Neuropsychobiology最新文献

Introduction: Sleep disturbances are highly prevalent across most major psychiatric disorders. Alterations in the hypothalamic-pituitary-adrenal axis, neuroimmune mechanisms, and circadian rhythm disturbances partially explain this connection. The gut microbiome is also suspected to play a role in sleep regulation, and recent studies suggest that certain probiotics, prebiotics, synbiotics, and fecal microbiome transplantation can improve sleep quality.

Methods: We aimed to assess the relationship between gut-microbiota composition, psychiatric disorders, and sleep quality in this cross-sectional, cross-disorder study. We recruited 103 participants, 63 patients with psychiatric disorders (major depressive disorder [n = 31], bipolar disorder [n = 13], psychotic disorder [n = 19]) along with 40 healthy controls. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The fecal microbiome was analyzed using 16S rRNA sequencing, and groups were compared based on alpha and beta diversity metrics, as well as differentially abundant species and genera.

Results: A transdiagnostic decrease in alpha diversity and differences in beta diversity indices were observed in psychiatric patients, compared to controls. Correlation analysis of diversity metrics and PSQI score showed no significance in the patient and control groups. However, three species, Ellagibacter isourolithinifaciens, Senegalimassilia faecalis, and uncultured Blautia sp., and two genera, Senegalimassilia and uncultured Muribaculaceae genus, were differentially abundant in psychiatric patients with good sleep quality (PSQI >8), compared to poor-sleep quality patients (PSQI ≤8).

Conclusion: In conclusion, this study raises important questions about the interconnection of the gut microbiome and sleep disturbances.

Introduction: Social anxiety disorder (SAD) is characterized by abnormal processing of performance-related social stimuli. Previous studies have shown altered emotional experiences and activations of different sub-regions of the striatum during processing of social stimuli in patients with SAD. However, whether and to what extent social comparisons affect behavioural and neural responses to feedback stimuli in patients with SAD is unknown.

Materials and methods: To address this issue, emotional ratings and functional magnetic resonance imaging (fMRI) responses were assessed while patients suffering from SAD and healthy controls (HC) were required to perform a choice task and received performance feedback (correct, incorrect, non-informative) that varied in relation to the performance of fictitious other participants (a few, half, or most of others had the same outcome).

Results: Across all performance feedback conditions, fMRI analyses revealed reduced activations in bilateral putamen when feedback was assumed to be received by only a few compared to half of the other participants in patients with SAD. Nevertheless, analysis of rating data showed a similar modulation of valence and arousal ratings in patients with SAD and HC depending on social comparison-related feedback.

Conclusions: This suggests altered neural processing of performance feedback depending on social comparisons in patients with SAD.

3q29 deletion syndrome is characterized by various developmental abnormalities, medical issues, and neuropsychiatric symptoms, including psychosis. Although this syndrome may confer the greatest risk for schizophrenia of any copy number variation, response to antipsychotic medication has infrequently been described in the literature, and no reviews on the topic currently exist. As such, the purpose of this article was to review treatment response in 3q29 deletion syndrome-associated psychosis. A review of the literature was completed in December 2022 for English language articles that described treatment response to antipsychotic medications in affected individuals with schizophrenia-like presentations. Five articles that collectively described eight individuals were included. Four individuals had a poor treatment response to non-clozapine antipsychotic medications, three had a partial response, and one individual's response to treatment was not described, despite having taken psychotropic medications of some kind. Additionally, three individuals received clozapine; one of whom partially responded, while two exhibited a good response. Treatment response did not clearly differ according to developmental history. 3q29 deletion syndrome may be associated with treatment-resistant psychotic symptoms. As such, clozapine therapy should be considered in such individuals, provided they meet criteria for treatment-resistant schizophrenia and no contraindications exist. However, this mini-review also highlights the need for more published case reports/series before more specific treatment recommendations can be made.

Introduction: Psychodynamic psychotherapy is an effective and widely used treatment for major depressive disorder (MDD); however, little is known about neurobiological changes associated with induced symptom improvement.

Methods: Proton magnetic resonance spectroscopy with a two-dimensional J-resolved sequence served to test the relationship between glutamate (Glu) and glutamine (Gln) levels, measured separately in pregenual anterior cingulate cortex (pgACC) and the anterior midcingulate cortex (aMCC) as a control region, with change in depression symptoms after 6 months of weekly psychodynamic psychotherapy sessions in MDD patients. Depressed (N = 45) and healthy (N = 30) subjects participated in a baseline proton magnetic resonance spectroscopy measurement and a subgroup of MDD subjects (N = 21) then received once-a-week psychodynamic psychotherapy and participated in a second proton magnetic resonance spectroscopy measurement after 6 months. Change in depression symptoms was assessed using the Hamilton Depression Rating Scale (HAMD).

Results: Higher pretreatment pgACC Gln concentrations in MDD patients compared to healthy controls were associated with symptom severity. Patients and controls did not differ regarding Gln levels in aMCC nor regarding Glu levels in both regions. The association of pgACC Gln concentration and severity of depressive symptoms was reversed after 6 months of psychotherapy in MDD subjects. Regarding Gln in aMCC as well as Glu in both regions, there were no significant associations with improvement of depressive symptoms in the course of psychotherapy.

Discussion: Findings indicate specific regional effects of psychodynamic psychotherapy on glutamatergic neurotransmission and thereby highlight the key role of the pgACC in both depression pathophysiology and recovery.

Introduction: Little is known regarding genetic factors associated with treatment outcome of psychotic depression. We explored genomic associations of remission and relapse of psychotic depression treated with pharmacotherapy.

Methods: Genomic analyses were performed in 171 men and women aged 18-85 years with an episode of psychotic depression who participated in the Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II). Participants were treated with open-label sertraline plus olanzapine for up to 12 weeks; those who achieved remission or near-remission and maintained it following 8 weeks of stabilization were eligible to participate in a 36-week randomized controlled trial that compared sertraline plus olanzapine with sertraline plus placebo in preventing relapse.

Results: There were no genome-wide significant associations with either remission or relapse. However, at a suggestive threshold, SNP rs1026501 (31 kb from SYNPO2) in the whole sample and rs6844137 (within the intronic region of SYNPO2) in the European ancestry subsample were associated with a decreased likelihood of remission. In polygenic risk analyses, participants who had greater improvement after antidepressant treatments showed a higher likelihood of reaching remission. Those who achieved remission and had a higher polygenic risk for Alzheimer's disease had a significantly decreased likelihood of relapse.

Conclusion: Our analyses provide preliminary insights into the genetic architecture of remission and relapse in a well-characterized group of patients with psychotic depression.

Introduction: In our previous study, we successfully constructed the recombinant brain-derived neurotrophic factor (BDNF)-adeno-associated virus (AAV) modified by the influenza virus hemagglutinin-2 (HA2) and trans-transcriptional activator (TAT). BDNF-HA2TAT/AAV has been confirmed to have antidepression effects. BDNF-HA2TAT/AAV seems a promising therapy for post-traumatic stress disorder (PTSD) as the BDNF plays an important role in the function of the nervous system. However, the effects of BDNF-HA2TAT/AAV on PTSD caused by the single prolonged stress (SPS) model are unknown.

Methods: After the SPS model was established, BDNF-HA2TAT/AAV was administered (1 × 1011 vg per rat) through inhalation in the SPS + BDNF group for 2 weeks. Next, the rats underwent behavioral tests including an open-field test (OFT), elevated plus maze (EPM), and a forced swimming test (FST). Sera and hippocampi were obtained from the rats, and an enzyme-linked immune sorbent assay was performed to determine corticosterone concentration. Western blotting was conducted to determine BDNF, tyrosine kinase receptor B (TrkB), cAMP-response element-binding protein, and protein kinase B levels.

Results: BDNF-HA2TAT/AAV released anxiety-like and depression-like behaviors in OFT, EPM, and FST. BDNF-HA2TAT/AAV also results in high plasma concentrations of corticosterone, BDNF, and TrkB in the hippocampus.

Conclusions: SPS is an excellent animal model to assess PTSD. BDNF-HA2TAT/AAV therapeutically effects PTSD caused by SPS, with changes seen in plasma corticosterone and BDNF-TrkB pathways within the hippocampus; therefore, BDNF-HA2TAT/AAV may be a promising treatment for patients with PTSD.

Introduction: In recent years, several studies were conducted to explore the potential augmenting effect of oxytocin for the treatment of individuals with severe mental illness. Nonetheless, studies exploring its effects in routine inpatient settings using high-quality randomized controlled trials are scarce. The current study assessed the effect of oxytocin administration on treatment process and outcome among psychiatric inpatients, while employing a rigorous experimental methodology.

Methods: A double-blind, placebo-controlled, randomized trial was conducted at a public psychiatric hospital in Israel. Patients (N = 87, 71.3% female participants) were administered intranasal oxytocin/placebo twice daily for 4 weeks, as add-on to usual care. Patients were assessed for severity of anxiety and depression symptoms and their working alliance with their therapist after each therapy session, and treatment outcome was assessed weekly. Multilevel modeling was performed to assess the linear change from pre- to post-treatment.

Results: Patients receiving OT demonstrated significantly larger symptomatic improvements (B = -0.01, t [437] = -2.36, p = 0.01). Larger gains were also observed for depression (B = -0.14, p < 0.001 in the OT group, B = -0.06, p = 0.02 in the placebo group) and general distress (B = -0.57, p < 0.001 in the OT group, B = -0.29, p = 0.02 in the placebo group). No significant effect was observed for anxiety, the working alliance, or attachment.

Discussion: Oxytocin has the potential to improve treatment outcome among inpatients. Nonetheless, additional controlled research is needed to further assess its effects on therapy process, as well as to account for therapeutic, pharmacological, and neuronal intervening factors.

Introduction: Inflammation is closely associated with the pathogenesis of vascular dementia (VD). Dl-3-n-butylphthalide (NBP) is a small molecule compound extracted from the seeds of Chinese celery, which have anti-inflammatory properties in animal models of acute ischemia and patients with stroke. In this experiment, we studied the protective effects of NBP in a rat model of VD induced by permanent bilateral occlusion of the common carotid arteries and investigated the role of the TLR-4/NF-κB inflammatory signaling pathway in the pathology of VD.

Methods: The Morris water maze test was used to evaluate cognitive deficits in the VD rats. Western blot, immunohistochemistry, and PCR analyses were used to analyze the molecular basis of the inflammatory response.

Results: NBP significantly improved the learning and memory ability of VD rats. With regard to the protective mechanism, the results showed that NBP significantly downregulated the relative expression of Cleaved Cas-1/Cas-1 and Cleaved GSDMD/GSDMD. Moreover, NBP decreased the levels of the TLR-4 and NF-κB (P65) protein and phosphorylation of P65 in the hippocampus of VD rats via the TLR-4/NF-κB signaling pathway.

Conclusion: These findings demonstrate that NBP protects against memory deficits in permanent bilateral common carotid artery occlusion-induced VD rats by attenuating pyroptosis via the TLR-4/NF-κB signaling pathway.

Introduction: Currently, major depressive disorder (MDD) treatment plans are based on trial-and-error, and remission rates remain low. A strategy to replace trial-and-error and increase remission rates could be treatment stratification. We explored the heartbeat-evoked potential (HEP) as a biomarker for treatment stratification to either antidepressant medication or rTMS treatment.

Methods: Two datasets were analyzed: (1) the International Study to Predict Optimized Treatment in Depression (iSPOT-D; n = 1,008 MDD patients, randomized to escitalopram, sertraline, or venlafaxine, and n = 336 healthy controls) and (2) a multi-site, open-label rTMS study (n = 196). The primary outcome measure was remission. Cardiac field artifacts were removed from the baseline EEG using independent component analysis (ICA). The HEP-peak was detected in a bandwidth of 20 ms around 8 ms and 270 ms (N8, N270) after the R-peak of the electrocardiogram signal. Differences between remitters and non-remitters were statistically assessed by repeated-measures ANOVAs for electrodes Fp1, Cz, and Oz.

Results: In the venlafaxine subgroup, remitters showed a lower HEP around the N8 peak than non-remitters on electrode site Cz (p = 0.004; d = 0.497). The rTMS group showed a non-significant difference in the opposite direction (d = -0.051). Retrospective stratification to one of the treatments based on the HEP resulted in enhanced treatment outcome prediction for venlafaxine (+22.98%) and rTMS (+10.66%).

Conclusion: These data suggest that the HEP could be used as a stratification biomarker between venlafaxine and rTMS; however, future out-of-sample replication is warranted.

Introduction: The therapeutic structure of occupational therapy (OT) includes groups. Although the presence of others is expected to be relaxing due to the social buffering effect and the tend and befriend theory, it has not been sufficiently validated in accordance with the therapeutic structure of OT. The aim of this study was to investigate the electrophysiological evidence for the effectiveness of parallel groups and states of concentration on craft activities used in OT.

Methods: Thirty healthy young adults were used as controls to measure EEG and autonomic activity during craft activities in three conditions: alone, parallel, and nonparallel. EEG was analyzed using exact low-resolution electromagnetic tomography, and autonomic activity was analyzed using Lorenz plot analysis.

Results: Parasympathetic activity was significantly higher in the parallel condition than in the alone condition. A significant negative correlation was found between current source density and parasympathetic activity in the region centered on the right insular cortex in the α1 band, and functional connectivity in regions including the anterior cingulate cortex and insular cortex was associated with autonomic activity.

Conclusion: Craft activities that occurred during frontal midline theta rhythm also increased parasympathetic activity. The results suggest that the parallel groups used in OT and the intensive state of craft activities induce a social buffering effect that increases parasympathetic activity despite the absence of physical contact or social support. This provides evidence for the effectiveness of the therapeutic structure of occupational activities and groups in OT.