Pub Date : 2026-02-04DOI: 10.1016/j.schres.2026.01.022
Jehanita Jesuthasan , Kate Merritt , Francesca Solmi , Pedro Luque Laguna , Anthony S. David
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.
刚地弓形虫（弓形虫）是一种可以通过猫传播给人类的寄生虫，已被认为是精神分裂症和相关疾病的可改变危险因素。然而，许多检验这种关系的研究都依赖于养猫作为弓形虫暴露的替代指标。本研究考察了血清弓形虫水平与后期精神病经历（PEs）和脑容量之间的关系。我们还探讨了养猫与弓形虫血清学之间的关系。利用雅芳父母与儿童纵向研究（ALSPAC），我们研究了3542名个体，这些个体在儿童时期和18岁时的血清弓形虫数据是可用的。基于体素的形态计量学评估了20岁时灰质体积的MRI测量是否与一部分参与者（N = 334）的弓形虫水平相关。校正模型中血清弓形虫与PE组无相关性(疑似PE风险比(RR) = 1.06, 95%可信区间（CI） [0.89-1.27]；明确pe RR = 0.86, 95% CI [0.65 ~ 1.13]；精神障碍RR = 1.00, 95% CI[0.73-1.38])。妊娠期接触猫与青春期弓形虫较高相关（β = 0.08, p = 0.033），而儿童期接触猫与此无关（β = 0.05, p = 0.310）。弓形虫与脑灰质体积无相关性（pfes≥0.882,Zs≤3.86）。未来研究弓形虫与精神分裂症谱系障碍之间关系的工作应侧重于血清学或妊娠期间养猫作为弓形虫暴露的替代措施，因为童年养猫与弓形虫之间没有关联。
{"title":"The association between childhood Toxoplasma gondii, psychotic experiences and grey matter volume: A population-based cohort study","authors":"Jehanita Jesuthasan , Kate Merritt , Francesca Solmi , Pedro Luque Laguna , Anthony S. David","doi":"10.1016/j.schres.2026.01.022","DOIUrl":"10.1016/j.schres.2026.01.022","url":null,"abstract":"<div><div><em>Toxoplasma gondii</em> (<em>T. gondii</em>), 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 <em>T. gondii</em> exposure. This study examined the relationship between serum <em>T. gondii</em> levels and later psychotic experiences (PEs) and brain volume. We also explored the relationship between cat ownership and <em>T. gondii</em> serology. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we studied 3542 individuals for whom data on serum <em>T. gondii</em> 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 <em>T. gondii</em> levels among a subset of the participants (<em>N</em> = 334). Serum <em>T. gondii</em> was not associated with PE group in adjusted models (suspected PEs risk ratio (<em>RR</em>) = 1.06, 95% confidence interval (CI) [0.89–1.27]; definite PEs <em>RR</em> = 0.86, 95% CI [0.65–1.13]; psychotic disorder <em>RR</em> = 1.00, 95% CI [0.73–1.38]). Exposure to cats during gestation was associated with higher <em>T. gondii</em> in adolescence (<em>β</em> = 0.08, <em>p</em> = 0.033), while exposure to cats during childhood was not (<em>β</em> = 0.05, <em>p</em> = 0.310). <em>T. gondii</em> was not associated with grey matter volume in the neuroimaging sample (<em>pFWEs</em> ≥ 0.882, <em>Zs</em> ≤ 3.86). Future work examining the relationship between <em>T. gondii</em> and schizophrenia-spectrum disorders should focus on serology or cat ownership during gestation as a proxy measure of <em>T. gondii</em> exposure, as there was no association between childhood cat ownership and <em>T. gondii</em>.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"290 ","pages":"Pages 65-72"},"PeriodicalIF":3.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-04DOI: 10.1016/j.schres.2026.01.023
Erich J. Aschenbrenner , Andrew C. Voluse
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.
{"title":"Predicting the prognosis of primary and substance-associated psychoses using urine drug screens: A 5-year retrospective longitudinal study using medical records","authors":"Erich J. Aschenbrenner , Andrew C. Voluse","doi":"10.1016/j.schres.2026.01.023","DOIUrl":"10.1016/j.schres.2026.01.023","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"290 ","pages":"Pages 57-64"},"PeriodicalIF":3.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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 & SI1mV (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.
背景：在精神分裂症患者中，尽管接受了适当的抗精神病药物治疗，但阳性症状持续存在是一个具有挑战性的临床情况。皮层可塑性受损被认为是精神分裂症抗精神病药物耐药性的基础。本研究利用短间隔皮质抑制（SICI）配对脉冲方案评估了精神分裂症患者高清晰度tdcs （HD-tDCS）驱动的运动皮质可塑性。方法：53例抗精神病性精神分裂症（ARS）患者和31名健康受试者分别在左M1区进行单次阴极HD-tDCS （2 mA, 20 min）前后（10,20,30,40 min）进行经颅磁刺激肌电图（TMS-EMG）评估。皮质可塑性通过SICI和SI1mV （1mv时的运动诱发电位）的变化来确定。使用线性混合效应模型评估时间和组的影响。结果：在阴极HD-tDCS后40分钟的SICI中发现了组*时间相互作用（t = 2.23），表明与健康对照组相比，ARS患者在阴极HD-tDCS后的运动皮质兴奋性变化明显较差且持续时间较短。此外，氯氮平耐药，即超耐药精神分裂症（URS）患者与一线抗精神病药患者相比，表现出更差的可塑性[Cohen’s d = 0.764, p = 0.004]。结论：研究结果再次证实了ARS患者的运动皮质可塑性受损。此外，我们注意到症状负担较高、治疗抵抗和功能较差的URS运动皮质可塑性最差。未来的研究可以探索皮质可塑性作为预测、机制和治疗性生物标志物的潜力。
{"title":"Aberrant motor cortical plasticity in antipsychotic-resistant schizophrenia: A cross-sectional study using transcranial direct current and magnetic stimulation","authors":"Kiran Bagali , Chithra Uppinkudru , Harsh Pathak , Rujuta Parlikar , Shubham Samantaray , Ashok Jammigumpula , Makarand Pantoji , Sachin Reddy , Manul Das , Jithin Thekkelkuthiyathottill Joseph , Srinivas Balachander , Vanteemar S. Sreeraj , Abhiram Purohith Narasimhan , Sonia Shenoy , Umesh Shreekantiah , Preeti Sinha , Shyam Sundar Arumugham , Samir Kumar Praharaj , Nishant Goyal , Muralidharan Kesavan , Jagadisha Thirthalli","doi":"10.1016/j.schres.2026.01.025","DOIUrl":"10.1016/j.schres.2026.01.025","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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<sub>mV</sub> (Motor Evoked Potential at 1 mV). The effect of time and group was assessed using linear mixed-effects models.</div></div><div><h3>Results</h3><div>A group*time interaction (<em>t</em> = 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, <em>p</em> = 0.004].</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"290 ","pages":"Pages 48-56"},"PeriodicalIF":3.5,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-03DOI: 10.1016/j.schres.2026.01.016
Paola Dazzan , Gurubhaskar Shivakumar , Kinga Szymaniak , Erica Bell , Giulia Cattarinussi , Gin S. Malhi
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 …
{"title":"Restoring scientific resilience through European collaboration","authors":"Paola Dazzan , Gurubhaskar Shivakumar , Kinga Szymaniak , Erica Bell , Giulia Cattarinussi , Gin S. Malhi","doi":"10.1016/j.schres.2026.01.016","DOIUrl":"10.1016/j.schres.2026.01.016","url":null,"abstract":"<div><div>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 …<span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (85KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"290 ","pages":"Pages 30-33"},"PeriodicalIF":3.5,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-03DOI: 10.1016/j.schres.2026.01.021
Kristian Varden Gjerde , Christoffer Bartz-Johannessen , Else-Marie Løberg , Vidar Martin Steen , Nils Eiel Steen , Ole A. Andreassen , Thor Ueland , Maria Rettenbacher , Inge Joa , Solveig Klæbo Reitan , Farivar Fathian , Erik Johnsen , Rune Andreas Kroken
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.
{"title":"Neural and vascular cellular adhesion molecules are associated with cognitive function in patients with schizophrenia-spectrum disorders: A longitudinal study","authors":"Kristian Varden Gjerde , Christoffer Bartz-Johannessen , Else-Marie Løberg , Vidar Martin Steen , Nils Eiel Steen , Ole A. Andreassen , Thor Ueland , Maria Rettenbacher , Inge Joa , Solveig Klæbo Reitan , Farivar Fathian , Erik Johnsen , Rune Andreas Kroken","doi":"10.1016/j.schres.2026.01.021","DOIUrl":"10.1016/j.schres.2026.01.021","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>N-CAD levels correlated positively with overall cognition (<em>p</em> = 0.002), working memory (<em>p</em> = 0.034), and executive functions (<em>p</em> = 0.0011). ICAM-1 levels correlated positively with overall cognition (<em>p</em> = 0.037). Conversely, JAM-A levels correlated negatively with executive functions (<em>p</em> = 0.021).</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"290 ","pages":"Pages 34-41"},"PeriodicalIF":3.5,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-03DOI: 10.1016/j.schres.2026.01.019
Menahem Krakowski , Pal Czobor
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.
{"title":"Disentangling violence in schizophrenia: Interactions between symptom trajectories, conduct disorder, and pharmacotherapy","authors":"Menahem Krakowski , Pal Czobor","doi":"10.1016/j.schres.2026.01.019","DOIUrl":"10.1016/j.schres.2026.01.019","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"290 ","pages":"Pages 42-47"},"PeriodicalIF":3.5,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-02DOI: 10.1016/j.schres.2026.01.007
Graham Blackman , Hamilton Morrin , Claire Carstairs , Jack B. Fanshawe , Cameron Watson , Mao Fong Lim , Jonathan Phillips , Adam E. Handel , Robert A. McCutcheon , John Headley Ward , Elisavet Pappa , Emily M.L. Bowman , Rachel T.S. Chow , Thomas A. Pollak , Philip McGuire , Vaughan Bell
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.
少数精神病患者有潜在的医学（“器质性”）病因。其中一些次要原因是可逆的；因此，早期发现至关重要。在初步评估中，精神病理学可以提供信息，以确定哪些患者有潜在医学原因的风险增加，并应优先加强调查。通过预注册（CRD42024511546）系统评价和荟萃分析，我们比较了从开始到2025年9月PubMed病例对照研究中继发于医学原因的精神病患者与原发性精神病患者的精神病理学。我们确定了13项研究和1564人的汇总样本量（原发性精神病= 781，继发性精神病= 783）。语言障碍（RR = 18.18, 95% CI = 1.43-231.5）和视觉幻觉（RR = 1.35, 95% CI 1.02-1.80）更可能是继发于潜在医学原因的精神病的特征，而不是原发性精神病。相反，幻听（RR = 0.55, 95% CI = 0.50-0.61）、思想插入（RR = 0.24, 95% CI = 0.12-0.48）、思想传播（RR = 0.30, 95% CI = 0.09-0.98）、未明确的妄想（RR = 0.44, 95% CI = 0.30-0.66）、迫害妄想（RR = 0.72, 95% CI = 0.62-0.84）、嗅觉幻觉（RR = 0.34, 95% CI = 0.18-0.63）和触觉幻觉（RR = 0.26, 95% CI = 0.19-0.35）更有可能是原发性精神病的特征。研究结果强调了对未分化精神病患者进行全面精神病学评估的临床价值。继发性精神病表现出精神病理上的差异，某些症状可能是继发性原因的“危险信号”。这些指标可以帮助临床医生优先考虑进一步调查的患者。
{"title":"Psychopathology distinguishing secondary (“organic”) psychoses: A systematic review and meta-analysis","authors":"Graham Blackman , Hamilton Morrin , Claire Carstairs , Jack B. Fanshawe , Cameron Watson , Mao Fong Lim , Jonathan Phillips , Adam E. Handel , Robert A. McCutcheon , John Headley Ward , Elisavet Pappa , Emily M.L. Bowman , Rachel T.S. Chow , Thomas A. Pollak , Philip McGuire , Vaughan Bell","doi":"10.1016/j.schres.2026.01.007","DOIUrl":"10.1016/j.schres.2026.01.007","url":null,"abstract":"<div><div>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.</div><div>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.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"289 ","pages":"Pages 106-111"},"PeriodicalIF":3.5,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-28DOI: 10.1016/j.schres.2026.01.015
Bao-Yu Chen , Jin-Jia Lin , Huai-Hsuan Tseng , Chih-Chun Huang , Po-See Chen , Chia-Hsuan Li , Chi-Yu Yao , Wan-Lin Cheng , Tzu-Yun Wang , Fong-Lin Jang , Sheng-Hsiang Lin
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.
{"title":"Small EVs miRNA profiles and their expressions in EVs-depleted plasma as an optimal combination panel for treatment-resistant schizophrenia","authors":"Bao-Yu Chen , Jin-Jia Lin , Huai-Hsuan Tseng , Chih-Chun Huang , Po-See Chen , Chia-Hsuan Li , Chi-Yu Yao , Wan-Lin Cheng , Tzu-Yun Wang , Fong-Lin Jang , Sheng-Hsiang Lin","doi":"10.1016/j.schres.2026.01.015","DOIUrl":"10.1016/j.schres.2026.01.015","url":null,"abstract":"<div><div>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 (<em>N</em> = 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 (<em>N</em> = 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.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"290 ","pages":"Pages 17-29"},"PeriodicalIF":3.5,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-28DOI: 10.1016/j.schres.2026.01.017
Özgü Şişman, Sinay Önen
{"title":"Corrigendum to “prevalence and multidimensional impact of sarcopenia in schizophrenia: Associations with oxidative stress, functioning, and symptom severity” [Schizophr. Res. volume 289, March 2026, pages–61-70]","authors":"Özgü Şişman, Sinay Önen","doi":"10.1016/j.schres.2026.01.017","DOIUrl":"10.1016/j.schres.2026.01.017","url":null,"abstract":"","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"289 ","pages":"Page 112"},"PeriodicalIF":3.5,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146087007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-26DOI: 10.1016/j.schres.2026.01.014
Lais Fonseca , Lucas Toshio Ito , Carolina Ziebold , Luis A. Rohde , Eurípedes C. Miguel , Rodrigo A. Bressan , Pedro M. Pan , Sintia I. Belangero , Marcos L. Santoro , Felipe V. Gomes , Anthony A. Grace , Ary Gadelha
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.
{"title":"Executive function mediates the effects of genetic liability to schizophrenia on behavior and functioning in a community sample of children and adolescents","authors":"Lais Fonseca , Lucas Toshio Ito , Carolina Ziebold , Luis A. Rohde , Eurípedes C. Miguel , Rodrigo A. Bressan , Pedro M. Pan , Sintia I. Belangero , Marcos L. Santoro , Felipe V. Gomes , Anthony A. Grace , Ary Gadelha","doi":"10.1016/j.schres.2026.01.014","DOIUrl":"10.1016/j.schres.2026.01.014","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Study design</h3><div>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.</div></div><div><h3>Study results</h3><div>PRS-SZ predicted lower EF scores (β = −0.091, <em>t</em> = −2.435, <em>p</em> = 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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":21417,"journal":{"name":"Schizophrenia Research","volume":"290 ","pages":"Pages 9-16"},"PeriodicalIF":3.5,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146065958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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