Psychiatry and Clinical Neurosciences最新文献

Aim: Cognition varies across people with psychosis, including within a specific diagnosis. An important issue is identifying psychosis-specific neuro-cognitive dysfunctions. We addressed this issue by studying patterns of relationships between cognition and multiple other measures in persons with psychosis, their first-degree biological relatives, and healthy individuals (largest possible n = 2826).

Methods: Brief Assessment of Cognition and Wide Range Achievement Test estimated cognitive performance. Neuroanatomical measures were FreeSurfer parcellations of 3T MRI structural brain scans. Brain functioning measures included saccades, smooth pursuit eye movements, stop signal, EEG, ERPs, resting state fMRI, plus clinical characteristics. Overall associations between 452 measures of brain structure-function and clinical characteristics (predictors) with cognitive performance (criterion) were estimated using the High Dimensional Empirical Bayes Screening algorithm.

Results: The model yielded a common slope of predictors on cognitive performance (slope = 0.18, r = 0.33, P < 0.001). The majority (85%) of predictors fit this function, called the BAsic NeuroCognitive Continuum (BANCC). This relationship was stronger for psychosis probands (slope = 0.20, r = 0.38) than for relatives (slope = 0.09, r = 0.17) and healthy persons (slope = 0.11, r = 0.22). There were predictor-specific deviations from the common slope. Variables more strongly associated with cognitive performance (frontal-temporal-parietal lobe volumes, hippocampal regions, antisaccade performance) may tap neural architecture common to primary psychosis pathology. Variables unrelated to cognitive performance (intrinsic neural activity, volumes of lateral thalamic nuclei) distinguish specific neurophysiologically defined B-SNIP psychosis Biotypes and may capture signatures of psychosis pathophysiology.

Discussion: BANCC is identifiable across humans, but deviations from that common attribute identify features of brain structure-function perhaps most central and specific to psychosis-related pathophysiology.

This commentary discusses potential structural biases in the study by Miyake et al., which reported an inverse association between adherence to a Japanese-style diet and depressive symptoms. Two key concerns are raised: unmeasured confounding by health consciousness, and limitations in the diet score's construction, which may reflect food quantity rather than dietary quality. These biases may impact the interpretation of the observed association and highlight the need for more refined methodological approaches in future research.

Background: Reliable biomarkers for predicting treatment response and suicide risk in treatment-resistant depression (TRD) are limited. Functional near-infrared spectroscopy (fNIRS) offers a noninvasive means to assess prefrontal cortical activation linked to therapeutic outcomes.

Methods: In a double-blind, randomized, sham-controlled trial, 100 inpatients with TRD received either active or sham prolonged intermittent theta-burst stimulation (aiTBS) over the left dorsolateral prefrontal cortex (DLPFC) across 2 weeks. fNIRS measured oxyhemoglobin (oxy-Hb) levels at rest and during a verbal fluency task (VFT) and two-back working memory task, both before and after aiTBS. Clinical outcomes included Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale item 3 (HAMD-3), and Beck Scale for Suicide Ideation (BSS).

Results: Baseline BSS, HAMD-3, and MADRS scores did not differ between groups (all P > 0.05). Post-treatment, the active group showed significant improvements in BSS, HAMD-3, and MADRS (all P < 0.05). Active aiTBS increased oxy-Hb in the left DLPFC and right orbitofrontal cortex (OFC) during the two-back task, and in the left DLPFC, OFC, and frontopolar cortex (FPC) during the VFT. Greater left DLPFC activation during the VFT correlated with MADRS improvement, and baseline OFC activation predicted antidepressant response. No fNIRS measures predicted changes in suicidality.

Conclusions: Task-evoked prefrontal activation-especially in the left DLPFC and OFC-may serve as a biomarker for antidepressant efficacy in TRD, though fNIRS did not predict suicide risk reduction.

Background: Various diagnoses in psychosomatic medicine have been found to exhibit features of autonomic activity, primarily characterized by low parasympathetic activity. However, because depression, anxiety, and somatic symptoms often coexist, it remains to be clarified whether certain diagnoses are more strongly associated with autonomic activity than others. We also aim to explore whether the relationship between diagnosis and autonomic activity is through a top-down (from brain to autonomic nervous system) mechanism.

Methods: A total of 502 participants were included in this study. All participants underwent standardized diagnostic interviews. Seven indices about autonomic activity, including heart rate variability, skin conductance, and finger temperature, were collected in a resting state. We used multiple linear regression analyses to clarify the relationship between diagnoses and autonomic activity, adjusting for various diagnoses and demographic factors. We also examined whether quality of life (QOL) could serve as a mediator between the diagnoses and autonomic activity.

Results: Major depressive disorder and obsessive-compulsive disorder were the diagnoses most significantly negatively associated with parasympathetic activity. Psychological factors affecting other medical conditions, adjustment disorder, and functional dyspepsia showed significant negative associations with sympathetic activity. Path analysis indicated that QOL could serve as a complete mediator between major depressive disorder and parasympathetic activity.

Conclusion: The results indicate that among the diagnoses commonly seen in psychosomatic medicine, the negative association between major depressive disorder and parasympathetic activity is relatively robust. Analyses incorporating QOL suggest that the relationship between depression and parasympathetic activity is more likely to operate through a top-down pathway.

This article relates to Structural Biases in the Japanese Diet-Depression Association.

Aim: The genetic architecture of bipolar disorder (BD) remains incompletely understood despite extensive genomic studies. Postzygotic mosaic variants have emerged as promising contributors to BD; however, the landscape of such variants in the BD brain has yet to be elucidated.

Methods: We analyzed mosaic variants in the paraventricular thalamic region (PVR) from 18 Japanese BD cases and 11 controls using deep whole-exome sequencing. Candidate variants were validated via targeted amplicon sequencing. To explore their biological implications, we performed gene ontology analysis by integrating the brain-derived mosaic variants identified in this study with mosaic variants previously detected in peripheral tissues.

Results: We identified 99 exonic and 13 mitochondrial heteroplasmic variants in the PVR. There was a significant enrichment of deleterious mosaic variants in constrained genes (P = 0.0402) and of non-synonymous mosaic variants in neurodevelopmental genes, particularly those involved in the positive regulation of neuron projection development (false discovery rate = 2.32 × 10^-3). These genes also formed a significantly enriched protein-protein interaction network (P = 0.0106). Notably, we detected one mitochondrial variant known to be pathogenic for mitochondrial disease and two predicted pathogenic mitochondrial tRNA variants in BD cases, but none in controls.

Conclusion: Despite the modest sample size and potential confounding factors such as age and cancer status, our direct analysis of brain tissue supports previous findings of an enrichment of mosaic variants in neurodevelopmental and mitochondrial tRNA genes. These results advance our understanding of the genetic underpinnings of BD.

Background: Depression is a complex mental disorder with a multifactorial etiology. Recent research has highlighted the potential of microRNAs (miRNAs) as novel biomarkers and their involvement in the molecular pathways underlying depression; yet, these studies often focus on limited clinical samples and specific subsets of miRNAs. Here we aimed to explore plasma miRNA expression profiles associated with depressive symptoms in a population-based study of middle-aged and older adults.

Methods: We analyzed the levels of 591 circulating miRNAs well-expressed in plasma samples of 2,703 participants of the Rotterdam Study. The Center for Epidemiologic Studies Depression Scale was used to assess depressive symptoms in these participants. Negative-binomial regression models were employed to explore the relationship between individual miRNA levels and depressive symptoms, adjusting for potential confounders including age, sex, BMI, and other factors.

Results: Our analysis suggests 38 circulating miRNAs to be potentially associated with depressive symptoms (P < 0.05). Although these miRNAs did not survive multiple testing correction, our subsequent in silico analysis of their target genes suggests involvement in neural and psychiatric pathways, as well as enrichment for associations with depressive symptoms based on previous genome-wide association studies.

Conclusions: This study proposes several circulating miRNAs that may be associated with depressive symptoms within the general population. Our follow-up analyses indicate that the miRNAs with the largest effect estimates were potentially involved in neurological and psychiatric processes, warranting further investigation into their potential role in the biological mechanisms of depression. These results provide preliminary insights and should be considered exploratory and hypothesis-generating, warranting validation in future studies with larger and independent cohorts.

The potential role of autoantibodies in the etiology of schizophrenia is a key research focus because growing evidence suggests an association between immune dysfunction and psychotic disorders. This hypothesis is supported by findings indicating immune-related abnormalities in patients with schizophrenia, including chronic inflammation and genetic alterations associated with immune system dysregulation. Epidemiological studies have reinforced this perspective by demonstrating a significant correlation between autoimmune diseases and schizophrenia, suggesting shared pathological mechanisms including autoantibodies. A particularly compelling line of evidence comes from the identification of autoantibodies targeting synaptic molecules in patients with schizophrenia. Autoantibodies against N-methyl-D-aspartate (NMDA) receptors, gamma-aminobutyric acid (GABA) receptors, neural cell adhesion molecule 1 (NCAM1), and neurexin 1 (NRXN1) have been detected in patients, raising the possibility that immune-mediated synaptic dysfunction contributes to the disorder's pathophysiology. Experimental studies support this notion because the administration of these autoantibodies in mice induces molecular, cellular, and behavioral abnormalities that mirror aspects of schizophrenia. This review summarizes the relationships among schizophrenia, inflammation, immune-related genetic factors, autoimmune diseases, and autoantibodies. Furthermore, this review discusses future research directions for further elucidating the role of autoantibodies in schizophrenia.