Schizophrenia is often a persistent mental illness characterized by cognitive deficits and altered brain network dynamics especially affecting the cortico-subcortical salience processing system. Childhood trauma has been implicated in mechanisms contributing to schizophrenia, but the role of genetic vulnerability remains unclear.

A total of 164 schizophrenia patients and 114 healthy controls were included. First, a matched subsample of 117 patients (76 with and 41 without childhood trauma), and 59 healthy controls were compared on polygenic risk scores for schizophrenia (SczPRS). SczPRS was then correlated with neurocognitive performance using a comprehensive cognitive battery (n = 147 patients) and brain-wide static and dynamic functional connectivity (sFC and dFC) using resting-state fMRI (n = 117 patients). Patients were also stratified into high-SczPRS and low-SczPRS (n = 25 each) subgroups.

Patients with childhood trauma had significantly lower SczPRS than those without. Higher Childhood Trauma Questionnaire (CTQ) scores related to lower cognitive PC score (r = −0.282, p < 0.001), but CTQ did not affect brain-wide dysconnectivity or subcortical/salience system among patients. Patients with the highest SczPRS showed lower dFC between the cingulo-opercular network and subcortical networks (F = 7.949, p = 0.007), but SczPRS did not affect cognitive performance.

Our findings reveal distinct effects of childhood trauma and polygenic risk in the neural and cognitive substrates of schizophrenia. Childhood trauma relates to poor cognitive function, while polygenic risk primarily affects salience/subcortical network dynamics. These patterns indicate that in genetically predisposed individuals who experience childhood trauma, a “double mechanistic hit” may influence the schizophrenia phenotype.

Cognitive reserve (CR) is considered a positive factor in the onset, progression, and prognosis of diseases. It may also help explain the clinical heterogeneity observed in schizophrenia (SZ).

This cross-sectional study included 70 patients with SZ and 64 healthy controls. Participants were assessed on CR, symptoms, cognition, and functional outcomes. Following PRISMA guidelines, we also searched PubMed, Scopus, Web of Science, Embase, the Cochrane Library, and PsycINFO for studies published up to September 25, 2025. Study quality was evaluated using the Newcastle-Ottawa Scale (NOS).

Patients with higher CR showed less severe negative and general psychopathological symptoms, along with better functional outcomes. Meta-analysis confirmed this relationship and further revealed positive correlations between CR and multiple cognitive domains, including speed of processing, working memory, verbal learning, visual learning, and reasoning and problem solving.

This study demonstrates a positive association between CR and symptoms severity, cognitive performance, and functional outcomes in SZ.

Schizophrenia-spectrum disorders (SSD) are characterized by structural and functional brain abnormalities, including disrupted functional connectivity within networks such as the salience network. The anterior cingulate cortex (ACC), a core hub of this network, has shown alterations in the major neurotransmitter systems comprising glutamate (Glu) and γ-aminobutyric acid (GABA). While dysfunctional glutamatergic signaling has been proposed as a key mechanism in SSDs, the relationship between anterior cingulate cortex (ACC) functional connectivity, glutamatergic neurotransmission, and clinical symptomatology remains poorly understood.

Here, we combined resting-state functional MRI to measure functional brain connectivity with proton magnetic resonance spectroscopy to measure Glu and GABA levels in the dorsal ACC of 26 patients with schizophrenia spectrum disorders and 38 healthy controls.

Patients showed reduced connectivity within the salience network compared to controls. Across the whole sample, a dorsal ACC-seed showed glutamate-dependent connectivity to several clusters, including right insula, thalamus, and cerebellum. In patients, the averaged connectivity of these clusters was associated with positive symptom severity.

These findings suggest that disrupted glutamatergic modulation of large-scale brain networks may underlie core clinical features in schizophrenia spectrum disorders.

Cognitive impairment associated with schizophrenia (CIAS) is a prevalent, meaningful feature of schizophrenia with limited real-world data on its recognition and care setting impact. The LUCIA initiative is an international multi-stakeholder study that explored awareness, assessment practices, and the burden of CIAS to inform future care pathways.

A three phase, Delphi-informed design was applied, comprising expert interviews to frame the enquiry, qualitative interviews with health and social care professionals (HCPs; n = 74) and caregiver advocates (n = 11), two waves of a Delphi survey among HCPs (n=449 and 343, respectively) and one round among 61 patients and 112 caregivers across 15 countries (n = 964).

The results showed poor awareness of CIAS across stakeholders. Structured cognitive assessment was infrequent, and clinicians largely relied on the dementia oriented Mini-Mental State Examination (MMSE) rather than schizophrenia specific tools, citing time, training, and unclear actionability as key barriers. CIAS imposed broad humanistic, clinical, societal, and economic burden – poorer quality of life, social isolation, higher comorbidities, increased hospital days and health care costs, and heavy informal care. Consensus actions prioritized the development of brief, validated screening instruments, improved psychoeducation, and accelerated research into effective pharmacological and non pharmacological interventions.

These results provide additional evidence for the under-recognition of CIAS worldwide, despite its substantial multidimensional societal burden. The use of dementia-oriented cognitive tests carries significant risks of misclassification and inappropriate management. Therefore, improving awareness, implementing assessment guidelines, and accelerating therapeutic innovation is critical to improve the quality of life of CIAS patients and the wider community.

Thought disorder (TD) is a core feature of severe mental illnesses such as schizophrenia, characterized by disruptions in speech, language, and communication. People with TD face unique barriers that hinder their involvement in research, both as participants and as partners. Their systematic underrepresentation in psychiatric research is driven by pervasive assumptions about their decisional capacity, willingness to participate, and ability to engage in research. This perpetuates a biased evidence base, likely hindering the therapeutic progress toward addressing this core problem.

This review, informed by professional (clinical and research) and lived (bottom-up and phenomenological) experience of TD, examines how flawed assumptions regarding capacity, engagement, and participatory abilities serve as active barriers to inclusion.

We argue for a shift toward supported inclusion through tailored capacity assessments, enhanced informed consent procedures, targeted training of research personnel, and systemic institutional practices. Incorporating lived experiences of those with TD as research partners is integral to this approach, fostering co-production of research that is more valid, inclusive, and applicable.

Without these inclusion-focused changes, the development of treatments for TD is likely to have very slow progress and a critical segment of the severely unwell population will continue to be underrepresented from the scientific process, undermining both the utility and generalizability of psychiatric research.

Improving quality of life (QoL) is a primary objective in the treatment of schizophrenia. The current analysis aimed to evaluate the impact of antipsychotic administration routes on QoL in early-phase schizophrenia (SZ) patients randomized to treatment with either long-acting injectable (LAI) or oral aripiprazole or paliperidone as part of the “European Long-acting Antipsychotics in Schizophrenia Trial” (EULAST).

A total of 492 patients were followed for up to 19 months. QoL was assessed using the EQ-5D-5L. In the primary analysis, the relationships between oral versus LAI treatment and between treatment with paliperidone versus aripiprazole were investigated by fitting generalized estimating equation models. In secondary analyses, we examined the individual dimensions of the EQ-5D-5L, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. In subgroup analyses, we estimated the treatment effect on the EQ-5D-5L across clinically relevant subgroups, including sex, age, symptomatology, and side effects.

Overall, EQ-5D-5L scores improved over the course of the study, with no significant differences between patients treated with LAI versus oral antipsychotics (p = 0.662) or between those treated with aripiprazole versus paliperidone (p = 0.266). Subgroup analyses based on sex, age, medication side effects, and psychopathology also did not reveal any significant differences in EQ-5D-5L outcomes between LAI and oral antipsychotic treatment.

These findings indicate comparable QoL in SZ patients starting LAI or oral antipsychotic treatment with aripiprazole or paliperidone. Further research with extended follow-up periods is required to gain deeper insights into potential subgroup-specific benefits and the long-term effects of different antipsychotic administration routes on QoL.

People with psychotic disorders have high cardiometabolic risk, yet prediction tools are rarely validated outside early-intervention settings. We externally validated and recalibrated the UK Psychosis Metabolic Risk Calculator (PsyMetRiC) in a Dutch cohort of young adults with psychotic disorders in long-term care.

We used data from the PHAMOUS registry. Individuals aged 16–35 years, without metabolic syndrome (MetS) at baseline (prevalence 21.2%), were included. MetS incidence over approximately 6 years (last assessment 1–6 years; cumulative incidence 29.1%) was defined using international criteria. Full (biochemical + clinical) and partial (clinical only) PsyMetRiC models were applied to 10 multiply imputed datasets. Discrimination, calibration, and decision-curve analysis (DCA) were assessed before and after logistic recalibration of intercept and slope.

In external validation, C-statistics were about 0.69 for the full and 0.67 for the partial model. Both systematically underpredicted MetS risk; recalibration yielded calibration intercepts near 0 and slopes near 1, while discrimination was unchanged. DCA suggested that, across risk thresholds of 0.10–0.35, using recalibrated PsyMetRiC could provide higher net benefit than “treat all” or “treat none.”

In this chronic-care cohort, PsyMetRiC showed moderate discrimination and improved calibration after logistic recalibration. The recalibrated models may support more targeted metabolic monitoring and prevention, but interpretation is limited by registry design, variable follow-up times, reliance on multiple imputation, and modest power for subgroup analyses.

This systematic review evaluates specialized psychosocial and complex interventions for early bipolar disorder (BD), early borderline personality disorder (BPD), early depression, early psychosis, and first-episode mental illness in general (FEMI).

We included systematic reviews and randomized controlled trials (RCTs) of interventions with psychosocial components, excluding trials that focused on pharmacological-only interventions and stand-alone psychotherapies. Searches were conducted in January 2023 across five databases. Review quality was assessed using AMSTAR-2 and risk of bias for RCTs using the Cochrane tool.

Ten studies met the inclusion criteria: seven reviews and three RCTs. High-to moderate-quality evidence supports complex psychosocial interventions combined with pharmacotherapy for early psychosis. The most robust effects were reductions in relapse and improvements in psychosocial functioning; additional benefits were observed for symptom burden, remission, treatment discontinuation, and hospital admissions. Benefits were most sustained in longer-duration, community-based programs. For early BD, limited evidence suggests that combining pharmacotherapy with family-focused therapy or structured psychoeducation may improve the course of illness and treatment satisfaction. One RCT in early BPD reported improved engagement with a developmentally tailored program. Two FEMI RCTs found that nurse-led psychoeducation and psychosocial programs improved in-patient duration, symptoms, insight, self-efficacy, quality of life, and engagement. No eligible studies addressed early-stage depression, indicating a notable evidence gap for multimodal psychosocial interventions.

Complex psychosocial interventions are strongly supported for early psychosis. Preliminary data in BD, BPD, and FEMI suggest consistent benefits for engagement, but further rigorous trials – especially in early depression – focusing on different outcomes – are required.

Sex differences in psychosis pathoetiology are insufficiently understood. This study explores how childhood adversity (CA) and coping mechanisms relate to psychosis expression (PE) across males and females in the general population.

Data from the TwinssCan project (males: n = 312; females: n = 478) were used. The Childhood Trauma Questionnaire assessed CA domains. The Utrecht Coping List assessed coping strategies. Psychosis expression was assessed using the Community Assessment of Psychic Experiences (CAPE). Mixed linear regression analyses examined sex-stratified associations of CAPE scores with CA, coping strategies, and their interactions.

Emotional abuse (EA) was associated with increased total CAPE scores (T-CAPE), explaining the greatest variance among CA across sexes. Sex-specific effects showed that sexual abuse (SA) and physical abuse (PA) were linked to higher T-CAPE in females, whereas physical neglect (PN) was linked to higher T-CAPE in males. Passive-reacting was associated with increased T-CAPE, explaining the greatest variance among coping styles across both sexes. Sex-specific effects showed that, in females, seeking social support was linked to decreased T-CAPE, while emotional expression increased it. The only sex-shared interaction effect was between reassuring thoughts and emotional neglect (EN), associated with decreased T-CAPE. In females, social support (× PA/PN/EA), reassuring thoughts (× PA/PN), and palliative-reacting (× PN/PA) were associated with decreased T-CAPE, while passive-reacting (× EN) increased it. In males, avoidance (× SA/PA) and passive-reacting (× PN) were associated with increased T-CAPE.

Sex differences in the associations of PE with CA and coping underscore the necessity for sex-specific interventions that promote adaptive coping strategies.

Psychiatric comorbidities are common in first-episode psychosis (FEP) and hinder recovery. Problem gambling (PBG), despite potentially serious clinical consequences, remains under-investigated in this population. This study aimed to estimate the incidence of PBG in FEP and identify predictive factors.

This prospective cohort study was conducted at two FEP programmes in Quebec, Canada. Individuals aged 18–35 years diagnosed with FEP between November-1-2019 and January-31-2023 were screened for PBG using the Problem Gambling Severity Index through May-1-2023. The primary outcome was incident PBG. Time-varying Cox regression models were used to estimate hazard ratios (HRs) for candidate predictors.

Among 520 individuals without prior PBG (mean age = 24.6±4.0 years; 28.8% women), 18 developed PBG during a mean follow-up of 478 days, yielding an incidence rate of 2.6 cases/ 100 person-years. In site-adjusted analyses, white ethnicity (HR = 9.7; 95%CI = 1.3–74.8), incomplete high school education (HR = 2.8; 95%CI = 1.1–7.2), stimulant use disorder (HR=2.8; 95%CI = 1.0–7.3), use of D2/D3-5-HT1A partial agonists (HR = 4.6; 95%CI = 1.5–14.1), and prior non-problematic gambling (HR = 3.1; 95%CI = 1.1–8.4) predicted increased risk. Thirteen cases occurred during aripiprazole treatment, which remained associated with increased PBG risk after multivariable adjustment (adjusted HR = 4.7; 95%CI = 1.6–13.9).

Despite the limited number of incident cases, these results suggest that PBG is relatively common PBG and is associated with potential risk factors, including white ethnicity, incomplete high school education, stimulant use disorder, prior non-problematic gambling, and treatment with D2/D3-5-HT1A partial agonists, particularly aripiprazole. These findings underscore the importance of routine screening for PBG and risk-informed antipsychotic prescribing in FEP.

Social cognitive impairments are a fundamental aspect of schizophrenia, exerting a substantial influence on patients’ functional outcomes. However, to date, there have been no meta-analyses of comprehensive pharmacological interventions covering all domains of social cognition. The aim of the present study was to address this knowledge gap by conducting a network meta-analysis, a comprehensive approach that systematically compares the efficacy of pharmacological interventions across all domains of social cognition.

A literature search for randomized controlled trials (RCTs) was conducted using PubMed, Embase, the Cochrane Central Register of Controlled Trials, PsycINFO, ClinicalTrials.gov, and the International Clinical Trials Registry Platform. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed.

A total of 8,752 records were screened, and 60 RCTs involving 4,270 subjects were included in the systematic review. Thirty-six pharmacological interventions were extracted, but no compounds had a significant ameliorative effect on social cognition in comparison with placebo. In each domain of social cognition, the following compounds were identified as the most probable candidates for treatment selection: selective glycine uptake inhibitor (standardized mean difference [SMD], 0.46; 95% credible interval [CI], −0.52 to 1.44) and stimulant (SMD, 0.44; 95% CI, −0.57 to 1.45) for emotion perception in comparison with placebo. In the context of emotion processing, γ-aminobutyric acid (A) α2/α3 partial agonist (SMD, 0.33; 95% CI, −0.53 to 1.19) emerged as the top compound.

To date, no pharmacological interventions have demonstrated efficacy for social cognitive impairments in schizophrenia.

Volumetric changes in the superior temporal gyrus and anterior cingulate cortex have been repeatedly reported in studies on schizophrenia. Tractography and functional magnetic resonance imaging studies have suggested that alterations in connectivity involving the superior temporal gyrus and the anterior cingulate cortex are relevant to psychotic symptoms of schizophrenia.

We analyzed nanometer-scale three-dimensional structures of brain tissues of the superior temporal gyrus and the anterior cingulate cortex in eight schizophrenia and eight control cases and evaluated structural parameters of their neurons. We then examined the relation between the neuronal parameters and clinical information including auditory hallucination score.

The obtained results indicated that 1) neurites become thin and tortuous in schizophrenia and that 2) somata become small in schizophrenia. The frequency distribution of neurite curvatures had a broad profile in the schizophrenia cases, whereas the control cases showed sharp peaks. In the scatter diagram of the standard deviation of neurite curvatures, the schizophrenia and control cases formed separate clusters, indicating that all 16 cases analyzed in this study can be assigned to either the schizophrenia or control group simply by using the diagram. The cingulate/temporal ratio of the standard deviation of neurite curvatures showed a strong positive correlation with the auditory hallucination score.

The structural alteration of neurites observed in the schizophrenia cases should influence the function of affected brain areas by hindering communication between distant neurons. We suggest that the interplay of the temporal and cingulate cortices in the whole-brain network is relevant to auditory hallucination.

Language impairments are common in affective and psychotic disorders, yet their patterns and underlying pathomechanisms remain insufficiently understood. A transdiagnostic perspective provides a framework for identifying shared and disorder-specific language alterations across diagnostic boundaries. Combining natural language processing (NLP) with network analysis enables the investigation of complex associations between linguistic, cognitive, and psychopathological features.

Spontaneous speech from N = 372 participants (119 MDD, 27 BD, 48 SSD and 178 HC) was elicited using four Thematic Apperception Test pictures (~12 min per participant). NLP models were applied to extract latent linguistic variables across various levels, including lexical diversity, syntactic complexity, semantic coherence, and disfluencies. Network analysis was used to relate linguistic variables, psychopathology (SAPS, SANS, HAM-A, HAM-D, YMRS, TLI, GAF), and cognitive performance (attention, verbal memory, recognition, and verbal fluency).

Linguistic variables formed the densest network cluster, with type–token ratio, mean length of utterance, and syntactic complexity emerging as central nodes. Psychopathology variables were less cohesive, while TLI “Impoverishment”, coherence mean, and executive functioning bridged linguistic, cognitive, and psychopathological domains. Network comparison tests revealed no significant differences in linguistic–cognitive network structure across HC, MDD, BD, and SSD.

Linguistic networks show high structural consistency across healthy individuals and patients, whereas psychopathological symptom networks reflect transdiagnostic profiles. These findings support a dimensional and transdiagnostic framework underscore shared language–cognition mechanisms, and highlight executive functioning as key cross-domain connection, which opens up new avenues for dimensional research into the pathophysiological and etiological mechanisms underlying language dysfunctions.

Tobacco smoking is highly prevalent in patients with psychosis, who also often experience negative affect (NA) and stress. The relationship between these factors remains unclear in this population. We aimed to investigate everyday life associations in 158 patients with psychosis, 136 unaffected siblings, and 117 controls from the Genetic Risk and Outcome of Psychosis (GROUP) study with Experience Sampling Method measurements.

Generalized linear mixed models were used to evaluate across time and within-subject associations. Across time analyses investigated the relationship between smoking status and overall NA and stress. Within-subject analyses assessed whether smoking between two measurements (t−1 and t0) was associated with changes in NA and stress at the measurement after smoking a cigarette (t0) and at the subsequent measurement (t+1).

Across assessments, smoking status was initially associated with NA in patients (B=0.26, p=0.036), but this association disappeared after controlling for psychotic symptoms and cannabis use. Within-subject analyses in smokers showed a decrease in NA in patients after smoking (t0: −0.23, p=0.016), which remained significant after correcting for confounders (t0: −0.20, p=0.015). Siblings showed a decrease in NA (t0: −0.22, p=0.009), also after controlling for confounders (t0: −0.14, p=0.018). No time-lagged effect was found at t+1 after correction for subsequent smoking.

Overall smoking behavior was not associated with NA in patients with psychosis. In the short term, smoking in the daily life context is associated with a reduction in NA in people vulnerable to psychosis, possibly due to alleviation of withdrawal symptoms, which may complicate smoking cessation.

Negative symptoms (NS) represent an important unmet need in schizophrenia (SZ) assessment and management. Despite NS are strongly associated with poorer functioning and quality of life, they are frequently underrecognized, inconsistently evaluated, and show limited response to current treatments. Although specific assessment tools and European Psychiatric Association (EPA) guidance on NS have been developed, their impact on routine clinical practice appears limited. This study aimed to investigate the competence and confidence of European Early Career Psychiatrists (ECPs) in NS evaluation and management.

The CARE project was a cross-sectional online survey directed towards ECPs from European countries.

828 ECPs’ responses were collected from 19 countries. The majority of ECPs were trainees (65.8%), reported theoretical training in negative symptoms (NS) and placements in schizophrenia-specialized settings (67.9% and 70.3%), while about half reported extracurricular NS training (51.1%) and involvement in clinical research (46.1%). Only 11% correctly identified NS domains, despite 65.7% felt well-trained in NS assessment tools. Just 15.9% correctly answered questions based on the EPA guidance papers. 46.7% and 25.9% ECPs reported feeling competent in NS evaluation and management, respectively. Gender (men) specialist status, research involvement, theoretical NS training, and placements in specialized SZ services predicted perceived competence. However, in-depth NS knowledge was predicted only by specialist status, engagement in clinical research, and extracurricular NS training.

Despite reported exposure to NS training, ECPs demonstrated limited knowledge of NS. Actions need to be taken to ensure that ECPs receive the highest standard of training in NS.

In the ultra-high risk for psychosis (UHR) field, it is unknown whether understanding symptom relationships, beyond symptom severity alone, may hold prognostic value and inform preventive care. In this study, network analysis was performed to examine the interconnections between baseline symptoms in UHR youth who did and did not transition to psychosis over three years.

In a sample selected from the UHR1000+ cohort, positive and basic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental States. Network analyses and network comparison tests were performed.

195 UHR youth transitioned to psychosis within three years and 346 did not. The two groups did not differ in the network structure, global strength (i.e., the overall level of connectivity between symptoms), or centrality of symptoms (i.e., their importance within networks). The transitioned group was characterized by unusual thought content not being connected to other symptoms; however, its centrality between networks was comparable. Across networks, impaired cognitive functioning connected disorganized speech to impaired emotional functioning, motor functioning, and tolerance to normal stress. Impaired bodily sensation connected perceptual abnormalities to other symptoms.

The networks of youth who transitioned and who did not transition were similar, indicating similar baseline symptom relationships. Across groups, unusual thought content, despite being traditionally associated with transition, had little to no interactions with other symptoms. Clinical manifestations that may need attention include impaired cognitive functioning, which connected several symptoms, and impaired bodily sensation. Future research using time series data may support progress toward individualized care.

The Virtual Reality Functional Capacity Assessment Tool (VRFCAT) is a performance-based measure developed to assess functional capacity through simulations of daily activities. This study examined its psychometric properties in a Spanish sample, including individuals with first-episode psychosis (FEP), schizophrenia, and healthy controls.

A total of 370 participants (99 FEP, 116 schizophrenia, and 155 controls) completed the VRFCAT in a multicenter study. Internal consistency (McDonald’s omega), discriminative validity (group comparisons and ROC curves), and convergent validity via correlations with cognitive performance and clinical symptoms were examined. Reference percentiles were calculated from the healthy control sample using quantile regression, stratified by age and education.

Item-level VRFCAT completion times showed acceptable to good internal consistency overall and in controls and schizophrenia samples, but poor in FEP. Differences in VRFCAT performance emerged (χ2 = 108.88, p < .001), with controls performing best, schizophrenia worst, and FEP in between. ROC analyses indicated good discriminative accuracy in distinguishing patients from controls (area under the curve [AUC] = 0.779, sensitivity = 80.0%, specificity = 64.2%); but limited discrimination between schizophrenia and FEP. Age and education, but not sex, significantly affected performance. VRFCAT showed small-to-moderate correlations with cognitive performance, and no significant associations with symptom severity.

The VRFCAT is a reliable and valid tool for assessing functional capacity in Spanish-speaking individuals with psychotic disorders. Its ecological validity, objectivity, psychometric properties, brief administration time, and ease of use support its potential use in clinical and research settings for evaluating functional recovery and treatment outcomes.

A better mechanistic understanding of schizophrenia spectrum disorders is crucial to developing efficient treatment approaches. Therefore, this study investigated longitudinal interrelations between clinical outcomes, brain structure, and somatic health in post-acute individuals from the schizophrenia spectrum.

A sample of 63 post-acute patients from two independent physical exercise studies was included in the final analyses. Demographic, clinical, cognitive, and somatic data were acquired at baseline and follow-up, as were structural magnetic resonance imaging scans. Multivariate cross-lagged panel modeling including mediators was used to study the mutual interrelations over time between the clinical, neural, and somatic levels.

A higher baseline global gray matter volume and larger regional gray matter volumes of the hippocampal formation, precuneus, and posterior cingulate predicted improved clinical outcomes, such as daily-life functioning, negative symptoms, and cognition. Increases in white matter volume from baseline to follow-up resulted in significantly reduced positive symptoms and higher daily-life functioning.

Our findings suggest that stimulating neuroplasticity, especially in the hippocampal formation, precuneus, and posterior cingulate gyrus, may represent a promising treatment target in post-acute schizophrenia spectrum disorders. Physical exercise therapies and other lifestyle interventions, and brain stimulation approaches reflect potential treatment candidates. Given the exploratory character of the statistical analysis performed, these findings need to be replicated in independent longitudinal imaging cohorts of patients with schizophrenia spectrum disorders.