Psychiatry and Clinical Neurosciences最新文献

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.

Aim: White matter (WM) alterations in the corpus callosum (CC) and visual cortex have been implicated in early psychosis, with the visual regions particularly linked to psychotic symptoms. Whether similar WM patterns occur in early-onset bipolar disorder (EOBD) remains unclear. This study investigated WM alterations in EOBD and their associations with psychiatric symptoms.

Methods: Eighty-seven individuals with EOBD and 57 healthy controls (HCs) underwent diffusion magnetic resonance imaging (dMRI) and psychiatric assessments. Whole-brain WM changes between groups were examined using TractSeg and tract-based spatial statistics. Partial correlations with multiple comparison corrections assessed associations between altered tracts and symptoms.

Results: Compared with HCs, EOBD showed widespread lower fractional anisotropy (FA) and altered other WM parameters, particularly in the CC and visual-related tracts. Lower FA in the anterior midbody CC (r = -0.307, q = 0.038), right superior longitudinal fascicle I (r = -0.305, q = 0.038), thalamo-parietal (r = -0.315, q = 0.038), and parieto-occipital pontine tracts (r = -0.329, q = 0.038) correlated with greater depressive symptoms. Lower FA in the left inferior fronto-occipital fascicle (r = -0.371, q = 0.030), left optic radiation (r = -0.381, q = 0.030), and left thalamo-occipital tract (r = -0.392, q = 0.030) were associated with greater positive symptoms. These visual-related lower FAs were found more frequently in individuals with visual hallucinations.

Conclusion: EOBD was associated with WM abnormalities in the CC and visual pathways linked to depressive symptoms and visual hallucinations, supporting its characterization as a neurodevelopmentally distinct subtype with persistent WM dysconnectivity.

Autopsies have long been performed to determine the cause of death in the medical field. In fact, autopsies have significantly contributed to our understanding of neurological and psychiatric disorders. Patients and their families who wish to donate bodies for autopsy may have various expectations, such as contributing to the development of treatments for the diseases they experienced or facilitating the investigation of their causes. They may also hope that the removed and stored organs will be used effectively and appropriately by academic institutions and pharmaceutical companies, both in Japan and abroad. Accordingly, brain banks store samples that can be utilized for future medical research. The Japan Brain Bank Net (JBBN) was established to help fulfill this purpose. The network currently includes 19 institutions. In addition to storing and providing pathological tissue - functions traditionally associated with brain banks - JBBN also offers detailed and standardized neuropathological diagnoses. Currently, JBBN is working toward storing tissue suitable for emerging research methodologies, digitizing pathological images, applying artificial intelligence (AI) in neuropathological studies, and building a publicly accessible database. JBBN also aims to establish a permanent brain bank infrastructure to support the next generation of research.

Aims: Mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD), are highly heritable and linked to fronto-limbic circuit dysfunction. This longitudinal fMRI study examined whether baseline responses of the amygdala, anterior cingulate cortex (ACC), and ventrolateral prefrontal cortex (vlPFC) evoked by facial emotional expressions predicted first-onset or recurrence of mood episodes over 7 years in monozygotic twins.

Methods: The sample comprised 68 unaffected twins (UT) without a history of mood disorders but varying familial risk, and 62 affected twins (AT) in remission from MDD or BD. At baseline, participants underwent functional Magnetic Resonance Imaging (fMRI) of fearful and happy face processing and completed behavioral measures of emotional processing, which were repeated at follow-up.

Results: Lower baseline activation of the bilateral amygdala (left hazard ratio, HR = 1.69, 95% CI 1.15-2.45; right HR = 1.80, 95% CI 1.23-2.25), dorsal ACC (HR = 1.27, 95% CI 1.02-1.57), and right anterior vlPFC (HR = 2.28, 95% CI 1.56-3.26) by fearful (vs. happy) faces was associated with higher risk of first-onset mood episodes in the UT group. In the AT group, baseline fronto-limbic emotional activations were not associated with recurrence risk. Behaviorally, the UT group that later developed a mood episode showed slower recognition of happy faces and greater avoidance of subliminal fearful faces compared with the UT group that remained well.

Conclusion: Dysfunctional fronto-limbic processing of facial emotions indicates increased propensity to develop a mood disorder, but is not associated with increased risk for recurrence of mood episodes. This dissociation suggests that distinct neural mechanisms underlie the first-onset versus the recurrence of mood disorders.