Psychiatry and Clinical Neurosciences最新文献

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.

Aim: The concomitant use of lamotrigine and valproic acid, a uridine diphosphate (UDP)-glucuronosyltransferase inhibitor, is a known risk factor for lamotrigine-induced rashes, which may develop into fatal or severe cutaneous adverse reactions. No drugs other than valproic acid have been shown to increase lamotrigine concentrations in humans by inhibiting UDP-glucuronosyltransferase. The treatment of bipolar disorder and epilepsy is often combined with other medications, which may affect the risk of rash. We aimed to identify medications that increased the risk of lamotrigine-induced rashes using clinical data.

Methods: We used VigiBase to search for drugs associated with the increased number of reported severe cutaneous adverse reactions when combined with lamotrigine. In a retrospective study, we collected information on patients from electronic medical records and used propensity score matching to compare the incidence of lamotrigine-induced rash with and without flunitrazepam use. Furthermore, we compared lamotrigine concentrations between patients treated with and without flunitrazepam in a prospective observational study.

Results: VigiBase analysis showed that flunitrazepam significantly increased the reporting odds ratio for lamotrigine-related severe cutaneous adverse reactions. In the retrospective study, combining lamotrigine with flunitrazepam significantly increased the incidence of rashes. In the prospective observational study, lamotrigine with flunitrazepam significantly increased the concentration-to-dose ratio.

Conclusion: Flunitrazepam use may affect lamotrigine concentration and increase the risk of rash. These results have implications for the choice of sleep medication. In addition, when lamotrigine is used in combination with flunitrazepam, the lamotrigine dosing design should address lamotrigine-induced rash management.

Aims: Schizophrenia (SZ) is associated with abnormalities in both spontaneous and task-evoked neural oscillations, and growing evidence shows that shift patterns of oscillatory activity between resting and task states are also disturbed. However, no study has simultaneously examined the frequency- and state-specific characteristics of oscillatory deficits in SZ. Using an auditory steady-state response (ASSR) paradigm, we aimed to examine the differential sensitivity of oscillatory measures to SZ and to assess rest-task shifts across multiple frequency bands.

Methods: We recorded resting-state activity and 40 Hz ASSR of 66 neurotypical controls (NC) and 68 SZ patients using electroencephalography (EEG). 40 Hz stimulus-evoked activity was measured using evoked power, phase-locking factor (PLF), and phase-locking angle, whereas multi-frequency (4-100 Hz) spontaneous activity during ASSR and resting states was assessed using induced and resting power. The state-dependent shifts in spontaneous activity between the resting and ASSR states were evaluated over a broad frequency range.

Results: Both induced and resting power in the low-frequency range (4-10 Hz) were elevated over widespread regions in SZ patients relative to NC. Gamma-band (39-100 Hz) induced power then demonstrated excellent ability to discriminate between SZ and NC. In addition, SZ patients showed a reduced rest-task shift in the theta-beta band (5-23 Hz) spontaneous power, most pronounced in the alpha-band (8-13 Hz).

Conclusion: The present study confirmed the utility of gamma-band induced power during ASSR stimulation for differentiating SZ patients from NC. Importantly, our results also highlight the pathophysiological significance of the reduced rest-task shift pattern of spontaneous activity mainly in the alpha-band in SZ patients.

Aims: Postoperative delirium (PD) is a common and severe complication in older adult patients undergoing invasive cancer resections. This study explored the plasma metabolome associated with PD and evaluated the efficacy of Yokukansan (YKS), a traditional Japanese Kampo medicine, in preventing PD.

Methods: An ancillary study was conducted alongside a double-blind, placebo-controlled randomized clinical trial involving patients 65 years and older, focusing on patients older than 75 years as a primary analysis population. Plasma samples were analyzed using targeted and nontargeted metabolomics. An in vivo study using aged mice assessed the effects of YKS on plasma and brain metabolites.

Results: A total of 83 patients, including 21 patients older than 75 years, were enrolled. Patients with PD had lower levels of several lipid mediators, free fatty acids, and phospholipids. YKS administration led to increased nine phospholipids and four hydrophilic metabolites in patients older than 75 years, including phosphatidylcholine (40:7) and phosphatidylcholine (42:8), which were also altered in delirium patients. In the patients older than 65 years, only two metabolites increased in the YKS administration group. In aged mice, YKS elevated plasma phospholipids, similar to findings in patients older than 75 years, and influenced brain citrulline and creatine, which related to oxidative stress and cognitive function. Correlation analyses revealed associations between plasma and brain metabolite changes.

Conclusion: Our findings suggest that the plasma metabolome provides insight into the pathophysiology of PD and the potential mechanism underlying the preventive effect of YKS against PD.

Aims: This study aimed to identify and characterize cognitive subtypes among youth at clinical high risk (CHR) for psychosis.

Methods: We conducted a cluster analysis on cognitive measures in a large sample of CHR patients (CHR; n = 764) and healthy controls (HCs; n = 280) from NAPLS-2 (North American Prodrome Longitudinal Study 2). These findings were independently validated using a comparably large sample from NAPLS-3 (n = 628 CHR, 84 HCs). Statistical approaches were employed to compare cognitive, clinical, and functional trajectories at baseline and during 24 months of follow-up, with further analysis of conversion status within these clusters.

Results: Two cognitive clusters, "impaired" and "intact," were identified in the CHR group. Baseline differences in verbal abilities and attention and working memory domains distinguished the cognitively intact cluster from HCs. Longitudinally, the impaired group displayed a 'floor' effect, with no noticeable deterioration, but showed a "catch-up" trajectory in attention and working memory. This group had a higher conversion rate and more cases diagnosed with psychotic disorders than the intact group. In the intact group, converters exhibited a decline in attention and functioning. Most cognitive trajectories showed a positive relationship with functional outcomes.

Conclusions: The study provides evidence for distinct cognitive subtypes in CHR, independent of conversion status. Early evaluation across cognitive domains is crucial for identifying trajectories to tailor interventions that aim to enhance outcomes for individuals at CHR for psychosis. Future research should focus on longer follow-up trajectories targeting attention and working memory and explore related intervention strategies.