Journal of Psychiatry & Neuroscience最新文献

Background: The default mode network (DMN) is not a single system, but rather is composed of smaller and distinct functional subsystems that interact with each other. The functional relevance of these subsystems in tobacco use disorder (TUD) and the neurobiological features associated with smoking motivation are still unclear; thus, we sought to assess causal or direct connectivity alterations within 3 subsystems of the DMN among people with TUD.

Methods: We recruited male smokers and nonsmokers. We conducted resting-state functional magnetic resonance imaging (rs-fMRI) and collected ratings on smoking-related clinical scales. We applied dynamic causal modelling (DCM) to rs-fMRI to characterize changes of effective connectivity in TUD from 3 DMN subsystems, including the midline core network (i.e., the posterior cingulate cortex and the anterior medial prefrontal cortex [PCC-aMPFC] core DMN), the medial temporal subsystem (MTL-DMN), and the dorsal medial prefrontal cortex subsystem (dMPFC-DMN). We used leave-one-out cross-validation to investigate whether the neural response could predict smoking reasons, evaluated using the Russell Reason for Smoking Questionnaire).

Results: We recruited 88 smokers and 54 nonsmokers. Among people with TUD, the parahippocampal cortex (PHC) region showed enhanced self-connection, which was associated with the severity of TUD after nighttime withdrawal. Compared with nonsmokers, people with TUD displayed significant increased effective connectivity within the dMPFC-DMN, and decreased effective connectivity from the dMPFC-DMN to the PCC-aMPFC core DMN. Moreover, decreased effective connectivity from the lateral temporal cortex to the dMPFC could predict the smoking reason related to automatic behaviour.

Limitations: Although we found aberrance in causal connections in DMN subsystems among people with TUD, our cross-sectional study could not be used to investigate changes in effective connectivity over time and their relationship with clinical features.

Conclusion: This study emphasized the aberrant causal connections of different functional subsystems of the DMN in TUD and revealed the neural correlates of automatic smoking behaviours. These findings suggested DMN subsystem-derived indicators could be a potential biomarker for TUD and could be used to identify the heterogeneity in motivation for smoking behaviour.

Background: The intricate interplay between peripheral adaptive immune cells and the central nervous system (CNS) has garnered increasing recognition. Given that alterations in cell quantities often translate into modifications in metabolite profiles and that these metabolic changes can potentially traverse the bloodstream and enter the CNS, thereby modulating the progression of mental illnesses, we sought to explore the metabolic profiles of peripheral immune cells in a ketamine-treated mouse model of schizophrenia.

Methods: We used flow cytometry to scrutinize the alterations in peripheral adaptive immune cells in a ketamine-induced schizophrenia mouse model. Subsequently, we implemented an untargeted metabolomic approach with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to detect the metabolite profiles of peripheral abnormal lymphocytes and identify differential metabolites present in plasma. We then employed targeted metabolomics using UPLC-MS/MS to quantify the common differential metabolites detected in mouse plasma.

Results: Flow cytometry analysis detected a notable increase in the count of peripheral CD3⁺ T cells in a ketamine-induced schizophrenia mouse model. Subsequent untargeted metabolomics analysis revealed that the amino acid metabolism pathway underwent substantial alterations. A detailed quantification of 22 amino acid profiles in the peripheral plasma indicated significant elevation in the levels of glycine, alanine, asparagine, and aspartic acid.

Limitations: Our ongoing research has yet to conclusively identify the precise amino acid metabolism pathway that serves as the pivotal factor in the manifestation of the schizophrenia-like phenotype induced by ketamine.

Conclusion: The peripheral amino acid metabolism pathway is involved in the ketamine-induced schizophrenia-like phenotype. The metabolic profile of peripheral immune cells could provide accurate biomarkers for the diagnosis and treatment of psychiatric diseases.

Background: Panic disorder is a common disabling condition with limited biomarkers. We aimed to explore the diagnostic and treatment response prediction value of functional temporal variability in people with panic disorder.

Methods: Patients with panic disorder and healthy controls received resting-state functional magnetic resonance imaging scans and assessments. After 2 weeks of treatment, the patients with panic disorder were divided into remitted (RPD; n = 39) or nonremitted (NRPD; n = 43) subgroups. Baseline temporal variability was analyzed between the panic disorder and control groups as well as between RPD and NRPD subgroups.

Results: Our sample included 82 patients with panic disorder (39 RPD, 43 NRPD) and 105 controls. The panic disorder group showed decreased temporal variability in the left posterior cingulate gyrus (PCG), right lingual gyrus, right fusiform gyrus, and right thalamus (all p < 0.05, Bonferroni-corrected). A combination of variability in the lingual gyrus, PCG, and thalamus had optimal predictive value for distinguishing between the panic disorder and control groups (area under the curve = 0.776, sensitivity = 0.781, specificity = 0.732). In addition, the RPD subgroup showed significantly lower temporal variability in the left insula, right PCG, and bilateral lingual gyrus than the NRPD subgroup and control group (all p < 0.05, Bonferroni-corrected). Variability in the left insula and left lingual gyrus negatively correlated with the reduction rate of panic symptoms (all p < 0.05, Bonferroni-corrected).

Limitations: Functional brain images were collected only at baseline and may have been affected by medication use. Also, the follow-up period was only 2 weeks; sustained clinical remission may require longer follow-up.

Conclusion: Combining lingual gyrus, PCG, and thalamus temporal variability alterations helped distinguish patients with panic disorder from healthy controls. The temporal variability in the insula and lingual gyrus are potential biomarkers for the treatment of panic disorder.

Background: Reduced glutamatergic excitability of the anterior cingulate cortex (ACC) has been long suspected in schizophrenia; recent observations support low glutamatergic tone as the primary pathophysiology contributing to subtle early features of this illness, with a secondary disinhibition (higher glutamate tone) resulting in more prominent clinical symptoms later in its course. We sought to investigate whether people with genetic high risk (GHR) for schizophrenia have lower glutamate levels in the ACC than those at later stages of clinical high risk (CHR) and those with first-episode schizophrenia (FES), among whom symptoms are already prominent.

Methods: We recruited people with CHR, GHR, or FES, as well as healthy controls. Using proton magnetic resonance spectroscopy, we determined glutamate levels in the perigenual ACC (pACC) and dorsal ACC (dACC) using a 3 T scanner.

Results: We recruited 302 people across multiple stages of psychosis, including 63 with CHR, 76 with GHR, and 96 with FES, as well as 67 healthy controls. Those with GHR had lower glutamate levels in the dACC than those with CHR, while those with CHR had higher glutamate levels in the pACC than those with FES. Higher disorganization, but not any other symptom domain, was associated with lower levels of glutamate in the GHR group (dACC and pACC) and in the CHR group (pACC).

Limitations: The cross-sectional design precluded inferences regarding individual clinical trajectory and resolution at 3 T was insufficient to separate spectra of glutamine from glutamate.

Conclusion: Reduced glutamatergic tone among people genetically predisposed to schizophrenia supports diminished excitability as an early feature of schizophrenia, contributing to the subtle symptom of disorganization across high-risk states. Higher glutamate levels become apparent when psychotic symptoms become prominent, possibly as a disinhibitory effect and, at the full-blown stage of psychosis, the relationship between glutamate concentrations and symptoms ceases to be simply linear.

Background: Deficient neural activities during emotion regulation have been reported in depression. We sought to conduct a meta-analysis to provide a comprehensive description of these neural alterations during use of emotion regulation strategies among patients with depression, including major depressive disorder (MDD) and bipolar disorder (BD).

Methods: We identified neuroimaging studies of abnormal neural activities during emotion regulation in depression. We extracted the peak coordinates and effect sizes of differences in brain activity between patients and healthy controls. Using seed-based d mapping, we conducted voxel-wise meta-analyses of the neural activation pattern differences between the 2 groups across conditions involving emotion regulation and those where emotion regulation was not needed.

Results: We included 33 studies reporting 34 data sets, including 23 involving MDD (571 people with MDD and 578 matched controls) and 11 involving BD (358 people with BD and 369 matched controls). Overall, compared with controls, patients with depression showed hyperactivity in the insula and postcentral gyrus, and hypoactivity in the prefrontal part of the inferior, middle, and superior frontal gyrus, the middle temporal gyrus, and the supplementary motor area. In subgroup analyses, data from patients with MDD and studies focused on decreasing negative emotions or using the emotional strategy of reappraisal reported specific hypoactivity in the middle cerebellar peduncles.

Limitations: Given limited studies involving patients with BD, we were unable to detect the common and distinct abnormalities in neural activation between MDD and BD. We did not conduct any meta-regression analyses because of limited information.

Conclusion: In this meta-analysis, we identified hyperactivity in brain regions associated with emotional experience and hypoactivity in brain regions associated with cognitive control during emotion regulation among patients with depression, relative to healthy controls. These findings could help indicate a target for future interventions aimed at increasing emotion regulation capacity for patients with depression.

Background: The underlying functional alterations of brain structural changes among patients with empathy impairment following stroke remain unclear. We sought to investigate functional connectivity changes informed by brain structural abnormalities in multimodal magnetic resonance imaging (MRI) among patients with empathy impairment following stroke.

Methods: We enrolled people who had experienced their first ischemic stroke, along with healthy controls. We assessed empathy 3 months after stroke using the Chinese version of the Empathy Quotient (EQ). During the acute phase, all patients underwent basic magnetic resonance imaging (MRI), followed by multimodal MRI during follow-up. Our MRI analyses encompassed acute infarction segmentation, volumetric brain measurements, regional quantification of diffusion parameters, and both region-of-interest-based and seed-based functional connectivity assessments. We grouped patients based on the severity of their empathy impairment for comparative analysis.

Results: We included 84 patients who had stroke and 22 healthy controls. Patients had lower EQ scores than controls. Patients with low empathy had larger left cortical infarcts (odds ratio [OR] 4.082, 95% confidence interval [CI] 1.183-14.088), more pronounced atrophy in the right cingulate cortex (OR 1.248, 95% CI 1.038-1.502), and lower scores on the Montreal Cognitive Assessment (OR 0.873, 95% CI 0.74-0.947). In addition, the cingulate cortex served as the seed in the seed-based analysis, which showed heightened functional connectivity between the anterior cingulate gyrus and the right superior parietal lobule, specifically in the low-empathy group.

Limitations: We did not evaluate the relationship between specific network involvement and empathy impairment among patients following stroke.

Conclusion: Among patients with subacute ischemic stroke, reduced empathy was strongly associated with a more severe cognitive profile and atrophy of the right cingulate cortex. Our subsequent structural-informed functional MRI analysis suggests that the enhanced connectivity between the anterior cingulate gyrus and the superior parietal lobule may function as a compensatory mechanism for this atrophy.

Background: Adult hippocampal neurogenesis has been extensively characterized in rodent models, but its existence in humans remains controversial. We sought to assess the phenomenon in postmortem human hippocampal samples by combining spatial transcriptomics and multiplexed fluorescent in situ hybridization.

Methods: We computationally examined the spatial expression of various canonical neurogenesis markers in postmortem dentate gyrus (DG) sections from young and middle-aged sudden-death males. We conducted in situ assessment of markers expressed in neural stem cells, proliferative cells, and immature granule neurons in postmortem DG sections from infant, adolescent, and middle-aged males.

Results: We examined frozen DG tissue from infant (n = 1, age 2 yr), adolescent (n = 1, age 16 yr), young adult (n = 2, mean age 23.5 yr), and middle-aged (n = 2, mean age 42.5 yr) males, and frozen-fixed DG tissue from middle-aged males (n = 6, mean age 43.5 yr). We detected very few cells expressing neural stem cell and proliferative markers in the human DG from childhood to middle age. However, at all ages, we observed a substantial number of DG cells expressing the immature neuronal marker DCX. Most DCX ⁺ cells displayed an inhibitory phenotype, while the remainder were non-committed or excitatory in nature.

Limitations: The study was limited by small sample sizes and included samples only from males.

Conclusion: Our findings indicate very low levels of hippocampal neurogenesis throughout life and the existence of a local reserve of plasticity in the adult human hippocampus. Overall, our study provides important insight into the distribution and phenotype of cells expressing neurogenesis markers in the adult human hippocampus.