Psychiatry and Clinical Neurosciences最新文献

Aim: To determine whether catatonia is associated with increased long-term all-cause and cause-specific mortality.

Methods: Using Taiwan's National Health Insurance Database (2000-2022), we assembled a population-based cohort of all adults (≥18 years) with catatonia and matched each to four controls without catatonia on sex and birthdate. Mortality was compared between (1) individuals with catatonia and their unaffected siblings and (2) individuals with schizophrenia spectrum disorders with catatonia and those with schizophrenia spectrum disorders without catatonia. The primary outcome was all-cause mortality; secondary outcomes were natural- and unnatural-cause deaths. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated with Cox models controlling for age, sex, socioeconomic status, urbanization level, and comorbidities.

Results: We included 6642 individuals with catatonia and 26,568 matched controls. Over mean follow-ups of 11.4 and 13.1 years, respectively, 2150 versus 3459 deaths occurred (adjusted HR 2.60, 95% CI 2.46-2.75). Risks were higher for natural causes (2.42, 2.28-2.57) and unnatural causes (5.57, 4.59-6.77). Compared with unaffected siblings, catatonia remained associated with excess all-cause (1.82, 1.34-2.49), natural (1.57, 1.07-2.30), and unnatural mortality (2.73, 1.56-4.77). Within schizophrenia spectrum disorders, catatonia conferred higher all-cause (1.20, 1.12-1.28) and natural mortality (1.27, 1.18-1.36), whereas unnatural mortality was similar (1.01, 0.87-1.17).

Conclusions: Catatonia conferred a substantial, independent risk of premature mortality across multiple causes. Clinicians should recognize that catatonia is a serious disorder with long-term consequences and should remain vigilant to prevent and manage complications beyond the acute episode.

Aim: Noninvasive neuromodulation techniques, including transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and transcranial focused ultrasound stimulation (tFUS), are promising interventions for acute treatment of depressive episodes. However, the comparative efficacy and acceptability of stimulation protocols remain unclear. This network meta-analysis (NMA) aimed to compare the efficacy and tolerability of various noninvasive neuromodulation strategies.

Methods: We conducted a systematic review and NMA of randomized controlled trials (RCTs) enrolling patients with major depressive disorder or bipolar depression, including nine repetitive TMS (rTMS) protocols, three theta burst stimulation (TBS) protocols, as well as tDCS and tFUS. Primary outcomes were response and all-cause discontinuation rates. Subgroup analyses examined treatment-resistant depression (TRD) and monotherapy versus add-on therapy.

Results: A total of 129 RCTs (7667 patients; 272 treatment arms) were included. All protocols except low-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC) showed higher response rates than sham. tFUS demonstrated the highest response rate (OR: 7.24, 95% CI: 1.35-38.47), followed by bilateral rTMS (OR: 5.75, 95% CI: 3.29-10.07) and bilateral TBS (OR: 5.37, 95% CI: 2.51-11.36), both effective for general depression and TRD. Bilateral TBS showed the highest response rate when administered as monotherapy, whereas bilateral rTMS was most effective as add-on therapy. Most studies (87.6%) were rated as having low or unclear risk of bias.

Conclusions: Our findings provide preliminary evidence that bilateral stimulation over DLPFC is more beneficial than unilateral stimulation for treating depressive episodes. Nonetheless, tFUS may represent a highly promising novel intervention warranting further investigation.

Background: The mechanism of memory impairment in patients with major depressive disorder (MDD) after modified electroconvulsive therapy (MECT) is still unclear. This study explored the role of the circular RNA-miRNA interaction network in MECT treatment of MDD to provide new evidence on the possible mechanism of memory impairment caused by MECT.

Methods: Differentially expressed miRNAs in peripheral blood of patients with MDD before and after MECT were screened, and a prediction model for the circular RNA-miRNA interaction network was constructed based on this. Then, the relationship between MECT and the expression of circular RNA (circRNA) and miRNA was analyzed. Finally, the correlations among circRNA, miRNA and clinical symptoms and memory function in patients with MDD were analyzed.

Results: After MECT, 26 significantly differentially expressed miRNAs were found in peripheral blood of patients with MDD. According to the prediction model, three miRNAs were significantly downregulated and two circRNAs were significantly upregulated after MECT. In addition, the expression of miRNA was significantly correlated with that of circRNA. The circRNA-miRNA regulatory network was associated with multiple clinical symptoms and memory scores in patients with MDD treated with MECT.

Conclusion: The circRNA-miRNA interaction network may be involved in the neuropsychiatric mechanism of MECT in the treatment of MDD. The expression levels of multiple regulatory factors in this network can be used as biomarkers to reflect the improvement of some symptoms and the risk of memory impairment in patients with MDD after MECT.

Aims: Antidepressants may induce antibiotic resistance, yet their impact on antibiotic treatment outcomes in clinical settings remains unexplored. This study investigates the association between antidepressant use and antibiotic treatment failure in outpatients with urinary tract infections (UTIs) and pneumonia, conditions with distinct pathogen origins.

Methods: Using Taiwan's National Health Insurance database (2010-2021), this cohort study analyzed new outpatient antibiotic treatments for UTIs (n = 4,176,347) and pneumonia (n = 498,156). Antidepressant use was defined as prescriptions within 6 months before treatment initiation. Treatment failure occurring between days 4 and 14 after antibiotic initiation was defined as any antibiotic change, hospitalization, or emergency department visit. Subgroup analyses considered age, gender, comorbidities, and antibiotic types, along with antidepressant usage patterns.

Results: Antidepressant use was linked to a higher risk of treatment failure in UTIs (adjusted hazard ratio = 1.11 [1.09, 1.13]) but not pneumonia. The risk was higher in females than in males and higher in older adults than in middle-aged individuals. In addition, the use of specific antidepressants (e.g., imipramine, citalopram, paroxetine, sertraline, fluvoxamine, trazodone, and mirtazapine), particularly in combination (polypharmacy), was associated with a further increase in risk.

Conclusion: Antidepressants are associated with a modest rise in UTI treatment failure risk, possibly due to antibiotic resistance or other mechanisms. Despite this, their essential role in mental health management outweighs the small risk, emphasizing the need for judicious use, particularly in females and older adults. Further research is warranted to clarify underlying mechanisms.

This article relates to clinical relevance of venlafaxine ER for generalized anxiety disorder.

Background: Inflammatory factors interact with brain imaging-derived phenotypes (IDPs); however, the specific causal relationships between inflammatory factors and brain white matter (WM)-related IDPs remain unclear. Thus, we sought to analyze the potential causal effects of inflammatory factors on brain WM-related IDPs using Mendelian randomization (MR).

Methods: We obtained the data of 41 inflammatory factors from a genome-wide association study (GWAS) from the Cardiovascular Risk in Young Finns Study and the FINRISK surveys, as well as the data of 144 neurite orientation dispersion and density imaging (NODDI) IDPs including intracellular volume fraction (ICVF), isotropic volume fraction (ISOVF), and orientation dispersion index (ODI) from the United Kingdom Biobank (UKB). We then conducted two-sample MR analyses to examine their causal interactions by employing the inverse variance weighting (IVW), MR Egger, weighted median, simple mode, and weighted mode methods, collectively enhancing the robustness of our results. Besides, bibliometric analysis was employed to investigate the overview of inflammatory factor-brain WM research.

Results: Pronounced correlations are discerned between extensive inflammatory factors and NODDI IDPs, primarily involving cerebellar peduncle, corpus callosum, uncinate fasciculus, posterior thalamic radiation, posterior corona radiata, medial lemniscus, superior longitudinal fasciculus, superior fronto-occipital fasciculus, and internal capsule. Besides, bibliometric analysis demonstrates that microglia play an important role in inflammation-mediated white matter changes.

Conclusions: This study identified genetic evidence indicating that dysbiosis of inflammatory factors exerts causal effects on microstructural diffusion properties of brain WM. Our findings provide novel insights into the diagnostic and therapeutic management of central nervous system (CNS) disorders.

Bipolar disorder is a psychiatric disorder marked by recurrent mood episodes and a strong genetic component. Despite widespread use of mood stabilizers and atypical antipsychotics, effective treatments remain limited, highlighting the need for mechanistic insights. Early studies revealed decreased phosphocreatine and increased mitochondrial DNA (mtDNA) deletions in the brains of bipolar disorder patients, leading to the mitochondrial dysfunction hypothesis. This framework proposes that mtDNA mutations impair Ca²⁺ buffering, producing neuronal dysfunction and mood instability. Supporting evidence spans neuroimaging, postmortem, genetic, and cellular studies, as well as therapeutic responses to mitochondrial modulators. Large-scale genomic analyses implicate both rare and common variants affecting Ca²⁺ signaling and mitochondrial-endoplasmic reticulum function, while somatic mtDNA mutations further link mitochondrial pathology to bipolar disorder. Animal and induced pluripotent stem cell models converge on neuronal hyperexcitability as a downstream effect of impaired Ca²⁺ regulation. Recent work highlights the paraventricular thalamic nucleus (PVT) as a critical site of pathology. The PVT integrates serotonergic and limbic circuits, regulates salience, and exhibits the highest burden of mtDNA deletions in mutant Polg (mtDNA polymerase) mice. In humans, single-nucleus RNA sequencing reveals a ~50% reduction of PVT neurons in bipolar disorder, with marked transcriptional dysregulation enriched for bipolar disorder risk loci in PVT, with additional changes in microglia. Neuropathological studies further suggest neurodegenerative changes in PVT, particularly in late-onset bipolar disorder. Collectively, these findings position PVT pathology at the core of bipolar disorder pathophysiology, offering a framework that integrates genetic risk, neuronal hyperexcitability, and circuit-level dysregulation and guiding future therapeutic strategies.

Aim: Hikikomori, a social withdrawal syndrome, has been suggested to be rooted in family dynamics. Early parental bonding (PB) has been linked to attachment and adulthood relationship patterns, possibly impacting the emergence of hikikomori. These outcomes have been connected to early experiences of the parents themselves, suggesting their intergenerational 'transmission'; we conducted two online cross-sectional surveys to clarify the above hypothesis.

Methods: The first survey presents three groups: non-hikikomori adults (C), non-pathological hikikomori (Non-PH), and pathological hikikomori (PH); the second involved parents of individuals categorized according to the abovementioned groups. PB and attachment were evaluated through the parental bonding instrument (PBI) and Relationship Structures-Experiences in Close Relationships Scale (ECR-RS).

Results: PH was associated with lower PBI 'Care', higher 'Anxious' and 'Avoidant' attachment, and the combination of 'Affectionless Control' PB and 'Fearful-Avoidant' attachment. Non-PH was linked to paternal 'Neglect', especially when combined with 'Dismissing' and 'Fearful-Avoidant' attachment. A mediation role of attachment-related 'Avoidance' between PB and hikikomori was confirmed. Parents of PH showed higher PBI 'Protection', 'Avoidant' and 'Anxious' attachment, and lower PBI 'Care': They were linked to paternal 'Affectionless Control' and 'Fearful-Avoidant' attachment. Paternal 'Neglect' was overrepresented in parents of Non-PH.

Conclusions: Our results suggest that PB and attachment are involved in the appearance of hikikomori. PH may be connected to family history of 'Affectionless Control' and 'Fearful-Avoidant' attachment, whereas Non-PH may be linked to 'Neglectful' parenting, which could promote attachment-related 'Avoidance'. Specific interventions aimed at enhancing parents' sensitivity and mentalization could reduce the risk and the severity of hikikomori.