Journal of Psychiatry & Neuroscience最新文献

Background: Converging evidence suggests that stress alters behavioural responses in a sex-specific manner; however, the underlying molecular mechanisms of stress remain largely unknown.

Methods: We adapted unpredictable maternal separation (UMS) and adult restraint stress (RS) paradigms to mimic stress in rats in early life or adulthood, respectively. The sexual dimorphism of the prefrontal cortex was noted, and we performed RNA sequencing (RNA-Seq) to identify specific genes or pathways responsible for sexually dimorphic responses to stress. We then performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) to verify the results of RNA-Seq.

Results: Female rats exposed to either UMS or RS showed no negative effects on anxiety-like behaviours, whereas the emotional functions of the PFC were impaired markedly in stressed male rats. Leveraging differentially expressed genes (DEG) analyses, we identified sex-specific transcriptional profiles associated with stress. There were many overlapping DEGs between UMS and RS transcriptional data sets, where 1406 DEGs were associated with both biological sex and stress, while only 117 DEGs were related to stress. Notably, Uba52 and Rpl34-ps1 were the first-ranked hub gene in 1406 and 117 DEGs respectively, and Uba52 was higher than Rp134-ps1, suggesting that stress may have led to a more pronounced effect on the set of 1406 DEGs. Pathway analysis revealed that 1406 DEGs were primarily enriched in ribosomal pathway. These results were confirmed by qRT-PCR.

Limitations: Sex-specific transcriptional profiles associated with stress were identified in this study, but more in-depth experiments, such as single-cell sequencing and manipulation of male and female gene networks in vivo, are needed to verify our findings.

Conclusion: Our findings show sex-specific behavioural responses to stress and highlight sexual dimorphism at the transcriptional level, shedding light on developing sex-specific therapeutic strategies for stress-related psychiatric disorders.

Background: In major depressive disorder (MDD), cognitive dysfunctions strongly contribute to functional impairments but are barely addressed in current therapies. Novel treatment strategies addressing cognitive symptoms in depression are needed. As the gut microbiota-brain axis is linked to depression and cognition, we investigated the effect of a 4-week high-dose probiotic supplementation on cognitive symptoms in depression.

Methods: This randomized controlled trial included 60 patients with MDD, of whom 43 entered modified intention-to-treat analysis. A probiotic supplement or indistinguishable placebo containing maltose was administered over 31 days in addition to treatment as usual for depression. Participant scores on the Verbal Learning Memory Test (VLMT), Corsi Block Tapping Test, and both Trail Making Test versions as well as brain-derived neurotrophic factor levels were assessed at 3 different time points: before, immediately after and 4 weeks after intervention. Additionally, brain activation changes during working memory processing were investigated before and immediately after intervention.

Results: We found a significantly improved immediate recall in the VLMT in the probiotic group immediately after intervention, and a trend for a time × group interaction considering all time points. Furthermore, we found a time × group interaction in hippocampus activation during working memory processing, revealing a remediated hippocampus function in the probiotic group. Other measures did not reveal significant changes.

Limitations: The modest sample size resulting from our exclusion of low-compliant cases should be considered.

Conclusion: Additional probiotic supplementation enhances verbal episodic memory and affects neural mechanisms underlying impaired cognition in MDD. The present findings support the importance of the gut microbiota-brain axis in MDD and emphasize the potential of microbiota-related regimens to treat cognitive symptoms in depression.

Clinical trial registration: clinicaltrials.gov identifier NCT02957591.

Background: To interact successfully with their environment, humans need to build a model to make sense of noisy and ambiguous inputs. An inaccurate model, as suggested to be the case for people with psychosis, disturbs optimal action selection. Recent computational models, such as active inference, have emphasized the importance of action selection, treating it as a key part of the inferential process. Based on an active inference framework, we sought to evaluate previous knowledge and belief precision in an action-based task, given that alterations in these parameters have been linked to the development of psychotic symptoms. We further sought to determine whether task performance and modelling parameters would be suitable for classification of patients and controls.

Methods: Twenty-three individuals with an at-risk mental state, 26 patients with first-episode psychosis and 31 controls completed a probabilistic task in which action choice (go/no-go) was dissociated from outcome valence (gain or loss). We evaluated group differences in performance and active inference model parameters and performed receiver operating characteristic (ROC) analyses to assess group classification.

Results: We found reduced overall performance in patients with psychosis. Active inference modelling revealed that patients showed increased forgetting, reduced confidence in policy selection and less optimal general choice behaviour, with poorer action-state associations. Importantly, ROC analysis showed fair-to-good classification performance for all groups, when combining modelling parameters and performance measures.

Limitations: The sample size is moderate.

Conclusion: Active inference modelling of this task provides further explanation for dysfunctional mechanisms underlying decision-making in psychosis and may be relevant for future research on the development of biomarkers for early identification of psychosis.

Background: Adolescents with borderline personality disorder often have cognitive impairment, but the underlying mechanism for this is not clear. This study was aimed at assessing alterations in regional homogeneity using resting-state functional MRI (fMRI) in adolescents with borderline personality disorder, and evaluating the associations between regional homogeneity and cognitive testing scores.

Methods: We enrolled 50 adolescents with borderline personality disorder (age 12-17 years) and 21 age- and sex-matched healthy controls. We performed regional homogeneity and seed-based functional connectivity analysis for both groups. We also performed correlative analysis for regional homogeneity and cognitive testing scores.

Results: Compared with healthy controls, adolescents with borderline personality disorder had reduced regional homogeneity values in the frontal cortex (including the left inferior orbitofrontal cortex and the bilateral superior frontal cortex) as well as in the left precuneus in the default mode network. Adolescents with borderline personality disorder also had higher regional homogeneity values in several cortical regions: the right middle temporal gyrus, the right cuneus, the right precentral gyrus and the left middle occipital gyrus. Regional homogeneity values in the left middle occipital gyrus, left inferior orbitofrontal cortex and right superior frontal gyrus were associated with cognitive testing scores in adolescents with borderline personality disorder. We also found increased functional connectivity between the left middle occipital gyrus and right superior frontal gyrus in adolescents with borderline personality disorder.

Limitations: This study had a modest sample size, with a possible case selection bias for patients with more severe illness. This cohort also included patients with comorbidities or taking psychotropic medications, which may have confounded study results.

Conclusion: Alterations in regional homogeneity and functional connectivity in brain regions that involve the limbic-cortical circuit could be neural correlates for cognitive impairment in adolescents with borderline personality disorder.

Background: Few studies have empirically tested the relationships between anatomically defined thalamic nuclei and functionally defined cortical networks, and little is known about their implications in attention-deficit/hyperactivity disorder (ADHD). This study aimed to investigate the functional connectivity of the thalamus in youth with ADHD, using both anatomically and functionally defined thalamic seed regions.

Methods: Resting-state functional MRIs obtained from the publicly available ADHD-200 database were analyzed. Thalamic seed regions were defined functionally and anatomically based on Yeo's 7 resting-state-network parcellation atlas and the AAL3 atlas, respectively. Functional connectivity maps of the thalamus were extracted, and thalamocortical functional connectivity was compared between youth with and without ADHD.

Results: Using the functionally defined seeds, significant group differences in thalamocortical functional connectivity and significant negative correlations between thalamocortical connectivity and ADHD symptom severity were observed within the boundaries of corresponding large-scale networks. However, in the analysis using the anatomically defined thalamic seeds, significant group differences in connectivity and significant positive correlations were observed outside the expected boundaries of major anatomic projections. The thalamocortical connectivity originating from the lateral geniculate nuclei of the thalamus was significantly correlated with age in youth with ADHD.

Limitations: The small sample size and smaller proportion of girls were limiting factors.

Conclusion: Thalamocortical functional connectivity based on the intrinsic network architecture of the brain appears to be clinically relevant in ADHD. The positive association between thalamocortical functional connectivity and ADHD symptom severity may represent a compensatory process recruiting an alternative neural network.

Background: In recent years, many studies have explored the associations among impulsivity, history of abuse, the emergence of eating disorders with episodes of binge eating (EDBE) and their severity. Nevertheless, factors associated with successful clinical outcomes of EDBE are still unknown. Our study aimed to test the hypothesis that a history of abuse is associated with unsuccessful clinical outcomes of EDBE through an effect mediated by impulsivity.

Methods: We assessed patients older than 15 years, 3 months with EDBE at inclusion and at 1 year. Recovery was defined as the absence of eating disorders at 1 year. A mediation analysis was performed by means of structural equation modelling.

Results: We included 186 patients in our analyses (54% bulimia nervosa, 29% anorexia nervosa binge eating/purging type and 17% binge-eating disorder); 179 (96%) were female. One-third (n = 63) of patients reported a history of abuse, and recovery was observed for 20% of the sample (n = 38). Contrary to our assumption, a history of abuse was not associated with the absence of recovery of EDBE at 1 year. Factors unfavourable for achieving recovery were anxiety disorders (odds ratio [OR] 0.41), vomiting (OR 0.39), physical hyperactivity (OR 0.29), negative urgency and a lack of perseverance (OR 0.85 for both). Only positive urgency was positively associated with recovery (OR 1.25).

Limitations: We excluded 219 patients lost to the 1-year follow-up.

Conclusion: Our findings may help to deconstruct the empirical belief that traumatic events may interfere with the successful course of treatment for eating disorders. A high level of positive urgency may be associated with more receptivity to care.

Background: Hippocampal disturbances are important in the pathophysiology of both schizophrenia and major depressive disorder (MDD). Imaging studies have shown selective volume deficits across hippocampal subfields in both disorders. We aimed to investigate whether these volumetric alterations in hippocampal subfields are shared or divergent across disorders.

Methods: We searched PubMed and Embase from database inception to May 8, 2021. We identified MRI studies in patients with schizophrenia, MDD or both, in which hippocampal subfield volumes were measured. We excluded nonoriginal, animal or postmortem studies, and studies that used other imaging modalities or overlapping data. We conducted a network meta-analysis to estimate and contrast alterations in subfield volumes in the 2 disorders.

Results: We identified 45 studies that met the initial criteria for systematic review, of which 15 were eligible for network metaanalysis. Compared to healthy controls, patients with schizophrenia had reduced volumes in the bilateral cornu ammonis (CA) 1, granule cell layer of the dentate gyrus, subiculum, parasubiculum, molecular layer, hippocampal tail and hippocampus-amygdala transition area (HATA); in the left CA4 and presubiculum; and in the right fimbria. Patients with MDD had decreased volumes in the left CA3 and CA4 and increased volumes in the right HATA compared to healthy controls. The bilateral parasubiculum and right HATA were smaller in patients with schizophrenia than in patients with MDD.

Limitations: We did not investigate medication effects because of limited information. Study heterogeneity was noteworthy in direct comparisons between patients with MDD and healthy controls.

Conclusion: The volumes of multiple hippocampal subfields are selectively altered in patients with schizophrenia and MDD, with overlap and differentiation in subfield alterations across disorders. Rigorous head-to-head studies are needed to validate our findings.