Journal of Psychiatry & Neuroscience最新文献

Background: Borderline personality disorder (BPD) is a mental health condition characterized by an inability to regulate emotions or accurately process the emotional states of others. Previous neuroimaging studies using classical univariate analyses have tied such emotion dysregulation to aberrant activity levels in the amygdala of patients with BPD. However, multivariate analyses have not yet been used to investigate how representational spaces of emotion information may be systematically altered in patients with BPD.

Methods: Patients with BPD performed an emotional face matching task while undergoing MRI before and after a 10-week inpatient program of dialectical behavioural therapy. Representational similarity analysis (RSA) was applied to activity patterns (evoked by angry, fearful, neutral and surprised faces) in the amygdala and temporo-occipital fusiform gyrus of patients with BPD and in the amygdala of healthy controls.

Results: We recruited 15 patients with BPD (8 females, 6 males, 1 transgender male) to participate in the study, and we obtained a neuroimaging data set for 25 healthy controls for a comparative analysis. The RSA of the amygdala revealed a negative bias in the underlying affective space (in that activity patterns evoked by angry, fearful and neutral faces were more similar to each other than to patterns evoked by surprised faces), which normalized after therapy. This bias-to-normalization effect was present neither in activity patterns of the temporo-occipital fusiform gyrus of patients nor in amygdalar activity patterns of healthy controls.

Limitations: Larger samples and additional questionnaires would help to better characterize the association between specific aspects of therapy and changes in the neural representational space.

Conclusion: Our findings suggest a more refined role for the amygdala in the pathological processing of perceived emotions and may provide new diagnostic and prognostic imaging-based markers of emotion dysregulation and personality disorders.Clinical trial registration: DRKS00019821, German Clinical Trials Register (Deutsches Register Klinischer Studien).

Background: Impaired functional connectivity between the bilateral hemispheres may serve as the neural substrate for anxiety and depressive disorders, yet its role in comorbid generalized anxiety disorder (GAD) and depression, as well as the effect of treatment on this connectivity, remains unclear. We sought to examine functional connectivity between homotopic regions of the 2 hemispheres (voxel-mirrored homotopic connectivity [VMHC]) among people with GAD with and without comorbid depression at baseline and after a 4-week paroxetine treatment.

Methods: Drug-naïve patients with GAD, with or without comorbid depression and healthy controls underwent functional magnetic resonance imaging and clinical assessments at baseline and after treatment. We compared VMHC and seed-based functional connectivity across the 3 groups. We performed correlation analysis and support vector regression (SVR) to examine the intrinsic relationships between VMHC and symptoms.

Results: Both patient groups (n = 40 with GAD only, n = 58 with GAD and depression) showed decreased VMHC in the precuneus, posterior cingulate cortex and lingual gyrus compared with healthy controls (n = 54). Moreover, they showed decreased VMHC in different brain regions compared with healthy controls. However, we did not observe any significant differences between the 2 patient groups. Seeds from abnormal VMHC clusters in patient groups had decreased functional connectivity. Voxel-mirrored homotopic connectivity in the precuneus, posterior cingulate cortex and lingual gyrus was negatively correlated with cognitive impairment among patients with GAD only and among all patients. The SVR analysis based on abnormal VMHC showed significant positive correlations (p < 0.0001) between predicted and actual treatment responses. However, we did not observe significant differences in VMHC or functional connectivity after treatment.

Limitations: A notable dropout rate and intergroup somatic symptom variations may have biased the results.

Conclusion: Patients with GAD with or without comorbid depression exhibited shared and distinct abnormal VMHC patterns, which might be linked to their cognitive deficits. These patterns have the potential to serve as prognostic biomarkers for GAD.Clinical trial registration: ClinicalTrials.gov NCT03894085.

Background: Psychosocial interventions have emerged as an important component of a comprehensive therapeutic approach in early-onset schizophrenia, typically representing a more severe form of the disorder. Despite the feasibility and efficacy of Theory of Mind (ToM) psychotherapy for schizophrenia, relatively little is known regarding the neural mechanism underlying its effect on early-onset schizophrenia.

Methods: We performed a randomized, active controlled trial in patients with early-onset schizophrenia, who were randomly allocated into either an intervention (ToM psychotherapy) or an active control (health education) group. Diffusion tensor imaging data were collected to construct brain structural networks, with both global and regional topological properties measured using graph theory.

Results: We enrolled 28 patients with early-onset schizophrenia in our study. After 5 weeks of treatment, both the intervention and active control groups showed significant improvement in psychotic symptoms, yet the improvement was greater in the intervention group. Importantly, in contrast with no brain structural network change after treatment in the active control group, the intervention group showed increased nodal centrality of the left insula that was associated with psychotic symptom improvement.

Limitations: We did not collect important information concerning the participants' cognitive abilities, particularly ToM performance.

Conclusion: These findings suggest a potential neural mechanism by which ToM psychotherapy exerts a beneficial effect on early-onset schizophrenia via strengthening the coordination capacity of the insula in brain structural networks, which may provide a clinically translatable biomarker for monitoring or predicting responses to ToM psychotherapy.Clinical trial registration: NCT05577338; ClinicalTrials.gov.

Background: There have been conflicting reports on whether conventional verbal fluency measures can predict the prognosis of individuals at clinical high risk (CHR) for psychosis. We aimed to investigate whether verbal fluency task measures that represent semantic processing more directly than conventional measures could be more reliable predictors of later remission in CHR individuals.

Methods: We recruited CHR individuals and healthy controls to participate in a baseline verbal fluency assessment. We identified semantic clusters within the verbal fluency task responses based on cosine similarity between consecutive words, calculated from the word embedding model. Binomial logistic regression was performed to test whether average semantic cluster size and number of words produced could be predictors of remission in CHR individuals.

Results: Our study sample included 96 CHR individuals and 178 healthy controls. According to clinical assessment at the last follow-up, 23 CHR individuals were classified as remitters and 73 as nonremitters, including 29 individuals who converted to psychosis. The CHR remitters showed larger average and maximum semantic cluster sizes than CHR nonremitters and healthy controls. Average semantic cluster size, but not the number of words, was a significant predictor of later remission in CHR individuals.

Limitations: Our sample included only native Korean speakers.

Conclusion: A verbal fluency task measure that more specifically represents semantic processing may be a better neurocognitive predictive marker for remission in CHR individuals than conventional verbal fluency measures. Our results provide an explanation for heterogeneous reports on whether verbal fluency can predict prognosis in CHR individuals and suggest that semantic processing is a putative cognitive predictor of their prognosis.

Background: Apathy is associated with reduced antidepressant response and dementia in late-life depression (LLD). However, the functional cerebral basis of apathy is understudied in LLD. We investigated the functional connectivity of 5 resting-state networks (RSN) hypothesized to underlie apathy in LLD.

Methods: Resting-state functional MRI data were collected from individuals with LLD who did not have dementia as well as healthy older adults between October 2019 and April 2022. Apathy was evaluated using the diagnostic criteria for apathy (DCA), the Apathy Evaluation Scale (AES) and the Apathy Motivation Index (AMI). Subnetworks whose connectivity was significantly associated with each apathy measure were identified via the threshold-free network-based statistics. Regions that were consistently associated with apathy across the measures were reported as robust findings.

Results: Our sample included 39 individuals with LLD who did not have dementia and 26 healthy older adults. Compared with healthy controls, individuals with LLD had an altered intra-RSN and inter-RNS connectivity in the default mode, the cingulo-opercular and the frontoparietal networks. All 3 apathy measurements showed associations with modified intra-RSN connectivity in these networks, except for the DCA in the cingulo-opercular network. The AMI scores showed stronger associations with the cingulo-opercular and frontoparietal networks, whereas the AES had stronger associations with the default mode network and the goal-oriented behaviour network.

Limitations: The study was limited by the small number of participants without apathy according to the DCA, which may have reduced the statistical power of between-group comparisons. Additionally, the reliance on specific apathy measures may have influenced the observed overlap in brain regions.

Conclusion: Our findings indicate that apathy in LLD is consistently associated with changes in both intra-RSN and inter-RSN connectivity of brain regions implicated in goal-oriented behaviours. These results corroborate previous findings of altered functional RSN connectivity in severe LLD.

Background: Human navigation of social interactions relies on the processing of emotion on faces. This meta-analysis aimed to produce an updated brain atlas of emotional face processing from whole-brain studies based on a single emotional face-viewing paradigm (PROSPERO CRD42022251548).

Methods: We conducted a systematic literature search of Embase, MEDLINE and PsycINFO from May 2008 to October 2021. We used seed-based d mapping with permutation of subject images to conduct a quantitative meta-analysis of functional neuroimaging contrasts between emotional (e.g., angry, happy) and neutral faces. We conducted agglomerative hierarchical clustering of meta-analytic map contrasts of emotional faces relative to neutral faces. We investigated lateralization of emotional face processing.

Results: From 5549 studies identified, 55 data sets (1489 healthy participants) met our inclusion criteria. Relative to neutral faces, we found extensive activation clusters by fearful faces in the right inferior temporal gyrus, right fusiform area, left putamen and amygdala, right parahippocampalgyrus and cerebellum; we found smaller activation clusters by angry faces in the right cerebellum and right middle temporal gyrus (MTG) and by disgusted faces in the left MTG. Happy and sad faces did not reach statistical significance. Clustering analyses showed similar activation patterns of fearful and angry faces; activation patterns of happy and sad faces showed the least correlation with other emotional faces. Emotional face processing was predominantly left-lateralized in the amygdala and anterior insula, and right-lateralized in the ventromedial prefrontal cortex.

Limitations: Reliance on discretized effect sizes based on peak coordinate location instead of statistical brain maps, and the varying level of statistical threshold reporting from original studies, could lead to underdetection of smaller clusters of activation.

Conclusion: Processing of emotional faces appeared to be oriented toward identifying threats on faces, from highest (i.e., angry or fearful faces) to lowest level (i.e., happy or sad faces), with a more complex lateralization pattern than previously theorized. Emotional faces may be processed in latent grouping but organized by threat content rather than emotional valence.

Background: Attention deficit/hyperactivity disorder (ADHD) is a highly prevalent childhood disorder. Maternal smoking during pregnancy is a replicated environmental risk factor for this disorder. It is also a robust modifier of gene methylation during the prenatal developmental period. In this study, we sought to identify loci differentially methylated by maternal smoking during pregnancy and relate their methylation levels to various behavioural and physical outcomes relevant to ADHD.

Methods: We extracted DNA from blood samples from children diagnosed with ADHD and deeply phenotyped. Genome-wide DNA methylation was assessed using Infinium MethylationEPIC BeadChip. Maternal smoking during pregnancy was self-declared and assessed retrospectively.

Results: Our sample included 231 children with ADHD. Statistically significant differences in DNA methylation between children exposed or not to maternal smoking during pregnancy were detected in 3457 CpGs. We kept 30 CpGs with at least 5% of methylation difference between the 2 groups for further analysis. Six genes were associated with varied phenotypes of clinical relevance to ADHD. The levels of DNA methylation in RUNX1 were positively correlated with the CBCL scores, and DNA methylation in MYO1G correlated positively with the score at the Conners rating scale. Methylation level in a CpG located in GFI1 correlated with birthweight, a risk factor for ADHD. Differentially methylated regions were also identified and confirmed the association of RUNX1 methylation levels with the CBCL score.

Limitations: The study has several limitations, including the retrospective recall with self-report of maternal smoking during pregnancy as well as the grouping of individuals of varying age and developmental stage and of both males and females. In addition, the correlation design prevents the building of causation models.

Conclusion: This study provides evidence for the association between the level of methylation at specific loci and quantitative dimensions highly relevant for ADHD as well as birth weight, a measure that has already been associated with increased risk for ADHD. Our results provide further support to public health educational initiatives to stop maternal smoking during pregnancy.

Background: Among healthy participants, the interindividual variability of brain response to facial emotions is associated with genetic variation, including common risk variants for schizophrenia, a heritable brain disorder characterized by anomalies in emotion processing. We aimed to identify genetic variants associated with heritable brain activity during processing of facial emotions among healthy participants and to explore the impact of these identified variants among patients with schizophrenia.

Methods: We conducted a data-driven stepwise study including samples of healthy twins, unrelated healthy participants and patients with schizophrenia. Participants approached or avoided pictures of faces with negative emotional valence during functional magnetic resonance imaging (fMRI).

Results: We investigated 3 samples of healthy participants - including 28 healthy twin pairs, 289 unrelated healthy participants (genome-wide association study [GWAS] discovery sample) and 90 unrelated healthy participants (replication sample) - and 1 sample of 48 patients with schizophrenia. Among healthy twins, we identified the amygdala as the brain region with the highest heritability during processing of angry faces (heritability estimate 0.54, p < 0.001). Subsequent GWAS in both discovery and replication samples of healthy non-twins indicated that amygdala activity was associated with a polymorphism in the miR-137 locus (rs1198575), a micro-RNA strongly involved in risk for schizophrenia. A significant effect in the same direction was found among patients with schizophrenia (p = 0.03).

Limitations: The limited sample size available for GWAS analyses may require further replication of results.

Conclusion: Our data-driven approach shows preliminary evidence that amygdala activity, as evaluated with our task, is heritable. Our genetic associations preliminarily suggest a role for miR-137 in brain activity during explicit processing of facial emotions among healthy participants and patients with schizophrenia, pointing to the amygdala as a brain region whose activity is related to miR-137.