Journal of Psychiatry & Neuroscience最新文献

Background: Brain network dynamics are responsive to task induced fluctuations, but such responsivity may not hold in schizophrenia (SCZ). We introduce and implement Centrality Dynamics (CD), a method developed specifically to capture task-driven dynamic changes in graph theoretic measures of centrality. We applied CD to functional MRI (fMRI) data in SCZ and Healthy Controls (HC) acquired during associative learning.

Methods: fMRI (3T Siemens Verio) was acquired in 88 participants (49 SCZ). Time series were extracted from 246 functionally defined cerebral nodes. We applied a dynamic windowing technique to estimate 280 partially overlapping connectomes (with 30 135 unique region-pairs per connectome). In each connectome, we calculated every node's Betweenness Centrality (BC) following which we built 246 unique time series from a node's BC in successive connectomes (where each such time series represents a node's CD). Next, in each group similarities in CD were used to cluster nodes.

Results: Clustering revealed fewer sub-networks in SCZ, and these sub-networks were formed by nodes with greater functional heterogeneity. The averaged CD of nodes in these sub-networks also showed greater Approximate Entropy (ApEn) (indicating greater stochasticity) but lower amplitude variability (suggesting less adaptability to task-induced dynamics). Finally, higher ApEn was associated with worse clinical symptoms and poorer task performance.

Limitations: Centrality Dynamics is a new method for network discovery in health and schizophrenia. Further extensions to other task-driven and resting data in other psychiatric conditions will provide fuller understanding of its promise.

Conclusion: The brain's functional connectome under task-driven conditions is not static. Characterizing these task-driven dynamics will provide new insight on the dysconnection syndrome that is schizophrenia. Centrality Dynamics provides novel characterization of task-induced changes in the brain's connectome and shows that in the schizophrenia brain, learning-evoked sub-network dynamics were (a) less responsive to learning evoked changes and (b) showed greater stochasticity.

Background: Suicide remains a critical public health issue, with self-report-based clinical assessments often failing to detect imminent risk. This study aimed to identify objective electroencephalography (EEG)-based neurobiological markers for differentiating a suicide attempt (SA) from suicidal ideation (SI) using EEG microstate and microstate-based functional connectivity (FC) analyses.

Methods: From 2017 to 2020, this study enrolled 130 medication-naïve major depressive disorder patients (68 SA, evaluated within 7 days of the attempt; 62 SI) at Soonchunhyang University Cheonan Hospital. Resting-state EEG data were analyzed using microstate analysis to explore temporal dynamics of brain topography and microstate-based FC to assess connectivity in theta, alpha, and beta bands. Correlations between EEG features and psychological measures (e.g., suicidal ideation, depression, emotion regulation) were examined.

Results: Compared with the SI group, the SA group showed a marginally lower frequency of occurrence for microstates A (auditory/language processing) and B (visual processing) (p = 0.078 for both). The SA group demonstrated significantly higher alpha-band FC during microstate E (linked to the default mode network (DMN)) for several electrode pairs (e.g., F7-C5, p = 0.009; FC5-C5, p = 0.005). The SA group also exhibited marginally higher FC in the alpha band during microstates C (DMN-related) and B, and in the theta band during microstate E. A subsequent within-group analysis revealed that in the SI group, alpha-band FC during microstate E positively correlated with scores for difficulties in emotion regulation (r = 0.433, p = 0.017).

Limitations: Findings are limited by potential physiological confounds in the SA group and by the limited anatomical specificity inherent in sensor-space EEG analysis.

Conclusion: EEG microstate dynamics and microstate-based FC differ between patients with SA and SI. Specifically, enhanced alpha-band connectivity during microstate E in the SA group potentially reflects condition-specific DMN functions. These EEG-based measures show promise as objective markers that complement clinical suicide risk assessment and inform early intervention strategies.

Clozapine is an effective antipsychotic medication for the management of treatment-resistant schizophrenia. However, the use of clozapine is limited due to severe and sometimes fatal adverse events, including cardiac inflammation (myocarditis). To date, studies of clozapine dosing and genetic studies have not identified robust risk markers. Our study aimed to identify potential epigenetic markers for clozapine-induced myocarditis using genome-wide profiling of DNA methylation and RNA sequencing in a novel in vitro model using patient-derived cells. Induced pluripotent stem cells (iPSCs) from treatment-resistant schizophrenia patients with (case) and without (control) a history of clozapine-induced myocarditis were differentiated into beating cardiomyocytes (iPSC-CMs). These cells were exposed to clozapine at a physiologically relevant concentration (2.8 µmol/L) for 24 h. Before and after clozapine treatment, RNA from the iPSC-CMs was sequenced (RNA-seq), and DNA was assessed for methylation using the EPIC array. Our analysis revealed that hypermethylation at the promoter regions of GSTM1 and ZNF559 is associated with reduced gene expression in cases relative to controls, regardless of clozapine exposure. Additionally, hypermethylation in the gene bodies of AKAP7 and HLA-DRB1 was associated with increased expression in cases relative to controls. Conversely, hypomethylation in the gene bodies of GAL3ST3 and PDPR correlated with lowered gene expression in cases relative to controls. These findings highlight a potential involvement of DNA methylation in gene expression regulation and its putative impact on clozapine-induced myocarditis. Additional studies are warranted to validate our findings and further elucidate a potential mechanism.

Background: Despite the effectiveness of specialized therapies, people with borderline personality disorder (BPD) continue to face substantial psychosocial challenges, which may be partially attributed to neuropsychological deficits arising from imbalances in the corticolimbic system. Transcranial direct current stimulation (tDCS) targeting the dorsolateral prefrontal cortex (DLPFC) could enhance impulse control, emotional regulation, and cognitive functions; thus, we sought to explore the effectiveness of tDCS combined with online cognitive training on cognitive functions, BPD symptoms, and psychosocial functioning among patients with BPD.

Methods: This open-label study recruited adults with BPD who were not undergoing psychotherapy. Participants completed informational psychoeducation sessions, followed by 10 daily sessions of 20-minute tDCS over 2 weeks. Stimulation involved a continuous 2-mA current with the anode over the left DLPFC and the cathode over the right DLPFC. During each session, participants simultaneously engaged in online cognitive training using the Lumosity app (aspredicted.org no. 206 001).

Results: We included 29 participants. We noted significant improvements in cognitive functions, including the Towers of London task (Cohen d = -0.38 to -0.78), the Corsi Block-Tapping direct and total scores (d = -0.41 and -0.42, respectively), and the Stroop Interference and Alternance tests (d = 0.80 and 0.94, respectively). Emotional dysregulation showed a substantial reduction (d = 0.44), while impulsivity did not change significantly. Symptoms of BPD decreased (d = 0.69), while general functioning (d = 0.33) and the internal component of BPD functioning improved (d = -0.51).

Limitations: Although these preliminary findings are encouraging, further controlled studies are necessary to validate the efficacy and long-term effect of the intervention.

Conclusion: This combined approach appears to be well tolerated and produced promising short-term improvements in cognitive performance, BPD symptoms, and overall functioning. The results underscore the relevance of the left DLPFC in developing neuropsychologically integrative interventions for BPD.

Background: Intrauterine exposure of the developing fetus or neonate to bendodiazepine may lead to fetal abnormalities or adverse reactions. We sought to investigate whether benzodiazepine use before or during different trimesters of pregnancy had different associations with incident preterm births (PTB) or small for gestational age (SGA) infants.

Methods: We conducted a 13-year longitudinal cohort study incorporating population-wide, sibling, and paternal comparisons. We used nation-wide population-based data on diagnoses and drug prescriptions from the Taiwan National Health Insurance Research Database, with linkages to the Taiwan Birth Certificate Registration and the Taiwan Maternal and Child Health Database between 2004 and 2016. We obtained data on live births to mothers exposed or unexposed to benzodiazepine. Children born by the same mother without benzodiazepine exposures before or during pregnancy were ascertained to create the sibling comparison cohort. We also gathered information on newborns with benzodiazepine-exposed or unexposed fathers. We determined the risks of subsequent PTB and SGA during the 13-year follow-up period.

Results: We included data on 2 572 125 births to mothers exposed to benzodiazepine and 2 265 685 births to mothers unexposed to benzodiazepine. After adjustments and from our sibling comparison group, the increased risks of preterm births (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.53-1.91) and SGA (OR 1.47, 95% CI 1.14-1.89) were significant only among children born from mothers exposed to benzodiazepine in the third trimester.

Limitations: Our results are subject to unmeasured confounding factors, such as smoking and the severity of parental mental illness, which were not available in the administrative claims data.

Conclusion: Benzodiazepine exposure during the third trimester, but not the first or second trimesters, increased the risks of PTB and SGA. This result may reflect the direct effects of benzodiazepine on fetal development or the intrauterine environment.

Background: Although the processes underlying the relationship between developmental trauma and psychosis remain to be elucidated, alterations in hippocampal-dependent memory (HDM) processing may underlie this relationship. We hypothesized that exposure to developmental trauma would be negatively associated with HDM and hippocampal volume and positively associated with intrusive memories among people with psychosis.

Methods: We conducted a systematic search of studies published from Dec. 18, 2020, to Nov. 14, 2023, using the search terms "childhood," "trauma," "psychosis," and "memory processing" in Embase, PsycINFO, MEDLINE, OpenGrey, Google Scholar, and PTSDpubs. We conducted meta-analyses of studies that measured developmental trauma (self-report questionnaires or interviews), HDM (episodic memory performance and trauma-memory intrusions), semantic and recognition-memory performance, and hippocampal volume among people with psychosis. Subsample analysis determined whether these associations differed across the psychosis spectrum or for specific abuse types.

Results: We included 26 studies. Meta-analyses found that developmental trauma was not associated with total hippocampal volume (n = 4, outcomes = 6, d = -0.12, standard error [SE] = 0.20, p = 0.2), episodic memory performance (n = 10, outcomes = 42, d = 0.11, SE = 0.19, p = 0.5), recognition (n = 3, outcomes = 4, d = -0.55, SE = 0.58, p = 0.3), or semantic memory performance (n = 4, outcomes = 6, d = 0.08, SE = 0.13, p = 0.6) in participants across the psychosis spectrum. One study found that developmental trauma was associated with impaired episodic memory performance in participants with schizotypal disorder and participants with a mixed phenotype of affective and psychotic symptoms. Two studies found developmental trauma to be associated with increased involuntary memory intrusions in a sample of people with psychosis.

Limitations: We did not control for age of trauma, sex, or chronicity of trauma. Results should be considered with caution, given the high publication bias and study heterogeneity seen within meta-analyses.

Conclusion: The association between developmental trauma and memory processing may not affect HDM more than the psychotic symptoms already experienced by affected individuals. However, future studies should focus on the effects of developmental trauma on involuntary memory among people with psychosis.