Annals of General Psychiatry最新文献

Background: Trazodone, an antidepressant, has only been approved for use in major depressive disorder (MDD), but has demonstrated potent therapeutic potential in various conditions, such as insomnia and anxiety. It targets multiple serotonergic, adrenergic, and histaminergic receptors. Given this multimodal and multifunctional profile, we aimed to provide a comprehensive overview of the pharmacodynamic and pharmacokinetic properties of trazodone and its clinical applications across various conditions.

Main text: Trazodone demonstrates sedative and anxiolytic effects even at a low dose (25-75 mg) and a full antidepressant effect at higher doses (150-300 mg). The availability of trazodone in immediate-release, extended-release, intravenous, and intramuscular formulations enables flexible and personalized treatment based on the patient's symptoms, medical history, tolerability, and clinical settings. Clinical evidence also demonstrates that trazodone is effective and well-tolerated across various conditions, including MDD, treatment-resistant depression, insomnia (off-label), neurological disorders, dementia, and delirium, highlighting its versatility. Additionally, the low risk of sexual dysfunction, limited withdrawal symptoms, and weight-neutral effects make it suitable for use in patients with comorbid conditions.

Conclusion: Trazodone is a multimodal and multifunctional antidepressant that exhibits a broad range of therapeutic effects in MDD and other comorbid conditions. Further research on the pharmacokinetic and pharmacodynamic relationship of trazodone, its parenteral use in acute settings, and the development of prescribing algorithms for predicting treatment responses may enhance its therapeutic outcomes in patients with MDD.

Background: Although Schizophrenia is a serious mental illness which more common in adults, it can also manifest in childhood with disease onset before age 18 as "early-onset schizophrenia" (EOS). While our previous research identified circulating oxysterols-24(S)-hydroxycholesterol (24 S-OHC) and 27-hydroxycholesterol (27-OHC)-as potential biomarkers in adult schizophrenia, their role in EOS remains unknown. This study aimed to characterize the developmental trajectories of these oxysterols during early life and evaluate their clinical relevance in EOS, with particular emphasis on sex-specific effects.

Methods: We recruited 142 healthy individuals (aged 1 to 41 years) to define age-related oxysterol patterns and 71 EOS patients (aged 4 to 18 years) to identify disease-associated changes. Plasma concentrations of 24 S-OHC and 27-OHC were measured using liquid chromatography-tandem mass spectrometry.

Results: Healthy participants exhibited significant age-dependent variations, with younger individuals showing higher 24 S-OHC and lower 27-OHC levels. While EOS patients showed no overall differences in oxysterol levels compared to age-matched healthy controls, a striking sex-based divergence emerged: male patients exhibited significantly elevated levels of 27-OHC compared to females. Additionally, the 24 S-OHC/27-OHC ratio showed a positive correlation with negative symptom severity, which did not survive correction for multiple comparisons but may still indicate a potential relationship. Notably, sex-stratified analysis revealed opposing correlations between 27-OHC levels and PANSS scores, most prominently for positive symptoms.

Conclusions: This study represents the first evidence of sexually dimorphic oxysterol regulation in EOS and highlights 27-OHC as a sex-sensitive factor linked to clinical symptom expression, even in the absence of group-level oxysterol alterations.

Background: Medication adherence among patients with psychiatric disorders is a significant challenge that often leads to poor clinical outcomes. Although pharmacist-led interventions have demonstrated the potential to improve medication adherence, evidence remains limited, particularly in patients treated with antipsychotics. This study aimed to evaluate the effectiveness of a brief pharmacist-led intervention in enhancing medication adherence among outpatients receiving antipsychotic therapy.

Methods: This exploratory, prospective, single-arm study was conducted at a community pharmacy in Japan. Fifty outpatients prescribed antipsychotic medications participated in the study. A brief pharmacist-led intervention was delivered focusing on identifying and addressing barriers to adherence. The primary outcomes were changes in Drug Attitude Inventory-10 (DAI-10) scores and the proportion of participants with unused medications.

Results: Participants taking preexisting medications exhibited a significant improvement in DAI-10 scores (mean increase, + 2.05 points; from 5.81 ± 4.00 to 7.86 ± 2.90, p = 0.00619). The proportion of participants who reported non-adherence to medication regimens decreased significantly from 42% to 24% (p= 0.0159).

Conclusions: The brief pharmacist-led intervention was effective in improving attitudes toward medication and behavioral adherence among patients receiving antipsychotic treatment in our study group. These findings underscore the importance of active pharmacist engagement for supporting medication adherence.

Aims: To explore how global challenges such as climate change, artificial intelligence (AI), and migration intersect with generational change among psychiatric trainees and reshape specialist training.

Methods: An integrative review drawing on symposium contributions and a comprehensive literature review to assess the evolving priorities and challenges in psychiatric training.

Results: Younger psychiatrists increasingly prioritize work-life balance, sustainability, and participatory learning environments. However, gaps remain in integrating climate-related knowledge, transcultural competence, AI literacy and neurodevelopmental disorders within psychiatric curricula. Generational tensions and traditional hierarchical structures further complicate training.

Conclusions: A new training model is needed that fosters mutual understanding between generations, encourages reflective dialogue, and supports collaborative learning. Preparing psychiatrists for the future requires updated content and a commitment to relational transformation and co-created educational practices.

Background: This study examines the bidirectional association between hemorrhoidal disease and mental health conditions, specifically depression and anxiety. While a plausible connection exists, research on their interplay is limited.

Methods: Using data from the UK Biobank (until March 2024), this prospective study analyzed two cohorts: 48,620 participants in the hemorrhoids-to-mental disorder cohort and 87,310 in the mental disorder-to-hemorrhoids cohort. Analyses were adjusted for multiple sociodemographic, lifestyle, and clinical covariates, including age, sex, ethnicity, BMI, smoking status, alcohol consumption, socioeconomic indicators, and comorbidities. We employed time-varying Cox proportional hazards models in conjunction with propensity score matching to estimate associations, assessing risk within 5 years, within 10 years, and over long-term follow-up.

Results: Fully adjusted models revealed significant associations between hemorrhoidal disease and mental disorders. A diagnosis of hemorrhoidal disease was associated with a higher risk of subsequent depression (HR, 1.56 [95% CI, 1.46-1.66]) and anxiety (HR, 1.55 [95% CI, 1.46-1.66]). Conversely, a diagnosis of depression was associated with an increased risk of subsequent hemorrhoidal disease (HR, 1.14 [95% CI, 1.09-1.19]), as was a diagnosis of anxiety (HR, 1.46 [95% CI, 1.38-1.54]).

Conclusion: This study identifies a significant bidirectional association between hemorrhoidal disease and mental health conditions. Notably, the interaction between smoking and anxiety highlights a subgroup at elevated risk that may benefit from closer clinical attention. These findings support an integrated care perspective that considers both gastrointestinal and mental health conditions, while acknowledging that causal inferences cannot be definitively established from observational data.

Background: Psoriasis is a chronic inflammatory skin disease frequently comorbid with depression, yet the underlying neurobiological mechanisms remain unclear. This study investigated functional connectivity (FC) alterations of emotion-regulation circuits and their association with inflammatory markers in psoriasis patients with depression.

Methods: Seventeen psoriasis patients with depression and 17 matched controls underwent resting-state functional magnetic resonance imaging (rs-fMRI) examination. Seed-based FC analysis was performed to examine connectivity abnormalities of the subgenual anterior cingulate cortex (sgACC), a key emotional regulation region, with the following statistical thresholds: voxel-level p < 0.001 (uncorrected) with cluster-level false discovery rate (FDR) correction at p < 0.05 for multiple comparisons. Correlation analyses were conducted to evaluate relationships between sgACC connectivity patterns and depression severity (Self-rating Depression Scale, SDS), pruritus intensity (Visual Analog Scale, VAS), and serum levels of IL-6 and IL-17 in a subgroup of participants (n = 7).

Results: Psoriasis patients with depression showed increased sgACC connectivity with DMN nodes (posterior cingulate cortex(PCC), angular gyrus(AG)) and executive network regions (superior frontal gyrus (SFG), middle frontal gyrus (MFG)) versus controls. FC between sgACC-AG correlated with SDS scores (r = 0.598, p = 0.011), while sgACC with right SFG (r = 0.893, p = 0.007) and left MFG (r = 0.929, p = 0.003) connectivity positively associated with IL-17 levels.

Conclusions: The findings reveal a "dual-circuit" dysfunction pattern in psoriatic depression: sgACC-DMN hyperconnectivity linked to depressive symptoms, and sgACC-dlPFC (dorsolateral prefrontal cortex) alterations associated with IL-17 elevation. These results establish the sgACC as a neural hub bridging inflammation and mood dysregulation, supporting the "skin-brain axis" hypothesis. The identified FC patterns may serve as biomarkers for targeted interventions in inflammation-related depression.