Pub Date : 2026-01-06DOI: 10.1016/j.jpsychires.2026.01.011
Che-Sheng Chu , Yen-Yue Lin , Cathy Chia-Yu Huang , Wei-Zhe Liang , Wei-Chou Chang , Alexander T. Sack , Chuan-Chia Chang , Hsin-An Chang
Background
The modulation of brain dynamics by melatonin antidepressants in patients with major depressive disorder (MDD) remains unclear.
Methods
Resting-state electroencephalographic (EEG) was recorded in 84 drug-free patients with MDD and 143 healthy controls. EEG data were collected at baseline and after 8-week agomelatine treatment. K-means clustering identified four canonical microstates (MS-A–D), and topographic analysis of variance assessed group differences.
Results
At baseline, patients with MDD showed increased occurrence and coverage of MS-C and MS-D, along with a higher transition probability between these two states, compared to healthy controls. In contrast, the duration and coverage of MS-A and MS-B, as well as their transition probabilities, were reduced in the MDD group. Following treatment, patients with MDD exhibited increased MS-A coverage and a higher transition probability from MS-A to MS-B, while the transition probability between MS-C and MS-D decreased. Several microstate parameters were normalized to those of healthy controls. Notably, MS-B occurrence negatively correlated with baseline anhedonia severity, although no microstate measures predicted changes in anhedonia over time.
Conclusions
This study demonstrates altered EEG microstate dynamics in patients with MDD and provides insights into the neural mechanisms underlying MDD. Microstate abnormalities may serve as potential clinical biomarkers for MDD.
{"title":"Altered electroencephalographic microstate dynamics in major depressive disorder and their modulation by melatonergic treatment","authors":"Che-Sheng Chu , Yen-Yue Lin , Cathy Chia-Yu Huang , Wei-Zhe Liang , Wei-Chou Chang , Alexander T. Sack , Chuan-Chia Chang , Hsin-An Chang","doi":"10.1016/j.jpsychires.2026.01.011","DOIUrl":"10.1016/j.jpsychires.2026.01.011","url":null,"abstract":"<div><h3>Background</h3><div>The modulation of brain dynamics by melatonin antidepressants in patients with major depressive disorder (MDD) remains unclear.</div></div><div><h3>Methods</h3><div>Resting-state electroencephalographic (EEG) was recorded in 84 drug-free patients with MDD and 143 healthy controls. EEG data were collected at baseline and after 8-week agomelatine treatment. K-means clustering identified four canonical microstates (MS-A–D), and topographic analysis of variance assessed group differences.</div></div><div><h3>Results</h3><div>At baseline, patients with MDD showed increased occurrence and coverage of MS-C and MS-D, along with a higher transition probability between these two states, compared to healthy controls. In contrast, the duration and coverage of MS-A and MS-B, as well as their transition probabilities, were reduced in the MDD group. Following treatment, patients with MDD exhibited increased MS-A coverage and a higher transition probability from MS-A to MS-B, while the transition probability between MS-C and MS-D decreased. Several microstate parameters were normalized to those of healthy controls. Notably, MS-B occurrence negatively correlated with baseline anhedonia severity, although no microstate measures predicted changes in anhedonia over time.</div></div><div><h3>Conclusions</h3><div>This study demonstrates altered EEG microstate dynamics in patients with MDD and provides insights into the neural mechanisms underlying MDD. Microstate abnormalities may serve as potential clinical biomarkers for MDD.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 294-302"},"PeriodicalIF":3.2,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145978073","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}
When patients with schizophrenia on antipsychotic medication present neurological symptoms, it is often considered to be side effects of antipsychotics. In contrast, Niemann-Pick disease type C (NPC) has a wide variety of symptoms, and the diagnosis of adult-onset NPC is difficult. In this study, we measured novel biomarkers of NPC and examined the possibility of NPC in patients diagnosed with schizophrenia.
Methods
Five patients with schizophrenia and neurological symptoms were evaluated using the NPC Suspicion Index, and urinary bile acid and blood oxysterol levels were measured by LC-MS/MS and Q-TOF LC/MS. Lysosphingomyelin (SPC) and Lyso-SM-509(PPCS), reported as novel biomarkers for NPC, were measured in the plasma of 163 patients with schizophrenia and 111 healthy controls using LC-MS/MS. NPC1 and NPC2 gene analyses were performed on 124 patients using the next-generation sequencer. In one patient, Filipin staining was performed using skin fibroblasts.
Results
Among the five patients, one patient had an abnormal urinary bile acid level. Levels of SPC were significantly higher in patients than in healthy controls. Genetic analysis revealed no genetic mutations associated with the etiology. The patient who underwent Filipin staining had cholesterol-stained pale and was determined to be a variant type. However, it would be more accurate to state that no patients were identified as NPC based on these biomarkers.
Conclusion
Among the patients with schizophrenia, there were no cases that were definitively diagnosed as NPC, but some patients had features of NPC. It is important to evaluate mental and neurological symptoms in light of this possibility.
{"title":"The possibility of patients with adult-onset Niemann-Pick disease type C in cases diagnosed with schizophrenia: Analysis of NPC novel biomarkers","authors":"Kumiko Fujii , Masamitsu Maekawa , Aya Narita , Yoshikatsu Eto , Masataka Shinozaki , Yosefu Arime , Hiroaki Okayasu , Kazutaka Shimoda , Yuji Ozeki","doi":"10.1016/j.jpsychires.2026.01.009","DOIUrl":"10.1016/j.jpsychires.2026.01.009","url":null,"abstract":"<div><h3>Background</h3><div>When patients with schizophrenia on antipsychotic medication present neurological symptoms, it is often considered to be side effects of antipsychotics. In contrast, Niemann-Pick disease type C (NPC) has a wide variety of symptoms, and the diagnosis of adult-onset NPC is difficult. In this study, we measured novel biomarkers of NPC and examined the possibility of NPC in patients diagnosed with schizophrenia.</div></div><div><h3>Methods</h3><div>Five patients with schizophrenia and neurological symptoms were evaluated using the NPC Suspicion Index, and urinary bile acid and blood oxysterol levels were measured by LC-MS/MS and Q-TOF LC/MS. Lysosphingomyelin (SPC) and Lyso-SM-509(PPCS), reported as novel biomarkers for NPC, were measured in the plasma of 163 patients with schizophrenia and 111 healthy controls using LC-MS/MS. NPC1 and NPC2 gene analyses were performed on 124 patients using the next-generation sequencer. In one patient, Filipin staining was performed using skin fibroblasts.</div></div><div><h3>Results</h3><div>Among the five patients, one patient had an abnormal urinary bile acid level. Levels of SPC were significantly higher in patients than in healthy controls. Genetic analysis revealed no genetic mutations associated with the etiology. The patient who underwent Filipin staining had cholesterol-stained pale and was determined to be a variant type. However, it would be more accurate to state that no patients were identified as NPC based on these biomarkers.</div></div><div><h3>Conclusion</h3><div>Among the patients with schizophrenia, there were no cases that were definitively diagnosed as NPC, but some patients had features of NPC. It is important to evaluate mental and neurological symptoms in light of this possibility.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 252-258"},"PeriodicalIF":3.2,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145952467","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 : 2026-01-05DOI: 10.1016/j.jpsychires.2026.01.002
Brandi Francis , Emanuele Fino , Nadja Heym
Borderline Personality Disorder (BPD) is highly comorbid with depression and anxiety, creating additional difficulty in treating the conditions and poorer prognosis than BPD alone. Dialectical behaviour therapy (DBT) and Mentalisation-Based Treatment (MBT) are specialised psychotherapies for BPD that have demonstrated positive effects for reducing BPD symptoms and scores on depression and anxiety measures. Although developed for treating PTSD, Internal Family Systems (IFS) therapy is effective for addressing past trauma that is also common in BPD. This systematic review investigated the effectiveness of DBT, MBT and IFS for treating BPD with comorbid depression and/or anxiety (BPD + D/A). Using the PRISMA protocol, five academic databases were searched for relevant studies and relevant treatment outcomes. Findings were extracted from 12 included studies. Only studies with a confirmed diagnosis of comorbid depression and/or anxiety disorders were included. This review found that DBT and MBT demonstrated significant reductions in BPD and depressive/anxious symptomatology, emotional and interpersonal difficulties, and impulsive behaviours. These therapeutic approaches also demonstrated reduced numbers of visits to emergency departments, reduced numbers of contacts with mental health services and reduced duration of contacts. None of the studies investigated IFS therapy outcomes for BPD + D/A. These findings are concordant with past research and have implications for increasing the use of DBT and MBT for BPD + D/A. Findings also demonstrate the effectiveness of brief DBT interventions as a more practical option for service users with BPD who experience frequent crisis periods and may struggle to commit to a traditional 12-month program. However, findings should be interpreted cautiously due to small and majority-female samples, mixed study designs and a lack of follow-up data.
{"title":"A systematic review of dialectical behaviour therapy, mentalisation-based treatment and internal family systems therapy for borderline personality disorder with comorbid depression and/or anxiety","authors":"Brandi Francis , Emanuele Fino , Nadja Heym","doi":"10.1016/j.jpsychires.2026.01.002","DOIUrl":"10.1016/j.jpsychires.2026.01.002","url":null,"abstract":"<div><div>Borderline Personality Disorder (BPD) is highly comorbid with depression and anxiety, creating additional difficulty in treating the conditions and poorer prognosis than BPD alone. Dialectical behaviour therapy (DBT) and Mentalisation-Based Treatment (MBT) are specialised psychotherapies for BPD that have demonstrated positive effects for reducing BPD symptoms and scores on depression and anxiety measures. Although developed for treating PTSD, Internal Family Systems (IFS) therapy is effective for addressing past trauma that is also common in BPD. This systematic review investigated the effectiveness of DBT, MBT and IFS for treating BPD with comorbid depression and/or anxiety (BPD + D/A). Using the PRISMA protocol, five academic databases were searched for relevant studies and relevant treatment outcomes. Findings were extracted from 12 included studies. Only studies with a confirmed diagnosis of comorbid depression and/or anxiety disorders were included. This review found that DBT and MBT demonstrated significant reductions in BPD and depressive/anxious symptomatology, emotional and interpersonal difficulties, and impulsive behaviours. These therapeutic approaches also demonstrated reduced numbers of visits to emergency departments, reduced numbers of contacts with mental health services and reduced duration of contacts. None of the studies investigated IFS therapy outcomes for BPD + D/A. These findings are concordant with past research and have implications for increasing the use of DBT and MBT for BPD + D/A. Findings also demonstrate the effectiveness of brief DBT interventions as a more practical option for service users with BPD who experience frequent crisis periods and may struggle to commit to a traditional 12-month program. However, findings should be interpreted cautiously due to small and majority-female samples, mixed study designs and a lack of follow-up data.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 221-232"},"PeriodicalIF":3.2,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927685","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 : 2026-01-03DOI: 10.1016/j.jpsychires.2026.01.004
Kristoffer Bele Ødegård , Martin Øverlien Myhre , Ole Klungsøyr , Lars Mehlum , Anita Johanna Tørmoen , Fredrik A. Walby
Background
The month following discharge from inpatient mental health treatment is the period associated with the highest short-term risk of suicide. The nature of this risk is not well understood. We aim to assess a potential short term causal effect of discharge on suicide risk using a novel counterfactual framework for causal inference.
Methods
National registry linkage study with individuals 18 years or older who died by suicide from 1.1.2018 to 31.12.2022 and was discharged in the last year (N = 731). We used a Case-crossover design comparing risk at a case-time and five randomly selected control-times within subjects and employed the Mantel-Haenszel estimator.
Results
We found an effect of discharge on the Incidence Rate Ratio (IRR) for suicide within 14 days (IRR = 5.48 95 % CI:4.37–6.72). Comparing the first four weeks, the IRR was 6.32 (95 % CI 4.87–8.00) for the first week, with significantly reduced risk for subsequent weeks.
Conclusion
Our findings are consistent with a causal effect of discharge on short-term suicide risk, under the assumptions described and controlling for confounders not addressed in prior studies. Recognizing this risk as causal enhances our understanding of the suicides that happen shortly after discharge and emphasizes the importance of identifying realistic targets for intervention in the post discharge period, which can then be evaluated through clinical trials.
{"title":"Discharge from mental health service admissions as a short-term causal risk factor for suicide: A case-crossover study","authors":"Kristoffer Bele Ødegård , Martin Øverlien Myhre , Ole Klungsøyr , Lars Mehlum , Anita Johanna Tørmoen , Fredrik A. Walby","doi":"10.1016/j.jpsychires.2026.01.004","DOIUrl":"10.1016/j.jpsychires.2026.01.004","url":null,"abstract":"<div><h3>Background</h3><div>The month following discharge from inpatient mental health treatment is the period associated with the highest short-term risk of suicide. The nature of this risk is not well understood. We aim to assess a potential short term causal effect of discharge on suicide risk using a novel counterfactual framework for causal inference.</div></div><div><h3>Methods</h3><div>National registry linkage study with individuals 18 years or older who died by suicide from 1.1.2018 to 31.12.2022 and was discharged in the last year (N = 731). We used a Case-crossover design comparing risk at a case-time and five randomly selected control-times within subjects and employed the Mantel-Haenszel estimator.</div></div><div><h3>Results</h3><div>We found an effect of discharge on the Incidence Rate Ratio (IRR) for suicide within 14 days (IRR = 5.48 95 % CI:4.37–6.72). Comparing the first four weeks, the IRR was 6.32 (95 % CI 4.87–8.00) for the first week, with significantly reduced risk for subsequent weeks.</div></div><div><h3>Conclusion</h3><div>Our findings are consistent with a causal effect of discharge on short-term suicide risk, under the assumptions described and controlling for confounders not addressed in prior studies. Recognizing this risk as causal enhances our understanding of the suicides that happen shortly after discharge and emphasizes the importance of identifying realistic targets for intervention in the post discharge period, which can then be evaluated through clinical trials.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 174-180"},"PeriodicalIF":3.2,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917841","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 : 2026-01-03DOI: 10.1016/j.jpsychires.2026.01.005
Ke Wang, Shan Cai, Xin-Rong Duanmu, Chen-Yu Ma, Rui Yan, Yan-Rui Cui, Lin Zhou, Liu-Liu Xu
Objective
Quetiapine is an atypical antipsychotic with a broad spectrum of use including anti-anxiety and mood stabilizing properties and has proved effective in mood disorders, such as major depressive disorder and bipolar depression. An integration of cognitive behavioral therapy (CBT) with pharmacological treatment has shown to outperform drugs alone in reducing suicide risk for patients with mood disorders. In this study, we investigated the effect of adding cognitive behavioral therapy (CBT) to quetiapine on suicide risk, depressive symptoms, and coping style in adult patients with mood disorders.
Methods
One hundred and thirty-seven patients were randomized to QUE group (n = 70) and QUE + CBT group (n = 67). The primary outcome was suicide risk assessed by the Nurses’ Global Assessment of Suicide Risk (NGASR) scale. The secondary outcomes were depressive symptoms assessed by the 24-item Hamilton Depression Rating Scale (HDRS-24) and coping style assessed by the Simplified Coping Style Questionnaire (SCSQ).
Results
The QUE + CBT group showed a significantly lower percentage with high suicide risk in the modified intention-to-treat population than the QUE group after 12-week intervention (χ2 = 5.50; p = 0.02). The analysis of covariance (ANCOVA) controlling for baseline scores indicated a significantly main effect of treatment in scores of NGASR [F(1, 135) = 25.30, p < 0.01, partial η2 = 0.16], HDRS-24 [F(1, 135) = 27.00, p < 0.01, partial η2 = 0.17], positive coping [F(1, 135) = 10.00, p < 0.01, partial η2 = 0.07] and negative coping of SCSQ [F(1, 135) = 26.70, p < 0.01, partial η2 = 0.17], suggesting that lower scores of NGASR and HDRS-24, a higher positive coping score, and a lower negative coping score in the QUE + CBT group than in the QUE group after 12-week intervention.
Conclusion
These results suggest that adding CBT to quetiapine could decrease suicide risk, improve depressive symptoms, and enhance coping style for adult patients with mood disorders.
目的：喹硫平是一种非典型抗精神病药物，具有广泛的抗焦虑和情绪稳定特性，已被证明对情绪障碍（如重度抑郁症和双相抑郁症）有效。认知行为疗法（CBT）与药物治疗相结合，在降低情绪障碍患者自杀风险方面的效果优于单独使用药物。在本研究中，我们研究了认知行为疗法（CBT）与喹硫平联合治疗对成年情绪障碍患者自杀风险、抑郁症状和应对方式的影响。方法：137例患者随机分为QUE组（n = 70）和QUE + CBT组（n = 67）。主要结果是自杀风险评估护士全球自杀风险评估（NGASR）量表。次要结局采用24项汉密尔顿抑郁评定量表（HDRS-24）评估抑郁症状，采用简化应对方式问卷（SCSQ）评估应对方式。结果：干预12周后，QUE + CBT组在修改意向治疗人群中的高自杀风险百分比明显低于QUE组（χ2 = 5.50; p = 0.02）。控制基线得分的协方差分析（ANCOVA）显示，治疗对NGASR得分[F(1,135) = 25.30, p 2 = 0.16]、HDRS-24得分[F(1,135) = 27.00, p 2 = 0.17]、积极应对[F(1,135) = 10.00, p 2 = 0.07]、SCSQ消极应对[F(1,135) = 26.70, p 2 = 0.17]有显著的主效应，提示NGASR和HDRS-24得分越低，积极应对得分越高。干预12周后，QUE + CBT组的消极应对得分低于QUE组。结论：在喹硫平基础上加用CBT可降低成年心境障碍患者自杀风险，改善抑郁症状，改善应对方式。
{"title":"Effect of adding cognitive behavioral therapy to quetiapine on suicide risk, depressive symptoms, and coping style in adult patients with mood disorders","authors":"Ke Wang, Shan Cai, Xin-Rong Duanmu, Chen-Yu Ma, Rui Yan, Yan-Rui Cui, Lin Zhou, Liu-Liu Xu","doi":"10.1016/j.jpsychires.2026.01.005","DOIUrl":"10.1016/j.jpsychires.2026.01.005","url":null,"abstract":"<div><h3>Objective</h3><div>Quetiapine is an atypical antipsychotic with a broad spectrum of use including anti-anxiety and mood stabilizing properties and has proved effective in mood disorders, such as major depressive disorder and bipolar depression. An integration of cognitive behavioral therapy (CBT) with pharmacological treatment has shown to outperform drugs alone in reducing suicide risk for patients with mood disorders. In this study, we investigated the effect of adding cognitive behavioral therapy (CBT) to quetiapine on suicide risk, depressive symptoms, and coping style in adult patients with mood disorders.</div></div><div><h3>Methods</h3><div>One hundred and thirty-seven patients were randomized to QUE group (n = 70) and QUE + CBT group (n = 67). The primary outcome was suicide risk assessed by the Nurses’ Global Assessment of Suicide Risk (NGASR) scale. The secondary outcomes were depressive symptoms assessed by the 24-item Hamilton Depression Rating Scale (HDRS-24) and coping style assessed by the Simplified Coping Style Questionnaire (SCSQ).</div></div><div><h3>Results</h3><div>The QUE + CBT group showed a significantly lower percentage with high suicide risk in the modified intention-to-treat population than the QUE group after 12-week intervention (χ<sup>2</sup> = 5.50; p = 0.02). The analysis of covariance (ANCOVA) controlling for baseline scores indicated a significantly main effect of treatment in scores of NGASR [F(1, 135) = 25.30, p < 0.01, partial η<sup>2</sup> = 0.16], HDRS-24 [F(1, 135) = 27.00, p < 0.01, partial η<sup>2</sup> = 0.17], positive coping [F(1, 135) = 10.00, p < 0.01, partial η<sup>2</sup> = 0.07] and negative coping of SCSQ [F(1, 135) = 26.70, p < 0.01, partial η<sup>2</sup> = 0.17], suggesting that lower scores of NGASR and HDRS-24, a higher positive coping score, and a lower negative coping score in the QUE + CBT group than in the QUE group after 12-week intervention.</div></div><div><h3>Conclusion</h3><div>These results suggest that adding CBT to quetiapine could decrease suicide risk, improve depressive symptoms, and enhance coping style for adult patients with mood disorders.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 145-150"},"PeriodicalIF":3.2,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912053","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}
SARS-CoV-2 infection has been implicated in hippocampal damage, contributing to the pathogenesis of dysexecutive syndrome observed in post-COVID-19 patients. Given the growing prevalence of long-COVID worldwide, understanding how SARS-CoV-2 affects hippocampal structure and function has become an urgent scientific and clinical priority. The hippocampus—crucial for memory, emotional regulation, and executive functioning—is especially susceptible to viral-driven neuroinflammatory cascades. SARS-CoV-2 triggers astrocyte and microglia activation, disrupts blood–brain barrier integrity, and induces cytokine-mediated neurotoxicity, ultimately impairing neuroplasticity and neurogenesis. These mechanisms converge to produce cognitive and affective disturbances—most notably fatigue, apathy, low mood, and executive dysfunction—that typify dysexecutive syndrome in long-COVID.
This review synthesizes current evidence from clinical and experimental studies, integrating findings on viral neurotropism, hippocampal hypometabolism, and astrocyte-mediated neurodegeneration. Distinctions between depressive symptoms driven by neuroinflammation and classical depressive disorders are clarified to improve diagnostic accuracy and guide personalized treatment. Emerging data on the neuroprotective role of COVID-19 vaccination—particularly its capacity to modulate microglial activation and support hippocampal neurogenesis—are also examined. Overall, the findings underscore the need for targeted therapeutic strategies aimed at modulating neuroinflammation and supporting hippocampal plasticity, including cognitive rehabilitation approaches.
Longitudinal studies are essential to elucidate the enduring impact of SARS-CoV-2 on hippocampal function and to inform effective clinical interventions.
{"title":"Astrocyte-mediated hippocampal damage in the pathogenesis of dysexecutive syndrome following COVID-19: A narrative review","authors":"Antonino Messina , Fabrizio Bella , Giuliana Maccarone , Gabriele Avincola , Maria Salvina Signorelli","doi":"10.1016/j.jpsychires.2026.01.007","DOIUrl":"10.1016/j.jpsychires.2026.01.007","url":null,"abstract":"<div><div>SARS-CoV-2 infection has been implicated in hippocampal damage, contributing to the pathogenesis of dysexecutive syndrome observed in post-COVID-19 patients. Given the growing prevalence of long-COVID worldwide, understanding how SARS-CoV-2 affects hippocampal structure and function has become an urgent scientific and clinical priority. The hippocampus—crucial for memory, emotional regulation, and executive functioning—is especially susceptible to viral-driven neuroinflammatory cascades. SARS-CoV-2 triggers astrocyte and microglia activation, disrupts blood–brain barrier integrity, and induces cytokine-mediated neurotoxicity, ultimately impairing neuroplasticity and neurogenesis. These mechanisms converge to produce cognitive and affective disturbances—most notably fatigue, apathy, low mood, and executive dysfunction—that typify dysexecutive syndrome in long-COVID.</div><div>This review synthesizes current evidence from clinical and experimental studies, integrating findings on viral neurotropism, hippocampal hypometabolism, and astrocyte-mediated neurodegeneration. Distinctions between depressive symptoms driven by neuroinflammation and classical depressive disorders are clarified to improve diagnostic accuracy and guide personalized treatment. Emerging data on the neuroprotective role of COVID-19 vaccination—particularly its capacity to modulate microglial activation and support hippocampal neurogenesis—are also examined. Overall, the findings underscore the need for targeted therapeutic strategies aimed at modulating neuroinflammation and supporting hippocampal plasticity, including cognitive rehabilitation approaches.</div><div>Longitudinal studies are essential to elucidate the enduring impact of SARS-CoV-2 on hippocampal function and to inform effective clinical interventions.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 164-173"},"PeriodicalIF":3.2,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912068","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 : 2026-01-03DOI: 10.1016/j.jpsychires.2026.01.008
Ye Tu , Shenrui Li , Shaodi Guan , Yueyang Xin , Hong Tao , Zhiqiang Zhou , Shaofang Wang , Hongwei Jiang , Hui Xu
Background
Schizophrenia, a debilitating neuropsychiatric disorder with profound socioeconomic consequences, manifests characteristic cortical thinning patterns observable through neuroimaging. While structural magnetic resonance imaging (MRI) studies consistently demonstrate these anatomical disturbances, their molecular signatures remain poorly understood.
Methods
We employed an integrative neuroimaging-transcriptomic approach, combining structural MRI data from 50 schizophrenia patients and 125 healthy controls with postmortem gene expression profiles from the Allen Human Brain Atlas. Spatial relationships between transcriptional patterns and cortical thickness variations were quantified using partial least squares regression. Subsequent analyses included gene ontology enrichment, cell-type deconvolution, and protein-protein interaction network.
Results
Schizophrenia patients demonstrated significant cortical thinning in limbic and paralimbic regions critical for emotional processing, including anterior cingulate and insular cortices. Imaging transcriptomic analyses revealed strong associations between cortical alterations and schizophrenia-risk genes STON2, ANK3, and KCNN3. Enriched biological pathways included stress-responsive signaling, calcium homeostasis, and synaptic plasticity. Cell-type analyses implicated excitatory and inhibitory neurons, together with microglia, while network analysis identified KCNB1, PTGS2, and TPT1 as central molecular hubs.
Conclusions
This study reveals specific molecular correlates of cortical thinning in schizophrenia, highlighting biological mechanisms that may contribute to structural abnormalities. The identified genes and pathways offer potential therapeutic targets for addressing both neuroanatomical changes and affective disturbances in schizophrenia.
{"title":"Imaging transcriptomics identifies gene signatures associated with cortical thinning in schizophrenia","authors":"Ye Tu , Shenrui Li , Shaodi Guan , Yueyang Xin , Hong Tao , Zhiqiang Zhou , Shaofang Wang , Hongwei Jiang , Hui Xu","doi":"10.1016/j.jpsychires.2026.01.008","DOIUrl":"10.1016/j.jpsychires.2026.01.008","url":null,"abstract":"<div><h3>Background</h3><div>Schizophrenia, a debilitating neuropsychiatric disorder with profound socioeconomic consequences, manifests characteristic cortical thinning patterns observable through neuroimaging. While structural magnetic resonance imaging (MRI) studies consistently demonstrate these anatomical disturbances, their molecular signatures remain poorly understood.</div></div><div><h3>Methods</h3><div>We employed an integrative neuroimaging-transcriptomic approach, combining structural MRI data from 50 schizophrenia patients and 125 healthy controls with postmortem gene expression profiles from the Allen Human Brain Atlas. Spatial relationships between transcriptional patterns and cortical thickness variations were quantified using partial least squares regression. Subsequent analyses included gene ontology enrichment, cell-type deconvolution, and protein-protein interaction network.</div></div><div><h3>Results</h3><div>Schizophrenia patients demonstrated significant cortical thinning in limbic and paralimbic regions critical for emotional processing, including anterior cingulate and insular cortices. Imaging transcriptomic analyses revealed strong associations between cortical alterations and schizophrenia-risk genes <em>STON2, ANK3,</em> and <em>KCNN3</em>. Enriched biological pathways included stress-responsive signaling, calcium homeostasis, and synaptic plasticity. Cell-type analyses implicated excitatory and inhibitory neurons, together with microglia, while network analysis identified KCNB1, PTGS2, and TPT1 as central molecular hubs.</div></div><div><h3>Conclusions</h3><div>This study reveals specific molecular correlates of cortical thinning in schizophrenia, highlighting biological mechanisms that may contribute to structural abnormalities. The identified genes and pathways offer potential therapeutic targets for addressing both neuroanatomical changes and affective disturbances in schizophrenia.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 151-163"},"PeriodicalIF":3.2,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912036","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 : 2026-01-03DOI: 10.1016/j.jpsychires.2026.01.001
K. Wolfova , B.H. Strand , J. Weiss , P. Brennan Kearns , T. Mekonnen , Y. Stern , H.-P. Kohler , V.F. Skirbekk , S.E. Tom
Objectives
We explored the relationship between the number of children and cognitive outcomes in later life in a large cohort of older females and males from Norway.
Design
Cross-sectional analysis using multinomial logistic regression.
Settings
The Norwegian HUNT4 70+ Study.
Participants
Males and females aged ≥70 years.
Measurments
The exposure was the number of biological children (none, one, two, three, or four or more). The primary outcome was categorized as dementia, mild cognitive impairment (MCI), or no cognitive impairment.
Results
Among 9263 participants (mean age 78 years; 54 % females), those without children had higher risk of dementia (relative risk ratio [RRR] 1.82, 95 % confidence interval [CI] 1.37 to 2.42) and MCI (RRR 1.31, 95 % CI 1.08 to 1.59) compared to those who had two children, adjusting for age and sex. Similar pattern was observed for those with one child, whereas those with three children did not have an increased MCI or dementia risk. Having four or more children was marginally associated with higher dementia risk (RRR 1.22, 95 % CI 1.00–1.49), but not with MCI risk. This association was attenuated after adjusting for education and marital status, whereas those without children and with one child had still higher risk. In sex-stratified analysis, having no children was associated with higher risk of dementia only in males.
Conclusions
The weak association with high parity, along with the increased dementia risk observed in males without children, contrasts with previous findings. Our results highlight the need for further investigation into the social mechanisms linking reproductive history to cognitive health.
目的：我们对来自挪威的一大群老年男女进行研究，探讨子女数量与晚年认知结局之间的关系。设计采用多项逻辑回归进行横断面分析。挪威HUNT4 70+研究。参与者：年龄≥70岁的男女。暴露量是指亲生子女的数量（没有、一个、两个、三个、四个或更多）。主要结局分为痴呆、轻度认知障碍（MCI）或无认知障碍。结果在9263名参与者中（平均年龄78岁，女性占54%），与有两个孩子的参与者相比，没有孩子的参与者患痴呆（相对风险比[RRR] 1.82, 95%可信区间[CI] 1.37至2.42）和MCI （RRR 1.31, 95% CI 1.08至1.59）的风险更高，调整了年龄和性别。有一个孩子的人也观察到了类似的模式，而有三个孩子的人则没有增加轻度认知障碍或痴呆的风险。有4个或4个以上孩子与较高的痴呆风险有轻微关联（RRR 1.22, 95% CI 1.00-1.49），但与轻度认知障碍风险无关。在调整了教育程度和婚姻状况后，这种关联减弱了，而没有孩子和只有一个孩子的人的风险仍然更高。在性别分层分析中，没有孩子的男性患痴呆症的风险更高。结论：在没有孩子的男性中观察到的高胎次与痴呆风险增加的弱关联，与先前的研究结果形成了对比。我们的研究结果强调需要进一步研究生殖史与认知健康之间的社会机制。
{"title":"Reproductive history and cognitive health among older Norwegian females and males: the population-based HUNT Study","authors":"K. Wolfova , B.H. Strand , J. Weiss , P. Brennan Kearns , T. Mekonnen , Y. Stern , H.-P. Kohler , V.F. Skirbekk , S.E. Tom","doi":"10.1016/j.jpsychires.2026.01.001","DOIUrl":"10.1016/j.jpsychires.2026.01.001","url":null,"abstract":"<div><h3>Objectives</h3><div>We explored the relationship between the number of children and cognitive outcomes in later life in a large cohort of older females and males from Norway.</div></div><div><h3>Design</h3><div>Cross-sectional analysis using multinomial logistic regression.</div></div><div><h3>Settings</h3><div>The Norwegian HUNT4 70+ Study.</div></div><div><h3>Participants</h3><div>Males and females aged ≥70 years.</div></div><div><h3>Measurments</h3><div>The exposure was the number of biological children (none, one, two, three, or four or more). The primary outcome was categorized as dementia, mild cognitive impairment (MCI), or no cognitive impairment.</div></div><div><h3>Results</h3><div>Among 9263 participants (mean age 78 years; 54 % females), those without children had higher risk of dementia (relative risk ratio [RRR] 1.82, 95 % confidence interval [CI] 1.37 to 2.42) and MCI (RRR 1.31, 95 % CI 1.08 to 1.59) compared to those who had two children, adjusting for age and sex. Similar pattern was observed for those with one child, whereas those with three children did not have an increased MCI or dementia risk. Having four or more children was marginally associated with higher dementia risk (RRR 1.22, 95 % CI 1.00–1.49), but not with MCI risk. This association was attenuated after adjusting for education and marital status, whereas those without children and with one child had still higher risk. In sex-stratified analysis, having no children was associated with higher risk of dementia only in males.</div></div><div><h3>Conclusions</h3><div>The weak association with high parity, along with the increased dementia risk observed in males without children, contrasts with previous findings. Our results highlight the need for further investigation into the social mechanisms linking reproductive history to cognitive health.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 181-187"},"PeriodicalIF":3.2,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927689","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 : 2026-01-03DOI: 10.1016/j.jpsychires.2026.01.003
Rachel M. Ranney , Beth E. Cohen , Hui Shen , Katherine J. Hoggatt , Shira Maguen
This study aimed to investigate associations between social determinants of health (SDoH, the conditions in which people live) and receipt of psychotherapy among Veterans with posttraumatic stress disorder (PTSD) engaged in care at the Veterans Health Administration. Past research has identified disparities in receipt of PTSD care related to demographics, but there is a lack of research on disparities related to SDoH. This study investigated three SDoH: homelessness, socioeconomic disadvantage, and rurality. Using VHA electronic health records, we included Veterans with a PTSD diagnosis from 2015 to 2018, a total of 435,381 Veterans, and reviewed receipt of PTSD psychotherapy through 2019. In regression models accounting for demographics, trauma exposure, and mental and physical health factors, we found that Veterans who had experienced lifetime homelessness were more likely to receive any PTSD psychotherapy and a minimally adequate dose of PTSD psychotherapy (eight sessions within a 24-week period). We found that Veterans with greater socioeconomic disadvantage and Veterans who resided in rural areas were less likely to receive a minimally adequate dose of PTSD psychotherapy. These findings suggest that efforts are needed to promote engagement with mental healthcare for rural Veterans and those with greater socioeconomic disadvantage.
{"title":"Social determinants of health associated with receipt of psychotherapy for veterans with posttraumatic stress disorder","authors":"Rachel M. Ranney , Beth E. Cohen , Hui Shen , Katherine J. Hoggatt , Shira Maguen","doi":"10.1016/j.jpsychires.2026.01.003","DOIUrl":"10.1016/j.jpsychires.2026.01.003","url":null,"abstract":"<div><div>This study aimed to investigate associations between social determinants of health (SDoH, the conditions in which people live) and receipt of psychotherapy among Veterans with posttraumatic stress disorder (PTSD) engaged in care at the Veterans Health Administration. Past research has identified disparities in receipt of PTSD care related to demographics, but there is a lack of research on disparities related to SDoH. This study investigated three SDoH: homelessness, socioeconomic disadvantage, and rurality. Using VHA electronic health records, we included Veterans with a PTSD diagnosis from 2015 to 2018, a total of 435,381 Veterans, and reviewed receipt of PTSD psychotherapy through 2019. In regression models accounting for demographics, trauma exposure, and mental and physical health factors, we found that Veterans who had experienced lifetime homelessness were more likely to receive any PTSD psychotherapy and a minimally adequate dose of PTSD psychotherapy (eight sessions within a 24-week period). We found that Veterans with greater socioeconomic disadvantage and Veterans who resided in rural areas were less likely to receive a minimally adequate dose of PTSD psychotherapy. These findings suggest that efforts are needed to promote engagement with mental healthcare for rural Veterans and those with greater socioeconomic disadvantage.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 188-195"},"PeriodicalIF":3.2,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927688","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}
Major depressive disorder (MDD) affects approximately 280 million people worldwide, yet its neurobiological mechanisms remain largely unclear. Anti-myelin basic protein (anti-MBP) antibodies, markers of autoimmune activity, have been associated with various neuropsychiatric conditions, but their role in depression is poorly understood. This study examined the associations between serum anti-MBP levels, depression severity, functioning, and hippocampal volume, and compared anti-MBP levels between patients with MDD and healthy controls.
Methods
Thirty patients diagnosed with MDD who applied to the psychiatry outpatient clinic of Farabi Hospital and 30 healthy controls matched for age, gender and education were included. All participants were assessed using the Hamilton Depression Rating Scale (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Functioning Assessment Short Test (FAST). Venous blood samples were collected to determine anti-MBP levels. Hippocampal volumes were assessed using T1-weighted magnetic resonance imaging.
Results
Linear regression analysis in the total sample of participants demonstrated that anti-MBP levels were significantly associated with a decrease in total (p = 0.020), right (p = 0.013), and left (p = 0.046) hippocampal volume. Furthermore, ROC analysis revealed that anti-MBP levels could distinguish MDD patients from healthy controls with high diagnostic accuracy.
Conclusions
These results suggest a potential association between anti-MBP antibodies and neuroimmune alterations in depression. Across all participants, age- and sex-adjusted regression analyses showed an inverse association between anti-MBP and hippocampal volume. Notably, anti-MBP levels were higher in patients, suggesting its potential utility as a biomarker candidate for future studies in MDD. Consistently, ROC analysis performed well in discriminating between patients and controls.
{"title":"The relationship between Antibody levels against myelin basic protein in depressive disorder, neuroimaging, and functioning","authors":"Samet Öksüz , Aykut Karahan , Hüseyin Yaman , Selçuk Akkaya","doi":"10.1016/j.jpsychires.2025.12.048","DOIUrl":"10.1016/j.jpsychires.2025.12.048","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) affects approximately 280 million people worldwide, yet its neurobiological mechanisms remain largely unclear. Anti-myelin basic protein (anti-MBP) antibodies, markers of autoimmune activity, have been associated with various neuropsychiatric conditions, but their role in depression is poorly understood. This study examined the associations between serum anti-MBP levels, depression severity, functioning, and hippocampal volume, and compared anti-MBP levels between patients with MDD and healthy controls.</div></div><div><h3>Methods</h3><div>Thirty patients diagnosed with MDD who applied to the psychiatry outpatient clinic of Farabi Hospital and 30 healthy controls matched for age, gender and education were included. All participants were assessed using the Hamilton Depression Rating Scale (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Functioning Assessment Short Test (FAST). Venous blood samples were collected to determine anti-MBP levels. Hippocampal volumes were assessed using T1-weighted magnetic resonance imaging.</div></div><div><h3>Results</h3><div>Linear regression analysis in the total sample of participants demonstrated that anti-MBP levels were significantly associated with a decrease in total (p = 0.020), right (p = 0.013), and left (p = 0.046) hippocampal volume. Furthermore, ROC analysis revealed that anti-MBP levels could distinguish MDD patients from healthy controls with high diagnostic accuracy.</div></div><div><h3>Conclusions</h3><div>These results suggest a potential association between anti-MBP antibodies and neuroimmune alterations in depression. Across all participants, age- and sex-adjusted regression analyses showed an inverse association between anti-MBP and hippocampal volume. Notably, anti-MBP levels were higher in patients, suggesting its potential utility as a biomarker candidate for future studies in MDD. Consistently, ROC analysis performed well in discriminating between patients and controls.</div></div>","PeriodicalId":16868,"journal":{"name":"Journal of psychiatric research","volume":"194 ","pages":"Pages 90-98"},"PeriodicalIF":3.2,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863347","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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