Clinical Psychopharmacology and Neuroscience最新文献

Objective: Suicide is a significant public health issue, particularly among older adults, where the risk is heightened. Early identification of individuals at risk for suicidal ideation is essential for timely interventions, greatly improving prevention efforts. This study aimed to develop a predictive model for suicidal ideation in community-dwelling older adults using psychiatric self-report scales and machine learning classifiers.

Methods: A total of 238 older adults were assessed using the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7, Perceived Stress Scale-10, and World Health Organization Quality of Life Scale - Abbreviated Version. A nested 5-fold cross-validation procedure repeated 100 times was used for feature selection and model evaluation. Various classifiers-including support vector machines, random forest, logistic regression, linear discriminant analysis, and gradient boosting-were employed.

Results: As the number of PHQ-9 items increased from two to six, the area under the curve (AUC) rose from 0.835 to 0.892. When a set of nine features-selected based on feature stability across iterations-was used, the AUC further improved to 0.904. This progression indicates that inclusion of additional informative items enhances classification performance.

Conclusion: This study demonstrates that psychiatric self-report scales can effectively predict suicidal ideation risk in community-dwelling older adults. By utilizing efficient features, the predictive accuracy of the model can be enhanced, offering valuable insights for developing early identification systems for high-risk groups. These findings suggest that a community-based suicide prevention program could be promoted by implementing a screening system to identify individuals at high risk for suicidal ideation among the elderly.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique used to treat major depressive disorder (MDD), particularly in patients with treatment resistant depression. More recently, accelerated transcranial magnetic stimulation (aTMS) has shown comparable efficacy while offering a faster treatment option. This review assesses whether aTMS is non-inferior to rTMS. This systematic review compared aTMS and rTMS protocols for MDD treatment. Studies were identified through PubMed, Cochrane Library, and Web of Science (September 2024). Non-MDD populations and non-aTMS techniques were excluded, such as studies that did not qualify as clinical trials, cohort or randomized controlled trial. Inclusion criteria required direct protocol comparisons and a minimum sample of 10 participants. Bias assessment followed the Cochrane Collaboration's robvis tool. Four studies were included, encompassing a total sample of 219 patients. Results showed symptom improvement across all groups, with accelerated protocols demonstrating faster response in some cases. However, long-term efficacy varied, and no study provided conclusive superiority of one protocol over the other. This study reveals the variability in aTMS protocols and the inconsistency in the depression rating scales selected across studies, noting that the lack of standardised assessment methods limits meta-analytical potential. Short follow-up durations contrast with antidepressant studies, restricting long-term efficacy evaluation. Additionally, improvements in sham methodologies have increased placebo responses, further influencing treatment outcome interpretation. This systematic review highlights the efficacy, tolerability, and cost-effectiveness of aTMS, suggesting its non-inferiority to rTMS and underscoring the need for further research to define the optimal accelerated protocol.

Objective: This study aimed to explore treatment outcomes and pharmacological treatment intensities across major depressive disorder (MDD) subtypes over a 24-month period in a naturalistic clinical setting.

Methods: A total of 1,079 MDD patients were classified into melancholic (n = 182; 16.9%), atypical (n = 68; 6.3%), and unspecified (n = 829; 76.8%) subtypes and followed in a longitudinal cohort study. Treatment intensity and outcomes, including 12-week and 12-month remission and 24-month relapse rates, were measured using the Hamilton Depression Rating Scale.

Results: There were no significant differences in remission or relapse rates across subtypes at 12 weeks, 12 months, or 24 months. However, melancholic and atypical subtypes received more intensive pharmacological treatments compared to the unspecified subtype, particularly during the initial 12-week treatment phase. This increased treatment intensity was associated with equivalent outcomes across subtypes.

Conclusion: Despite similar long-term outcomes across MDD subtypes, variations in treatment intensity were crucial for achieving these results. Our findings suggest that tailoring treatment plans according to depressive subtype severity and characteristics is essential for effective management. Future research should investigate the genetic and biomolecular bases of these subtypes to further optimize treatment strategies.

Objective: Body scan meditation is a popular mindfulness practice in which a person directs their attention toward internal bodily sensations. Although its neural mechanisms have been investigated using functional magnetic resonance imaging, few studies have used functional near-infrared spectroscopy (fNIRS) to directly measure prefrontal networks during body scan meditation.

Methods: In this study, symptoms of depression and anxiety were measured in 40 healthy young adults without prior meditation experience. Participants' prefrontal networks were evaluated using fNIRS during body scan meditation and resting with nature sounds.

Results: Analyses of fNIRS data revealed significant positive prefrontal network connectivity in both conditions, with greater connectivity between the dorsolateral prefrontal cortex and medial prefrontal cortex observed when participants were resting with nature sounds than during body scan meditation. Correlation analyses showed that the left dorsolateral superior frontal gyrus-right medial superior frontal gyrus connectivity during body scan meditation was negatively associated with depressive and anxiety symptoms and positively associated with emotion regulation abilities.

Conclusion: Enhanced prefrontal networks induced by meditation may have therapeutic implications for mental health. The fNIRS findings, which measured direct changes in prefrontal networks during body scan meditation, could serve as a cornerstone for understanding the neural correlates.

Objective: 3,4-Methylenedioxymethamphetamine (MDMA) is widely used recreationally but also modulates serotonergic signaling in the gut, potentially influencing the microbiota. Because low bone mineral density (BMD) is common in depression and other psychiatric disorders, we tested whether repeated, intermittent MDMA attenuates BMD loss in ovariectomized (OVX) mice.

Methods: OVX mice received MDMA (10 mg/kg) three times per week for six weeks. BMD was measured, and untargeted metabolomics of plasma samples along with gut microbiota profiling of fecal samples were performed.

Results: Compared with vehicle, MDMA increased whole-body and femoral BMD and shifted circulating bone-remodeling markers toward an antiresorptive profile-lower receptor activator of nuclear factor-κB ligand (RANKL) and higher osteoprotegerin. Gut microbiota profiling and untargeted metabolomics showed reduced Clostridia and enrichment of Bacilli, along with a marked decrease in plasma β-D-allose, a metabolite linked to Lactobacillus johnsonii.

Conclusion: These findings suggest that intermittent MDMA may mitigate OVX-induced BMD loss in association with remodeling of a gut microbiota-bone axis. Future studies should define causal microbial and metabolic mediators and evaluate generalizability across additional bone-loss models.

Depression is increasingly conceptualized as a disorder of impaired synaptic plasticity and excitation-inhibition imbalance within corticolimbic circuits. Two rapid-acting therapeutic classes, NMDA receptor modulators (ketamine, esketamine) and neuroactive-steroid GABA-A positive allosteric modulators (brexanolone, zuranolone), offer complementary approaches to restore circuit function. Clinically, intravenous ketamine and intranasal esketamine show superiority over placebo and active comparators in treatment-resistant depression (TRD), with esketamine supported for continuation-phase relapse prevention and, in the United States, is approved both as adjunctive therapy and as monotherapy in adults with TRD. Evidence of efficacy extends to bipolar depression with careful mood-stabilizer coverage. Both agents reduce suicidal ideation within hours to days, although effects on suicidal behavior have not been demonstrated. Safety profiles include dissociation and hemodynamic changes; concerns with prolonged or high-cumulative exposure include cystitis and misuse liability. Neurosteroid GABA-A modulators are effective in post partum depression with some preliminary evidence in major depression, particularly in combination with antidepressants, while adverse events are mainly dose-dependent sedation. Brexanolone requires monitored infusion, whereas zuranolone enables a 14-day outpatient course. Patient selection should integrate diagnosis, comorbidity, concomitant medications (e.g. benzodiazepines), logistics, and perinatal goals. Robust efficacy/tolerability predictors remain limited, though early symptomatic change is clinically informative. In conclusion, NMDA receptor modulators and neuroactive-steroid GABA-A positive allosteric modulators have improved the treatment for mood disorders and accelerated a transition to mechanism-driven care.

Objective: The choice of emotion regulation (ER) strategies depends on contextual characteristics, and the flexible choice of ER strategies based on context is essential for psychological health, including depression. Focusing on reappraisal, this study examined how perceived reappraisal affordances (the inherent potential of a situation for semantic reappraisal) -a reappraisal-related situational factor-are linked to the success of reappraisal use via reappraisal choice and investigated the role of depression in this mediation.

Methods: Eighty participants (40 individuals with major depressive disorder [MDD] and 40 non-depressed controls) read eight vignettes describing negative-emotion-evoking situations and reported reappraisal affordance, the likelihood of choosing reappraisal, and negative emotional responses for each vignette. Then, they were asked to implement reappraisal for each situation, followed by reporting their negative emotional responses again.

Results: Reappraisal affordance predicted greater reductions in negative emotions following reappraisal use (i.e., greater success) via an increased choice of the strategy. Group moderated the affordance-choice relationship, with a significant positive relationship observed only in the MDD group, while the relationship was not significant in the controls.

Conclusion: These results support the idea that considering contextual factors is crucial in understanding ER; however, adjusting ER choice based on situational factors may not always reflect flexible ER, as indicated by the significant affordance-choice link only in the MDD group.

Objective: Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by the presence of obsessions and/or compulsions that cause significant distress and functional impairment. Despite extensive research, its etiopathogenesis remains incompletely understood. Recent evidence suggests that dysfunction in tight junctions may contribute to the pathophysiology of various psychiatric disorders. Tight junction proteins play a crucial role in maintaining blood-brain barrier integrity and regulating neuronal signaling. This study aims to investigate the involvement of tight junction proteins in the etiopathogenesis of OCD, providing new insights into their potential role in the disorder's neurobiological mechanisms.

Methods: A total of 41 medication-free children and adolescents with OCD and 41 healthy controls were included in this study. The participants filled out self-report scales to determine various psychological variables. Blood samples were collected from all participants to measure the levels of claudin-5, claudin-12, occludin, angulin-1, and tricellulin.

Results: The levels of claudin-5, claudin-12, occludin, and tricellulin were significantly higher in the OCD group compared to the control group. However, there was no significant difference in angulin-1 levels between the groups.

Conclusion: Our findings indicate that claudin-5, claudin-12, occludin, and tricellulin levels differ between individuals with OCD and healthy controls. These results suggest that tight junction proteins may contribute to the etiopathogenesis of OCD. Further research is needed to better understand the relationship between OCD and tight junction proteins.

Objective: In vitro models are useful for exploring the molecular mechanisms underlying impaired neuroplasticity in depression. In this study, we developed a three-dimensional spheroid model in which we investigated the effects of the synthetic glucocorticoid dexamethasone on key pathways involved in neuroplasticity, specifically BDNF, sirtuin 1, and mTORC1 signaling.

Methods: A micro-spheroid device was fabricated using photolithography and soft lithography, and cortical spheroids were generated from primary rat cortical cells. These spheroids, which contained neurons, astrocytes, microglia, and oligodendrocytes, were treated with various concentrations of dexamethasone.

Results: Dexamethasone treatment (100, 200, and 300 μM) resulted in a dose-dependent reduction in cell viability, BDNF mRNA expression, and neurite outgrowth. At 100 μM, dexamethasone reduced the expression of BDNF and sirtuin 1 and decreased the phosphorylation of ERK1/2. It also decreased the phosphorylation of mTORC1, 4E-BP1, and p70S6K, as well as synaptic proteins such as PSD-95 and GluA1.

Conclusion: Dexamethasone treatment inhibited pathways related to neuroplasticity. While dexamethasone-treated spheroids may serve as a basis for developing an in vitro model of depression, further validation is needed to confirm their broader applicability.

Objective: Levels of circulating cytokines has been shown to be related to psychological distress. We have earlier shown that the symptoms of hostility may be related to levels of interferon γ inducible protein 10 (IP-10) in a group of general psychiatric in-patients receiving psychotropic medication. Here we investigate this association in a group of patients with chronic hepatitis C virus (HCV) infection with or without opioid maintenance treatment (OMT).

Methods: In a cross-sectional study, out-patients were interviewed for psychological distress using the Symptoms Check-List-90-R (SCL-90-R) and blood samples were drawn to measure serum levels of IP-10. Hierarchical linear regression analysis was used to investigate the association between hostility and IP-10 hostility in the whole group, and in the non-OMT and the OMT-patients, respectively.

Results: One hundred and twenty patients with chronic HCV infection were included, of whom 53 received OMT. There was no association between hostility and IP-10 in the patient group as a whole. In the OMT group we observed a negative association throughout the steps including adjusting for age, gender and BMI (β = -0.48, p = 0.011).

Conclusion: We observed that only in OMT patients was there a negative association between hostility and IP-10. This might support previous findings that drugs, self-reported mental health symptoms and cytokines interact.