Cognitive deficits in schizophrenia are detectable at the onset of illness and during the preceding prodromal period. Additionally, adolescents and young adults at clinical high risk for psychosis (CHR-P) demonstrate cog...Cognitive deficits in schizophrenia are detectable at the onset of illness and during the preceding prodromal period. Additionally, adolescents and young adults at clinical high risk for psychosis (CHR-P) demonstrate cognitive impairment regardless of future conversion. The cortical substrates of these deficits have yet to be established within CHR-P samples, including the differential relations of cortical thickness (CTh) versus surface area (SA) as they differ in underlying cytoarchitecture and genetic influences. Youth at CHR-P (N = 463) and healthy control participants (N = 210) from the second cohort of the North American Prodrome Longitudinal Study (ages 12-35) completed the two-subtest form of the Wechsler Abbreviated Scale of Intelligence and structural MRI scans at baseline. The associations between regional cortical morphometry and Full-Scale IQ (FSIQ-2) were examined using multiple linear regression. Increased CTh in frontoparietal regions (left lateral orbitofrontal cortex; left precentral gyrus; left postcentral gyrus; right supramarginal gyrus) and lateral occipital areas associated with better cognitive functioning in CHR-P. In contrast, among healthy control participants, no associations between CTh and cognitive functioning were observed. Additionally, increased SA across the cortex was associated with better cognitive functioning for both groups, though people at CHR-P demonstrated a more diffuse pattern of associations. These results underscore the importance of decomposing cortical volume into CTh and SA and how variation in cognitive functioning may be potentially supported by shared and group-specific substrates. Results generate hypotheses about how aberrant neurodevelopmental processes, such as cortical thinning, may disturb cognitive functioning in the early stage of psychosis.
BACKGROUND: Hippocampal volume reductions are among the most robust neuroanatomical findings in schizophrenia spectrum disorders (SSD). However, how these structural alterations relate to core functional domains such as...BACKGROUND: Hippocampal volume reductions are among the most robust neuroanatomical findings in schizophrenia spectrum disorders (SSD). However, how these structural alterations relate to core functional domains such as cognition, sensorimotor functioning, and impulsivity remains largely unclear. To address this gap, we applied network analysis to elucidate the complex interplay between hippocampal volume, cognition, neurological soft signs (NSS) and impulsivity, while controlling for overall psychopathology and global functional status. METHODS: We included 204 SSD individuals (mean age: 38.00 years; 80 females) from two separate in-house cohorts, who underwent structural 3 T magnetic resonance imaging (MRI). Hippocampal volumes were automatically segmented using FreeSurfer version 7.3.2. Assessments included the Brief Cognitive Assessment Tool for Schizophrenia (B-CATS), the Heidelberg Neurological Soft Signs (NSS) scale, the Barratt Impulsiveness Scale (BIS-11), the Positive and Negative Syndrome Scale (PANSS), and the Global Assessment of Functioning (GAF). RESULTS: Total hippocampal volume was negatively associated with PANSS (edge weight [ew] = -0.08), reversed GAF scores (ew = -0.04) and B-CATS (ew = -0.03), but showed no association with BIS-11 or NSS scores. Hippocampal body volume was negatively associated with PANSS (ew = -0.08), B-CATS (ew = -0.03), NSS (ew = -0.03) and reversed GAF (ew = -0.02) scores. CONCLUSION: This is the first study that incorporated structural MRI-derived volume measures into a network analysis framework to model the interplay between hippocampus, cognitive symptoms, NSS, impulsivity, psychopathology and global functioning in SSD. Our findings indicated that hippocampal volume is more strongly linked to cognition, psychopathology and global functioning than to impulsivity or NSS.
OBJECTIVE: Recent approaches in psychosis research have emphasized the importance of the combined analysis of risk and resilience factors. A resilience-integrated approach offers a more comprehensive understanding of the...OBJECTIVE: Recent approaches in psychosis research have emphasized the importance of the combined analysis of risk and resilience factors. A resilience-integrated approach offers a more comprehensive understanding of the mechanisms underlying symptom associations and progression in individuals at clinical high-risk (CHR) for psychosis. Network analysis allows the examination of relationships among mental health conditions together with both risk and resilience factors. To our knowledge, this is the first study that investigated associations between resilience, risk factors, and psychosis-risk using network analysis. METHODS: This secondary analysis of data from the ZInEP study (Zurich Early Recognition Program) examined 116 individuals at CHR for psychosis aged 18-35 years. We investigated the relationships between two candidate resilience factors (self-efficacy and self-esteem), daily hassles as a candidate risk factor, functioning level, and psychosis risk symptoms using network analysis. RESULTS: Self-esteem and self-efficacy were negatively associated with general symptoms, negative symptoms, and daily hassles. Resilience factors and daily hassles were not associated with positive and disorganized symptoms, nor with functioning level. Centrality analyses further revealed that self-esteem had stronger node strength and bridge strength than self-efficacy. CONCLUSIONS: This study emphasizes the utility of a resilience-oriented approach in psychosis risk. Self-esteem and self-efficacy may play a crucial role in negative and general symptoms. Resilience factors may enrich our theoretical understanding of psychosis risk and help pave the way for resilience-based interventions.
BACKGROUND: This study examined the functional and clinical effects of extending Early Intervention Service (EIS) for individuals with first-episode psychosis (FEP) by one additional year, compared with transitioning to...BACKGROUND: This study examined the functional and clinical effects of extending Early Intervention Service (EIS) for individuals with first-episode psychosis (FEP) by one additional year, compared with transitioning to standard care (SC) after completing two years of EIS. Age and duration of untreated psychosis (DUP) were explored as potential moderators across a broad age range (15-55 years). METHODS: Secondary analyses were conducted on two randomised controlled trials involving 400 FEP patients who had completed two years of EIS (extended EIS: n = 202; SC: n = 198). Participants were assessed at two years and again at three years. Multiple linear regression and mixed-effects models were used to evaluate treatment effects and the moderating roles of age (<25 vs ≥25 years) and DUP (<92 vs. ≥92 days). RESULTS: Extended EIS improved functioning relative to SC, including higher employment rates (p = 0.024), increased Role Functioning Scale (RFS) total and subdomain scores (p < 0.001 to 0.015), and better Social and Occupational Functioning Assessment Scale (SOFAS) scores (p < 0.001). Short DUP was associated with greater gains in certain RFS subdomains (p = 0.003 to 0.008) and SOFAS (p < 0.001). Younger patients showed greater improvements in RFS independent living and self-care (p = 0.019), and reductions in overall symptom severity (p = 0.014) and general psychopathology (p = 0.020). CONCLUSIONS: A one-year extension of EIS produced additional functional benefits, with stronger effects observed among younger patients and those with shorter DUP. Extending EIS for individuals who continue to demonstrate functional or clinical difficulties after the initial two-year programme may help optimise long-term recovery and guide efficient service planning.
Toxoplasma gondii (T. gondii), a parasite that can be transmitted to humans by cats, has been proposed as a modifiable risk factor for schizophrenia and related disorders. However, much of the research examining this rel...Toxoplasma gondii (T. gondii), a parasite that can be transmitted to humans by cats, has been proposed as a modifiable risk factor for schizophrenia and related disorders. However, much of the research examining this relationship has relied on cat ownership as a proxy measure for T. gondii exposure. This study examined the relationship between serum T. gondii levels and later psychotic experiences (PEs) and brain volume. We also explored the relationship between cat ownership and T. gondii serology. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we studied 3542 individuals for whom data on serum T. gondii during childhood and PEs at age 18 were available. Voxel-based morphometry assessed whether MRI measures of grey matter volume at age 20 were associated with T. gondii levels among a subset of the participants (N = 334). Serum T. gondii was not associated with PE group in adjusted models (suspected PEs risk ratio (RR) = 1.06, 95% confidence interval (CI) [0.89-1.27]; definite PEs RR = 0.86, 95% CI [0.65-1.13]; psychotic disorder RR = 1.00, 95% CI [0.73-1.38]). Exposure to cats during gestation was associated with higher T. gondii in adolescence (β = 0.08, p = 0.033), while exposure to cats during childhood was not (β = 0.05, p = 0.310). T. gondii was not associated with grey matter volume in the neuroimaging sample (pFWEs ≥ 0.882, Zs ≤ 3.86). Future work examining the relationship between T. gondii and schizophrenia-spectrum disorders should focus on serology or cat ownership during gestation as a proxy measure of T. gondii exposure, as there was no association between childhood cat ownership and T. gondii.
Substance use is frequently implicated in psychosis. However, the prognostic assumptions guiding differential treatment decisions between substance-induced and primary/affective psychoses have received inconsistent suppo...Substance use is frequently implicated in psychosis. However, the prognostic assumptions guiding differential treatment decisions between substance-induced and primary/affective psychoses have received inconsistent support. Substance-induced psychosis research has often been limited by aggregating substances or using diagnosis as both a grouping variable and an outcome (i.e., diagnostic conversion). The current study examined medical records for 1379 patients for 5 years following their first presentation with psychosis after January 2013 to a regional medical center. Clinically relevant outcomes were compared across groups defined by the substances detected in patients' urine at their initial presentation. Initial drug screen results predicted the initial encounter duration, the likelihood of a future presentation with psychosis and a negative drug screen, and the total hospital days associated with psychosis over 5 years, but not patients' number of psychiatric hospitalizations. Cocaine alone and cannabis combined with stimulants exhibited the courses expected of substance-induced psychosis, including quick remission, infrequent recurrence with negative drug screens, and low healthcare utilization. Amphetamines and cannabis alone exhibited improved prognoses compared to those with negative initial screens, but more chronic courses than expected of substance-induced psychosis. Depressants exhibited similar courses to those with negative initial screens. Other polysubstance combinations displayed divergent outcomes. The chronicity of psychosis associated with certain substances suggests further examination of their course with protracted abstinence, response to psychosis-focused treatments, and the potentially diverse mechanisms by which use precipitates psychosis. Additionally, the dissimilar courses observed for distinct polysubstance combinations emphasize the importance of disambiguating these groups in future research.
BACKGROUND: Persistence of positive symptoms despite adequate antipsychotic treatment is a clinically challenging situation in schizophrenia. Impaired cortical plasticity is hypothesized to underlie the antipsychotic res...BACKGROUND: Persistence of positive symptoms despite adequate antipsychotic treatment is a clinically challenging situation in schizophrenia. Impaired cortical plasticity is hypothesized to underlie the antipsychotic resistance in schizophrenia. This study evaluated High-Definition-tDCS (HD-tDCS) driven motor cortical plasticity using short-interval cortical inhibition (SICI) paired-pulse protocol in schizophrenia. METHODS: Fifty-three individuals with antipsychotic-resistant schizophrenia (ARS) and 31 healthy subjects underwent transcranial magnetic stimulation-electromyography (TMS-EMG) evaluation before and after (10, 20, 30, and 40 min) of a single session of cathodal HD-tDCS (2 mA; 20 min) over the left M1 area. Cortical plasticity was determined as a change in SICI & SI1 (Motor Evoked Potential at 1 mV). The effect of time and group was assessed using linear mixed-effects models. RESULTS: A group*time interaction (t = 2.23) was noted in SICI at 40th minute after cathodal HD-tDCS, revealing that patients with ARS had significantly poorer and ill-sustained motor cortical excitatory changes following cathodal HD-tDCS compared to healthy controls. Furthermore, clozapine-resistant, ie, Ultra Resistant Schizophrenia (URS) participants exhibited poorer plasticity compared to first-line antipsychotic resistant [Cohen's d = 0.764, p = 0.004]. CONCLUSION: The results reaffirm the finding of impaired motor cortical plasticity in ARS. Additionally, we note that URS with a higher symptom burden, treatment resistance and poorer functioning had the poorest motor cortical plasticity. Future studies could explore the potential of cortical plasticity as a predictive, mechanistic, and theranostic biomarker.
BACKGROUND: Violence in schizophrenia poses a major clinical and public health challenge. This study examined how core psychopathological features, conduct disorder (CD), and pharmacological treatment influence violent b...BACKGROUND: Violence in schizophrenia poses a major clinical and public health challenge. This study examined how core psychopathological features, conduct disorder (CD), and pharmacological treatment influence violent behavior by looking at the interaction among these variables. We also investigated the clinical differences between CD and non-CD patients. METHODS: 99 individuals with schizophrenia and with assaultive behaviors were randomly assigned in a double-blind design to clozapine, olanzapine, or haloperidol. Participants were further classified by presence or absence of CD. Clinical evaluation included the Positive, Excitement, and Depression factors of the Positive and Negative Syndrome Scale (PANSS), the Buss-Perry Aggression Questionnaire (BPAQ), and Barratt Impulsiveness Scale. RESULTS: Individuals with CD displayed higher trait aggression on the BPAQ and elevated endpoint PANSS Excitement, Hostility, and Anger scores compared with non-CD participants. Reductions in assaults were related to improvements in psychopathological measures in both the CD and non-CD groups, though these associations were stronger among non-CD participants. The relationship between symptom improvement and reduced aggression also varied by medication: in the haloperidol group, aggression reduction was closely associated with symptom improvement; in the clozapine group, no such association was found, suggesting a strong and direct anti-aggressive effect independent of symptom improvement; olanzapine showed an intermediate pattern. CONCLUSION: These findings highlight the importance of interactions among symptoms, conduct disorder, and medication in determining violence. They also point to the multifactorial etiology of violence in patients with schizophrenia and to the need for tailored treatment strategies to effectively reduce violence, especially in high-risk population.
BACKGROUND: Schizophrenia patho-etiology may involve endothelial inflammation and blood-brain barrier (BBB) dysregulation with cellular adhesion molecules (CAMs) as important mediators. CAMs are essential for cellular in...BACKGROUND: Schizophrenia patho-etiology may involve endothelial inflammation and blood-brain barrier (BBB) dysregulation with cellular adhesion molecules (CAMs) as important mediators. CAMs are essential for cellular integrity but can show increased levels in inflammation. Cognitive dysfunction precedes and exists independently of psychotic symptoms in schizophrenia patients. CAMs could impact cognition through influence on BBB integrity. To gain insights into disease mechanisms and potential therapeutic targets, we explored the relationship between CAMs protein levels and neurocognitive tests in schizophrenia-spectrum disorders in the BeSt InTro study. METHODS: Seventy-one in- and out-patients underwent CAMs measurements and neuropsychological testing on a minimum of one time point: baseline, 6, 26, or 52 weeks. Cognitive domains included working memory, processing speed, verbal abilities, executive functions, and overall cognition. CAMs analyzed were neural CAMs: junctional adhesion molecule (JAM-A) and neural cadherin (N-CAD); vascular CAMs: intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, mucosal addressin cell adhesion molecule (MADCAM), and platelet (P)-selectin from fasting blood samples. Linear mixed effects models, adjusted for age, sex, body mass index, smoking, education, and drug naivety, estimated CAMs effect on cognitive outcome measures. RESULTS: N-CAD levels correlated positively with overall cognition (p = 0.002), working memory (p = 0.034), and executive functions (p = 0.0011). ICAM-1 levels correlated positively with overall cognition (p = 0.037). Conversely, JAM-A levels correlated negatively with executive functions (p = 0.021). CONCLUSION: Associations between CAMs (N-CAD, ICAM-1, JAM-A) and neurocognitive tests suggest CAMs may impact cognition in schizophrenia. Contrary to our hypothesis, most associations between CAMs levels and cognitive tests were positive. Future research on mechanisms is mandatory.
Recent policies by the current United States (US) administration have had significant repercussions for science and the confidence of researchers to continue their work. In this Editorial, we explore the current and futu...Recent policies by the current United States (US) administration have had significant repercussions for science and the confidence of researchers to continue their work. In this Editorial, we explore the current and future impact of these political actions, and contrast them with the historical scientific developments underpinning schizophrenia research, both in Europe and the US. Europe has an opportunity to shape a future where science has the resources and security it needs to flourish ….
Blackman G, Morrin H, Carstairs C
… +13 more, Fanshawe JB, Watson C, Lim MF, Phillips J, Handel AE, McCutcheon RA, Ward JH, Pappa E, Bowman EML, Chow RTS, Pollak TA, McGuire P, Bell V
Schizophr Res
· 2026 Mar · PMID 41633151
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A significant minority of patients who present with psychosis have an underlying medical ("organic") cause. Some of these secondary causes are reversible; therefore, early detection is critical. Psychopathology may be in...A significant minority of patients who present with psychosis have an underlying medical ("organic") cause. Some of these secondary causes are reversible; therefore, early detection is critical. Psychopathology may be informative during initial assessment to determine which patients are at an increased risk of having an underlying medical cause and should be prioritised for enhanced investigation. Through a pre-registered (CRD42024511546) systematic review and meta-analysis, we compared the psychopathology of patients with psychosis secondary to a medical cause compared to patients with primary psychosis as reported in case-control studies using PubMed from inception to September 2025. We identified 13 studies and a pooled sample size of 1564 individuals (primary psychosis = 781, secondary psychosis = 783). Poverty of speech (RR = 18.18, 95% CI = 1.43-231.5) and visual hallucinations (RR = 1.35, 95% CI 1.02-1.80) were more likely to be features of psychosis that was secondary to an underlying medical cause compared to a primary psychotic disorder. Conversely, auditory hallucinations (RR = 0.55, 95% CI = 0.50-0.61), thought insertion (RR = 0.24, 95% CI = 0.12-0.48), thought broadcast (RR = 0.30, 95% CI = 0.09-0.98), unspecified delusions (RR = 0.44, 95% CI = 0.30-0.66), delusions of persecution (RR = 0.72, 95% CI = 0.62-0.84), olfactory hallucinations (RR = 0.34, 95% CI = 0.18-0.63), and tactile hallucinations (RR = 0.26, 95% CI = 0.19-0.35) were more likely to be features of a primary psychosis. Findings underscore the clinical value of a comprehensive psychiatric assessment in patients with undifferentiated psychosis. Secondary psychoses show psychopathological differences, with certain symptoms potentially serving as 'red flags' for secondary causes. These indicators may assist clinicians in prioritising patients for further investigation.
Treatment-resistant schizophrenia (TRS) remains a major clinical challenge, with limited progress in identifying reliable biomarkers for targeted intervention. MicroRNAs (miRNAs) encapsulated in small extracellular vesic...Treatment-resistant schizophrenia (TRS) remains a major clinical challenge, with limited progress in identifying reliable biomarkers for targeted intervention. MicroRNAs (miRNAs) encapsulated in small extracellular vesicles (sEVs) have emerged as candidates for long-range intercellular communication due to their stability and cell specificity. Whiles sEV-derived miRNAs (sEV-miRNAs) profiling elucidates vesicle-mediated signaling, parallel assessment in sEV-associated miRNAs in EVs-depleted (dEV) plasma is critical to determine their packaging selectivity and potential roles in systemic regulation. In this proof-of-concept study, we hypothesized that specific miRNAs are selectively enriched in sEVs, and compared sEV-miRNA expression profiles between TRS and non-TRS (NTRS). We then conducted a side-by-side comparison of selective sEV-associated miRNAs expression in dEV plasma. In the screening set (N = 16), three differentially expressed sEV-miRNAs (miR-184, miR-3131, and miR-3135b) were identified and advanced for validation in sEVs and dEV compartments. In the validation set (N = 95), miR-184 and miR-3131 were elevated in sEVs from TRS patients, yet displayed reduced expression in dEV plasma, suggesting compartment-specific roles and their origin in signal transduction. An optimal marker panel combining sEV-miR-184 and dEV-miR-3131 achieved robust performance in distinguishing TRS from NTRS, yielding an area under the curve (AUC) = 0.986; accuracy = 0.926, with sustained performance in 5-fold cross-validation (AUC = 0.920; accuracy = 0.865). Functional enrichment implicated these miRNAs in synaptic signaling and neuroinflammatory pathways. Collectively, these findings highlight altered post-transcriptional regulation in TRS and the potential of sEV-miRNAs in advancing treatment strategies in precision psychiatry.
BACKGROUND: Genetic liability for schizophrenia has been associated with cognitive deficits and clinical phenotypes during neurodevelopment. However, the possible role of executive function (EF) as a mediator between the...BACKGROUND: Genetic liability for schizophrenia has been associated with cognitive deficits and clinical phenotypes during neurodevelopment. However, the possible role of executive function (EF) as a mediator between the polygenic risk score for schizophrenia (PRS-SZ) and subsequent outcomes, including transdiagnostic general psychopathology (the p-factor), has yet to be examined. In this study, we investigated whether EF mediates the effect of PRS-SZ on psychopathology and functional phenotypes in a community-based youth sample. STUDY DESIGN: We analyzed cross-sectional data from 698 participants (aged 6-14) of the Brazilian High-Risk Cohort. PRS-SZ was calculated using summary statistics from the Psychiatric Genetics Consortium (PGC-3). EF was assessed through working memory, inhibitory control, and time processing tasks, condensed into a single latent EF trait. Independent linear models were tested to examine direct associations between PRS-SZ and EF, general psychopathology, anxiety symptoms, psychotic experiences (PE), and school performance. Mediation models were applied to evaluate EF as a mediator of the associations between PRS-SZ and each outcome. STUDY RESULTS: PRS-SZ predicted lower EF scores (β = -0.091, t = -2.435, p = 0.015). No direct associations were found between PRS-SZ and the other measures. EF mediated the association between PRS-SZ and general psychopathology (p-factor) (Effect = 0.0079, BootSE = 0.0049, LLCI = 0.0004, ULCI = 0.0191), anxiety symptoms (Effect = 0.0075, BootSE = 0.0047, LLCI = 0.0001, ULCI = 0.0182), and school performance (Effect = -0.0167, BootSE = 0.0077, LLCI = -0.0327, ULCI = -0.0028), but not PE. CONCLUSIONS: PRS-SZ was associated with poorer EF, which in turn mediated its associations with increased general psychopathology (p-factor) and anxiety symptoms, and reduced school performance in this community youth sample. EF may represent a hub through which PRS-SZ contributes to negative behavioral and functional outcomes.
Schizophr Res
· 2026 Mar · PMID 41587508
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Negative symptoms are a core feature of schizophrenia and other psychoses that contribute substantially to functional disability but benefit little from standard treatment, thus representing an unmet therapeutic need. In...Negative symptoms are a core feature of schizophrenia and other psychoses that contribute substantially to functional disability but benefit little from standard treatment, thus representing an unmet therapeutic need. In fact, mechanisms underlying negative symptoms emerge in the early years of development and progress across various developmental stages of psychosis course. In premorbid period, subtle social withdrawal as well as deficits in emotion expression and social communication may represent early signals indicating vulnerability for a variety of disorders including schizophrenia. Attenuated negative symptoms, which manifest in the 5 consensus domains of anhedonia, avolition, asociality, alogia and blunted affect, are prevalent in prodromal period, predictive of conversion to full-blown psychosis, and associated with role and social dysfunction. Negative symptoms in both early psychosis and chronic schizophrenia are best conceptualized by the 5 consensus symptom domains. Greater severity of negative symptoms in first-episode psychosis is associated with more functional impairment, poorer premorbid adjustment and longer duration of untreated psychosis. There is progressive accrual of negative symptoms along the course of illness, in particular primary persistent negative symptoms which are more prevalent in the chronic illness stage, contributing to pronounced functional impairment and worse prognosis. In this article, we review the manifestations of negative symptoms in the context of developmental framework, highlighting the trajectory of negative symptoms across and the unique relevance for different stages of psychotic illness, as well as its relationships with functional disability, other illness-related factors, and treatment implications.
High-intensity interval training (HIIT) improves metabolic health, psychiatric symptoms, and functioning in individuals with psychotic disorders. However, research on the maintenance of HIIT benefits is limited. This stu...High-intensity interval training (HIIT) improves metabolic health, psychiatric symptoms, and functioning in individuals with psychotic disorders. However, research on the maintenance of HIIT benefits is limited. This study examines whether benefits were maintained six months post-supervised HIIT and identifies factors influencing their maintenance. Sixty-six individuals (61% men; 30.73 ± 7.23 years old) with psychotic disorders participated in a 6-month supervised HIIT intervention (T1-T2), followed by a 6-month unsupervised period with free access to exercise facilities (T2-T3). Psychiatric symptoms and functioning were assessed at T1, T2, and T3. To examine the maintenance of supervised HIIT benefits, we used linear mixed model to compare scores between T1 and T3. To identify factors associated with maintenance of supervised HIIT benefits, participants were divided into two groups based on their attendance to T3 assessment. A one-way ANOVA compared these groups on psychiatric symptoms and functioning T2. Benefits on negative (p = 0.01) and general (p = 0.03) symptoms observed at T2 were maintained at T3. Only younger age was significantly associated with HIIT benefit maintenance (p = 0.02). Consistent with prior research, long-term benefits were observed only for negative and general symptoms. Neither functioning nor symptoms predicted maintenance of supervised HIIT benefits. Lack of improvement in functioning may relate to the absence of social components in the PA intervention. Also, missing data on physical activity during the follow-up period limits interpretation. Finally, future studies should assess the role of continued physical activity and social factors in sustaining benefits.
Wang LC, Lu AK, Zhu ZH
… +9 more, Hou WL, Yin X, Yang Q, Man LJ, Chen J, Zhu HL, Yu X, Zhang H, Hui L
Schizophr Res
· 2026 Mar · PMID 41576833
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Dopamine β-hydroxylase (DBH) is an enzyme that catalyzes the conversion of dopamine (DA) to norepinephrine (NE). The dysregulation of these neurotransmitters is implicated in the etiology and cognitive impairments of sch...Dopamine β-hydroxylase (DBH) is an enzyme that catalyzes the conversion of dopamine (DA) to norepinephrine (NE). The dysregulation of these neurotransmitters is implicated in the etiology and cognitive impairments of schizophrenia. However, the relationship between DBH and cognitive impairments of schizophrenia, independent of confounding effects of medication and chronic illness, remains unclear. Thus, this case-control study aimed to investigate plasma DBH levels, cognitive performance, and their association in patients with first-episode drug-naïve schizophrenia (FDS). A total of 56 FDS patients and 56 age- and gender-matched healthy controls (HCs) were enrolled. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and plasma DBH levels were measured via sandwich enzyme-linked immunosorbent assays (ELISAs). After adjusting for covariates, plasma LogDBH levels were significantly lower in FDS patients compared to HCs (F = 9.17, p = 0.003). Moreover, plasma LogDBH levels showed a positive correlation with immediate memory score in patients (r = 0.27, p = 0.04). Linear regression further confirmed a significant association between LogDBH levels and immediate memory score in patients (β = 50.18, t = 2.82, p = 0.008). Additionally, FDS patients scored significantly lower than HCs on the RBANS total score and all subdomains, except visuospatial/constructional score (all, p < 0.001). These findings suggest that reduced plasma DBH levels might be strongly associated with schizophrenia and might contribute to immediate memory impairment in FDS patients.