC10655817 DOI: 10.1007/s11682-020-00302-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Compared to healthy controls (HCs), individuals with attention-deficit/hyperactivity disorder (ADHD) exhibit more symptoms of sensory processing disorder (SPD), which is associated with difficulties in educational and social activities. Most studies examining comorbid SPD-ADHD have been conducted with children and have not explored relations to brain volumes. In this pilot study, we assessed a subtype of SPD, sensory modulation disorder (SMD), and its relation to select brain volumes in adults with ADHD. We administered part of the Sensory Processing 3-Dimensions Scale (SP3D) to assess subtypes of SMD and collected structural imaging scans from 25 adults with ADHD and 29 healthy controls (HCs). Relative to HCs, subjects with ADHD scored higher on sensory craving (SC) and sensory under-responsivity (SUR) subscales. Although sensory over-responsivity (SOR) was marginally higher, this was no longer true when accounting for co-occurring anxiety. In individuals with ADHD, both SC and SUR were positively associated with amygdalar volume, SUR was also positively associated with striatal volume, whereas SOR was negatively associated with posterior ventral diencephalon volume. These preliminary findings suggest that SC and SUR may be characteristic of ADHD while SOR may be driven by co-occurring anxiety. Because different modalities were associated with different brain volumes, our findings also suggest that the modalities may involve unique neural circuits, but with a partial overlap between SC and SUR. These pilot data provide support for conducting studies examining SMD in larger samples of adults with ADHD to determine reproducibility, applicability and implications of these findings.
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Affiliation(s)
- Noor Adra
- Wellesley College, Wellesley, MA, USA
- Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, USA
- Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
| | - Aihua Cao
- Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, USA
- Department of Pediatrics, Qilu hospital of Shandong University, Jinan, 250012, Shandong, China
- Brain Science Research Institute, Shandong University, Jinan, China
| | - Nikos Makris
- Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, USA
- Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA
| | - Eve M Valera
- Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, USA.
- Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
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Atagun MI, Drukker M, Hall MH, Altun IK, Tatli SZ, Guloksuz S, van Os J, van Amelsvoort T. Meta-analysis of auditory P50 sensory gating in schizophrenia and bipolar disorder. Psychiatry Res Neuroimaging 2020; 300:111078. [PMID: 32361172 DOI: 10.1016/j.pscychresns.2020.111078] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 03/16/2020] [Accepted: 03/19/2020] [Indexed: 11/15/2022]
Abstract
The ability of the brain to reduce the amount of trivial or redundant sensory inputs is called gating function. Dysfunction of sensory gating may lead to cognitive fragmentation and poor real-world functioning. The auditory dual-click paradigm is a pertinent neurophysiological measure of sensory gating function. This meta-analysis aimed to examine the subcomponents of abnormal P50 waveforms in bipolar disorder and schizophrenia to assess P50 sensory gating deficits and examine effects of diagnoses, illness states (first-episode psychosis vs. schizophrenia, remission vs. episodes in bipolar disorder), and treatment status (medication-free vs. medicated). Literature search of PubMed between Jan 1st 1980 and March 31st 2019 identified 2091 records for schizophrenia, 362 for bipolar disorder. 115 studies in schizophrenia (4932 patients), 16 in bipolar disorder (975 patients) and 10 in first-degree relatives (848 subjects) met the inclusion criteria. P50 sensory gating ratio (S2/S1) and S1-S2 difference were significantly altered in schizophrenia, bipolar disorder and their first-degree relatives. First-episode psychosis did not differ from schizophrenia, however episodes altered P50 sensory gating in bipolar disorder. Medications improve P50 sensory gating alterations in schizophrenia significantly and at trend level in bipolar disorder. Future studies should examine longitudinal course of P50 sensory gating in schizophrenia and bipolar disorder.
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Affiliation(s)
- Murat Ilhan Atagun
- Department of Psychiatry, Ankara Yildirim Beyazit University Medical School, Universities Region, Ihsan Dogramaci Boulevard. No: 6, Bilkent, Cankaya, Ankara Turkey.
| | - Marjan Drukker
- Department of Psychiatry and Neuropsychology, Maastricht University School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht, the Netherlands
| | - Mei Hua Hall
- Psychosis Neurobiology Laboratory, Harvard Medical School, McLean Hospital, Belmont, Massachusetts, USA
| | - Ilkay Keles Altun
- Department of Psychiatry, Bursa Higher Education Training and Education Hospital, Bursa, Turkey
| | | | - Sinan Guloksuz
- Department of Psychiatry and Neuropsychology, Maastricht University School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht, the Netherlands; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
| | - Jim van Os
- Department of Psychiatry and Neuropsychology, Maastricht University School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht, the Netherlands; King's Health Partners Department of Psychosis Studies, King's College London, Institute of Psychiatry, London, United Kingdom; Department of Psychiatry, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, the Netherlands
| | - Thérèse van Amelsvoort
- Department of Psychiatry and Neuropsychology, Maastricht University School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht, the Netherlands
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Auditory sensory gating in young adolescents with early-onset psychosis: a comparison with attention deficit/hyperactivity disorder. Neuropsychopharmacology 2020; 45:649-655. [PMID: 31649298 PMCID: PMC7021818 DOI: 10.1038/s41386-019-0555-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Revised: 09/23/2019] [Accepted: 10/17/2019] [Indexed: 01/08/2023]
Abstract
Numerous studies have demonstrated impaired sensory gating in schizophrenia and this impairment has been proposed as a candidate biomarker for the disorder. The typical age of onset for schizophrenia is early adulthood, however a sizable group of patients present with psychotic symptoms before the age of 18, commonly referred to as early-onset psychosis (EOP). How an earlier onset influences sensory gating is currently unknown. Impaired sensory gating may not be specific to psychosis, but rather a shared disturbance of neurodevelopmental disorders, such as attention deficit/hyperactivity disorder (ADHD). Therefore, the current study investigated P50 suppression in young adolescents (12-17 years old) with either EOP (N = 55) or ADHD (N = 28) and age and gender matched healthy controls (HC) (N = 71). In addition to P50 suppression, N100 and P200 suppression data were also analyzed. No significant group differences in either raw mean P50 amplitude or mean P50 gating ratios were observed between EOP, ADHD, and HC. Additionally, we observed no P50 suppression deficit in those EOP patients diagnosed with schizophrenia (N = 39). Similarly, we observed no differences in N100 or P200 between the three groups. Healthy levels of P50 suppression were found in both patient groups. The results are in line with some previous studies showing healthy levels of P50 suppression in the early phases of schizophrenia. Our findings do not support P50 sensory gating as a valid biomarker for EOP or ADHD.
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11
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Association of cognitive and P50 suppression deficits in chronic patients with schizophrenia. Clin Neurophysiol 2020; 131:725-733. [DOI: 10.1016/j.clinph.2019.12.405] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 12/03/2019] [Accepted: 12/23/2019] [Indexed: 12/30/2022]
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12
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P50 inhibition deficit in patients with chronic schizophrenia: Relationship with cognitive impairment of MATRICS consensus cognitive battery. Schizophr Res 2020; 215:105-112. [PMID: 31780341 DOI: 10.1016/j.schres.2019.11.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 11/01/2019] [Accepted: 11/05/2019] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Cognitive impairment is a core symptom of schizophrenia (SCZ); however, its pathophysiological mechanisms remain unclear. The sensory gating (SG) deficits reflected by P50 inhibition are recurring in SCZ, and this inhibition may be related to the cognitive deficits seen in these individuals. This study aimed to investigate the relationship between P50 inhibition and cognitive dysfunction in SCZ, which has not been fully investigated up to this point. METHODS A total of 270 individuals with chronic SCZ and 116 healthy controls were enrolled in the study. Psychopathology of SCZ was rated by the positive and negative syndrome scale (PANSS), while cognitive function and P50 inhibition of subjects were assessed by the MATRICS Consensus Cognitive Battery (MCCB) and the electroencephalography system. RESULTS The MCCB total and its 10 index scores were significantly lower in patients than those in healthy controls (all p < 0.001). SCZ patients had a lower amplitude of S1, and higher P50 ratio than healthy controls (both p < 0.01). However, there were no significant correlations between the P50 ratio and any of the PANSS total and its subscale scores in SCZ patients (all p > 0.05). Moreover, no correlation was found between the P50 components and the MCCB scores (all p > 0.05). CONCLUSIONS Our findings suggest that the P50 inhibition deficits occur in Chinese individuals with SCZ, which may not be associated with their clinical symptoms and cognitive impairment.
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13
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Chang Q, Liu M, Tian Q, Wang H, Luo Y, Zhang J, Wang C. EEG-Based Brain Functional Connectivity in First-Episode Schizophrenia Patients, Ultra-High-Risk Individuals, and Healthy Controls During P50 Suppression. Front Hum Neurosci 2019; 13:379. [PMID: 31803031 PMCID: PMC6870009 DOI: 10.3389/fnhum.2019.00379] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Accepted: 10/10/2019] [Indexed: 01/29/2023] Open
Abstract
Dysfunctional processing of auditory sensory gating has generally been found in schizophrenic patients and ultra-high-risk (UHR) individuals. The aim of the study was to investigate the differences of functional interaction between brain regions and performance during the P50 sensory gating in UHR group compared with those in first-episode schizophrenia patients (FESZ) and healthy controls (HC) groups. The study included 128-channel scalp Electroencephalogram (EEG) recordings during the P50 auditory paradigm for 35 unmedicated FESZ, 30 drug-free UHR, and 40 HC. Cortical sources of scalp electrical activity were recomputed using exact low-resolution electromagnetic tomography (eLORETA), and functional brain networks were built at the source level and compared between the groups (FESZ, UHR, HC). A classifier using decision tree was designed for differentiating the three groups, which uses demographic characteristics, MATRICS Consensus Cognitive Battery parameters, behavioral features in P50 paradigm, and the measures of functional brain networks based on graph theory during P50 sensory gating. The results showed that very few brain connectivities were significantly different between FESZ and UHR groups during P50 sensory gating, and that a large number of brain connectivities were significantly different between FESZ and HC groups and between UHR and HC groups. Furthermore, the FESZ group had a stronger connection in the right superior frontal gyrus and right insula than the HC group. And the UHR group had an enhanced connection in the paracentral lobule and the middle temporal gyrus compared with the HC group. Moreover, comparison of classification analysis results showed that brain network metrics during P50 sensory gating can improve the accuracy of the classification for FESZ, UHR and HC groups. Our findings provide insight into the mechanisms of P50 suppression in schizophrenia and could potentially improve the performance of early identification and diagnosis of schizophrenia for the earliest intervention.
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Affiliation(s)
- Qi Chang
- School of Biological Science and Medical Engineering, Beihang University, Beijing, China.,Beijing Advanced Innovation Centre for Biomedical Engineering, Beihang University, Beijing, China.,Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, China
| | - Meijun Liu
- School of Biological Science and Medical Engineering, Beihang University, Beijing, China.,Beijing Advanced Innovation Centre for Biomedical Engineering, Beihang University, Beijing, China.,Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, China
| | - Qing Tian
- The National Clinical Research Center for Mental Disorders and Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Hua Wang
- School of Biological Science and Medical Engineering, Beihang University, Beijing, China.,Beijing Advanced Innovation Centre for Biomedical Engineering, Beihang University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.,Hefei Innovation Research Institute, Beihang University, Hefei, China.,School of Biomedical Engineering, Anhui Medical University, Hefei, China
| | - Yu Luo
- School of Biological Science and Medical Engineering, Beihang University, Beijing, China.,Beijing Advanced Innovation Centre for Biomedical Engineering, Beihang University, Beijing, China.,Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, China
| | - Jicong Zhang
- School of Biological Science and Medical Engineering, Beihang University, Beijing, China.,Beijing Advanced Innovation Centre for Biomedical Engineering, Beihang University, Beijing, China.,Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, China.,Hefei Innovation Research Institute, Beihang University, Hefei, China.,School of Biomedical Engineering, Anhui Medical University, Hefei, China
| | - Chuanyue Wang
- The National Clinical Research Center for Mental Disorders and Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
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14
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Micoulaud-Franchi JA, Lopez R, Cermolacce M, Vaillant F, Péri P, Boyer L, Richieri R, Bioulac S, Sagaspe P, Philip P, Vion-Dury J, Lancon C. Sensory Gating Capacity and Attentional Function in Adults With ADHD: A Preliminary Neurophysiological and Neuropsychological Study. J Atten Disord 2019; 23:1199-1209. [PMID: 26896149 DOI: 10.1177/1087054716629716] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Objective: The inability to filter sensory input correctly may impair higher cognitive function in ADHD. However, this relationship remains largely elusive. The objectives of the present study is to investigate the relationship between sensory input processing and cognitive function in adult patients with ADHD. Method: This study investigated the relationship between deficit in sensory gating capacity (P50 amplitude changes in a double-click conditioning-testing paradigm and perceptual abnormalities related to sensory gating deficit with the Sensory Gating Inventory [SGI]) and attentional and executive function (P300 amplitude in an oddball paradigm and attentional and executive performances with a neuropsychological test) in 24 adult patients with ADHD. Results: The lower the sensory gating capacity of the brain and the higher the distractibility related to sensory gating inability that the patients reported, the lower the P300 amplitude. Conclusion: The capacity of the brain to gate the response to irrelevant incoming sensory input may be a fundamental protective mechanism that prevents the flooding of higher brain structures with irrelevant information in adult patients with ADHD.
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Affiliation(s)
| | - Régis Lopez
- 3 Unités des troubles du sommeil, Hôpital Gui-de-Chauliac Montpellier, France.,4 Inserm U1061, Montpellier, France
| | - Michel Cermolacce
- 5 Département de Psychiatrie, CHU de Marseille, France.,6 UMR CNRS 729 / Aix-Marseille Université, Marseille, France
| | | | - Pauline Péri
- 5 Département de Psychiatrie, CHU de Marseille, France
| | - Laurent Boyer
- 5 Département de Psychiatrie, CHU de Marseille, France.,7 EA 3279 / Aix-Marseille Université, Marseille, France
| | - Raphaëlle Richieri
- 5 Département de Psychiatrie, CHU de Marseille, France.,7 EA 3279 / Aix-Marseille Université, Marseille, France
| | - Stéphanie Bioulac
- 2 USR CNRS 3113 SANPSY / Université de Bordeaux, France.,8 Pôle Universitaire de Psychiatrie de l'Enfant et de l'Adolescent, Bordeaux, France
| | | | - Pierre Philip
- 1 Clinique du sommeil, CHU de Bordeaux, France.,2 USR CNRS 3113 SANPSY / Université de Bordeaux, France
| | - Jean Vion-Dury
- 5 Département de Psychiatrie, CHU de Marseille, France.,6 UMR CNRS 729 / Aix-Marseille Université, Marseille, France
| | - Christophe Lancon
- 5 Département de Psychiatrie, CHU de Marseille, France.,7 EA 3279 / Aix-Marseille Université, Marseille, France
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15
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Regan SL, Hufgard JR, Pitzer EM, Sugimoto C, Hu YC, Williams MT, Vorhees CV. Knockout of latrophilin-3 in Sprague-Dawley rats causes hyperactivity, hyper-reactivity, under-response to amphetamine, and disrupted dopamine markers. Neurobiol Dis 2019; 130:104494. [PMID: 31176715 DOI: 10.1016/j.nbd.2019.104494] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 05/03/2019] [Accepted: 06/05/2019] [Indexed: 12/14/2022] Open
Abstract
Attention deficit hyperactivity disorder is a pervasive developmental disorder characterized by inattention, impulsivity, and hyperactivity and is 75-90% heritable. Latrophilin-3 (LPHN3; or ADGRL(3)) is associated with a subtype of ADHD, but how it translates to symptoms is unknown. LPHN3 is a synaptic adhesion G protein coupled receptor that binds to fibronectin leucine rich transmembrane protein 3 and teneurin-3 (FLRT3 and TEN-3). We created a null mutation of Lphn3 (KO) in Sprague-Dawley rats using CRISPR/Cas9 to delete exon-3. The KO rats had no effects on reproduction or survival but reduced growth. KO females showed catch-up weight gain whereas KO males did not. We tested WT and KO littermates for home-cage activity, anxiety-like behavior, acoustic startle response, and activity after amphetamine challenge. Expression of Lphn3-related genes, monoamines, and receptors were determined. Lphn3 KO rats showed persistent hyperactivity, increased acoustic startle, reduced activity in response to amphetamine relative to baseline, and female-specific reduced anxiety-like behavior. Expression of Lphn1, Lphn2, and Flrt3 by qPCR and their protein products by western-blot analysis showed no compensatory upregulation. Striatal tyrosine hydroxylase, aromatic L-amino acid decarboxylase (AADC), and the dopamine transporter were increased and dopamine D1 receptor (DRD1) and dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32) decreased with no changes in DRD2, DRD4, vesicular monoamine transporter-2, N-methyl-d-aspartate (NMDA)-NR1, -NR2A, or -NR2B. LPHN3 is expressed in many brain regions but its function is largely unknown. Data from human, mouse, zebrafish, Drosophila and our new Lphn3 KO rat data collectively show that its disruption is significantly correlated with hyperactivity and associated striatal changes in dopamine markers.
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Affiliation(s)
- Samantha L Regan
- Neuroscience Graduate Program, University of Cincinnati, United States of America
| | - Jillian R Hufgard
- Department of Obstetrics and Gynecology, Indiana University School of Medicine, United States of America
| | - Emily M Pitzer
- Neuroscience Graduate Program, University of Cincinnati, United States of America
| | - Chiho Sugimoto
- Department of Pediatrics, University of Cincinnati College of Medicine, Division of Neurology, Cincinnati Children's Hospital Medical Center, United States of America
| | - Yueh-Chiang Hu
- Department of Pediatrics, University of Cincinnati College of Medicine, Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United States of America
| | - Michael T Williams
- Department of Pediatrics, University of Cincinnati College of Medicine, Division of Neurology, Cincinnati Children's Hospital Medical Center, United States of America
| | - Charles V Vorhees
- Department of Pediatrics, University of Cincinnati College of Medicine, Division of Neurology, Cincinnati Children's Hospital Medical Center, United States of America.
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16
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Boggs DL, Surti TS, Esterlis I, Pittman B, Cosgrove K, Sewell RA, Ranganathan M, D’Souza DC. Minimal effects of prolonged smoking abstinence or resumption on cognitive performance challenge the "self-medication" hypothesis in schizophrenia. Schizophr Res 2018; 194:62-69. [PMID: 28392208 PMCID: PMC5630481 DOI: 10.1016/j.schres.2017.03.047] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Revised: 03/27/2017] [Accepted: 03/29/2017] [Indexed: 01/22/2023]
Abstract
One prominent, long-standing view is that individuals with schizophrenia smoke cigarettes more than the general population to "self-medicate" cognitive deficits and other symptoms. This study tested the self-medication hypothesis by examining the effects of smoking abstinence and resumption on cognition in patients with schizophrenia. Nicotine-dependent smokers with schizophrenia (n=26) were trained on a cognitive battery and then hospitalized to achieve and maintain confirmed abstinence from smoking for ~1 week. Cognition was tested while smoking as usual (baseline), one day after smoking cessation (early abstinence), ~1 week later (extended abstinence), and within ~3 weeks of resuming smoking (resumption). The test battery included measures of processing speed, attention, conflict resolution, verbal memory, working memory, verbal fluency, and executive function to evaluate multiple cognitive domains affected by schizophrenia. Positive and negative symptoms of schizophrenia, depressive symptoms, and dyskinesia were also measured at baseline and after prolonged abstinence. There were no significant changes in global cognitive test performance with smoking cessation, abstinence, or resumption. There were small decreases in a measure of processing speed and delayed verbal recall with abstinence, but these findings failed to survive adjustments for multiple comparisons. Surprisingly, in this within subject "On-Off-Off-On" design, there were no significant effects of early or prolonged abstinence from smoking on cognitive and behavioral measures in smokers with schizophrenia. The results of this study challenge the widely held "self-medication" hypothesis of smoking and schizophrenia, question the extent of pro-cognitive effects of smoking and nicotine in schizophrenia, and support encouraging smoking cessation in schizophrenia.
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Affiliation(s)
- Douglas L Boggs
- Psychiatry Service, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT, 06516 USA,Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
| | - Toral S. Surti
- Psychiatry Service, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT, 06516 USA,Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
| | - Irina Esterlis
- Psychiatry Service, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT, 06516 USA,Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA,Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, CT, 06519 USA
| | - Brian Pittman
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA,Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, CT, 06519 USA
| | - Kelly Cosgrove
- Psychiatry Service, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT, 06516 USA,Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA,Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, CT, 06519 USA
| | - R. Andrew Sewell
- Psychiatry Service, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT, 06516 USA,Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA,Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, CT, 06519 USA
| | - Mohini Ranganathan
- Psychiatry Service, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT, 06516 USA,Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA,Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, CT, 06519 USA
| | - Deepak Cyril D’Souza
- Psychiatry Service, VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT, 06516 USA,Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA,Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, 34 Park Street, New Haven, CT, 06519 USA
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17
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Micoulaud-Franchi JA, Lopez R, Michel P, Brandejsky L, Bioulac S, Philip P, Lancon C, Boyer L. The development of the SGI-16: a shortened sensory gating deficit and distractibility questionnaire for adults with ADHD. ACTA ACUST UNITED AC 2016; 9:179-187. [PMID: 28039669 DOI: 10.1007/s12402-016-0215-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Accepted: 12/22/2016] [Indexed: 11/30/2022]
Abstract
The Sensory Gating Inventory (SGI) is a questionnaire composed of 36 items designed to investigate abnormal perception related to the inability to control sensitivity to sensory stimuli frequently reported in adult with ADHD. This questionnaire can be considered too lengthy to be taken by people with ADHD, and a shortened version is needed. One hundred and sixty-three adults with ADHD responded to the SGI-36. An item reduction process took into account both the results of statistical analyses and the expertise of a steering committee. Construct validity, reliability, and external validity were tested for a short version (16 items). The structure of the SGI-16 was confirmed by principal components factor analysis. Cronbach's alpha coefficients ranged from 0.78 to 0.89. The SGI-16 dimension scores were highly correlated with their respective SGI-36 dimension scores. The SGI-16 seems to be both appropriate and useful for use in clinical practice to investigate perceptual abnormalities in adults with ADHD.
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Affiliation(s)
- Jean-Arthur Micoulaud-Franchi
- Services d'explorations fonctionnelles du système nerveux, Clinique du sommeil, CHU de Bordeaux, Place Amélie Raba-Leon, 33076, Bordeaux, France. .,Univ Bordeaux, SANPSY, USR 3413, F-33000, Bordeaux, France. .,CNRS, SANPSY, USR 3413, F-33000, Bordeaux, France.
| | - Régis Lopez
- Service de Neurologie, Unité des Troubles du Sommeil, Hôpital Gui-de-Chauliac, Montpellier, France.,Inserm U1061, 34000, Montpellier, France
| | - Pierre Michel
- Laboratoire de santé publique évaluation des systèmes de soins et santé perçue, Université de la Méditerranée - EA 3279 - Faculté de Médecine, 27 bd Jean Moulin, 13385, Marseille Cedex 05, France
| | - Laura Brandejsky
- Laboratoire de santé publique évaluation des systèmes de soins et santé perçue, Université de la Méditerranée - EA 3279 - Faculté de Médecine, 27 bd Jean Moulin, 13385, Marseille Cedex 05, France.,Pôle de Psychiatrie Conception, 145 boulevard Baille, 13006, Marseille, France
| | - Stéphanie Bioulac
- Services d'explorations fonctionnelles du système nerveux, Clinique du sommeil, CHU de Bordeaux, Place Amélie Raba-Leon, 33076, Bordeaux, France.,Univ Bordeaux, SANPSY, USR 3413, F-33000, Bordeaux, France.,CNRS, SANPSY, USR 3413, F-33000, Bordeaux, France
| | - Pierre Philip
- Services d'explorations fonctionnelles du système nerveux, Clinique du sommeil, CHU de Bordeaux, Place Amélie Raba-Leon, 33076, Bordeaux, France.,Univ Bordeaux, SANPSY, USR 3413, F-33000, Bordeaux, France.,CNRS, SANPSY, USR 3413, F-33000, Bordeaux, France
| | - Christophe Lancon
- Laboratoire de santé publique évaluation des systèmes de soins et santé perçue, Université de la Méditerranée - EA 3279 - Faculté de Médecine, 27 bd Jean Moulin, 13385, Marseille Cedex 05, France.,Pôle de Psychiatrie Conception, 145 boulevard Baille, 13006, Marseille, France
| | - Laurent Boyer
- Laboratoire de santé publique évaluation des systèmes de soins et santé perçue, Université de la Méditerranée - EA 3279 - Faculté de Médecine, 27 bd Jean Moulin, 13385, Marseille Cedex 05, France.,Pôle de Psychiatrie Conception, 145 boulevard Baille, 13006, Marseille, France
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18
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Mao Q, Tan YL, Luo XG, Tian L, Wang ZR, Tan SP, Chen S, Yang GG, An HM, Yang FD, Zhang XY. Association of catechol-O-methyltransferase Val(108/158) Met genetic polymorphism with schizophrenia, P50 sensory gating, and negative symptoms in a Chinese population. Psychiatry Res 2016; 242:271-276. [PMID: 27315458 DOI: 10.1016/j.psychres.2016.04.029] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2015] [Revised: 01/08/2016] [Accepted: 04/13/2016] [Indexed: 01/17/2023]
Abstract
Catechol-O-methyltransferase (COMT), an enzyme involved in the degradation and inactivation of the neurotransmitter dopamine, is associated with the sensory gating phenomenon, protecting the cerebral cortex from information overload. The COMT Val(108/158)Met polymorphism is essential for prefrontal cortex processing capacity and efficiency. The current study was designed to investigate the role of COMT Val(108/158)Met polymorphism in development, sensory gating deficit, and symptoms of schizophrenia in Han Chinese population. P50 gating was determined in 139 schizophrenic patients and 165 healthy controls. Positive and Negative Syndrome Scale (PANSS) was used to assess the clinical symptomatology in 370 schizophrenic subjects. COMT Val(108/158)Met polymorphism was genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP). No significant differences in COMT allele and genotype distributions were observed between schizophrenic patients and control groups. Although P50 deficits were present in patients, there was no evidence for an association between COMT Val(108/158)Met polymorphism and the P50 biomarker. Moreover, PANSS negative subscore was significantly higher in Val allele carriers than in Met/Met individuals. The present findings suggest that COMT Val(108/158)Met polymorphism may not contribute to the risk of schizophrenia and to the P50 deficits, but may contribute to the negative symptoms of schizophrenia among Han Chinese.
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Affiliation(s)
- Qiao Mao
- Biological Psychiatry Research Center, Peking University Huilongguan Teaching Hospital, Beijing 100096, PR China
| | - Yun-Long Tan
- Biological Psychiatry Research Center, Peking University Huilongguan Teaching Hospital, Beijing 100096, PR China.
| | - Xing-Guang Luo
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
| | - Li Tian
- Neuroscience Center, University of Helsinki, Viikinkaari 4, FIN-00014 Helsinki, Finland
| | - Zhi-Ren Wang
- Biological Psychiatry Research Center, Peking University Huilongguan Teaching Hospital, Beijing 100096, PR China
| | - Shu-Ping Tan
- Biological Psychiatry Research Center, Peking University Huilongguan Teaching Hospital, Beijing 100096, PR China
| | - Song Chen
- Biological Psychiatry Research Center, Peking University Huilongguan Teaching Hospital, Beijing 100096, PR China
| | - Gui-Gang Yang
- Biological Psychiatry Research Center, Peking University Huilongguan Teaching Hospital, Beijing 100096, PR China
| | - Hui-Mei An
- Biological Psychiatry Research Center, Peking University Huilongguan Teaching Hospital, Beijing 100096, PR China
| | - Fu-De Yang
- Biological Psychiatry Research Center, Peking University Huilongguan Teaching Hospital, Beijing 100096, PR China
| | - Xiang-Yang Zhang
- Biological Psychiatry Research Center, Peking University Huilongguan Teaching Hospital, Beijing 100096, PR China; Department of Psychiatry and Behavioral Sciences, Harris County Psychiatric Center, The University of Texas Health Science Center at Houston, Houston, TX, USA
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19
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Zhang D, Xu F, Xu H, Shull PB, Zhu X. Quantifying Different Tactile Sensations Evoked by Cutaneous Electrical Stimulation Using Electroencephalography Features. Int J Neural Syst 2016; 26:1650006. [DOI: 10.1142/s0129065716500064] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Psychophysical tests and standardized questionnaires are often used to analyze tactile sensation based on subjective judgment in conventional studies. In contrast with the subjective evaluation, a novel method based on electroencephalography (EEG) is proposed to explore the possibility of quantifying tactile sensation in an objective way. The proposed experiments adopt cutaneous electrical stimulation to generate two kinds of sensations (vibration and pressure) with three grades (low/medium/strong) on eight subjects. Event-related potentials (ERPs) and event-related synchronization/desynchronization (ERS/ERD) are extracted from EEG, which are used as evaluation indexes to distinguish between vibration and pressure, and also to discriminate sensation grades. Results show that five-phase P1–N1–P2–N2–P3 deflection is induced in EEG. Using amplitudes of latter ERP components (N2 and P3), vibration and pressure sensations can be discriminated on both individual and grand-averaged ERP ([Formula: see text]). The grand-average ERPs can distinguish the three sensations grades, but there is no significant difference on individuals. In addition, ERS/ERD features of mu rhythm (8–13[Formula: see text]Hz) are adopted. Vibration and pressure sensations can be discriminated on grand-average ERS/ERD ([Formula: see text]), but only some individuals show significant difference. The grand-averaged results show that most sensation grades can be differentiated, and most pairwise comparisons show significant difference on individuals ([Formula: see text]). The work suggests that ERP- and ERS/ERD-based EEG features may have potential to quantify tactile sensations for medical diagnosis or engineering applications.
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Affiliation(s)
- Dingguo Zhang
- State Key Laboratory of Mechanical Systems and Vibration, School of Mechanical Engineering, Shanghai Jiao Tong University, #800 Dongchuan Road, Minhang District, Shanghai 200240, P. R. China
| | - Fei Xu
- State Key Laboratory of Mechanical Systems and Vibration, School of Mechanical Engineering, Shanghai Jiao Tong University, #800 Dongchuan Road, Minhang District, Shanghai 200240, P. R. China
| | - Heng Xu
- State Key Laboratory of Mechanical Systems and Vibration, School of Mechanical Engineering, Shanghai Jiao Tong University, #800 Dongchuan Road, Minhang District, Shanghai 200240, P. R. China
| | - Peter B. Shull
- State Key Laboratory of Mechanical Systems and Vibration, School of Mechanical Engineering, Shanghai Jiao Tong University, #800 Dongchuan Road, Minhang District, Shanghai 200240, P. R. China
| | - Xiangyang Zhu
- State Key Laboratory of Mechanical Systems and Vibration, School of Mechanical Engineering, Shanghai Jiao Tong University, #800 Dongchuan Road, Minhang District, Shanghai 200240, P. R. China
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20
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Micoulaud-Franchi JA, Lopez R, Vaillant F, Richieri R, El-Kaim A, Bioulac S, Philip P, Boyer L, Lancon C. Perceptual abnormalities related to sensory gating deficit are core symptoms in adults with ADHD. Psychiatry Res 2015; 230:357-63. [PMID: 26416589 DOI: 10.1016/j.psychres.2015.09.016] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2015] [Revised: 07/15/2015] [Accepted: 09/10/2015] [Indexed: 10/23/2022]
Abstract
This study investigated and compared perceptual abnormalities related to sensory gating deficit in adult patients with Attention Deficit Disorder with Hyperactivity (A-ADHD) and adult patients with schizophrenia. Subjects were evaluated with the Sensory Gating Inventory (SGI). We compared SGI scores between patients with A-ADHD, patients with schizophrenia and healthy subjects. We also assessed the relationship between SGI scores and clinical symptoms, and evaluated the ability of the SGI to detect perceptual abnormalities in A-ADHD. Seventy adult patients with ADHD reported higher SGI scores than the 70 healthy subjects and the 70 patients with schizophrenia. The inattention factor of the ASRS correlated significantly with the overall SGI score. The ROC AUC for the overall SGI score in the A-ADHD group (versus the healthy group) illustrated good performance. The findings suggest that i) perceptual abnormalities are core symptoms of adult patients with ADHD and ii) the attention of patients with A-ADHD may be involuntarily drowned by many irrelevant environmental stimuli leading to their impaired attention on relevant stimuli. They also confirm that the SGI could be a useful self-report instrument to diagnose the clinical features of A-ADHD.
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Affiliation(s)
- Jean-Arthur Micoulaud-Franchi
- Bordeaux Sleep Clinique, Pellegrin University Hospital, 33076 Bordeaux, France; Bordeaux University, USR CNRS 3413 SANPSY, Research Unit, 33000 Bordeaux, France.
| | - Régis Lopez
- Department of Neurology and Sleep Medicine, Gui-de-Chauliac University Hospital, 34000 Montpellier, France; Inserm U1061, Research Unit, 34000 Montpellier, France
| | - Florence Vaillant
- Department of Psychiatry, Sainte-Marguerite University Hospital, 13009 Marseille, France
| | - Raphaëlle Richieri
- Department of Psychiatry, Sainte-Marguerite University Hospital, 13009 Marseille, France; Aix-Marseille University, EA 3279, Public Health, Chronic Diseases and Quality of Life, Research Unit, 13005 Marseille, France
| | - Alexandre El-Kaim
- Department of Psychiatry, Sainte-Marguerite University Hospital, 13009 Marseille, France
| | - Stéphanie Bioulac
- Bordeaux Sleep Clinique, Pellegrin University Hospital, 33076 Bordeaux, France; Bordeaux University, USR CNRS 3413 SANPSY, Research Unit, 33000 Bordeaux, France; Department of Children Psychiatry, Charles Perrens Hospital, 33000 Bordeaux, France
| | - Pierre Philip
- Bordeaux Sleep Clinique, Pellegrin University Hospital, 33076 Bordeaux, France; Bordeaux University, USR CNRS 3413 SANPSY, Research Unit, 33000 Bordeaux, France
| | - Laurent Boyer
- Department of Psychiatry, Sainte-Marguerite University Hospital, 13009 Marseille, France; Aix-Marseille University, EA 3279, Public Health, Chronic Diseases and Quality of Life, Research Unit, 13005 Marseille, France
| | - Christophe Lancon
- Department of Psychiatry, Sainte-Marguerite University Hospital, 13009 Marseille, France; Aix-Marseille University, EA 3279, Public Health, Chronic Diseases and Quality of Life, Research Unit, 13005 Marseille, France
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Abstract
Endophenotypes are disease-associated phenotypes that are thought to reflect the neurobiological or other mechanisms that underlie the more overt symptoms of a psychiatric illness. Endophenotypes have been critical in understanding the genetics, neurobiology, and treatment of schizophrenia. Because psychiatric illnesses have multiple causes, including both genetic and nongenetic risk factors, an endophenotype linked to one of the mechanisms may be expressed more frequently than the disease itself. However, in schizophrenia research, endophenotypes have almost exclusively been studied in older adolescents or adults who have entered or passed through the age of risk for the disorder. Yet, schizophrenia is a neurodevelopmental disorder where prenatal development starts a cascade of brain changes across the lifespan. Endophenotypes have only minimally been utilized to explore the perinatal development of vulnerability. One major impediment to the development of perinatally-useful endophenotypes has been the established validity criteria. For example, the criterion that the endophenotype be more frequently present in those with disease than those without is difficult to demonstrate when there can be a decades-long period between endophenotype measurement and the age of greatest risk for onset of the disorder. This article proposes changes to the endophenotype validity criteria appropriate to perinatal research and reviews how application of these modified criteria helped identify a perinatally-usable phenotype of risk for schizophrenia, P50 sensory gating, which was then used to propose a novel perinatal primary prevention intervention.
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Affiliation(s)
- Randal G. Ross
- Department of Psychiatry, University of Colorado Denver, Aurora, CO,*To whom correspondence should be addressed; Department of Psychiatry, School of Medicine, University of Colorado Denver, 13001 E. 17th Place, Campus Box F546, Aurora, CO 80045, US; tel: 303-724-6203, fax: 303-724-6207, e-mail:
| | - Robert Freedman
- Department of Psychiatry, University of Colorado Denver, Aurora, CO
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Micoulaud-Franchi JA, Vaillant F, Lopez R, Peri P, Baillif A, Brandejsky L, Steffen ML, Boyer L, Richieri R, Cermolacce M, Bioulac S, Aramaki M, Philip P, Lancon C, Vion-Dury J. Sensory gating in adult with attention-deficit/hyperactivity disorder: Event-evoked potential and perceptual experience reports comparisons with schizophrenia. Biol Psychol 2015; 107:16-23. [DOI: 10.1016/j.biopsycho.2015.03.002] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2014] [Revised: 03/01/2015] [Accepted: 03/02/2015] [Indexed: 11/28/2022]
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Chronaki G, Benikos N, Fairchild G, Sonuga-Barke EJS. Atypical neural responses to vocal anger in attention-deficit/hyperactivity disorder. J Child Psychol Psychiatry 2015; 56:477-87. [PMID: 25117642 DOI: 10.1111/jcpp.12312] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/29/2014] [Indexed: 11/28/2022]
Abstract
BACKGROUND Deficits in facial emotion processing, reported in attention-deficit/hyperactivity disorder (ADHD), have been linked to both early perceptual and later attentional components of event-related potentials (ERPs). However, the neural underpinnings of vocal emotion processing deficits in ADHD have yet to be characterised. Here, we report the first ERP study of vocal affective prosody processing in ADHD. METHODS Event-related potentials of 6-11-year-old children with ADHD (n = 25) and typically developing controls (n = 25) were recorded as they completed a task measuring recognition of vocal prosodic stimuli (angry, happy and neutral). Audiometric assessments were conducted to screen for hearing impairments. RESULTS Children with ADHD were less accurate than controls at recognising vocal anger. Relative to controls, they displayed enhanced N100 and attenuated P300 components to vocal anger. The P300 effect was reduced, but remained significant, after controlling for N100 effects by rebaselining. Only the N100 effect was significant when children with ADHD and comorbid conduct disorder (n = 10) were excluded. CONCLUSION This study provides the first evidence linking ADHD to atypical neural activity during the early perceptual stages of vocal anger processing. These effects may reflect preattentive hyper-vigilance to vocal anger in ADHD.
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Affiliation(s)
- Georgia Chronaki
- Developmental Brain-Behaviour Laboratory, Psychology, University of Southampton, Southampton, UK; Section of Clinical & Cognitive Neuroscience, School of Psychological Sciences, University of Manchester, Manchester, UK
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Pallanti S, Salerno L. Raising attention to attention deficit hyperactivity disorder in schizophrenia. World J Psychiatry 2015; 5:47-55. [PMID: 25815254 PMCID: PMC4369549 DOI: 10.5498/wjp.v5.i1.47] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2014] [Revised: 11/20/2014] [Accepted: 12/31/2014] [Indexed: 02/05/2023] Open
Abstract
Schizophrenia and attention deficit hyperactivity disorder (ADHD) are two psychiatric disorders with a negative impact on quality of life of individuals affected. Although they are classified into distinct disorders categories, attentional dysfunction is considered as a core feature in both conditions, either at the clinical then pathophysiological level. Beyond the obvious clinical overlap between these disorders, the Research Domain Criteria approach might offer an interesting perspective for disentangling common circuits underpinning both disorders. Hence, we review evidences regarding the overlap between schizophrenia and ADHD, at the clinical level, and at the level of underlying brain mechanisms. The evidence regarding the influence of environmental risk factors in the emergence of both disorders, and their developmental trajectories is also reviewed. Among these, we will try to elucidate the complex relationship between stimulants use and psychotic symptoms, discussing the potential role of ADHD medication in inducing psychosis or in exacerbating it. We aim that, taken together, these findings may promote further investigation with important implications both for clinicians and research. In fact, considering the amounting evidence on the overlap between schizophrenia and ADHD, the delineation of their boundaries might help in the decision for diagnosis and treatment. Moreover, it may help to promote interventions focused on the prevention of both schizophrenia and ADHD, by the reduction of recognized environmental risk factors.
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Hazlett EA, Rothstein EG, Ferreira R, Silverman JM, Siever LJ, Olincy A. Sensory gating disturbances in the spectrum: similarities and differences in schizotypal personality disorder and schizophrenia. Schizophr Res 2015; 161:283-90. [PMID: 25482574 PMCID: PMC4308515 DOI: 10.1016/j.schres.2014.11.020] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Revised: 11/13/2014] [Accepted: 11/17/2014] [Indexed: 01/15/2023]
Abstract
BACKGROUND DSM-5 places schizophrenia on a continuum from severe, chronic schizophrenia to the attenuated schizophrenia-like traits of schizotypal personality disorder (SPD), the prototypic schizophrenia-related personality disorder. SPD shares common genetic and neurobiological substrates with schizophrenia, including information processing abnormalities, although they are less marked. This is the first study to directly compare the P50 evoked electroencephalographic response-a measure of sensory gating and a neurophysiological endophenotype-between schizophrenia-spectrum groups. Two hypotheses were tested: (1) Compared with healthy controls (HCs), schizophrenia patients show reduced P50 suppression and SPD patients resemble schizophrenia but exhibit less marked deficits; and (2) Deficient P50 suppression in SPD is associated with greater clinical symptom severity. METHODS P50 was assessed in 32 schizophrenia-spectrum disorder patients (12 SPD, 20 schizophrenia patients) and 25 demographically-matched HCs. The standard conditioning (C)-testing (T) paradigm was used and P50 suppression was quantified using the T-C difference and the T/C ratio. RESULTS All P50 measures showed a linear, stepwise pattern with the SPD group intermediate between the HC and schizophrenia groups. Compared with HCs, both patient groups had lower conditioning and T-C difference values. Among the SPD group, greater clinical symptom severity was associated with greater conditioning-response amplitude deficits. CONCLUSION These findings: (1) are novel in showing that P50 deficits in SPD resemble those observed in schizophrenia, albeit less marked; (2) support the concept that the phenomenological link between SPD and schizophrenia lies in shared neurocognitive/neurophysiological pathologies; and (3) provide evidence that P50 is a neurophysiological endophenotype for schizophrenia-spectrum disorders.
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Affiliation(s)
- Erin A. Hazlett
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY,Research and Development, James J. Peters Veterans Affairs Medical Center, Bronx, NY,Mental Illness Research, Education, and Clinical Center (VISN3), James J. Peters Veterans Affairs Medical Center, Bronx, NY,Corresponding Author: Mental Illness Research, Education, and Clinical Center (VISN3), James J. Peters VA Medical Center, 130 West Kingsbridge Road, Room 6A-44, Bronx, NY, 10468, United States, Phone: 718-584-9000 x3701; Fax: 718-364-3576,
| | - Ethan G. Rothstein
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Rui Ferreira
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Jeremy M. Silverman
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY,Research and Development, James J. Peters Veterans Affairs Medical Center, Bronx, NY
| | - Larry J. Siever
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY,Research and Development, James J. Peters Veterans Affairs Medical Center, Bronx, NY,Mental Illness Research, Education, and Clinical Center (VISN3), James J. Peters Veterans Affairs Medical Center, Bronx, NY
| | - Ann Olincy
- Department of Psychiatry, University of Colorado, Denver, CO
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Shaikh M, Dutt A, Broome MR, Vozmediano AG, Ranlund S, Diez A, Caseiro O, Lappin J, Amankwa S, Carletti F, Fusar-Poli P, Walshe M, Hall MH, Howes O, Ellett L, Murray RM, McGuire P, Valmaggia L, Bramon E. Sensory gating deficits in the attenuated psychosis syndrome. Schizophr Res 2015; 161:277-82. [PMID: 25556079 DOI: 10.1016/j.schres.2014.12.021] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2014] [Revised: 10/31/2014] [Accepted: 12/11/2014] [Indexed: 10/24/2022]
Abstract
BACKGROUND Individuals with an "Attenuated Psychosis Syndrome" (APS) have a 20-40% chance of developing a psychotic disorder within two years; however it is difficult to predict which of them will become ill on the basis of their clinical symptoms alone. We examined whether P50 gating deficits could help to discriminate individuals with APS and also those who are particularly likely to make a transition to psychosis. METHOD 36 cases meeting PACE (Personal Assessment and Crisis Evaluation) criteria for the APS, all free of antipsychotics, and 60 controls performed an auditory conditioning-testing experiment while their electroencephalogram was recorded. The P50 ratio and its C-T difference were compared between groups. Subjects received follow-up for up to 2 years to determine their clinical outcome. RESULTS The P50 ratio was significantly higher and C-T difference lower in the APS group compared to controls. Of the individuals with APS who completed the follow-up (n=36), nine (25%) developed psychosis. P50 ratio and the C-T difference did not significantly differ between those individuals who developed psychosis and those who did not within the APS group. CONCLUSION P50 deficits appear to be associated with the pre-clinical phase of psychosis. However, due to the limitations of the study and its sample size, replication in an independent cohort is necessary, to clarify the role of P50 deficits in illness progression and whether this inexpensive and non-invasive EEG marker could be of clinical value in the prediction of psychosis outcomes amongst populations at risk.
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Affiliation(s)
- Madiha Shaikh
- NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London, The South London and Maudsley NHS Foundation Trust, London, UK; Department of Psychology, Royal Holloway, University of London, UK.
| | - Anirban Dutt
- NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London, The South London and Maudsley NHS Foundation Trust, London, UK
| | | | - Alberto G Vozmediano
- Psychiatry Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Siri Ranlund
- Division of Psychiatry & Institute of Cognitive Neuroscience, University College London, W1W 7EJ, UK
| | - Alvaro Diez
- Division of Psychiatry & Institute of Cognitive Neuroscience, University College London, W1W 7EJ, UK
| | - Olalla Caseiro
- University Hospital Marqués de Valdecilla, IFIMAV, Spain
| | - Julia Lappin
- NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London, The South London and Maudsley NHS Foundation Trust, London, UK
| | - Susan Amankwa
- NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London, The South London and Maudsley NHS Foundation Trust, London, UK
| | - Francesco Carletti
- NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London, The South London and Maudsley NHS Foundation Trust, London, UK
| | - Paolo Fusar-Poli
- NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London, The South London and Maudsley NHS Foundation Trust, London, UK
| | - Muriel Walshe
- NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London, The South London and Maudsley NHS Foundation Trust, London, UK
| | - Mei-Hua Hall
- Psychology Research Laboratory, Harvard Medical School, McLean Hospital, Belmont, MA, USA
| | - Oliver Howes
- NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London, The South London and Maudsley NHS Foundation Trust, London, UK
| | - Lyn Ellett
- Department of Psychology, Royal Holloway, University of London, UK
| | - Robin M Murray
- NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London, The South London and Maudsley NHS Foundation Trust, London, UK
| | - Philip McGuire
- NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London, The South London and Maudsley NHS Foundation Trust, London, UK
| | - Lucia Valmaggia
- NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London, The South London and Maudsley NHS Foundation Trust, London, UK
| | - Elvira Bramon
- NIHR Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King's College London, The South London and Maudsley NHS Foundation Trust, London, UK; Division of Psychiatry & Institute of Cognitive Neuroscience, University College London, W1W 7EJ, UK
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Hunter SK, Gillow SJ, Ross RG. Stability of P50 auditory sensory gating during sleep from infancy to 4 years of age. Brain Cogn 2015; 94:4-9. [PMID: 25596494 DOI: 10.1016/j.bandc.2014.12.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2014] [Revised: 11/09/2014] [Accepted: 12/18/2014] [Indexed: 11/28/2022]
Abstract
The stability of cerebral inhibition was assessed across early childhood using a paired-click auditory sensory gating paradigm. The P50 ERP was measured during REM (or its infant analogue, active sleep) and NREM sleep in 14 children at approximately 3 months of age and again at approximately 4 years of age. Evoked response amplitudes, latencies, and the S2/S1 ratio of the amplitudes of the evoked responses were compared between the two visits. Significant reliability was found for the S2/S1 ratio (r = .73, p = .003) during REM but not non REM sleep (r = -.05, p = .88). A significant stimulus number by sleep stage interaction (F(1,12) = 17.1, p = .001) demonstrated that the response to the second stimulus decreased during REM but not NREM sleep. These findings suggest that this measure is stable during REM sleep across early childhood, is not affected by age, and is sleep-state dependent. P50 sensory gating is a biomarker which, if used properly, may provide a mechanism to further explore changes in the developing brain or may help with early screening for psychiatric illness vulnerability.
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Affiliation(s)
- Sharon K Hunter
- Department of Psychiatry, University of Colorado Denver, Aurora, CO, USA
| | | | - Randal G Ross
- Department of Psychiatry, University of Colorado Denver, Aurora, CO, USA.
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Cromwell HC, Atchley RM. Influence of emotional states on inhibitory gating: animals models to clinical neurophysiology. Behav Brain Res 2014; 276:67-75. [PMID: 24861710 DOI: 10.1016/j.bbr.2014.05.028] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2014] [Revised: 05/06/2014] [Accepted: 05/08/2014] [Indexed: 10/25/2022]
Abstract
Integrating research efforts using a cross-domain approach could redefine traditional constructs used in behavioral and clinical neuroscience by demonstrating that behavior and mental processes arise not from functional isolation but from integration. Our research group has been examining the interface between cognitive and emotional processes by studying inhibitory gating. Inhibitory gating can be measured via changes in behavior or neural signal processing. Sensorimotor gating of the startle response is a well-used measure. To study how emotion and cognition interact during startle modulation in the animal model, we examined ultrasonic vocalization (USV) emissions during acoustic startle and prepulse inhibition. We found high rates of USV emission during the sensorimotor gating paradigm and revealed links between prepulse inhibition (PPI) and USV emission that could reflect emotional and cognitive influences. Measuring inhibitory gating as P50 event-related potential suppression has also revealed possible connections between emotional states and cognitive processes. We have examined the single unit responses during the traditional gating paradigm and found that acute and chronic stress can alter gating of neural signals in regions such as amygdala, striatum and medial prefrontal cortex. Our findings point to the need for more cross-domain research on how shifting states of emotion can impact basic mechanisms of information processing. Results could inform clinical work with the development of tools that depend upon cross-domain communication, and enable a better understanding and evaluation of psychological impairment.
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Affiliation(s)
- Howard C Cromwell
- Department of Psychology and J.P. Scott Center for Neuroscience, Mind and Behavior at Bowling Green State University, Bowling Green, OH 43403, United States.
| | - Rachel M Atchley
- Department of Psychology and J.P. Scott Center for Neuroscience, Mind and Behavior at Bowling Green State University, Bowling Green, OH 43403, United States
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Pre-attentive information processing and impulsivity in bipolar disorder. J Psychiatr Res 2013; 47:1917-24. [PMID: 24054520 DOI: 10.1016/j.jpsychires.2013.08.018] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2013] [Accepted: 08/26/2013] [Indexed: 02/07/2023]
Abstract
Early responses to stimuli can be measured by sensory evoked potentials (EP) using repeated identical stimuli, S1 and S2. Response to S1 may represent efficient stimulus detection, while suppression of response to S2 may represent inhibition. Early responses to stimuli may be related to impulsivity. We compared EP reflecting stimulus detection and inhibition in bipolar disorder and healthy controls, and investigated relationships to impulsivity. Subjects were 48 healthy controls without family histories of mood disorder and 48 with bipolar disorder. EP were measured as latencies and amplitudes for auditory P50 (pre-attentional), N100 (initial direction of attention) and P200 (initial conscious awareness), using a paired-click paradigm, with identical stimuli 0.5 s apart. Impulsivity was measured by questionnaire and by laboratory tests for inability to suppress responses to stimuli or to delay response for a reward. Analyses used general linear models. S1 amplitudes for P50, N100, and P200, and gating of N100 and P200, were lower in bipolar disorder than in controls. P50 S1 amplitude correlated with accurate laboratory-task responding, and S2 amplitude correlated with impulsive task performance and fast reaction times, in bipolar disorder. N100 and P200 EP did not correlate with impulsivity. These findings were independent of symptoms, treatment, or substance-use history. EPs were not related to questionnaire-measured or reward-based impulsivity. Bipolar I disorder is characterized by reduced pre-attentional and early attentional stimulus registration relative to controls. Within bipolar disorder, rapid-response impulsivity correlates with impaired pre-attentional response suppression. These results imply specific relationships between ERP-measured response inhibition and rapid-response impulsivity.
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Holstein DH, Vollenweider FX, Geyer MA, Csomor PA, Belser N, Eich D. Sensory and sensorimotor gating in adult attention-deficit/hyperactivity disorder (ADHD). Psychiatry Res 2013; 205:117-26. [PMID: 23017654 DOI: 10.1016/j.psychres.2012.08.013] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2011] [Revised: 07/30/2012] [Accepted: 08/10/2012] [Indexed: 12/15/2022]
Abstract
Even though there is an impaired perceptual capacity in attention-deficit/hyperactivity disorder (ADHD) patients, psychophysiological alterations, such as impaired gating as indexed by prepulse inhibition (PPI) or suppression of P50 auditory event-related potentials, have not been found in patients with ADHD. Hence, potential relationships of psychophysiological measures of gating to psychopathology and cognitive performance remain unclear. The present study investigates two distinct operational measures of gating as well as cognitive performance within adult ADHD patients in order to assess the relationship of these measures to psychopathology. PPI, P50 suppression, cognitive performance, and psychopathologic symptoms were assessed in 26 ADHD patients and 26 healthy control subjects. ADHD patients compared to healthy control subjects exhibited impaired P50 suppression, performed worse in cognitive tasks, and reported more psychopathological symptoms, but were normal in the test of PPI. Thus, P50 gating deficits are not specific to schizophrenia-spectrum disorders. These findings highlight the differences between P50 gating and PPI as measures of the gating construct. In keeping with the lack of correlations between these two putative operational measures of gating seen in both humans and animals, adult ADHD patients exhibit deficient P50 suppression and poor cognitive performance, despite exhibiting normal levels of PPI.
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Affiliation(s)
- Dominique H Holstein
- Psychiatric University Hospital of Psychiatry Zurich, PO Box 1932, CH-8032 Zurich, Switzerland.
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Hunter SK, Mendoza JH, D’Anna K, Zerbe GO, McCarthy L, Hoffman C, Freedman R, Ross RG. Antidepressants may mitigate the effects of prenatal maternal anxiety on infant auditory sensory gating. Am J Psychiatry 2012; 169:616-24. [PMID: 22581104 PMCID: PMC3640273 DOI: 10.1176/appi.ajp.2012.11091365] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVE Prenatal maternal anxiety has detrimental effects on the offspring's neurocognitive development, including impaired attentional function. Antidepressants are commonly used during pregnancy, yet their impact on offspring attention and their interaction with maternal anxiety has not been assessed. The authors used P50 auditory sensory gating, a putative marker of early attentional processes measurable in young infants, to assess the impact of maternal anxiety and antidepressant use. METHOD A total of 242 mother-infant dyads were classified relative to maternal history of anxiety and maternal prenatal antidepressant use. Infant P50 auditory sensory gating was recorded during active sleep at a mean age of 76 days (SD=38). RESULTS In the absence of prenatal antidepressant exposure, infants whose mothers had a history of anxiety diagnoses had diminished P50 sensory gating. Prenatal antidepressant exposure mitigated the effect of anxiety. The effect of maternal anxiety was limited to amplitude of response to the second stimulus, while antidepressant exposure had an impact on the amplitude of response to both the first and second stimulus. CONCLUSIONS Maternal anxiety disorders are associated with less inhibition during infant sensory gating, a performance deficit mitigated by prenatal antidepressant exposure. This effect may be important in considering the risks and benefits of antidepressant use during pregnancy. Cholinergic mechanisms are hypothesized for both anxiety and antidepressant effects, although the cholinergic receptors involved are likely different for anxiety and antidepressant effects.
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Chang WP, Gavin WJ, Davies PL. Bandpass filter settings differentially affect measurement of P50 sensory gating in children and adults. Clin Neurophysiol 2012; 123:2264-72. [PMID: 22608969 DOI: 10.1016/j.clinph.2012.03.019] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2011] [Revised: 03/30/2012] [Accepted: 03/31/2012] [Indexed: 10/28/2022]
Abstract
OBJECTIVE This study investigated the effect of four different bandpass filter settings on measures of the P50 component and the signal-to-noise ratios (SNR) of averaged ERPs obtained from a sensory gating paradigm employing paired-click stimuli. METHODS Participants were adults (n=18) 20-55years old and children (n=25) 5-10years old who were free of neurological disorders. RESULTS Results show that the filter settings (0.23-75Hz, 10-50Hz, 10-75Hz, and 10-200Hz) differentially affected the P50 amplitude, noise power and SNR measures of the conditioning and test clicks, and P50 T/C ratios. CONCLUSIONS The 10-50Hz filter setting may be optimal in studies that include only adults as these settings resulted in the smallest mean P50 T/C ratio, a reasonable standard deviation (SD) for the ratio, and the highest SNRs. The 10-200Hz filter may be the best for studying young children as this setting had the smallest mean and SD of P50 T/C ratios for these participants. SIGNIFICANCE In studies that include both adults and children investigators are advised to use the 10-200Hz filter setting because the smaller variability of sensory gating in the child group helps ensure better homogeneity of variance measures between the groups.
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Affiliation(s)
- Wen-Pin Chang
- Department of Occupational Therapy, Creighton University, Omaha, NE 68178, USA
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Itagaki S, Yabe H, Mori Y, Ishikawa H, Takanashi Y, Niwa SI. Event-related potentials in patients with adult attention-deficit/hyperactivity disorder versus schizophrenia. Psychiatry Res 2011; 189:288-91. [PMID: 21458861 DOI: 10.1016/j.psychres.2011.03.005] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2010] [Revised: 03/06/2011] [Accepted: 03/09/2011] [Indexed: 10/18/2022]
Abstract
Event-related potentials (ERPs) such as Nd, N2b, and P300 in an attentional task and an auditory oddball task were compared among 54 adult AD/HD patients, 43 schizophrenic patients (SZ), and 40 healthy age-matched volunteers (HC). It is known that Nd, N2b, and P300 reflect selective attention, voluntary attention, and cognitive context updating respectively. The peak amplitude of P300 was significantly lower in the adult AD/HD and SZ groups than in the HC group. The peak latencies of late Nd, N2b, and P300 were significantly longer in the SZ group than in the HC and adult AD/HD groups. Thus, attenuated amplitude and prolonged latency of various ERP components in the SZ group suggest the possibility of impairment of basic mechanisms underlying cognitive processing. Unlike the SZ group, the adult AD/HD group exhibited reduced amplitude of P300 but not prolonged latency. These findings suggest the existence of a different type of cognitive dysfunction in the adult AD/HD group, which might be closely related to attentional function.
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Affiliation(s)
- Shuntaro Itagaki
- Department of Neuropsychiatry, Fukushima Medical University, Fukushima, Japan.
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Shaikh M, Hall MH, Schulze K, Dutt A, Walshe M, Williams I, Constante M, Picchioni M, Toulopoulou T, Collier D, Rijsdijk F, Powell J, Arranz M, Murray RM, Bramon E. Do COMT, BDNF and NRG1 polymorphisms influence P50 sensory gating in psychosis? Psychol Med 2011; 41:263-276. [PMID: 20102668 DOI: 10.1017/s003329170999239x] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Auditory P50 sensory gating deficits correlate with genetic risk for schizophrenia and constitute a plausible endophenotype for the disease. The well-supported role of catechol-O-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF) and neuregulin 1 (NRG1) genes in neurodevelopment and cognition make a strong theoretical case for their influence on the P50 endophenotype. METHOD The possible role of NRG1, COMT Val158Met and BDNF Val66Met gene polymorphisms on the P50 endophenotype was examined in a large sample consisting of psychotic patients, their unaffected relatives and unrelated healthy controls using linear regression analyses. RESULTS Although P50 deficits were present in patients and their unaffected relatives, there was no evidence for an association between NRG1, COMT Val158Met or BDNF Val66Met genotypes and the P50 endophenotype. CONCLUSIONS The evidence from our large study suggests that any such association between P50 indices and NRG1, COMT Val158Met or BDNF Val66Met genotypes, if present, must be very subtle.
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Affiliation(s)
- M Shaikh
- NIHR Biomedical Research Centre, Institute of Psychiatry, King's College London/South London and Maudsley NHS Foundation Trust, London, UK.
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Chang WP, Arfken CL, Sangal MP, Boutros NN. Probing the relative contribution of the first and second responses to sensory gating indices: a meta-analysis. Psychophysiology 2011; 48:980-92. [PMID: 21214588 DOI: 10.1111/j.1469-8986.2010.01168.x] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Sensory gating deficit in schizophrenia patients has been well-documented. However, a central conceptual issue, regarding whether the gating deficit results from an abnormal initial response (S1) or difficulty in attenuating the response to the repeating stimulus (S2), raise doubts about the validity and utility of the S2/S1 ratio as a measure of sensory gating. This meta-analysis study, therefore, sought to determine the consistency and relative magnitude of the effect of the two essential components (S1 and S2) and the ratio. The results of weighted random effects meta-analysis revealed that the overall effect sizes for the S1 amplitude, S2 amplitude, and P50 S2/S1 ratio were -0.19 (small), 0.65 (medium to large), and 0.93 (large), respectively. These results confirm that the S2/S1 ratio and the repeating (S2) stimulus differ robustly between schizophrenia patients and healthy controls in contrast to the consistent but smaller effect size for the S1 amplitude. These findings are more likely to reflect defective inhibition of repeating redundant input rather than an abnormal response to novel stimuli.
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Affiliation(s)
- Wen-Pin Chang
- Department of Occupational Therapy, Creighton University, Omaha, Nebraska 68178, USA.
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Abstract
OBJECTIVE We compared ratings of behavior and attention problems between youth-onset psychosis and ADHD, two disorders in which attentional impairments play a key role, and examined the effect of psychostimulant use on age of onset in psychosis. METHOD Parent and teacher ratings of behavioral problems and ADHD symptoms were collected using the Achenbach CBCL, TRF, and SNAP-IV Teacher Rating Scales on 42 participants with psychosis, 36 with ADHD and 57 controls (ages 8-19). RESULTS AND CONCLUSIONS Results suggested that academic, externalizing, and attention problems reflect symptoms shared between the disorders, whereas internalizing, social and thought problems reflect factors that differ between disorders. Furthermore, participants with psychosis who had been prescribed psychostimulants had a younger age of onset of psychotic symptoms than those who had not. This difference could reflect dissimilarities in symptom severity symptom between subgroups or potentially harmful effects of psychostimulants in individuals predisposed to develop psychosis.
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Affiliation(s)
- Canan Karatekin
- Institute of Child Development, University of Minnesota, Minneapolis, MN 55455, USA.
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P50 sensory gating is related to performance on select tasks of cognitive inhibition. COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE 2009; 9:448-58. [PMID: 19897797 DOI: 10.3758/cabn.9.4.448] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
P50 suppression deficits have been documented in clinical and nonclinical populations, but the behavioral correlates of impaired auditory sensory gating remain poorly understood. In the present study, we examined the relationship between P50 gating and healthy adults' performance on cognitive inhibition tasks. On the basis of load theory (Lavie, Hirst, de Fockert, & Viding, 2004), we predicted that a high perceptual load, a possible consequence of poor auditory P50 sensory gating, would have differential (i.e., positive vs. negative) effects on performance of cognitive inhibition tasks. A dissociation was observed such that P50 gating was negatively related to interference resolution on a Stroop task and positively related to response inhibition on a go/no-go task. Our findings support the idea that a high perceptual load may be beneficial to Stroop performance because of the reduced processing of distractors but detrimental to performance on the go/no-go task because of interference with stimulus discrimination.
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Allen AJ, Griss ME, Folley BS, Hawkins KA, Pearlson GD. Endophenotypes in schizophrenia: a selective review. Schizophr Res 2009; 109:24-37. [PMID: 19223268 PMCID: PMC2665704 DOI: 10.1016/j.schres.2009.01.016] [Citation(s) in RCA: 156] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2008] [Revised: 01/11/2009] [Accepted: 01/14/2009] [Indexed: 10/21/2022]
Abstract
BACKGROUND Given the wealth of data in the literature on schizophrenia endophenotypes, it is useful to have one source to reference their frequency data. We reviewed the literature on disease-liability associated variants in structural and functional magnetic resonance images (MRI), sensory processing measures, neuromotor abilities, neuropsychological measures, and physical characteristics in schizophrenia patients (SCZ), their first-degree relatives (REL), and healthy controls (HC). The purpose of this review was to provide a summary of the existing data on the most extensively published endophenotypes for schizophrenia. METHODS We searched PubMed and MedLine for all studies on schizophrenia endophenotypes comparing SCZ to HC and/or REL to HC groups. Percent abnormal values, generally defined as >2 SD from the mean (in the direction of abnormality) and/or associated effect sizes (Cohen's d) were calculated for each study. RESULTS Combined, the articles reported an average 39.4% (SD=20.7%; range=2.2-100%) of abnormal values in SCZ, 28.1% (SD=16.6%; range=1.6-67.0%) abnormal values in REL, and 10.2% (SD=6.7%; range=0.0-34.6%) in HC groups. CONCLUSIONS These findings are reviewed in the context of emerging hypotheses on schizophrenia endophenotypes, as well as a discussion of clustering trends among the various intermediate phenotypes. In addition, programs for future research are discussed, as instantiated in a few recent large-scale studies on multiple endophenotypes across patients, relatives, and healthy controls.
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Affiliation(s)
- Allyssa J. Allen
- Olin Neuropsychiatry Research Center, Institute of Living at Hartford Hospital, 200 Retreat Avenue, Hartford, CT 06106,Corresponding Author: Allyssa J. Allen, Olin Neuropsychiatry Research Center, Whitehall Building, 200 Retreat Avenue, Hartford, CT 06106, Tel: 860-459-7806, Fax: 860-545-7797,
| | - Mélina E. Griss
- Olin Neuropsychiatry Research Center, Institute of Living at Hartford Hospital, 200 Retreat Avenue, Hartford, CT 06106
| | - Bradley S. Folley
- Olin Neuropsychiatry Research Center, Institute of Living at Hartford Hospital, 200 Retreat Avenue, Hartford, CT 06106
| | - Keith A. Hawkins
- Dept. of Psychiatry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06511
| | - Godfrey D. Pearlson
- Olin Neuropsychiatry Research Center, Institute of Living at Hartford Hospital, 200 Retreat Avenue, Hartford, CT 06106,Dept. of Psychiatry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06511
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39
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Event-related potentials in adults with Attention-Deficit/Hyperactivity Disorder: An investigation using an inter-modal auditory/visual oddball task. Int J Psychophysiol 2009; 71:124-31. [DOI: 10.1016/j.ijpsycho.2008.09.009] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2008] [Revised: 09/04/2008] [Accepted: 09/14/2008] [Indexed: 11/23/2022]
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Feifel D, Minassian A, Perry W. Prepulse inhibition of startle in adults with ADHD. J Psychiatr Res 2009; 43:484-9. [PMID: 18674783 PMCID: PMC2669714 DOI: 10.1016/j.jpsychires.2008.06.004] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2007] [Revised: 05/29/2008] [Accepted: 06/10/2008] [Indexed: 12/31/2022]
Abstract
Prepulse inhibition of startle (PPI) is a measure of sensorimotor gating, a pre-conscious regulator of attention. PPI is impaired in adults with schizophrenia and several other neuropsychiatric disorders associated with attentional abnormalities. The core feature of ADHD involves deficits in attention and, like schizophrenia, ADHD is associated with dysregulation of cortical-striatal circuits and dopamine transmission. Therefore, PPI may be disrupted in ADHD. While ADHD persists into adulthood in approximately half the children with ADHD, there has not been any published report of PPI in ADHD adults. In this study, PPI was measured in a sample of ADHD adults and compared to a sample of healthy comparison (HC) subjects. Twenty unmedicated adults with ADHD (11 inattentive subtype, 9 combined subtype) and 17 HC subjects were administered an eyeblink startle PPI paradigm. The PPI of ADHD adults was not significantly different from that of HC subjects in any of the PPI conditions. There was no significant effect of ADHD subtype nor of gender. The lack of PPI deficits in ADHD adults has important implications and suggests that, despite the presence of PPI dysregulation in a large number of disparate neuropsychiatric disorders, it is not a general feature of all neuropsychiatric disorders with attention abnormalities. Furthermore, the attentional deficiency in ADHD may have a neurobiological substrate somewhat distinct from schizophrenia and other neuropsychiatric disorders that are associated with PPI deficits. This distinction may be related to a relative sparing of pre-conscious attentional functions in ADHD compared to other disorders with PPI impairment.
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Affiliation(s)
- David Feifel
- University of California San Diego, School of Medicine, Department of Psychiatry, San Diego, CA 92103-8218, USA.
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41
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Davies PL, Chang WP, Gavin WJ. Maturation of sensory gating performance in children with and without sensory processing disorders. Int J Psychophysiol 2008; 72:187-97. [PMID: 19146890 DOI: 10.1016/j.ijpsycho.2008.12.007] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2008] [Revised: 10/14/2008] [Accepted: 12/03/2008] [Indexed: 11/18/2022]
Abstract
Recent interest in sensory gating in children with and without neuropsychological disorders has resulted in a number of studies and the results regarding the developmental trajectory of sensory gating are inconsistent. We investigated the maturational course of sensory gating in samples of typically developing children and children with sensory processing deficits (SPD) and compared their performance to adults. Besides gating ratios, we also examined the brain responses to conditioning and test click stimuli in the sensory gating paradigm separately to clarify if the changes in click amplitudes could explain the maturational change in the T/C ratio in children. Eighteen adults with no known disorders, 25 typical children, and 28 children with SPD participated in this study. The children ranged in ages between 5 and 12 years. The three groups differed in their P50 and N100 ERP components. Both child groups displayed significantly less gating than the adults. Children with SPD demonstrated significantly less gating and more within-group variability compared to typical children. There were significant relationships between age and T/C ratios and between age and peak-to-peak amplitude of the conditioning click in typical children but not in children with SPD. Typical children demonstrated significantly smaller brain response amplitudes to the clicks as compared to adults. These findings suggest that there is a maturational course of sensory gating in typical children and if there is a maturational trajectory in children with SPD it appears to be different than typical children. In addition, children with SPD were found to be lacking in their ability to filter out repeated auditory input and failed to selectively regulate their sensitivity to sensory stimuli.
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Affiliation(s)
- Patricia L Davies
- Department of Occupational Therapy, Colorado State University, Fort Collins, CO 80523, USA.
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42
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de Wilde OM, Bour LJ, Dingemans PM, Koelman JHTM, Linszen DH. A meta-analysis of P50 studies in patients with schizophrenia and relatives: differences in methodology between research groups. Schizophr Res 2007; 97:137-51. [PMID: 17604606 DOI: 10.1016/j.schres.2007.04.028] [Citation(s) in RCA: 124] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2006] [Revised: 03/30/2007] [Accepted: 04/22/2007] [Indexed: 11/28/2022]
Abstract
OBJECTIVE To determine whether patients with schizophrenia as well as their relatives show deficits in sensory gating reflected by an abnormal P50 ratio and to quantify the differences from controls. METHODS A systematic search on articles published between 1982 and 2006 was conducted. 28 patient studies that were suitable for analysis including 891 patients and 686 controls were retrieved. Six studies on P50 of relatives of schizophrenic patients were identified, including 317 relatives and 294 controls. RESULTS In the patient studies we found an P50 effect size of 1.28 (SD=0.72). We confirmed high variability in outcomes across studies. Almost half of the studies included where published by one laboratory of the University of Colorado and these results differed significantly from the results found in studies performed in other laboratories. We found correlations between effect size outcome and sound intensity, filter settings and subjects' position which could be explained by differences between the Colorado laboratory and the other groups. In the relative studies we found a mean P50 effect size of 0.85 (+/-0.42). CONCLUSIONS The differences in methodology and lack of reported demographics and methodology including raters blinding in some studies makes it hard to compare results across studies and to evaluate the validity and reliability of P50 as a candidate endophenotype for schizophrenia. There are large differences in outcomes from Colorado studies and non-Colorado studies. In contrast to the Colorado studies in the non-Colorado studies P50 suppression would not qualify as an endophenotype for schizophrenia. These differences might be explained by the differences in methodology e.g. lower levels of sound intensity, differences in filter settings and subjects' position. Finally we make some recommendations for future research based on the outcomes of this meta-analysis.
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Affiliation(s)
- O M de Wilde
- Department of Psychiatry, Academic Medical Centre, University of Amsterdam, the Netherlands.
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43
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Cromwell HC, Klein A, Mears RP. Single unit and population responses during inhibitory gating of striatal activity in freely moving rats. Neuroscience 2007; 146:69-85. [PMID: 17321056 PMCID: PMC4127048 DOI: 10.1016/j.neuroscience.2007.01.025] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2006] [Revised: 12/29/2006] [Accepted: 01/13/2007] [Indexed: 10/23/2022]
Abstract
The striatum is thought to be an essential region for integrating diverse information in the brain. Rapid inhibitory gating (IG) of sensory input is most likely an early factor necessary for appropriate integration to be completed. Gating is currently evaluated in clinical settings and is dramatically altered in a variety of psychiatric illnesses. Basic neuroscience research using animals has revealed specific neural sites involved in IG including the hippocampus, thalamus, brainstem, amygdala and medial prefrontal cortex. The present study investigated local IG in the basal ganglia structure of the striatum using chronic recording microwires. We obtained both single unit activations and local field potentials (LFPs) in awake behaving rats from each wire during the standard two-tone paradigm. Single units responded with different types of activations including a phasic and sustained excitation, an inhibitory response and a combination response that contained both excitatory and inhibitory components. IG was observed in all the response types; however, non-gating was observed in a large proportion of responses as well. Positive wave field potentials at 50-60 ms post-stimulus (P60) showed consistent gating across the wire arrays. No significant correlations were found between single unit and LFP measures of gating during the initial baseline session. Gating was strengthened (Tamp/Camp ratios approaching 0) following acute stress (saline injection) at both the single unit and LFP level due to the reduction in the response to the second tone. Alterations in sensory responding reflected by changes in the neural response to the initial tone were primarily observed following long-term internal state deviation (food deprivation) and during general locomotion. Overall, our results support local IG by single neurons in striatum but also suggest that rapid inhibition is not the dominant activation profile observed in other brain regions.
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Affiliation(s)
- H C Cromwell
- Department of Psychology and The J. P. Scott Center for Neuroscience, Mind and Behavior at Bowling Green State University, Psychology Building, Bowling Green, OH 43403, USA.
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44
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Cromwell HC, Woodward DJ. Inhibitory gating of single unit activity in amygdala: effects of ketamine, haloperidol, or nicotine. Biol Psychiatry 2007; 61:880-9. [PMID: 17054921 DOI: 10.1016/j.biopsych.2006.06.037] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2006] [Revised: 05/26/2006] [Accepted: 06/27/2006] [Indexed: 11/18/2022]
Abstract
BACKGROUND Inhibitory gating is thought to be a basic process for filtering incoming stimuli to the brain. Little information is currently available concerning local neural networks of inhibitory gating or the intrinsic neurochemical substrates involved in the process. METHODS The goal of the present study was to examine the pharmacological aspects of inhibitory gating from single units in the amygdala. We tested the effects of ketamine (80 mg/kg) and haloperidol (1 mg/kg) on inhibitory gating. Additionally, we examined the effect of nicotine (1.2 mg/kg) on single unit gating in this same brain structure. RESULTS We found that in one subset of neurons, ketamine administration significantly reduced tone responsiveness with a subsequent loss of inhibitory gating, whereas the other subset persisted in both auditory responding and gating albeit at a weaker level. Haloperidol and nicotine had very similar effects, exemplified by a dramatic increase in the response to the initial "conditioning" tone with a subsequent improvement in inhibitory gating. CONCLUSIONS Tone responsiveness and inhibitory gating persists in a subset of neurons after glutamate N-methyl-D-aspartate receptor blockade. Dopamine and nicotine modulate gating in these normal animals and have similar effects of enhancing responsiveness to auditory stimulation at the single unit and evoked potential level.
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Affiliation(s)
- Howard C Cromwell
- Department of Physiology and Pharmacology, School of Medicine, Wake Forest University, Winston-Salem, North Carolina, USA.
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45
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Bearden CE, Freimer NB. Endophenotypes for psychiatric disorders: ready for primetime? Trends Genet 2006; 22:306-13. [PMID: 16697071 DOI: 10.1016/j.tig.2006.04.004] [Citation(s) in RCA: 169] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2005] [Revised: 03/06/2006] [Accepted: 04/07/2006] [Indexed: 02/02/2023]
Abstract
It is increasingly accepted that the imprecision of categorical psychiatric diagnoses can be a limiting factor in understanding the genetic basis of human behavioral abnormalities. Genetic investigation of endophenotypes--more precisely defined quantitative traits hypothesized to underlie disease syndromes--offers great promise as an alternative or complement to studies of categorical disease phenotypes. However, there is not yet standardization of the methods by which candidate endophenotypes should be chosen and applied. Fruitful endophenotype studies depend on the selection of heritable, quantitative traits that can be objectively and reliably measured. In this article, we propose guidelines for such investigations for psychiatric disorders, using endophenotypes previously proposed for bipolar disorder as particular examples. Gene expression studies and non-human primate models are recent developments in which an endophenotype approach might prove particularly valuable.
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Affiliation(s)
- Carrie E Bearden
- Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California-Los Angeles, Los Angeles, CA 90095, USA.
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46
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Mears RP, Klein AC, Cromwell HC. Auditory inhibitory gating in medial prefrontal cortex: Single unit and local field potential analysis. Neuroscience 2006; 141:47-65. [PMID: 16675142 DOI: 10.1016/j.neuroscience.2006.03.040] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2005] [Revised: 03/07/2006] [Accepted: 03/21/2006] [Indexed: 10/24/2022]
Abstract
Medial prefrontal cortex is a crucial region involved in inhibitory processes. Damage to the medial prefrontal cortex can lead to loss of normal inhibitory control over motor, sensory, emotional and cognitive functions. The goal of the present study was to examine the basic properties of inhibitory gating in this brain region in rats. Inhibitory gating has recently been proposed as a neurophysiological assay for sensory filters in higher brain regions that potentially enable or disable information throughput. This perspective has important clinical relevance due to the findings that gating is dramatically impaired in individuals with emotional and cognitive impairments (i.e. schizophrenia). We used the standard inhibitory gating two-tone paradigm with a 500 ms interval between tones and a 10 s interval between tone pairs. We recorded both single unit and local field potentials from chronic microwire arrays implanted in the medial prefrontal cortex. We investigated short-term (within session) and long-term (between session) variability of auditory gating and additionally examined how altering the interval between the tones influenced the potency of the inhibition. The local field potentials displayed greater variability with a reduction in the amplitudes of the tone responses over both the short and long-term time windows. The decrease across sessions was most intense for the second tone response (test tone) leading to a more robust gating (lower T/C ratio). Surprisingly, single unit responses of different varieties retained similar levels of auditory responsiveness and inhibition in both the short and long-term analysis. Neural inhibition decreased monotonically related to the increase in intertone interval. This change in gating was most consistent in the local field potentials. Subsets of single unit responses did not show the lack of inhibition even for the longer intertone intervals tested (4 s interval). These findings support the idea that the medial prefrontal cortex is an important site where early inhibitory functions reside and potentially mediate psychological processes.
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Affiliation(s)
- R P Mears
- Department of Psychology and the J.P. Scott Center for Neuroscience, Mind and Behavior, Psychology Building, Bowling Green State University, Bowling Green, OH 43403, USA
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47
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Banaschewski T, Hollis C, Oosterlaan J, Roeyers H, Rubia K, Willcutt E, Taylor E. Towards an understanding of unique and shared pathways in the psychopathophysiology of ADHD. Dev Sci 2005; 8:132-40. [PMID: 15720371 DOI: 10.1111/j.1467-7687.2005.00400.x] [Citation(s) in RCA: 95] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Most attention deficit hyperactivity disorder (ADHD) research has compared cases with unaffected controls. This has led to many associations, but uncertainties about their specificity to ADHD in contrast with other disorders. We present a selective review of research, comparing ADHD with other disorders in neuropsychological, neurobiological and genetic correlates. So far, a specific pathophysiological pathway has not been identified. ADHD is probably not specifically associated with executive function deficits. It is possible, but not yet established, that ADHD symptoms may be more specifically associated with motivational abnormalities, motor organization and time perception. Recent findings indicating common genetic liabilities of ADHD and other conditions raise questions about diagnostic boundaries. In future research, the delineation of the pathophysiological mechanisms of ADHD needs to match cognitive, imaging and genetic techniques to the challenge of defining more homogenous clinical groups; multi-site collaborative projects are needed.
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Affiliation(s)
- Tobias Banaschewski
- Child and Adolescent Psychiatry, University of Göttingen, von-Siebold-Str. 5, D-37075 Göttingen, Germany.
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48
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Kisley MA, Noecker TL, Guinther PM. Comparison of sensory gating to mismatch negativity and self-reported perceptual phenomena in healthy adults. Psychophysiology 2004; 41:604-12. [PMID: 15189483 DOI: 10.1111/j.1469-8986.2004.00191.x] [Citation(s) in RCA: 112] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
To better understand the possible functional significance of electrophysiological sensory gating measures, response suppression of midlatency auditory event related potential (ERP) components was compared to the mismatch negativity (MMN) and to self-rated indices of stimulus filtering and passive attention-switching phenomena in an age-restricted sample of healthy adults. P1 sensory gating, measured during a paired-click paradigm, was correlated with MMN amplitude, measured during an acoustic oddball paradigm (intensity deviation). Also, individuals that exhibited less robust P1 suppression endorsed higher rates of "perceptual modulation" difficulties, whereas component N1 suppression was more closely related to "over-inclusion" of irrelevant sounds into the focus of attention. These findings suggest that the ERP components investigated are not redundant, but correspond to distinct-possibly related-pre-attentive processing systems.
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Affiliation(s)
- Michael A Kisley
- Department of Psychology, University of Colorado at Colorado Springs, Colorado Springs, Colorado, USA.
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49
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Abstract
This article reviews the modulation of cognitive function by normal genetic variation. Although the heritability of "g" is well established, the genes that modulate specific cognitive functions are largely unidentified. Application of the allelic association approach to individual differences in cognition has begun to reveal the effects of single nucleotide polymorphisms on specific and general cognitive functions. This article proposes a framework for relating genotype to cognitive phenotype by considering the effect of genetic variation on the protein product of specific genes within the context of the neural basis of particular cognitive domains. Specificity of effects is considered, from genes controlling part of one receptor type to genes controlling agents of neuronal repair, and evidence is reviewed of cognitive modulation by polymorphisms in dopaminergic and cholinergic receptor genes, dopaminergic enzyme genes, and neurotrophic genes. Although allelic variation in certain genes can be reliably linked to cognition--specifically to components of attention, working memory, and executive function in healthy adults--the specificity, generality, and replicability of the effects are not fully known.
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50
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Arciniegas DB, Topkoff JL. Applications of the P50 evoked response to the evaluation of cognitive impairments after traumatic brain injury. Phys Med Rehabil Clin N Am 2004; 15:177-203, viii. [PMID: 15029905 DOI: 10.1016/s1047-9651(03)00104-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
This article reviews the applications of the P50 evoked response to paired auditory stimuli (P50 ERP) in the study and evaluation of cognitive impairments after traumatic brain injury (TBI). The cholinergic hypothesis of cognitive impairment after TBI and the relationship of impaired auditory sensory gating to that hypothesis are presented. The neurobiology of impaired sensory gating, the relationship of that neurobiology to the P50 ERP, and the principles of P50 ERP recording are discussed. Studies of the P50 ERP among patients with persistent cognitive complaints after TBI are reviewed. Finally, possible clinical applications and limitations of the P50 ERP in the study, evaluation, and treatment of patients with cognitive impairments after TBI are offered.
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Affiliation(s)
- David B Arciniegas
- Neuropsychiatry Service, Department of Psychiatry, University of Colorado School of Medicine, Campus Box C28-68, 4200 East Ninth Avenue, Denver, CO 80262, USA.
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