Research supports an association between diet and health, and emerging evidence suggests that diet is associated with neuropsychiatric symptoms. However, no human study has examined an anti-inflammatory diet across rigorously defined psychiatric diagnoses and its associations with symptom severity and cognition. As inflammation is implicated in mental illness, we investigated adherence to the Mediterranean diet (MD), an anti-inflammatory diet, and the standard American diet (SAD), and examined cross-sectional relationships with psychiatric symptoms and cognition.

Participants included 54 individuals with psychotic disorders, 30 with non-psychosis affective disorders and 40 healthy controls. Participants underwent diagnostic interviews, PANSS symptom ratings, and MATRICS cognitive assessments. The self-report GBAQ was used to assess adherence to the MD versus SAD.

The psychosis group was significantly more likely to consume the SAD than healthy controls (p = 0.007), with MD adherence predicting better working memory (r = 0.461, p < 0.001). In the non-psychosis affective disorders group, MD adherence predicted slower processing speed (r = -0.376, p = 0.049). In the non-psychosis affective disorders group, MD predicted reduced PANSS General Psychopathology scale (r = -0.449, p = 0.013), as well as the Activation (r = -0.362, p = 0.049), and Dysphoric Mood factors (r = -0.403, p = 0.027).

This first-of-its kind study identified poor dietary choices in persons with psychosis, showing significantly lower symptoms and better cognition in association with the MD in transdiagnostic analyses. It supports the study of dietary interventions for prevention and treatment of psychiatric conditions.

Cognitive flexibility (CF) is the ability to adapt cognitive strategies according to the changing environment. The deficit in CF has often been linked to various neurological and psychiatric disorders including schizophrenia. However, the operationalization and assessment of CF have not been unified and the current research suggests that the available instruments measure different aspects of CF. The main objective of the present study was to compare three frequently used neuropsychological measures of CF-Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT) and Stroop Color and Word Test (SCWT) in a population of patients (N = 220) with first-episode schizophrenia spectrum disorders in order to evaluate their convergent validity. The hypothesis of an underlying latent construct was tested via a confirmatory factor analysis. We used a one-factor CF model with scores from WCST, SCWT and TMT as observed variables. The established model showed a good fit to the data (χ2 = 1.67, p = 0.43, SRMR = 0.02, RMSEA = 0.0, CFI = 1.00). The highest factor loading was found in WCST as CF explained most of the variance in this neuropsychological measure compared to the other instruments. On the other hand, a TMT ratio index and a SCWT interference demonstrated lowest loadings in the model. The findings suggest that not all the frequently used measures share an underlying factor of CF or may capture different aspects of this construct.

Early-onset depression (EOD) and late-onset depression (LOD) are prevalent subtypes of major depressive disorder (MDD), but the clinical distinction between EOD and LOD remains blurred due to nonspecific symptoms and lack of biomarkers. This study aims to elucidate the characteristics in cognitive function and biochemical metabolism of EOD and LOD, and to identify biological factors influencing age of onset (AOO).

Seventy patients with MDD (40 with EOD and 30 with LOD) and sixty-eight age-matched healthy controls (HC) were included in this study. Participants were evaluated for clinical features, cognitive function, and serum trace elements levels. Proton magnetic resonance spectroscopy (1H-MRS) was employed to quantify neurometabolites levels, including N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr).

Patients with LOD experienced more episodes and severe depressive symptoms than those with EOD (p = 0.025, p < 0.001). EOD patients performed significantly worse than LOD patients on social cognition (p = 0.005), while LOD patients performed worse than EOD patients on reasoning and problem solving (p = 0.005). Additionally, LOD patients displayed higher ceruloplasmin (Cp) levels compared to EOD patients (p = 0.004), but no difference was found in neurometabolic levels between EOD and LOD. Multiple linear regression indicated a positive correlation between serum Cp levels and AOO of depression (p < 0.001), while bilateral thalamic NAA/Cr showed a negative correlation with AOO (p = 0.012, p = 0.016).

Patients with EOD were characterized by social cognition impairments, while patients with LOD were marked by reasoning and problem-solving deficits. Serum Cp levels demonstrated an AOO-related effect and served as a positive predictor for the AOO of depression. Furthermore, a negative correlation has been established between bilateral thalamic NAA/Cr and the AOO of MDD.

The limited sample size and the challenge in distinguishing whether observed results are attributed to age or AOO effects.

Patients with schizophrenia have a threefold higher mortality from cardiovascular disease than people in the general population. Atherosclerosis is linked to immune activation, a process tentatively entwined with the underlying pathophysiological mechanisms of schizophrenia. The aim of the present study was to investigate an extensive array of cardiovascular biomarkers in individuals experiencing their first episode of psychosis (FEP), either drug-naïve or exposed to short-term antipsychotic treatment, alongside a group of healthy controls (HC). Using the OLINK Proximity Extension Assay, Cardiovascular II Panel, we analyzed plasma from 72 FEP patients, including 42 later diagnosed with schizophrenia and 54 HCs. Biomarker levels, that significantly differed between patients and controls, were correlated with symptom severity, cognitive performance and cardiovascular risk factors. Fifteen out of 92 cardiovascular biomarkers were higher in individuals with FEP compared to HC, and one biomarker was lower in FEP patients compared to HC. BMI, waist size, blood pressure, fp-glucose, HbA1c and serum lipid levels were similar between the groups. No correlations that held for multiple comparisons were seen between biomarker concentrations and symptom severity, cognitive performance or cardiovascular risk factors in FEP patients. Higher concentrations of several cardiovascular biomarkers were observed in individuals with FEP compared to in HC. This suggests that patients with FEP are at an increased risk of developing cardiovascular disease from the onset of psychosis, even before changes in traditional biomarkers are detectable. It underscores the need for innovative approaches to detect and monitor this risk early.

Aerobic exercise (AE) and cognitive remediation (CR) have both shown promising effects on cognition in schizophrenia. However, the efficacy of combining these interventions has not been thoroughly evaluated. We conducted a randomized controlled trial to test the 3-month effects of AE, CR, and their combination on cognition and functioning in patients with schizophrenia. A total of 59 patients were randomized into three groups: AE alone (n = 19), CR alone (n = 19), or a combination of both (n = 21). The intervention consisted of a combination of individual and group AEs and a computer-assisted CR. The overall retention rate was 91.53 %. The primary outcome was the change in cognition from baseline, assessed using the Brief Assessment of Cognition in Schizophrenia (BACS). Significant improvements from baseline to post-treatment were observed in the combined AE and CR group compared to the AE alone group for verbal memory, executive function, and the composite score on the BACS. Similarly, greater improvements were found in the combined AE and CR group than in the CR group alone in verbal memory, working memory, attention, executive function, and the composite BACS score, with effect sizes ranging from moderate to large. No significant differences were found in functional level changes from baseline to post-treatment in the pairwise comparisons between groups, as assessed using the modified Global Assessment of Functioning for social functioning Scale. Our results indicate that patients with schizophrenia in the combined AE and CR group achieved greater cognitive improvement than those in the AE or CR alone group.

Cognitive dysfunction is a well-documented feature of schizophrenia (SZ) and bipolar (BD) disorder. The person's subjective experience of cognitive difficulties is less investigated. Here we investigated subjective cognition in SZ and BD compared to healthy controls (HC). Subjective and objective cognition were assessed in 91 SZ participants, 55 BD participants and 55 HC, applying a novel measure of subjective cognition, the self-assessed cognitive complaints scale (SACCS) and a clinically relevant neuropsychological test battery. The psychometric properties of SACCS were investigated. The relationship between subjective and objective cognition, and subjective cognition and clinical variables were explored in SZ and BD. The SACCS showed adequate psychometric properties. Clinical groups reported significantly more cognitive complaints than HCs, without differences between SZ and BD. There were no significant associations between subjective and objective cognitive measures. There was a small trend association between subjective cognition and insight in SZ participants, and moderate sized associations between subjective cognition and general psychopathology and functioning in BD participants. Although SZ participants are more cognitively impaired than BD participants, the two groups report similar levels of subjective cognitive complaints, with no association between subjective and objective cognition. Our results suggest that the expression of subjective cognition is associated with different clinical factors in SZ and BD.

Despite significant patient burden, there are no approved pharmacotherapies to treat symptoms of cognitive impairment associated with schizophrenia (CIAS). This double-blind, placebo-controlled, parallel-group Phase II trial assessed the efficacy and safety of pharmacological augmentation of at-home computerized cognitive training (CCT) with iclepertin (BI 425809, a glycine transporter-1 inhibitor). Participants with schizophrenia (aged 18-50 years) on stable antipsychotic therapy, who were compliant with CCT during the run-in period, were enrolled. Patients were randomized (1:1) to once daily iclepertin 10 mg or placebo for 12 weeks, and all patients completed adjunctive CCT. At Week 12, the change from baseline in neurocognitive composite T-score of the MATRICS Consensus Cognitive Battery (primary endpoint), Schizophrenia Cognition Rating Scale interviewer total score, and Positive and Negative Syndrome Scale total score (secondary endpoints) were assessed. Performance was also assessed using Virtual Reality Functional Capacity Assessment Tool adjusted total time T-score. Of 200 randomized patients, 154 (77.0 %) completed the trial. At efficacy endpoint assessment, no differences were observed between treatment groups. Adverse events (AEs) were reported by 39 patients in the iclepertin 10 mg + CCT group and 57 patients in the placebo + CCT group; most AEs were mild to moderate. To our knowledge, this trial is the largest of its kind combining daily pharmacotherapy for CIAS with at-home CCT. Although efficacy was not demonstrated, the safety profile of iclepertin 10 mg was consistent with previous studies and no new risks were identified.

ClinicalTrials.gov identifier: NCT03859973.

Prior studies suggest that cognitive batteries normed in the U.S. may not be suitable for populations that differ in English proficiency and/or cultural background. Here, we investigated how cultural variables (i.e., length of residence, native English speaker) influence cognitive performance within a U.S. and Canadian sample of people at clinical high risk for psychosis (CHR-P) and healthy control (HC) participants.

The sample consisted of 925 adolescents and adults (664 CHR-P, 261 HC) from the second cohort of the North American Prodromal Longitudinal Study, including 73 (7.9 %) foreign-born participants and 94 (10.2 %) who reported a language other than English as their first language. Multigroup structural equation modeling was used to estimate effects of cultural variables on MATRICS Consensus Cognitive Battery (MCCB) subtests, separately in each diagnostic group.

A structural model that generated unique estimates for all parameters in group models was selected. For CHR-P, longer length of residence in U.S./Canada related to better performance on Animal Naming (β = 0.09, p = .01), whereas being a native English speaker related to better performance on Letter-Number Span (β = 0.14, p = .001) and Hopkins Verbal Learning Test - Revised (β = 0.10, p = .03). In contrast, no such relationships were observed among HCs.

Findings extend our understanding of how cultural variables may influence presentation of psychosis-risk syndromes and suggest that being a non-native English speaker or having recently immigrated may hinder performance on certain verbal neuropsychological measures.

Psychosis is a complex brain disorder with diverse biological subtypes influenced by various pathogenic mechanisms, which can affect treatment efficacy. The ANR(Attenuated Niacin Response) subtype is characterized by pronounced negative symptoms and functional impairments, suggesting a distinct clinical profile. However, research on the cognitive characteristics associated with the ANR subtype in drug-naïve first-episode psychosis(FEP) patients remains limited.

This observational study involved 54 FEP patients and 52 healthy controls(HC). Clinical psychopathology was assessed using the Positive and Negative Syndrome Scale(PANSS), while cognitive performance was evaluated through the Chinese version of the MATRICS Consensus Cognitive Battery(MCCB). Additionally, niacin response was measured using aqueous methylnicotinate patches, with responses quantified to classify participants into ANR or normal niacin response (NNR) groups.

Among the FEP patients, 25.9 % were classified as having ANR, significantly higher than the 7.7 % in the HC group (χ 2  = 6.247, p = 0.012). The ANR group exhibited more severe negative symptoms and higher total PANSS scores compared to the NNR group, with significant differences in cognitive performance on the Trail Making test and the Brief Visuospatial Memory Test-Revised. Correlation analyses revealed a significant positive relationship between overall symptom severity and niacin response, as well as between cognitive performance and niacin response, particularly for the Trail Making and Symbol coding tests.

This study demonstrates that the ANR subtype in first-episode psychosis is linked to more severe negative symptoms and cognitive impairments. Targeted assessments and interventions for patients with ANR may improve treatment outcomes and enhance understanding of cognitive dysfunction in psychotic disorders.

Personal (or self-rated) recovery in schizophrenia represents an adaptive process of constructing meaning in life, finding hope, and establishing a positive identity. In this sense, recovery is linked to and dependent upon one's sense of future self. Although self-rated recovery has been explored in relation to various affective, social, and psychological factors, the relationship between personal recovery and future-self continuity has not been examined. Future self-continuity (or continuous identity) refers to the sense of connection between one's present and future self, as the same person now as in the future. Individuals, who cannot connect their present selves to future selves view their future self as a stranger and have a decreased sense of self-empowerment and feel less motivated to work towards future-oriented and personally meaningful treatment goals. We postulate that having good future self-continuity may be a prerequisite to success in recovery-oriented treatment programs. The current study explored the relationship between self-rated recovery and future self-continuity in individuals with schizophrenia.

Forty participants with schizophrenia were recruited from two inpatient units and completed a battery of assessments including cognitive functioning, symptom severity, level of functioning as well as an assessment of personal recovery.

The results indicated that higher future self-continuity predicted better personal recovery in individuals with schizophrenia after controlling for key demographic variables, symptom severity, psychosocial and cognitive functioning ability.

Future self-continuity was the only significant psychological variable that predicted personal recovery in individuals with schizophrenia. Clinical implications and future directions are discussed.

Myelin abnormalities in white matter have been implicated in the pathophysiology of psychotic spectrum disorders (PSD), which are characterized by brain dysconnectivity as a core feature. Among evidence from in vivo MRI studies, diffusion imaging findings have largely supported disrupted white matter integrity in PSD; however, they are not specific to myelin changes. Using a multimodal imaging approach, the current study aimed to further delineate myelin and microstructural changes in the white matter of a young PSD cohort. We utilized quantitative magnetization transfer (qMT) imaging combined with advanced diffusion imaging to estimate specific myelin-related biophysical properties in 51 young adult PSD patients compared with 38 age-matched healthy controls. The macromolecular proton fraction (MPF) obtained from qMT was used as a specific marker of myelin content. Additionally, MPF was employed along with diffusion metrics of axonal density (vic) and extra-cellular volume fraction to derive the g-ratio, a measure of relative myelin sheath thickness defined as the ratio of inner to outer axonal diameter. Compared to controls, we observed a widespread MPF reduction and localized g-ratio increase in patients, primarily those with a diagnosis of schizophrenia or depressive schizoaffective disorder. No between-group differences were noted in vic, suggesting similar axonal densities across groups. Correlation analysis revealed that lower MPF was significantly related to poorer working memory performance in PSD, while the HC group showed a positive association for working memory with both g-ratio and vic. The pattern of changes observed in our multimodal imaging markers suggests that PSD, depending on symptomatology, is characterized by specific alterations in white matter integrity and myelin-axonal geometry of major white matter tracts, which may impact working memory function. These findings provide a more detailed view of myelin-related white matter changes in early stages of PSD.

People with schizophrenia differ in the type and severity of symptoms experienced, as well as their response to medication. A better understanding of the factors that influence this heterogeneity is necessary for the development of individualised patient care. Here, we sought to investigate the relationships between phenotypic severity and both medication and pharmacogenomic variables in a cross-sectional sample of people with schizophrenia or schizoaffective disorder depressed type.

Confirmatory factor analysis derived five dimensions relating to current symptom severity (positive symptoms, negative symptoms of diminished expressivity, negative symptoms of reduced motivation and pleasure, depression and suicide) and cognitive ability in participants prescribed with antipsychotic medication. Linear models were fit to test for associations between medication and pharmacogenomic variables with dimension scores in the full sample (N = 585), and in a sub-sample of participants prescribed clozapine (N = 215).

Lower cognitive ability was associated with higher chlorpromazine-equivalent daily antipsychotic dose (β = -0.12; 95% CI, -0.19 to -0.05; p = 0.001) and with the prescription of clozapine (β = -0.498; 95% CI, -0.65 to -0.35; p = 3 × 10-10) and anticholinergic medication (β = -0.345; 95% CI, -0.55 to -0.14; p = 8 × 10-4). We also found associations between pharmacogenomics-inferred cytochrome P450 (CYP) enzyme activity and symptom dimensions. Increased genotype-predicted CYP2C19 and CYP3A5 activity were associated with reduced severity of the positive (β = -0.108; 95% CI, -0.19 to -0.03; p = 0.009) and both negative symptom dimensions (β = -0.113; 95% CI, -0.19 to -0.03; p = 0.007; β = -0.106; 95% CI, -0.19 to -0.02; p = 0.012), respectively. Faster predicted CYP1A2 activity was associated with higher cognitive dimension scores in people taking clozapine (β = 0.17; 95% CI, 0.05-0.29; p = 0.005).

Our results confirm the importance of taking account of medication history (and particularly antipsychotic type and dose) in assessing potential correlates of cognitive impairment or poor functioning in patients with schizophrenia. We also highlight the potential for pharmacogenomic variation to be a useful tool to help guide drug prescription, although these findings require further validation.

Medical Research Council (MR/Y004094/1) and The National Center for Mental Health, funded by the Welsh Government through Health and Care Research Wales. SKL was funded by a PhD studentship from Mental Health Research UK (MHRUK). DBK, JTRW, MCOD and AFP were supported by the European Union's Horizon 2020 research and innovation programme under grant agreement 964874.

People with schizophrenia (PSZ) showed preserved ability to unconsciously process simple social information (e.g., face and gaze), but not in higher-order cognition (e.g., memory). It is yet unknown how PSZ process social interactions across different cognitive domains. This study systematically investigated the cognitive characteristics of PSZ during social interaction processing from bottom-up perception to top-down memory, and established correlations with schizophrenic symptoms. In two experiments, social interactions were consistently displayed by face-to-face or back-to-back dyads. Experiment 1 enrolled 30 PSZ and 30 healthy control subjects (HCS) with a breaking continuous flash suppression (b-CFS) paradigm. Experiment 2 recruited 36 PSZ and 36 HCS for two memory tasks, wherein participants restored the between-model distance (working memory task) and recalled the socially bound pairs (long-term memory task). Results indicated that HCS showed advantageous processing of socially interactive stimuli against non-interactive stimuli throughout two experiments, including faster access to visual consciousness, closer spatial distance held in working memory and higher recollection accuracy in long-term memory. However, PSZ did not show any of these advantages, with significant interaction effects for all three tasks (task one: p = .018, ηp2 = .092; task two: p = .021, ηp2 = .074; task three: p = .015, ηp2 = .082). Moreover, correlation analyses indicated that PSZ with more severe negative symptoms (r = -.344, p = .040) or higher medication dosages (r = -.334, p = .046) showed fewer advantages in memorizing socially interactive information. Therefore, social interaction is not prioritized in schizophrenia from bottom-up perception to top-down memory, and the magnitude of such a domain-general cognitive alteration is clinically relevant to symptom severity and medication.

Despite the significant number of impairments shared by diagnostic groups on the schizophrenia-phenotypic-spectrum, no work has directly compared neuro- and social-cognition of individuals with schizotypal personality disorder (SPD) with that of schizophrenia. This is the first study to compare social-cognition and neuro-cognition across schizophrenia-spectrum-diagnostic groups and explore associations (1) between neuro- and social-cognition in these groups and (2) between change-over-time (nine-month follow-up) in cognition and negative-symptom-severity. This study identified 127 age- and gender-matched healthy controls (HC; N = 49), antipsychotic-naïve individuals with SPD (N = 32), and patients with recent onset schizophrenia (within eight years of illness-onset; N = 46). Detailed profiles of clinical symptoms and cognition were obtained using gold-standard measures (e.g., NIH MATRICS Battery). Schizophrenia patients exhibited global cognitive impairment; SPD patients only exhibited impairment in social-emotional cognition compared with HC (Cohen d = 0.51) but still performed better than the schizophrenia group F[2, 124]=15.18, p < 0.001, Cohen d = 0.61. Multivariable linear regression revealed that social-cognition was associated with neuro-cognition, β=0.49, p < 0.001. In the combined patient group, a greater increase in social-cognition over time was associated with greater reduction in negative symptoms, (B = -0.12, SE=0.09, p = 0.038). Distinct profiles emerged: generalized cognitive impairment in schizophrenia and higher-order social-cognition impairment in SPD. Furthermore, change in social-cognition over time is associated with a change in negative symptoms. Results suggest that social-cognition is impaired across the schizophrenia-spectrum, and detailed examination of social-cognitive treatments should be considered, particularly for individuals with SPD, as they receive minimal attention in research studies.

Despite the recognized importance of social cognition in predicting functional outcomes in schizophrenia, there is a lack of widely accepted measures that assess this broad domain while possessing psychometric validity and predictive utility. This study aimed to address this gap by providing incremental validity data for a promising social cognitive measure assessing facial affect recognition in patients presenting with treatment-resistant psychosis.

Using a clinical archival dataset comprising 59 consecutive admissions to an inpatient treatment-resistant psychosis unit, this study examined facial affect naming performance from the Advanced Clinical Solutions-Social Perception (ACS-SP) affect naming subtest, and the association with neuropsychological functioning and symptom severity. Hierarchical regression models were used to assess whether facial affect recognition predicted daily functioning, including measures of functional capacity and functional performance.

The ACS-SP affect naming measure showed limited sensitivity for impairment relative to other cognitive domains. Affect naming showed weak to moderate correlations with a broad range of non-memory cognitive functions, and no association with symptom severity. After controlling for cognitive functioning and symptoms, the ACS-SP affect naming task predicted poorer functioning with regard to functional performance but not functional capacity.

The ACS-SP affect naming task associates weakly to moderately with other measures of cognition, but also likely taps into social cognitive skills not measured by typical neuropsychological tests. This measure was predictive of some aspects of functional outcomes in patients with treatment-resistant psychosis, and therefore may be a useful tool to incorporate into routine neuropsychological assessments in such treatment settings.

Cognitive symptoms contribute to the worsening of functionality in people with schizophrenia. The objective of this study was to explore the current knowledge about cognitive symptoms (relevance, evaluation, and management) of psychiatrists and primary care physicians (PCPs) involved in the care of patients with schizophrenia in Spain.

The study was developed in two phases: a quantitative phase and a qualitative one. Both took place between November 2023 and January 2024. For the quantitative phase, an online questionnaire was developed and administered to 100 psychiatrists and 125 PCPs. In addition, further qualitative data were collected through individual semi-structured telephone interviews. Descriptive analyses and qualitative analyses (induction-deduction approach) were carried out.

Health professionals agreed that cognitive symptoms are present in patients with schizophrenia, with 75% of psychiatrists and 45% of PCPs acknowledging this. Both groups also considered the detection of these symptoms as crucial for improving patient functionality (89% psychiatrists vs 88% PCPs). However, over half of both psychiatrists and PCPs do not consistently evaluate cognitive symptoms, attributing this to factors such as time constraints, limited access to both pharmacological and non-pharmacological treatments, and a lack of effective diagnostic tools. PCPs additionally highlighted insufficient training regarding cognitive symptoms in schizophrenia. Both groups underscored the need for specific treatments for cognitive symptoms, with 87% agreement.

This study offers an overview of the current understanding regarding the relevance, evaluation, and management of various cognitive symptoms according to clinical practice in Spain. The results highlight the necessity for enhanced guidelines, training, and improved access to effective treatments to address cognitive symptoms in patients with schizophrenia.

Schizophrenia has been identified to exhibit significant abnormalities in brain functional networks, which are likely to underpin the cognitive and functional impairments observed in patients. Graph theoretical analysis revealed the disrupted modularity in schizophrenia, however, the dynamic network abnormalities in schizophrenia remains unclear. We collected the resting-state functional magnetic resonance imaging data from 82 first-episode schizophrenia (FES) patients and 55 healthy control (HC) subjects. Dynamic functional connectivity matrices were constructed and a multilayer network model was employed to run the dynamic modularity analysis. We also performed correlation analyses to investigate the relationship between flexibility, cognitive function and clinical symptoms. Our findings indicate that FES patients exhibit higher multilayer modularity. The node flexibility of FES patients were found elevated in several brain regions, which were included in the default mode network, fronto-parietal network, salience network and visual network. The node flexibility metrics in aberrant brain regions were found to demonstrate significant correlations with cognitive function and negative symptoms in patients with FES. These findings suggest a pathological imbalance in brain network dynamics, where abnormal modular organization might contribute to the cognitive impairment and functional deficits in schizophrenia.

From the first episode (FEP), the course of psychosis is marked by substantial heterogeneity of clinical and functional outcomes which poses significant challenges in providing prognostic guidance to patients and families. To better understand such heterogeneity within the context of early intervention services (EIS), this study aimed to examine latent trajectories of positive and negative symptoms and functioning among FEP individuals undergoing EIS.

The Prevention and Early Intervention Program for Psychoses (PEPP-Montreal) is a 2-year EIS for FEP that conducted longitudinal assessments of 689 individuals aged 14-35, including sociodemographics, cognition, psychopathology, and functioning. Latent growth mixture modeling was used to identify distinct patterns of clinical and functional trajectories. The inter-relationship between trajectories, and the association of trajectory membership with baseline characteristics and distal outcomes were investigated using the manual 3-step approach.

Two positive symptom trajectories (Stable-low-32%, Fluctuating-68%,), 3 negative symptom trajectories (Decreasing-41%, Fluctuating-15%, and Stable-high-44%), and 2 functioning trajectories (Increasing-57%, Stable-moderate-43%) were identified. Early treatment response, particularly on negative symptoms, consistently and strongly predicted better outcome trajectories (OR = [3.4-5.5]). Trajectories of higher symptom severity were associated with trajectory of worse functioning (RR = [1.5-2.2]), which exhibited lower rates of clinical and functional remission.

These findings offer insights into clinically meaningful subgroups of individuals that could inform the prognosis of FEP and the development of individually tailored EIS. Individuals who do not show early improvement in negative symptoms may benefit from earlier psychosocial interventions specifically targeting actionable factors that contribute to secondary negative symptoms.

In first episode psychosis (FEP), cognitive impairments are core features contributing to clinical and functional heterogeneity. Significant impairment indicates greater clinical severity throughout the course of the illness, particularly for negative symptoms. Hippocampal volume is smaller in FEP than in healthy controls (notably subfields like Cornu Ammonis 1-3 and subiculum), and is related to cognitive impairments and negative symptoms. The aim of this study was to compare the clinical and functional trajectories of FEP subgroups as a function of cognitive performance and hippocampal volumes.

One hundred FEP patients and sixty healthy controls initially assessed using the CogState research battery, underwent 3 T MRI to extract hippocampal subfields and adjacent structures using the MAGeT brain algorithm. Clinical assessments were carried out for negative (Motivational and Pleasure - MAP, and diminished expression - EXP) and depressive symptoms, and global functioning. Measurements were taken at 4 time points (3, 9, 15, 21 months following program entry). Based on available first timepoint standardized cognitive and hippocampal features, using healthy controls as reference, clusters were determined by a hierarchical ascending classification. Their clinical and functional longitudinal trajectories were analyzed using linear mixed-effects models.

Three baseline clusters were revealed: normal-range hippocampal volume with low attention, working and verbal memory (FEP 0), small hippocampus with low verbal memory and social cognition (FEP 1), and large hippocampus with low verbal memory (FEP 2). At baseline, the clusters did not differ on symptoms severity and global functioning. Longitudinally, MAP, EXP and depressive symptoms decreased over time in FEP 0. Global functioning improved in FEP 0 and FEP 1, while FEP 2 was clinically and functionally stable over time. Longitudinal inter-group comparisons did not yield any significant differences.

The clusters were dissociated between hippocampus and cognition, but their trajectories suggest the importance of hippocampal integrity in the clinical and/or functional outcome. Future studies are needed to understand intervention efficiency depending on hippocampal integrity.

Early childhood trauma has been linked to neurocognitive and emotional processing deficits in older children, yet much less is known about these associations in young children. Early childhood is an important developmental period in which to examine relations between trauma and executive functioning/emotion reactivity, given that these capacities are rapidly developing and are potential transdiagnostic factors implicated in the development of psychopathology. This cross-sectional study examined associations between cumulative trauma, interpersonal trauma, and components of executive functioning, episodic memory, and emotion reactivity, conceptualized using the RDoC framework and assessed with observational and performance-based measures, in a sample of 90 children (ages 4-7) admitted to a partial hospital program. Children who had experienced two or more categories of trauma had lower scores in episodic memory, global cognition, and inhibitory control as measured in a relational (but not computerized) task, when compared to children with less or no trauma. Interpersonal trauma was similarly associated with global cognition and relational inhibitory control. Family contextual factors did not moderate associations. Findings support examining inhibitory control in both relationally significant and decontextualized paradigms in early childhood, and underscore the importance of investigating multiple neurocognitive and emotional processes simultaneously to identify potential targets for early intervention.

Negative symptoms and social function have been known to predict work outcomes in patients with schizophrenia. Recent studies report that specific subdomains of these predictors were particularly important in prediction. The aims of this study were (1) to determine which subdomains of negative symptoms and social function were the most important predictors of work outcomes among patients with schizophrenia, and (2) to use these factors to produce charts to demonstrate the estimated probabilities of workable hours. Data were obtained from 293 patients with schizophrenia. Four separate logistic regression analyses were conducted using psychiatric symptoms, intellectual ability, and social function as independent variables to predict work hours (0, 10, 20, or 30 h per week). The Experiential deficit domain of negative symptoms, comprising of volitional, social, and hedonic deficits, and the Independence-Performance domain including self-care and daily-living skills were significant in most regression models. Charts illustrating the probabilities of the ability to work were produced based on these two predictors. Our study identified specific domains of negative symptoms and social function were relevant to work outcomes in patients with schizophrenia. The charts illustrating the probabilities of workable hours provide objective information about the capacity to work among patients with schizophrenia.

The current study aims to explore the efficacy of cognitive behavioral therapy (CBT) in normalizing social learning capabilities and its underlying neural processes among patients with MDD, in terms of enhancing learning towards positive social feedback, and reducing excessive learning towards negative social feedback. This study also explores the potential for learning impairments in social contexts as a biomarker to predict the effectiveness of CBT.

In a single-centre, single-arm, open-label trial, 60 outpatients with MDD will undergo 12 sessions of CBT in three months. Data collection of patients will be administered at baseline and at the endpoint of the treatment. Additionally, 60 heathy controls will be recruited as a comparative group to assess deviations from the normal functions in the patients with MDD before and after CBT. Data collection of the HC group will be administered at baseline. Data collection of the two groups comprises of demographic information, clinical assessments, psychological assessments, and behavioral experiments (i.e. the Door Game and the Trust Game) in conjuction with task-based function magnetic resonance imaging (fMRI) scanning. Data analysis comprises of an estimation of social learning capabilities by computational modeling, and identification of baseline abnormalities, treatment effects and endpoint abnormalities on social learning capabilities and its neural activities.

This trial aims to assess the efficacy of CBT in normalizing social learning capabilities among patients with MDD by leveraging high ecological validity paradigms and computational modeling. This trial also contributes to understanding psychosocial biomarkers of CBT treatment effectiveness in reducing depressive symptoms.

ChiCTR2400094841 ( www.chictr.org.cn ; registration date: 12/29/2024) (retrospectively registered).

The prevalence of mental disorders among young and middle-aged populations has demonstrated a significant upward trend, with first-episode psychosis (FEP) frequently associated with psychological distress and functional impairments during initial onset. While persons affected by FEP frequently report psychological distress and reduced quality of life during early illness stages, they may also experience post-traumatic growth (PTG), which fosters positive changes that facilitate their recovery. Yet there is limited attention on PTG in young and middle-aged patients with FEP. Therefore, this study aimed to investigate the level of PTG and identify significant correlates and mediators of PTG among young and middle-aged patients with FEP.

From January 2021 to December 2023, two hundred eight patients with first-episode psychosis were enrolled from a tertiary hospital in Shandong Province, China, through convenience sampling. The Perceived Social Support Scale (PSSS), Posttraumatic Growth Inventory-Short Form (PTGI-SF), and Connor-Davidson Resilience Scale (CD-RISC10) were administered. Hierarchical linear regression modeling was performed to examine the associations between perceived social support and PTG and the mediating effect of resilience.

The PTG score was 31.22 ± 6.59, and resilience and PSS could positively predict the variance in PTG. Resilience partially mediated the relationship between PSS and PTG, and the value of the mediating effect was 22.8%.

Young and middle-aged patients with FEP have a moderate level of PTG. Resilience partially mediates the relationship between PSS and PTG. Therefore, interventions focusing on promoting PSS and resilience should be developed to encourage PTG in young and middle-aged patients with FEP.

Antipsychotic (AP) medications are the primary treatment for severe mental illnesses, including schizophrenia and severe mood disorders. APs are currently categorized into typical or first-generation APs and atypical or second-generation APs. Although both first-generation and second-generation APs are considered effective in treating psychotic symptoms in severe mental disorders, they differ in their mechanisms, treatment strategies, and side effect profiles. Because of their potential motor and metabolic side effects, which often compromise patient adherence and clinical outcomes, whether and how to use APs remains controversial. The use of dietary interventions in combination with APs is emerging as a viable strategy to reduce AP adverse effects while maintaining their efficacy and enhance patient adherence to treatment. In contrast to drugs that possess a well defined molecular mechanism of action, dietary interventions act in pleiotropic ways by nature. While providing a holistic approach to patient care this pleiotropy needs to be analyzed and systematized to enhance the efficacy and safety of the combination of them with APs. Guidelines for this type of treatment are still needed. In this review, we explore the pharmacological properties, therapeutic applications, and limitations of APs, and discuss the potential benefits and limitations of those dietary interventions that are employed to improve the efficacy and counteract side effects of APs discussing also their mechanisms of action. Finally, we critically discuss the main results of clinical studies combining APs and dietary interventions and provide a view on future directions in terms of research and clinical use of these combinations. SIGNIFICANCE STATEMENT: Antipsychotic drugs are useful in a variety of psychiatric conditions, yet their use is hampered by issues of efficacy and safety. An important step toward therapy optimization is their use in combination with dietary interventions (ie, dietary supplements and nutraceuticals) that have shown promising results in clinical trials.

This study aims to investigate the link between Electroencephalography (EEG) microstate anomalies and cognitive impairments in individuals with drug-naive Major depressive disorder (MDD).

We recruited 29 patients with drug-naive MDD and 30 healthy controls. The Hamilton Depression Rating Scale (HDRS-17) measured symptom severity, the MATRICS Consensus Cognitive Battery (MCCB) assessed neurocognitive function, and resting-state EEG data were collected using 64 scalp electrodes. Analysis of EEG microstates was conducted via the Microstate Analysis plugin for EEGLAB.

MDD group had lower scores in six neurocognitive MCCB domains. For EEG microstates, four similar ones (A - D) were found in both groups. Notably, microstate C duration was lower in MDD group (t = 4.549, P < 0.001), microstate D occurrence (t = 2.258, P = 0.028) and proportion (t = 3.733, P < 0.001) were lower in MDD group. There were significant differences in all 4 microstate transition probabilities between groups. For example, A - B, B - A etc. transitions were higher in MDD, while A - C, A - D etc. were lower.The proportion of microstate D was found positively correlated with Speed of processing (SOP) score (r = 0.499, df = 26, P = 0.007) and Working memory (WM) score (r = 0.451, df = 26, P = 0.016). The Occurrence of microstate D was found positively correlated with SOP score (r = 0.383, df = 26, P = 0.044) and WM score (r = 0.389, df = 26, P = 0.041).

MDD patients show alterations in sub-second brain dynamics, characterized by a decreased proportion and occurrence of microstate D and shorter duration of microstate C, and significant shifts in microstate transition probabilities. These changes correlate with cognitive deficits across several domains, including processing speed and working memory.

Bipolar disorder (BD) is a chronic condition characterized by recurrent mood episodes and persistent cognitive deficits that span multiple domains, ultimately impacting daily functioning. Understanding the neural underpinnings of these impairments is crucial. In a systematic review and meta-analysis examining 80 studies (with 50 meeting criteria for meta-analysis) of adults with BD, relationships between structural brain measures and cognitive performance were evaluated. Participants were diagnosed according to standard criteria, underwent structural and diffusion-weighted MRI, and completed standardized cognitive assessments. The meta-analyses indicated significant associations between both grey matter and white matter indices and cognitive functioning, reflected in moderate effect sizes. Notably, these associations exhibited substantial heterogeneity. Meta-regression revealed that bipolar subtype and current mood state moderated the observed brain-cognition relationships, with bipolar I and euthymic individuals showing higher associations with grey matter metrics. Cognitive domain differences also played a key role, indicating that certain cognitive functions are more strongly linked to structural brain measures than others. Brain networks emerged as a global influence on cognition, with limited differences in pairwise comparisons. Age, sex, psychosis, and mania were not found to significantly moderate these relationships. Overall, this work suggests that structural alterations in grey and white matter in individuals with BD may contribute meaningfully to cognitive difficulties, while brain networks may provide a broad integrative framework for these associations. These findings underscore the importance of considering both global and specific neural factors when exploring the pathophysiology of cognitive impairment in BD.

An increasing interest in the assessment of neuropsychological performance variability in people with first-episode psychosis (FEP) has emerged. However, its association with clinical and functional outcomes requires further study. Furthermore, FEP neuropsychological subgroups have not been characterized by clinical insight or metacognition and social cognition domains. The aim of this exploratory study was to identify specific groups of patients with FEP based on neuropsychological variables and to compare their sociodemographic, clinical, metacognition and social cognition profiles. A sample of 149 FEP was recruited from adult mental health services. Neuropsychological performance was assessed by a neuropsychological battery (WAIS-III; TMT; WSCT; Stroop Test; TAVEC). The assessment also included sociodemographic characteristics, clinical, functional, metacognition and social cognition variables. Two distinct neuropsychological profiles emerged: one neuropsychological impaired cluster (N = 56) and one relatively intact cluster (N = 93). Significant differences were found between both profiles in terms of sociodemographic characteristics (age and level of education) (p = 0.001), clinical symptoms (negative, positive, disorganized, excitement and anxiety) (p = 0.041-0.001), clinical insight (p = 0.038-0.017), global functioning (p = 0.014), as well as in social cognition domains (emotional processing and theory of mind) (p = 0.001; p = 0.002). No significant differences were found in metacognitive variables (cognitive insight and 'jumping to conclusions' bias). Relationship between neurocognitive impairment, social cognition and metacognition deficits are discussed. Early identifying of neuropsychological profiles in FEP, characterized by significant differences in clinical and social cognition variables, could provide insight into the prognosis and guide the implementation of tailored early-intervention.

Individuals diagnosed with schizophrenia present diverse degrees and types of cognitive impairment, leading to variations in responses to antipsychotic treatments. Understanding the underlying cognitive structures is crucial for assessing this heterogeneity. Utilizing latent profile analysis (LPA) enables the delineation of latent categories of cognitive function. Integrating this approach with a dimensional perspective allows for the exploration of the relationship between cognitive function and treatment response.

This study examined 647 patients from two distinct cohorts. Utilizing LPA within the discovery cohort (n = 333) and the replication cohort (n = 314), latent subtypes were identified categorically. The stability of cognitive structures was evaluated employing Latent Transition Analysis (LTA). The relationship between cognitive function and treatment response were investigated by comparing Positive and Negative Syndrome Scale (PANSS) reduction rates across diverse cognitive subtypes. Furthermore, dimensional insights were gained through correlation analyses between cognitive tests and PANSS reduction rates.

In terms of categorical, individuals diagnosed with schizophrenia can be categorized into three distinct subtypes: those 'without cognitive deficit', those 'with mild-moderate cognitive 'eficit', and those 'with moderate-severe cognitive deficit'. There are significant differences in PANSS reduction rates among patients belonging to these subtypes following antipsychotic treatment (p < 0.05). Furthermore, from a dimensional perspective, processing speed at baseline is positively correlated with PANSS score reduction rates at week 8/week 10 (p < 0.01).

Our findings have unveiled the latent subtypes of cognitive function in schizophrenia, illuminating the association between cognitive function and responses to antipsychotic treatment from both categorical and dimensional perspectives.

The authors synthesized evidence from studies quantifying the relationship between anticholinergic medication and cognitive function in psychosis, and additionally explored studies that investigated whether reducing anticholinergic medications affects cognitive function in individuals with psychosis.

A database search was conducted in MEDLINE, Embase, and PsycINFO, from database inception to October 2023, for studies reporting objective cognitive assessment and quantification of anticholinergic burden using clinical scales, serological anticholinergic activity, or tapering of anticholinergic medications. Analyses were carried out in R using the metafor package. Random-effects meta-analysis models were employed, along with assessment of heterogeneity, study quality, and meta-regressions (age, sex, and antipsychotic dosage in chlorpromazine equivalents).

Of 1,337 citations retrieved, 40 met inclusion criteria, comprising 25 anticholinergic burden studies (4,620 patients), six serological anticholinergic activity studies (382 patients), and nine tapering studies (186 patients). A negative correlation was identified between anticholinergic burden and global cognition (r=-0.37, 95% CI=-0.48, -0.25), verbal learning (r=-0.28, 95% CI=-0.36, -0.21), visual learning (r=-0.17, 95% CI=-0.28, -0.06), working memory (r=-0.22, 95% CI=-0.29, -0.14), processing speed (r=-0.24, 95% CI=-0.35, -0.13), attention (r=-0.19, 95% CI=-0.29, -0.08), executive functions (r=-0.17, 95% CI=-0.27, -0.06), and social cognition (r=-0.12, 95% CI=-0.19, -0.05), and between serological anticholinergic activity and verbal learning (r=-0.26, 95% CI=-0.38, -0.14), working memory (r=-0.19, 95% CI=-0.35, -0.03), and executive functions (r=-0.16, 95% CI=-0.27, -0.04). Finally, tapering off anticholinergic medication improved the scores in verbal learning (d=0.77, 95% CI=0.44, 1.1), working memory (d=0.94, 95% CI=0.63, 1.26), and executive functions (d=0.44, 95% CI=0.26, 0.62).

Anticholinergic burden is associated with the cognitive impairments observed in psychosis. From a clinical perspective, tapering off anticholinergic medication in patients with psychosis may improve cognition. However, randomized clinical trials are needed for an unbiased quantification of benefit.

Neuropsychiatric disorders such as autism spectrum disorder (ASD) and schizophrenia (SCZ) share genetic risk factors, including rare high penetrance single nucleotide variants and copy number variants (CNVs), and exhibit both overlapping and distinct clinical phenotypes. Cognitive deficits and intellectual disability-critical predictors of long-term outcomes-are common to both conditions. To investigate shared and disorder-specific neurobiological impact of highly penetrant rare mutations in ASD and SCZ, we analyzed human single-nucleus whole-brain sequencing data to identify strongly affected brain cell types. Our analysis revealed Caudal Ganglionic Eminence (CGE)-derived GABAergic interneurons as a key nexus for cognitive deficits across these disorders. Notably, genes within 22q11.2 deletions, known to confer a high risk of SCZ, ASD, and cognitive impairment, showed a strong expression bias toward vasoactive intestinal peptide-expressing cells (VIP+) among CGE subtypes. To explore VIP+ GABAergic interneuron perturbations in the 22q11.2 deletion syndrome in vivo , we examined their activity in the Df(16)A +/- mouse model during a spatial navigation task and observed reduced activity along with altered responses to random rewards. At the population level, VIP+ interneurons exhibited impaired spatial encoding and diminished subtype-specific activity suggesting deficient disinhibition in CA1 microcircuits in the hippocampus, a region essential for learning and memory. Overall, these results demonstrate the crucial role of CGE-derived interneurons in mediating cognitive processes that are disrupted across a range of psychiatric and neurodevelopmental disorders.

While cognitive impairment is a core feature of psychosis, significant heterogeneity in cognitive and clinical outcomes is observed.

The aim of this study was to identify cognitive and clinical subgroups in first-episode psychosis (FEP) and determine if these profiles were linked to functional outcomes over time.

A total of 323 individuals with FEP were included. Two-step hierarchical and k-means cluster analyses were performed using baseline cognitive and clinical variables. General linear mixed models were used to investigate whether baseline cognitive and clinical clusters were associated with functioning at follow-up time points (6-9, 12 and 15 months).

Three distinct cognitive clusters were identified: a cognitively intact group (N = 59), a moderately impaired group (N = 77) and a more severely impaired group (N = 122). Three distinct clinical clusters were identified: a subgroup characterised by predominant mood symptoms (N = 76), a subgroup characterised by predominant negative symptoms (N = 19) and a subgroup characterised by overall mild symptom severity (N = 94). The subgroup with more severely impaired cognition also had more severe negative symptoms at baseline. Cognitive clusters were significantly associated with later social and occupational function, and associated with changes over time. Clinical clusters were associated with later social functioning but not occupational functioning, and were not associated with changes over time.

Baseline cognitive impairments are predictive of both later social and occupational function and change over time. This suggests that cognitive profiles offer valuable information in terms of prognosis and treatment needs.

Cognitive impairment occurs at higher rates in individuals at clinical high risk (CHR) for psychosis relative to healthy peers, and it contributes unique variance to multivariate prediction models of transition to psychosis. Such impairment is considered a core biomarker of schizophrenia. Thus, cognition is a key domain measured in the Accelerating Medicines Partnership® program for Schizophrenia (AMP SCZ initiative). The aim of this paper is to describe the rationale, processes, considerations, and final harmonization of the cognitive battery used in AMP SCZ across the two data collection networks. This battery comprises tests of general intellect and specific cognitive domains. We estimate premorbid intelligence at baseline and measure current intelligence at baseline and 2 years. Eight tests from the Penn Computerized Neurocognitive Battery (PennCNB), which measure verbal learning and memory, sensorimotor ability, attention, emotion recognition, working memory, processing speed, verbal memory, visual memory, and motor speed are administered repeatedly at baseline, and four follow-up timepoints over 2 years.