Annals Of General Psychiatry[JOURNAL]
Sun
200 papers
The predictive potential and relationship of peripheral non-enzymatic antioxidants with clinical symptoms in first-episode male adolescent-onset schizophrenia patients.
Du B, Ma J, Chen H … +6 more , Zhang K, Wang Z, Zhao Z, Li H, Meng X, Liu Z
Ann Gen Psychiatry · 2026 Feb · PMID 41639905 · Full text
BACKGROUND: Oxidative stress is associated with the pathophysiology of schizophrenia. Peripheral non-enzymatic antioxidants can reflect the degree of oxidative stress and antioxidant levels, and can be used as markers of...
BACKGROUND: Oxidative stress is associated with the pathophysiology of schizophrenia. Peripheral non-enzymatic antioxidants can reflect the degree of oxidative stress and antioxidant levels, and can be used as markers of oxidative stress. However, the relationships between these markers and the clinical phenotypes of first -episode adolescent-onset schizophrenia (AOS) is unclear. This study aimed to elucidate the impact of peripheral non - enzymatic antioxidants on male AOS patients and their association with clinical symptoms. METHODS: Serum albumin (ALB), total bilirubin (TBIL), and uric acid (UA) of 59 first-episode AOS patients and 55 healthy controls were measured respectively. Furthermore, schizophrenia-related clinical symptoms were evaluated using the five-factor model of the Positive and Negative Syndrome Scale (PANSS). RESULTS: In Han Chinese first-episode male AOS patients, levels of TBIL and UA were significantly increased (p < 0.05), while ALB decreased (p < 0.01) compared with healthy controls. Furthermore, multivariate logistic regression showed that UA, ALB, and TBIL (all p < 0.01) were independently associated with AOS. Moreover, correlation analysis revealed that ALB was positively correlated with the PANSS total, cognitive and excited factor scores (all p < 0.05); TBIL was positively correlated with the excited factor score (p < 0.01); UA was positively correlated with the PANSS total, negative, cognitive and excited factor scores (all p < 0.05). In addition, Receiver operating characteristics assessment indicated that ALB and TBIL could effectively distinguish AOS patients from healthy controls. CONCLUSIONS: This study confirms the association of peripheral non-enzymatic antioxidants (ALB, TBIL, and UA) with clinical manifestations and pathophysiology in schizophrenia. ALB and TBIL may serve as potential biomarkers for oxidative stress and symptom severity in AOS, particularly in males, providing insights for diagnostic and therapeutic strategies.
Risk of suicidal acts in patients with dissociative disorder: a population-based cohort study.
Tang WK, Tsoi KKF, Yip TCF … +2 more , Liew VWJ, Chan SKY
Ann Gen Psychiatry · 2026 Feb · PMID 41634844 · Full text
BACKGROUND: This study aimed to examine if individuals diagnosed with dissociative disorder (DD) are at a higher risk of suicidal acts compared to individuals without DD. METHODS: We conducted a matched cohort study by e...
BACKGROUND: This study aimed to examine if individuals diagnosed with dissociative disorder (DD) are at a higher risk of suicidal acts compared to individuals without DD. METHODS: We conducted a matched cohort study by examining electronic health records of patients admitted to Hong Kong public hospitals between January 1, 1993, through December 31, 2022. The study included 716 patients with DD and a matched comparison cohort of 716 individuals. Participants were tracked until they either received a diagnosis of suicidal acts, died from other causes, or until the end of 2023, whichever happened first. Cox proportional hazards regression models were applied to determine the risk of suicidal acts following DD onset. RESULTS: During the 30-year study period, 87 individuals (12.2%) in the DD cohort and 29 individuals (4.1%) in the comparison cohort exhibited suicidal acts, with the difference being statistically significant (χ = 25.21, p = 0.0001). The incidence rates of suicidal acts were 86.7 and 27.3 per 10,000 person-years for the DD and comparison cohorts, respectively. After adjustment, the hazard ratio for suicidal acts in the DD cohort compared with the comparison cohort was 1.89 (95% confidence interval, 1.17-3.06). CONCLUSIONS: DD is linked to a heightened risk of suicidal acts. Future research is required to replicate these findings and to more comprehensively identify the specific risk factors contributing to suicidal acts in this patient population.
Benzodiazepines at the crossroads: navigating therapeutic promise and perils of misuse.
Figg JW, Love CA, Sorathia V … +3 more , Engelbart M, Turner A, Elton A
Ann Gen Psychiatry · 2026 Feb · PMID 41622184 · Full text
Benzodiazepines (BZDs) are a widely prescribed class of psychoactive drugs known for their rapid anxiolytic, anticonvulsant, and sedative effects. Introduced as safer alternatives to barbiturates, BZDs quickly gained pop...
Benzodiazepines (BZDs) are a widely prescribed class of psychoactive drugs known for their rapid anxiolytic, anticonvulsant, and sedative effects. Introduced as safer alternatives to barbiturates, BZDs quickly gained popularity across clinical settings but have since become a subject of public health concern due to rising rates of misuse, dependence, and overdose, particularly when co-administered with opioids. This narrative review explores the historical development, pharmacologic mechanisms, clinical indications, and adverse outcomes associated with BZD use, while highlighting emerging areas of research such as pharmacogenetics (PGx) and genome-wide association studies (GWAS). BZDs act as positive allosteric modulators of the GABA receptor, enhancing inhibitory neurotransmission. This mechanism underlies both their therapeutic efficacy and their potential for physiological dependence and misuse. Clinical applications span acute anxiety, insomnia, seizure management, and alcohol withdrawal; however, long-term use carries significant risks including cognitive decline, fall-related injuries, paradoxical excitation, and withdrawal syndromes. Reinforcement and neuroadaptation processes within the mesolimbic dopamine system contribute to BZD addiction, especially with chronic exposure. Regulatory responses include Schedule IV classification under the Controlled Substances Act and FDA black box warnings. Despite declining prescription rates in recent years, misuse, including nonmedical use and use of illicit designer BZDs, remains prevalent, especially among older adults and those with comorbid psychiatric or substance use disorders. Pharmacogenomic studies have identified genetic polymorphisms in hepatic enzymes (e.g., Cyp2c19 and Cyp3a4) and GABA receptor subunits (e.g. Gabra2) that may influence BZD metabolism, efficacy, and addiction vulnerability, suggesting potential for personalized medicine approaches. In conclusion, the dual nature of BZDs, as essential tools in acute care and potential contributors to substance use disorders, demands a balanced, evidence-informed approach. Continued research, improved prescriber education, and integration of genetic insights into clinical care may help mitigate harm while preserving therapeutic benefit.
Shared genetic architecture between schizophrenia and gastrointestinal diseases: insights from large-scale genome-wide cross-trait analysis.
Ding Y, Wang J, Luo Q … +4 more , Deng C, Shen P, Xu Z, Zhang L
Ann Gen Psychiatry · 2026 Jan · PMID 41606734 · Full text
BACKGROUND: Patients with schizophrenia (SCZ) frequently present with comorbid gastrointestinal diseases. However, the cross-disorder genetic correlations and shared mechanisms remain largely unknown. This study aims to...
BACKGROUND: Patients with schizophrenia (SCZ) frequently present with comorbid gastrointestinal diseases. However, the cross-disorder genetic correlations and shared mechanisms remain largely unknown. This study aims to elucidate the shared genetic architecture between SCZ and five types of gastrointestinal diseases: inflammatory bowel disease, Crohn's disease, ulcerative colitis, constipation, and irritable bowel syndrome. Furthermore, we seek to identify shared genetic risk loci, pinpoint potentially implicated tissues, and conduct in-depth analyses of the genetic mechanisms. METHODS: Using summary statistics from large-scale genome-wide association studies (GWAS), we conducted an in-depth analysis of the genetic correlations between schizophrenia (SCZ) and gastrointestinal diseases via linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL) methods. Significant genetic correlations were observed between SCZ and gastrointestinal diseases. To further investigate the shared genetic basis, we performed cross-trait pleiotropy analyses to identify common pleiotropic loci and genes. Additionally, to uncover potential links between these complex traits, we conducted comprehensive functional annotation and tissue-specific enrichment analyses. Heritability enrichment analysis was employed to assess the contributions of key tissues. Finally, immune colocalization approaches were utilized to explore immune-mediated relationships between SCZ and gastrointestinal diseases. RESULTS: Our research highlighted shared genetic mechanisms between SCZ and five gastrointestinal diseases. A total of 2,367 novel SNPs were identified at a genome-wide significance level (P < 5 × 10⁻⁸), and annotation revealed 96 pleiotropic genome-wide risk loci, among which 32 passed causal colocalization analysis. Shared loci were identified at regions 1q32.1, 2q33.1, 3p21.31, 10q21.2, 16p11.2, and 18q21.2. Further gene-level analyses identified pleiotropic genes including C1orf106, SLC26A6, FES, BSN, C3orf62 and CELSR3. Pathway analyses revealed critical roles of FOXP3 target genes, lymphocyte activation, T cell activation, and PDZ domain-related pathways in these diseases. Finally, phenotype-level immune colocalization analysis uncovered immunological mediators including PD-L1, CD3, T cells, and CD28 that bridge SCZ and gastrointestinal diseases. CONCLUSION: Our findings support a shared genetic architecture between SCZ and gastrointestinal diseases and shed light on the potential mechanism that might involve in.These findings hold important implications for coordinated interventions targeting SCZ and its comorbid conditions.
Perceived social support in mental disorder: insights from the SSQ-6 and its associations with sociodemographic characteristics, clinical features, and admission patterns in a tertiary psychiatric care unit.
Dalliou MT, Hadjichristodoulou C, Stefanidis I … +1 more , Bonotis KS
Ann Gen Psychiatry · 2026 Jan · PMID 41580805 · Full text
OBJECTIVES: This study aims to evaluate perceived social support (SS) in inpatients with mental disorders, its association with sociodemographic and clinical characteristics, and its impact on hospitalization patterns, h...
OBJECTIVES: This study aims to evaluate perceived social support (SS) in inpatients with mental disorders, its association with sociodemographic and clinical characteristics, and its impact on hospitalization patterns, highlighting the importance of evaluating and enhancing SS. METHODS: This hospital-based study, using a cross-sectional design, was conducted at the Psychiatric Clinic of University Hospital Larissa, Greece and included 280 consecutive admitted patients. SS was assessed with short form social support questionnaire SSQ-6, and sociodemographic and clinical characteristics were examined along with possibility of reentry during a 32-month period. RESULTS: Most respondents reported low SS levels, with significant differences in SS quantity across diagnostic categories. Sociodemographic factors, including age, work status, housing conditions, medical insurance and the number of cohabitants, were significantly associated with both SS quantity and satisfaction. Clinical factors, including diagnosis, illness duration and prior admissions also showed significant associations with both dimensions of SS. Multivariate analysis identified increasing age, urbanicity, homelessness, retirement, and unemployment as independent risk factors for lower SS quantity, while cohabitation and affective disorder diagnoses were protective factors. Regarding SS satisfaction, homelessness, retirement, and prolonged illness duration, emerged as risk factors, while medical adherence was protective. Notably, SS quantity was marginally negatively associated with involuntary type of admission. Low SS significantly increased the likelihood of readmission during the 32- month follow-up period. CONCLUSIONS: The study highlights the critical role of assessing and enhancing SS in hospitalized patients with mental disorders. Sociodemographic and clinical factors significantly influence SS, with poor SS contributing to a higher risk of involuntary admission and increased readmission likelihood.
The prefrontal-striatal signatures of reduced model-based learning in depressed patients.
Wang X, Zhou X, Zhang D … +4 more , Zhang Z, Gong Y, Feng Z, Hou JM
Ann Gen Psychiatry · 2026 Jan · PMID 41572320 · Full text
BACKGROUND: Anhedonia is the core symptom of major depressive disorder (MDD). Accumulating evidence indicates that an imbalance between model-based (MB) and model-free (MF) reinforcement learning (RL) characterizes MDD,...
BACKGROUND: Anhedonia is the core symptom of major depressive disorder (MDD). Accumulating evidence indicates that an imbalance between model-based (MB) and model-free (MF) reinforcement learning (RL) characterizes MDD, but the underlying neural substrates remain unclear. We examined whether alterations in MB and MF reward prediction error (RPE) neural signature underlie deficits in RL in depressed patients. METHODS: We used a two-stage Markov decision task (MDT) in combination with computational modeling to examine model-based and model-free learning. A total of 49 MDD and 41 matched HC individuals performed the MDT. 19 MDD and 21 HC individuals underwent functional neuroimaging during the MDT. The stress-RL deficits model was tested using a mediation model with MB and MF RL as mediators between stress and depressive/anhedonic symptoms. RESULTS: Depressed patients showed RL deficits, with less reliance on MB strategies and more reliance on MF strategies. MB and MF RL deficits mediated the relationship between stress and anhedonic symptoms, with specific striatal signatures (i.e., RPEMF signals in VTA and caudate) mediating stress and anhedonia symptoms across MDD and HC groups. CONCLUSIONS: This study showed deficits in model-based RL for depressed patients, with underlying neural deficits in prefrontal-striatal RPE signals, which would be promising for improving therapeutic practice in depression.
Beyond inflammation and cholesterol: atherogenic index of plasma mediates the link between hsCRP/HDL-C ratio and depression in US adults NHANES 2015-2020.
Ma JY, Hu J, Tang F … +4 more , Meng Y, Ye F, Hu LL, Zhang YH
Ann Gen Psychiatry · 2026 Jan · PMID 41566323 · Full text
BACKGROUND: Dyslipidemia and inflammation play key roles in the pathophysiology of depression and are significantly associated with the plasma atherogenic index (AIP). However, a reliable biomarker for diagnosing depress...
BACKGROUND: Dyslipidemia and inflammation play key roles in the pathophysiology of depression and are significantly associated with the plasma atherogenic index (AIP). However, a reliable biomarker for diagnosing depression remains elusive. The hsCRP/HDL-C ratio, combining C-reactive protein (hs-CRP) and high-density lipoprotein cholesterol (HDL-C), may serve as a potential composite indicator. OBJECTIVE: This study aims to explore the relationship between the hsCRP/HDL-C ratio and depression. METHODS: NHANES data (2015-2020) from 10,357 participants were analyzed. Depression was assessed using the PHQ-9, and dyslipidemia with AIP. Participants were grouped based on their hsCRP/HDL-C ratio. Statistical methods included Student's t-test, chi-square test, logistic regression, restricted cubic spline (RCS) model, and mediation analysis. RESULTS: RCS regression analysis showed a nonlinear relationship between the hsCRP/HDL-C ratio and depression. The two-piece logistic regression model was used to calculate the threshold effect, and the likelihood ratio test (p < 0.05) indicated that the inflection point for hs-C/H was 11.608. When the hsCRP/HDL-C ratio was below this threshold, a positive correlation with depression was observed (OR: 1.04, 95% CI: 1.01-1.07). When the hsCRP/HDL-C ratio was equal to or greater than the threshold, a negative correlation was found (OR: 0.99, 95% CI: 0.97-1.00). Subgroup analysis showed consistent results, with marital status being the only factor that significantly influenced this relationship. Mediation analysis revealed that AIP partially mediated the relationship between hsCRP/HDL-C ratio and depression, explaining 11.2% of the total effect (95% CI: 2.26%-27.00%). CONCLUSIONS: A higher hsCRP/HDL-C ratio is associated with increased depression risk. Interventions targeting CRP levels and lipid abnormalities may help reduce this risk.
Transforming treatment-resistant depression (TRD) care in the Gulf Cooperation Council (GCC) countries: a narrative review of emerging therapies, advancements, and implementation barriers.
Alhassan MA
Ann Gen Psychiatry · 2026 Jan · PMID 41566311 · Full text
BACKGROUND: Treatment-resistant depression (TRD) remains a major clinical challenge worldwide and across the Gulf Cooperation Council (GCC) countries, where the burden of mental health disorders continues to rise. Conven...
BACKGROUND: Treatment-resistant depression (TRD) remains a major clinical challenge worldwide and across the Gulf Cooperation Council (GCC) countries, where the burden of mental health disorders continues to rise. Conventional TRD therapies, including antidepressants, augmentation strategies, and electroconvulsive therapy (ECT), often result in incomplete remission and are associated with significant adverse effects, highlighting the need for innovative therapeutic approaches. OBJECTIVE: This narrative review explores the mechanisms, clinical evidence, regional adoption, and recent advances of ketamine, esketamine, and rTMS in TRD, while examining barriers to implementation and outlining future directions for care in the GCC. KEY FINDINGS: Esketamine adoption is increasing in the GCC, with the United Arab Emirates (UAE) and Qatar leading implementation efforts. In both countries, esketamine and related treatments are currently administered in controlled clinical settings within leading psychiatry clinics. Region-specific governmental strategies, such as Qatar's national mental health initiatives, have further supported the structured introduction of these therapies. rTMS is also being gradually integrated into regional mental health services, with notable expansion through private providers in the UAE and Hamad Medical Corporation (HMC) in Qatar. Despite these advancements, access remains limited due to regulatory challenges, high costs, and infrastructure constraints. Implementation of these therapies may serve as a foundation for future regional mental health policies, although cultural stigma, limited insurance coverage, and workforce shortages continue to pose barriers. CONCLUSIONS: Novel therapies for TRD demonstrate clinical efficacy and feasibility in the GCC. Nevertheless, their wider adoption requires addressing accessibility challenges, reducing stigma, and expanding professional training. Strategic investments, policy reforms, and awareness initiatives will be critical to embedding these treatments into mental health systems and transforming TRD care in the region.
Predicting negative symptoms: a novel scale for assessing anticipatory cognitive mechanisms in psychosis.
Ceballos-Munuera C, Rodríguez-Testal JF
Ann Gen Psychiatry · 2026 Jan · PMID 41559799 · Full text
INTRODCUTION: Negative symptoms are a central feature of the schizophrenia spectrum and also appear subclinically in healthy individuals, being associated with poor functional outcomes. Although clinician-rated measures...
INTRODCUTION: Negative symptoms are a central feature of the schizophrenia spectrum and also appear subclinically in healthy individuals, being associated with poor functional outcomes. Although clinician-rated measures remain the gold standard, self-report tools offer efficiency and a direct insight into subjective experiences. OBJECTIVE: This study presents the development and validation of the Negative Symptoms Anticipation Scale (NSAS), a novel self-report instrument designed to assess anticipatory cognitions related to negative symptoms. METHOD: In a pilot study, an initial 28-item version was refined to a final 16-item version organized into three factors: [Kirkpatrick B, Fenton WS, Carpenter WT, Marder SR 1;32(2):214-9:2006] Anticipation of Social Difficulties [Sicras-Mainar A, Maurino J, Ruiz-Beato E, Navarro-Artieda R 14(1):225:2014], Anticipation of Relationship Difficulties, and [Stahl SM, Buckley PF 115(1):4-11:2007] Anticipation of Low Energy in Daily Activities. RESULTS: In a community sample (N = 3,237), the NSAS demonstrated excellent internal consistency (α = 0.927; ω = 0.926; α ordinal = 0.949) and test-retest reliability, as well as a robust factor structure confirmed via confirmatory exploratory analysis (CFI ≥ 0.997; RMSEA ≤ 0.025). Factorial invariance was established across gender and age, and ROC curve analysis indicated outstanding predictive ability for identifying individuals at risk for transitioning to psychosis (AUC = 0.905). Convergent validity was supported by moderate to high correlations with established measures of negative symptoms and negative schizotypy. Hierarchical linear regression showed that, when controlling for social anhedonia and depression, the anticipatory component contributed approximately 7-25% of the variance in negative symptoms. CONCLUSIONS: These findings support the validity of the NSAS and suggest that its application could facilitate early detection and intervention in psychosis.
The mediating role of insulin resistance in depression driving phenotypic age acceleration.
Zhang L, Yang Q, Yu J … +1 more , Hu Y
Ann Gen Psychiatry · 2026 Jan · PMID 41547857 · Full text
BACKGROUND: Depression, characterized by significant psychological and physiological alterations, has been proved to tightly associate with insulin resistance (IR) and hallmarks of biological aging. Phenotypic Age Accele...
BACKGROUND: Depression, characterized by significant psychological and physiological alterations, has been proved to tightly associate with insulin resistance (IR) and hallmarks of biological aging. Phenotypic Age Acceleration (PhenoAgeAccel), which quantifies the discrepancy between biological and chronological age, serves as a robust indicator of accelerated aging. However, the interplay between depression, IR, and accelerated aging remains unclear. This study aims to explore the relationship between depression and PhenoAgeAccel, and the potential mediating role of IR in this association. METHODS: A total of 4,555 adults participants from the National Health and Nutrition Examination Survey (NHANES) database with complete data on depression, PhenoAgeAccel, and other essential covariates were included in this study. Depression severity was assessed by the nine-item Patient Health Questionnaire (PHQ-9), with a PHQ-9 score ≥ 10 used to define depression. Four indicators, including triglyceride-glucose index (TyG), TyG-body mass index (TyG-BMI), TyG-waist height ratio (TyG-WHTR), and metabolic score for insulin resistance (METS-IR), were used to assess IR. Weighted multivariable linear regression analyses were performed to identify the association of depression/PHQ-9 score with PhenoAgeAccel. Moreover, subgroup analyses, interaction tests, and adjusted restricted cubic spline (RCS) analyses were employed to explore the robustness, stability, and potential nonlinearity of the associations between PHQ-9/depression and PhenoAgeAccel. Additionally, mediation analysis was conducted to investigate the mediating role of IR biomarkers in the association between PHQ-9 score and PhenoAgeAccel. RESULTS: In the fully-adjusted model, being depressive and one-unit increment in PHQ-9 score were associated with a 1.93-year (95% CI: 0.95-2.92) and 0.14-year (95% CI: 0.07-0.21) increase in PhenoAgeAccel, respectively. A positive linear dose-response relationship between PHQ-9 score and PhenoAgeAccel was identified via RCS analysis (P for overall = 0.001, P=0.867). Subgroup analyses and interaction tests revealed a more pronounced association between depression/PHQ-9 and PhenoAgeAccel in subgroups with diabetes, moderate-to-heavy alcohol consumption, and higher education levels (all P<0.05). IR biomarkers were observed to mediated 3.6-8.4% of the total effect, with METS-IR showing the highest mediation (8.4%, 95% CI: 0.024-0.222). CONCLUSIONS: Depression was associated with accelerated PhenoAgeAccel, with insulin resistance acting as a partial mediator. In depression management, interventions targeting metabolic issues like insulin resistance should also be considered to mitigate depression-associated aging.
Global prevalence of different levels of anxiety and stress symptoms in healthcare students: A meta-analysis and meta-regression.
Loh YX, Lau Y, Ang WW … +2 more , Shannen Lee SE, Lau ST
Ann Gen Psychiatry · 2026 Jan · PMID 41484624 · Full text
BACKGROUND: There are limited reviews to report the different levels of anxiety and stress symptoms among students studying nursing, pharmacy, and allied health. OBJECTIVE: To calculate the global prevalence of different...
BACKGROUND: There are limited reviews to report the different levels of anxiety and stress symptoms among students studying nursing, pharmacy, and allied health. OBJECTIVE: To calculate the global prevalence of different levels of anxiety and stress symptoms among healthcare students and examine the factors that affect the different levels of prevalence estimates. METHODS: A three-step comprehensive search of 10 databases was conducted. Meta-analysis, subgroup analyses, and meta-regression were performed using the meta package in R software. The Newcastle-Ottawa Scale and Grading of Recommendations Assessments, Development and Evaluation criteria were utilised for the quality appraisal of included studies and the certainty of the evidence, respectively. RESULTS: A total of 112 studies with 42,331 healthcare students across 43 countries were selected. The prevalences of unspecified, mild, moderate, severe, and extremely severe anxiety symptoms were 41% (95% CI: 33-50), 15% (95% CI: 12-19), 22% (95% CI: 19-26), 10% (95% CI: 8-13), 14% (95% CI: 11-17), respectively. The prevalences of unspecified, mild, moderate, severe, and extremely severe stress symptoms were 36% (95% CI: 25-47), 15% (95% CI: 12-18), 32% (95% CI: 25-40), 11% (95% CI: 8-15), 4% (95% CI: 2-5), respectively. A series of subgroup and meta-regression analyses identified geographic region, use of an instrument, type of healthcare students, sample size and study quality were significantly impacted prevalence estimates. CONCLUSION: Findings can contribute as evidence to raising awareness about different levels of anxiety and stress symptoms. Early screening and tailored preventive interventions can help eliminate the prevalence in healthcare students.
Managing schizophrenia with affective, sexual, metabolic and substance-use comorbidities: pharmacological considerations from an expert consensus.
Vieta E, Montejo ÁL, Pillinger T … +7 more , Dell'Osso BM, Dimitraka M, Farooq S, Jesus G, Torres CP, Wobrock T, Pappa S
Ann Gen Psychiatry · 2025 Dec · PMID 41466278 · Full text
BACKGROUND: Schizophrenia is a complex psychiatric disorder frequently complicated by comorbidities that contribute to functional impairment, poor treatment adherence, and elevated mortality. Among the most prevalent and...
BACKGROUND: Schizophrenia is a complex psychiatric disorder frequently complicated by comorbidities that contribute to functional impairment, poor treatment adherence, and elevated mortality. Among the most prevalent and burdensome are affective symptoms, sexual dysfunction, metabolic disturbances, and substance use disorders, which remain underrecognized and insufficiently addressed in routine care. OBJECTIVES: This expert consensus aimed to develop comorbidity-informed pharmacological strategies for schizophrenia, grounded in real-world challenges and individualized treatment needs. METHODS: A multidisciplinary panel of 10 European psychiatrists convened for an in-person meeting. Four expert-led presentations, each addressing a key comorbidity, were followed by open discussion. A modified two-round Delphi process was subsequently used to validate the consensus statements, which were thematically synthesized into actionable recommendations. RESULTS: Consensus-based recommendations were developed across four comorbidity domains, integrating current evidence with real-world clinical expertise. The panel emphasized the importance of individualized, patient-centered pharmacological strategies that balance efficacy, tolerability, and long-term functional outcomes. Partial dopamine agonists and other metabolically or hormonally favorable agents were identified as clinically useful across several comorbid profiles. Recommendations also addressed the optimization of antipsychotic selection, management of treatment-emergent side effects, and coordinated care for patients with dual diagnosis (also referred to as co-occurring disorders). Measurement-based monitoring and integrated service models were consistently highlighted as essential for improving outcomes. CONCLUSIONS: Effective management of schizophrenia requires a shift toward comorbidity-informed, recovery-oriented pharmacological care. These expert recommendations provide practical strategies to support individualized treatment planning in real-world clinical settings.
Too much of a good thing: OTC calcium carbonate overdose causing milk-alkali syndrome in a psychiatric patient.
She A, Bhutia S, Jenney FE
Ann Gen Psychiatry · 2025 Dec · PMID 41444901 · Full text
BACKGROUND: In the United States, milk-alkali syndrome or calcium-alkali syndrome is the third most common cause of hypercalcemia, after primary hyperparathyroidism and malignancy. Clinically, patients present with a tri...
BACKGROUND: In the United States, milk-alkali syndrome or calcium-alkali syndrome is the third most common cause of hypercalcemia, after primary hyperparathyroidism and malignancy. Clinically, patients present with a triad of hypercalcemia, acute kidney injury, and metabolic alkalosis. Classically, it has been associated with excessive intake of calcium and absorbable alkali, and recently it has become more common in postmenopausal females who ingest calcium supplements for osteoporosis. CASE PRESENTATION: Here, we present the case of a 72-year-old Caucasian female with a longstanding diagnosis of bipolar I disorder who presented to the Emergency Department (ED) with a sudden onset of generalized weakness, multiple falls, and altered mental status over the course of several days. On admission, she had elevated serum calcium, acute kidney injury, and metabolic alkalosis. CONCLUSIONS: This case underscores the importance of thorough medical and psychiatric assessment in patients presenting with altered mental status, particularly in those with a history of overdosing. It also highlights the need for close collaboration between psychiatry and internal medicine in the management of metabolic disturbances that may mimic or exacerbate psychiatric symptoms. A stepwise approach to the diagnosis and treatment of hypercalcemia is reviewed, with particular attention to considerations unique to psychiatric populations.
Structural equation modeling of associated factors and regional variations in major depressive disorders and generalized anxiety disorders among reproductive-age Bangladeshi women: a nationally representative study.
Suanrueang P, Peltzer K
Ann Gen Psychiatry · 2025 Dec · PMID 41361795 · Full text
BACKGROUND: The study's objective was to (1) assess the prevalence among women and associated factors of major depressive disorder (MDD) and generalized anxiety disorder (GAD); (2) identify associated factors and regiona...
BACKGROUND: The study's objective was to (1) assess the prevalence among women and associated factors of major depressive disorder (MDD) and generalized anxiety disorder (GAD); (2) identify associated factors and regional variations in the relationship between GAD-7 and PHQ-9 scores; and (3) yield insights to support and strengthen mental health policy and service delivery in Bangladesh. METHODS: Data from 19,987 women (aged 15-49 years) who participated in the 2022 Bangladesh Demographic and Health Survey and completed the mental health module were analyzed. Descriptive statistics assessed MDD/GAD prevalence. SEM analyzed factors associated with psychological distress, and regional variations were examined via linear regression. RESULTS: Among 2388 Bangladeshi women aged 15-49 who had MDD and/or GAD, who provided complete responses for all related variables, sociodemographic factors, resource-related determinants, and negative life events were significantly associated with higher levels of depression and anxiety. The path analysis model indicated that sociodemographic factors (β = 0.69), resource-related factors (β = 0.19), and negative life events (β = 0.05) contributed to depression (PHQ score: β = 0.81, p < 0.001) and anxiety (GAD score: β = 0.84, p < 0.001). Age (β = 0.21, p < 0.001) and marital status (β = 0.20, p < 0.001) were the strongest sociodemographic factors associated with psychological distress, while education (β = 0.41, p < 0.001) and wealth status (β = 0.41, p < 0.001) were the most important resource-related factors. The model demonstrated an acceptable to good fit (Chi-square = 240.67, df = 63, RMSEA = 0.050, GFI = 0.967, AGFI = 0.952, and CFI = 0.826). Regionally, Sylhet City indicated the strongest relationship between GAD and MDD (R = 0.567), followed by Khulna (R = 0.543) and Rajshahi (R = 0.508). An R Value of 0.567 indicated that approximately 57% of the variability in MDD score in Sylhet can be explained by GAD score. CONCLUSION: Path analysis highlighted a multidimensional approach to understanding psychological distress. Sociodemographic, resource factors, and negative life events as determinants collectively serve as associated factors of psychological distress among Bangladeshi females, highlighting the need for culturally tailored interventions with early anxiety screening and coping skills training to improve mental health outcomes.
Acceptability of active and sham home-based transcranial direct current stimulation in major depression: mixed methods qualitative analysis in a randomised controlled trial.
Lagerberg PJ, Woodham RD, Selvaraj S … +13 more , Lajmi N, Hobday H, Sheehan G, Ghazi-Noori AR, Rizvi M, Kwon SS, Orhii P, Machado-Vieira R, Soares JC, Young AH, Fidalgo AR, Rezaei H, Fu CHY
Ann Gen Psychiatry · 2025 Dec · PMID 41345653 · Full text
PURPOSE: Transcranial direct current stimulation (tDCS) is a novel non-invasive brain stimulation therapy that is a potential treatment for major depressive disorder (MDD). Acceptability impacts patient preference, treat...
PURPOSE: Transcranial direct current stimulation (tDCS) is a novel non-invasive brain stimulation therapy that is a potential treatment for major depressive disorder (MDD). Acceptability impacts patient preference, treatment adherence and outcomes, however, it has typically been assessed through measures of attrition, self-reported satisfaction levels, or adverse events. We sought to explore participant acceptability using structured questionnaires and individual interviews. METHODS: Acceptability was assessed in a fully remote, multisite, double-blind, placebo-controlled, randomized superiority trial of a 10-week course of home-based tDCS for MDD. Questionnaires were conducted at baseline and at the 10-week end of treatment. Participants were 174 adults (120 women) with MDD in a current depressive episode of at least moderate severity. Active or sham tDCS was self-administered over 10 weeks with remote supervision at regular intervals. A thematic analysis was conducted. RESULTS: Four themes were revealed: acceptability, ease of use, side effects, and trial participation. The themes indicated generally high acceptability of tDCS as a treatment of MDD in both the active and sham treatment groups. Some participants noted concerns about the technical functionality of the device and the impact of side effects. CONCLUSIONS: The first three themes are central to understanding participant perspectives of tDCS and its feasibility as a treatment option. In addition, the theme of trial participation highlights the value of participant support when introducing a new treatment, which may underscore treatment options in general. Furthermore, acceptability is a dynamic concept as participant views changed during treatment. TRIAL REGISTRATION: NCT05202119, registered on 9th January 2022.
Mental health of children in high-altitude regions: a bibliometric study and visualization analysis from 1979 to 2024.
Huang P, Deng X, Tang J … +2 more , Zhai Y, Wang T
Ann Gen Psychiatry · 2025 Dec · PMID 41339951 · Full text
BACKGROUND: Children's mental health in high-altitude areas is influenced by various environmental, socioeconomic, and biological factors. This study aims to explore the knowledge framework and key research areas in this...
BACKGROUND: Children's mental health in high-altitude areas is influenced by various environmental, socioeconomic, and biological factors. This study aims to explore the knowledge framework and key research areas in this domain, using bibliometric methods to analyze trends, collaboration patterns, and essential themes related to children's mental health at high altitudes. METHODS: A bibliometric analysis was conducted on publications from 1979 to 2024 retrieved from the Web of Science Core Collection database. The R package "Bibliometrix," VOSviewer, and CiteSpace were used to analyze publication trends, collaboration patterns, and research themes. RESULTS: A total of 520 English-language articles were included. The United States was the most prolific country (226 articles), and Duke University was the leading institution (66 articles). The Journal of the American Academy of Child and Adolescent Psychiatry was the most influential journal. E. Jane Costello was the most prolific author (50 publications). Co-occurrence network analysis identified four major clusters: possible mechanisms, outcomes, psychopathology, and management of mental health issues. Academic research in very high HDI countries focuses more on quality-of-life and mental health issues, whereas low and medium HDI countries prioritize fundamental public health and common disease prevention. CONCLUSIONS: This study provides a bibliometric foundation for quantitatively assessing research trends on mental health among children in high-altitude regions. Current research primarily focuses on underlying mechanisms, outcomes, mental health conditions, and management strategies. For countries at different development levels, research should be tailored to their specific social development stages and health challenges.
Efficacy of acupuncture for generalized anxiety disorder: a systematic review.
Lai J, Wang Y, Yao X … +4 more , Yu J, Lu S, Lu J, Liu J
Ann Gen Psychiatry · 2025 Nov · PMID 41316337 · Full text
BACKGROUND: This systematic review aimed to assess the efficacy and safety of acupuncture for generalized anxiety disorder (GAD), with a particular focus on acupuncture alone and acupuncture combined with medication, com...
BACKGROUND: This systematic review aimed to assess the efficacy and safety of acupuncture for generalized anxiety disorder (GAD), with a particular focus on acupuncture alone and acupuncture combined with medication, compared with medication or sham acupuncture. METHODS: We searched MEDLINE/PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP Database for Chinese Technical Periodicals, Chinese Biomedical Literature Database (CBM), and ClinicalTrials.gov up to August 31, 2025. Randomized controlled trials (RCTs) of acupuncture for GAD were independently screened and extracted by two reviewers following strict quality assessment. Risk of bias was evaluated using the RoB 2.0 tool, evidence certainty was assessed with the GRADE approach, and meta-analyses were conducted with RevMan 5.3. Subgroup analyses were performed according to comparator type and acupuncture parameters (treatment modality, duration, frequency, and sessions). RESULTS: A total of 41 RCTs involving 3,209 participants were included. Meta-analysis showed that acupuncture alone (MD -1.79, 95% CI -2.69 to -0.88; 19 studies) and acupuncture combined with medication (MD -2.26, 95% CI -3.05 to -1.48; 20 studies) were superior to medication alone in reducing Hamilton Anxiety Rating Scale (HAMA) scores. Acupuncture also outperformed sham acupuncture (MD -3.46, 95% CI -4.76 to -2.16; 3 studies). Significant improvements were also observed in total effective rate, Self-Rating Anxiety Scale (SAS) scores, and Clinical Global Impression-Efficacy Index (CGI-EI), with lower rates of adverse events in the acupuncture groups. Subgroup analyses suggested that a treatment duration of 4-6 weeks was associated with better outcomes; for stand-alone acupuncture, a frequency of seven sessions per week was more effective than medication, while for combined therapy, a frequency of 2-4 sessions per week was more effective than medication. DISCUSSIONS: This meta-analysis indicates that acupuncture, either as a monotherapy or in combination with medication, may provide superior efficacy to medication and sham acupuncture, with fewer adverse events. However, most included studies were rated as having "some concerns" in risk of bias by RoB 2.0, and GRADE assessment suggested low or very low certainty of evidence for the primary outcome (HAMA). Egger's test indicated no significant publication bias in HAMA. Further high-quality, large-scale RCTs are required to confirm these findings. REGISTRATION: The protocol of the review was registered in PROSPERO (CRD42015016033).
Anomalous self-experience in substance-induced and primary psychotic disorders: a cross-sectional comparative study using the EASE interview.
De Risio L, Mosca A, Pasino A … +4 more , Pompili E, Nicolò G, Pettorruso M, Martinotti G
Ann Gen Psychiatry · 2025 Nov · PMID 41291822 · Full text
BACKGROUND: Disturbances of the minimal self, or anomalous self-experiences (ASEs), are increasingly regarded as a core feature of primary psychotic disorders (PPDs). However, it remains unclear whether similar self-diso...
BACKGROUND: Disturbances of the minimal self, or anomalous self-experiences (ASEs), are increasingly regarded as a core feature of primary psychotic disorders (PPDs). However, it remains unclear whether similar self-disorders are present in substance-induced psychosis (SIP), a condition that often mimics PPDs in its early stages. OBJECTIVE: The study aims to compare ASEs between PPD and SIP using the EASE interview, to evaluate the diagnostic specificity of ASEs and determine whether these disturbances are exclusive to primary psychoses or also present in SIP. METHODS: A total of 54 clinically stable patients were recruited from psychiatric centers in Italy (27 with schizophrenia spectrum disorders (SSD), mean age ≈ 27 years; 27 with substance-induced psychosis, mean age ≈ 28 years).. Diagnoses were established according to DSM-5 criteria. ASEs were assessed using the Examination of Anomalous Self-Experience (EASE) interview, and scores were compared across five experiential domains. Non-parametric statistics and logistic regression were employed to identify domain-specific differences and their diagnostic utility. RESULTS: While total EASE scores did not differ significantly between groups, Domain 4 (Demarcation/Transitivism) was significantly higher in the SIP group (p < .0001, r = .72), contrary to classical phenomenological models that typically associate self-world boundary disturbances with schizophrenia spectrum disorders. In contrast, Domain 2 (Self-awareness and Presence) trended higher in the PPD group (p = .049, r = .27) and Domain 5 (Existential Reorientation) showed a similar trend (p = .098, r = .22)., aligning with classical phenomenological models of schizophrenia. Logistic regression confirmed the predictive value of these domains for group classification. CONCLUSION: ASEs are not exclusive to PPDs and may also manifest in SIP, particularly in the domain of "self-world boundary" disturbances. These findings challenge the assumption that self-disorders are unique to endogenous psychosis and highlight the need for refined phenomenological assessment in early diagnostic work. Longitudinal studies are needed to clarify whether ASEs in SIP represent transient phenomena or prodromal markers of schizophrenia.
Smoking status and the onset of suicidal ideation among adults in Japan during the COVID-19 pandemic.
Stickley A, Shirama A, Sumiyoshi T
Ann Gen Psychiatry · 2025 Nov · PMID 41272739 · Full text
PURPOSE: As previous research has linked smoking to suicidal behavior, it is possible that smoking may have played a role in suicidality during the COVID-19 pandemic. However, relatively little research has examined this...
PURPOSE: As previous research has linked smoking to suicidal behavior, it is possible that smoking may have played a role in suicidality during the COVID-19 pandemic. However, relatively little research has examined this association. To address this gap, the present study examined the relationship between smoking status and the onset of suicidal ideation in Japan during the pandemic. METHODS: Data were analyzed from 3,164 adults from the Japanese general population who participated in an online survey in early 2023. Information was collected on smoking status and incident suicidal ideation during the COVID-19 pandemic. Logistic regression was conducted to examine associations. RESULTS: In a fully adjusted analysis, current smoking was associated with significantly higher odds of the onset of suicidal ideation in the total sample (OR: 2.31, 95%CI: 1.37, 3.90). In a sex-stratified analysis, both former (OR: 4.49, 95%CI: 1.75, 11.50) and current smoking (OR: 6.12, 95%CI: 2.67, 14.01) were associated with the onset of suicidal ideation in men, whereas no such association was observed in women. CONCLUSION: Smoking was associated with the onset of suicidal ideation among adults in Japan during the COVID-19 pandemic, with the association observed in men but not women.
Pro-inflammatory cytokines level in depressed patients with suicidal behaviour: a systematic review and meta-analysis.
Moshfeghinia R, Ghahramani M, Naderian R … +8 more , Mostafavi S, Arman A, Mohagheghzadeh H, Haghighifard E, Tahmasebi S, Kanannejad Z, Javanbakht A, Ahmadi J
Ann Gen Psychiatry · 2025 Nov · PMID 41272690 · Full text
INTRODUCTION: The study assesses proinflammatory factors in major depressive disorder (MDD) patients with and without suicidal behaviors, and healthy controls, to identify potential biomarkers for suicidal behaviors and...
INTRODUCTION: The study assesses proinflammatory factors in major depressive disorder (MDD) patients with and without suicidal behaviors, and healthy controls, to identify potential biomarkers for suicidal behaviors and prevention strategies. METHODS: We conducted a systematic review, which we have registered in Prospero (#CRD42024547764), and searched through five databases until March 2024. We included observational studies in English that reported on depressed patients with and without suicidal behaviors, as well as healthy controls, and measured the levels of pro-inflammatory cytokines. The Newcastle- Ottawa Scale was used for quality evaluation of the studies and the main analysis was performed using Stata 17. RESULTS: One systematic review resulted in 4,369 articles but only 24 were selected for the review. The meta-analysis showed depressed patients with suicidal behaviors had significantly higher interleukin (IL)-6 levels compared to the control group with a standardized mean difference (SMD) of 1.26 [0.07, 2.45]; I² = 98.81%. There was no significant difference noted between the depressed patients suffering from suicidal behaviors and those not suffering (SMD 0.42 [-0.58, 1.42]; I² = 98.50%). There is no significant difference between the groups in the levels of tumor necrosis factor-alpha (TNF-α) and IL-10. Further analysis of IL-4, IL-2, IL-1β, IF-γ, and TGF-β1 also indicated no significant group differences. CONCLUSION: The review found no significant cytokine differences (including IFN-γ, IL-1β, IL-2, IL-4, IL-8, IL-10, TGF-β1, TNF-α) between depressed individuals with or without suicidal ideation and controls. Variations likely reflect methodological differences, highlighting the need for standardized, longitudinal research.
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