World Journal of Biological Psychiatry最新文献

Objectives: X-chromosome inactivation (XCI) is a dosage compensation mechanism in female mammals. Given that the Xchromosome harbours numerous genes implicated in cognitive function, variants in these genes can affect neurodevelopment and contribute to Intellectual Disability (ID). While research on ID has predominantly focused on males due to their hemizygous Xchromosome state, females, though often presenting with milder symptoms, may be affected by escape genes that evade XCI and influence the phenotype. This study investigated the role of escape genes in female ID.

Methods: We employed data mining to analyse X-chromosome genes based on their XCI status, followed by functional enrichment analyses. Additionally, we conducted co-expression module evaluations in the main brain regions associated with ID and a protein-protein interaction (PPI) network analysis.

Results: We identified 31 significant modules linking XCI escape genes with ID-associated genes. The PPI network analysis further revealed direct interactions between the products of 25 genes and ID-related proteins. Five new candidate genes (RBMX2, PNPLA4, UBA1, RPS4X, and EIF1AX) were identified, four linked to known ID pathways.

Conclusions: This study underscores the importance of escape genes in the context of female ID and paves the way for future experimental validation and molecular investigations into the functions of these genes.

Objectives: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, with symptoms including hyperactivity, inattention and impulsivity. Moreover, ADHD persists into adulthood in ∼50% cases, significantly affecting quality of life. Currently, the complex aetiology of ADHD remains unclear. Single nucleotide polymorphisms (SNPs) in the adhesion G protein-coupled receptor isoform L3 gene (ADGRL3) have been associated with ADHD development, with the rs1397547 SNP found associated with altered ADGRL3 transcription in fibroblast cells. However, ADGRL3 function has not been investigated in human neurodevelopment.

Methods: We used human induced pluripotent stem cell (hiPSC)-derived cortical neurons to characterise ADGRL3 expression during human neurogenesis and investigated the effects of the rs1397547 SNP on gene expression.

Results: We found that ADGRL3 expression peaks early in neurodevelopment. ADGRL3 protein was found primarily expressed in glutamatergic neurons, and localised to growth cone-like structures, supporting a role in neurite outgrowth and glutamatergic synapse development. We found rs1397547 was associated with significantly increased ADGRL3 transcription in early neurodevelopmental stages. Moreover, single-cell RNA sequencing of maturing cortical neurons revealed a unique transcriptional profile in SNP carriers.

Conclusions: Our results further implicate ADGRL3 in ADHD development and suggest that genetic variation may result in dysregulated glutamatergic neuron development.

Objectives: The dopaminergic reward system is involved in the aetiology of psychiatric disorders, and autophagy has been suggested to interfere with dopamine release. LC3 conjugation plays a key role in autophagy and comprises modification of autophagy protein LC3 with phosphatidylethanolamine. We investigated whether LC3 conjugation may influence the strength of activation in key regions of the mesolimbic reward system.

Methods: To test our hypothesis, responses of the reward system to conditioned stimuli were assessed using the desire-reason dilemma (DRD) paradigm. Association of a set of missense variants with reward system responses was analysed in a sample of 214 healthy participants (mean age: 24.12 years; 128 females, 86 males).

Results: We detected association of the gene set with both ventral tegmental area (VTA) and nucleus accumbens (NAc) responses to conditioned reward stimuli (empirical P-values: R-VTA:0.008, R-NAc:0.009). The strongest missense variants were MAP1LC3B rs113610787 (p = 3.219e-05) for association with response in the L-NAc, and ATG4B rs143448469 (p = 4.366e-05) for the R-NAc.

Conclusions: These exploratory results indicate that variation of the LC3 conjugation system influences responses of the VTA and NAc to conditioned reward stimuli. Further studies are required to replicate the findings and to investigate the possible role of LC3 conjugation in psychiatric disorders.

Objectives: Electroconvulsive therapy (ECT) is associated with cardiovascular stress. This led to a renewal of the question concerning the short- and long-term cardiac safety of ECT. In this review, we systematically analyzed the literature concerning physiological and pathological effects of ECT on the heart with special regard to these new developments.

Methods: A systematic search in PubMed and Web of Science led to 196 studies and case reports. The results were structured according to three questions: 1. What are the general effects of ECT on the heart? 2. What are the possible cardiovascular complications and their prevalence? These publications were subcategorized into the four topics: overall complication rate, alterations of electric transmission, structural defects, and vascular problems. 3. How can such complications be avoided and managed?

Results: In a healthy heart serious complications are very rare. In case of prior cardiac disease manifestations risk mitigation is recommended. There are no absolute cardiac contraindications against ECT.

Conclusions: In case of cardiac risk factors baseline measurements of surrogate markers like troponin might be beneficial. Arrhythmias and troponin level elevations are not necessarily indications of bad prognosis. Long-term cardiac effects of ECT might be beneficial through the attenuation of sympathetic activation and hormonal imbalances associated with psychiatric diseases.

Background: Bipolar disorder (BD) is a chronic psychiatric condition characterised by mood episodes and associated structural changes in the central nervous system. Optical coherence tomography (OCT) offers a non-invasive method to assess retinal layer thickness, potentially serving as an endophenotypic biomarker for neurodegeneration. This study aimed to compare retinal thickness among BD patients, their first-degree relatives, and healthy controls to identify structural markers and assess their alignment with existing literature.

Methods: Thirty-six BD patients, 30 first-degree relatives, and 38 healthy controls were recruited from Van Yüzüncü Yıl University. Comprehensive ophthalmologic examinations and retinal layer thickness measurements using Spectralis OCT were performed. Retinal layers were analysed at 1 mm, 3 mm, and 6 mm concentric circles per the ETDRS protocol. Peripapillary retinal nerve fibre layer (RNFL) thickness was evaluated across seven regions. Due to significant age differences among groups (p = 0.002), an ANCOVA analysis was used to control for the age effect.

Results: Retinal analysis revealed a significant increase in the inferonasal (NI) nerve fibre layer thickness in BD patients and their first-degree relatives compared to healthy controls (p = 0.008). Optic nerve head analyses showed non-significant thinning in the temporal (T), inferotemporal (TI), and superotemporal (TS) nerve fibre layer thicknesses in BD patients and their relatives compared to healthy controls. The thicknesses of the macular retinal layers did not differ significantly among the groups (p > 0.05).

Conclusions: The observed increase in NI optic nerve fibre layer thickness in BD patients and their first-degree relatives contrasts with the expected thinning reported in previous literature on neurodegeneration in psychiatric disorders. This finding underscores the complexity of structural changes in BD and raises the possibility of alternative pathophysiological mechanisms or methodological considerations influencing retinal measurements. Further research is needed to elucidate these phenomena and their implications for understanding BD.

Objectives: Erotic stimuli lead to activations in various brain regions, including the reward system. Several neuroimaging studies have investigated neurofunctional activations during visual erotic stimulation. Little research has investigated whether these functional activations are characterised by an intrinsic network architecture in the resting-state.

Methods: We therefore examined 37 healthy male heterosexual subjects by combining resting-state and task-related fMRI. In task-related fMRI, we used an established video clip task (erotic and non-erotic video clips). Vectors comprising different neuronal activations during the processing of visual erotic stimuli were then correlated with the strength of resting-state functional connectivity between two core regions of the human reward system (NAcc and midbrain).

Results: We observed an increase in neurofunctional activations in cortical and subcortical regions previously described in task-based fMRI studies during visual erotic stimulation. Increased rs-FC between midbrain and NAcc was associated with higher differential neuronal responsiveness in subcortical regions, particularly in the hypothalamus, thalamus and periaqueductal grey.

Conclusion: Our results support the role of the mesolimbic reward pathway in the processing of erotic stimuli. In particular they show that a higher rs-FC between midbrain and NAcc facilitates the simultaneous activation of subcortical brain regions that are relevant for the integration of processes in sexual behaviour.

This study examines immune markers-P2X7, NACHT, and IL-6-as potential diagnostic and therapeutic biomarkers in Bipolar Disorder (BD). Among 120 participants (76 BD patients and 20 healthy controls), P2X7 levels were significantly elevated in BD patients both before (p = 0.001) and after treatment (p < 0.001), indicating strong diagnostic potential. NACHT levels also increased significantly after treatment (p = 0.007). Subgroup analysis revealed significantly higher P2X7 and NACHT levels in female BD patients compared to female controls (p < 0.001 for both). ROC curve analysis confirmed P2X7 as the most sensitive and specific marker for distinguishing BD from controls (p < 0.001), while NACHT showed predictive value after treatment (p < 0.05). Correlation analysis found significant associations between changes in P2X7 and NACHT levels and clinical improvement (p < 0.05). Despite limitations such as small sample size and potential medication effects, the findings support P2X7 and NACHT as promising biomarkers for BD diagnosis and treatment monitoring. The study contributes to the understanding of immune dysregulation in BD and suggests potential for immune-targeted therapies.

Objectives: Major depressive disorder (MDD) is a leading cause of disability, and chronic inflammation is a contributing factor to its onset and progression. This study examined the relationship between genetic predisposition to inflammation and MDD risk in a nationally representative sample of U.S. military veterans, as well as psychosocial moderators of this association.

Methods: A composite polygenic risk score (PRS) for inflammatory biomarkers was derived from the UK Biobank and examined in relation to a positive MDD screen in 1,660 European-American veterans. The analysis adjusted for known correlates of inflammation and MDD, including medical conditions and cumulative trauma burden.

Results: Each standard deviation increase in the inflammatory PRS was associated with more than two-fold increased odds of screening positive for MDD (OR = 2.51, 95% CI = 1.39-4.54). Interaction analyses revealed that optimism moderated this association; among those in the highest PRS tertile, individuals with high optimism were more than 30 times less likely to screen positive for MDD compared to those with low optimism (0.7% vs. 22.6%). Pathway-based analyses identified enrichment of immune- and brain-related gene sets, highlighting potential biological mechanisms linking inflammation and MDD.

Conclusions: Findings suggest genetic risk for inflammation contributes to MDD vulnerability and that optimism may buffer this risk.

Objectives: The resting-state cerebral functional activity underlying chronic insomnia disorder (CID) remains inconsistent, and the effects of pharmacotherapy on such activity are unclear.

Methods: Imaging data and clinical variables were acquired from 82 patients with CID and 54 healthy controls (HCs). Patients were assigned to receive either modified Suanzaoren decoction (MSZRD) or estazolam treatment for six weeks. Spontaneous brain activity was evaluated by amplitude of low-frequency fluctuations (ALFF), Wavelet-ALFF, and fractional ALFF (fALFF). Machine-learning and cross-sample transcriptomic analysis were performed.

Results: Compared to HCs, patients with CID exhibited increased functional activity in the left precuneus/posterior cingulate cortex, left superior parietal gyrus, and bilateral angular gyrus; they also presented decreased activity in the right inferior parietal gyrus and bilateral middle frontal gyrus. After pharmacotherapy, patients in the MSZRD group showed increased activity in the left middle occipital gyrus compared to baseline. Receiver operating characteristic (ROC) curves based on these metrics were 0.98, 088, and 0.98; correlation coefficients between predicted and actual treatment responses ranged from 0.806 to 0.965.

Conclusion: Altered neural activity in regions of the default mode network, frontoparietal network and visual network might contribute to the neuropathological and therapeutic mechanisms of CID. (Clinical trial registration number: NCT06452953).

Objectives: Major depressive disorder (MDD) is associated with immune dysfunction. This study aimed to characterize the cellular immunophenotypes that may underpin immune dysregulation in MDD.

Methods: Peripheral blood mononuclear cell (PBMC) samples at baseline from participants with MDD from the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study were included. A panel of 33 antibodies was analyzed using mass cytometry to compare the immune cell abundance and marker expression profiles between participants with mild and moderate/severe depression. Mass cytometry data were investigated using (1) Uniform Manifold Approximation and Projection for Dimension Reduction (UMAP), (2) FlowSOM (self-organizing maps) for clustering, and (3) Significance Analysis of Microarrays (SAM) for statistical analyzes.

Results: FlowSOM identified 8 clusters of distinct cell types. The abundance of cytotoxic T, NK, NK T, and Naïve B cells was significantly lower in participants with moderate/severe depression compared to mild depression. NKT cells had significantly lower CD56 and CD16 expression in patients with moderate/severe depression compared to patients with mild depression.

Conclusion: Our observations provide evidence for alterations in B, NKT, and NK cell abundance and their cell surface markers in moderate/severe depression. Further investigations into immune cell dysfunction in moderate/severe depression are necessary.