World Journal of Biological Psychiatry最新文献

Objectives: While neuropsychological effects of conventional antidepressants are well-documented, more research is needed for rapid-acting antidepressants. This study examines the effects of esketamine on emotion processing and cognitive functioning, both acutely and sub-chronically.

Methods: Eighteen treatment-resistant depression (TRD) patients received repeated intravenous esketamine infusions. Mood state was reported daily, and the Facial Expression Recognition Task was administered 1h before and 4h after each infusion. Other assessments included the Digit Symbol Substitution Task.

Results: 66.7% participants who received at least five infusions (n = 12) showed significant improvement. Emotion recognition improved for all emotions except sadness, where accuracy decreased, particularly for low-intensity expressions (p = .007, d = -1.09). Misclassifications of other emotions as sad also decreased (p = .035, d = -0.79), indicating a reduced response bias towards sadness. This shift in bias emerged after the first infusion and then consolidated over time. In parallel, participants showed significant reductions in feelings of sadness (p = .015, d = -0.89) and irritability (p = .001, d = -1.35). Symptomatic improvement negatively correlated with accuracy for and misclassifications of sadness, and cognitive functioning also improved (p = .001, d = 1.62).

Conclusions: Improvement of TRD by esketamine may involve shifts in emotion processing and cognition, with the acute mood-lifting effects of esketamine being discernible from longer-lasting antidepressant response, which consolidates after repeated administration.

Background: Magnetic seizure therapy (MST) has emerged as a promising alternative to electroconvulsive therapy (ECT) for treatment-resistant depression. Previous systematic reviews and meta analysis already showed its primary results, however, there are no recent reviews updating these findings.

Objectives: This systematic review aimed to make an updated systematic review of MST on unipolar and bipolar depression.

Methods: We conducted a search considering databases (PubMed/MEDLINE, EMBASE, Web of Science, Scopus). Studies were included if they investigated MST in human subjects for unipolar or bipolar depression, and not restricting to year or language.

Results: Data resulted in 15 studies, corresponding to 300 participants that received MST. Most studies were pilot, open-label or secondary analyses (n = 12). Participants that received MST had a response and remission rates ranging from 26.9% to 72.2% and 11.1% to 61.1%, respectively. The most common stimulation regions were vertex and prefrontal cortex, with frequencies between 25-100 Hz and duration of 6-24 sessions (2-3 times a week). Few side effects were reported.

Conclusions: MST shows to be effective and well-tolerated treatment for depression. Larger, double-blinded RCTs with standardised mood, cognitive, and side effect assessments are needed to confirm these findings.

Objectives: This study investigates the effects of quercetin, an antioxidant and nitric oxide (NO) modulator, on depressive-like behaviours triggered by social isolation stress (SIS) in mice. SIS, known to harm psychosocial functioning and increase the risk of depression, involves oxidative stress and NO in its pathophysiology.

Methods: 72 male mice were divided into nine groups, including the social (SC) group as the control group (stress-free with normal saline intake). The isolation (IC) groups received normal saline, quercetin at doses of 10, 20, and 40 mg/kg, the nitric oxide synthetase inhibitor L-NAME at a dose of 5 mg/kg, the NO precursor L-arginine at a dose of 100 mg/kg, an ineffective dose of quercetin combined with L-NAME and an effective dose of quercetin combined with L-arginine. Behavioural tests (open-field, forced swimming, and splash tests) were conducted, followed by measuring hippocampal nitrite levels.

Results: Quercetin significantly reduced immobility in the forced swimming test, increased activity in the open-field test, and enhanced grooming behaviour, particularly at 40 mg/kg. Co-administration of an ineffective dose of quercetin (10 mg/kg) with L-NAME increased immobility and grooming activity time. Interestingly, co-administration of the effective dose of quercetin (40 mg/kg) with L-arginine increased immobility time in the FST. Additionally, administration of quercetin at doses of 20 and 40 mg/kg significantly reduced the nitrite level in the hippocampus of SIS mice. Furthermore, co-administration of L-NAME and L-arginine with ineffective and effective doses of quercetin decreased and increased nitrite levels in the hippocampus and increased immobility time in the FST compared to their respective counterparts administered alone.

Conclusions: These results suggest quercetin's potential in alleviating depression by modulating NO levels, pointing to its promise in treating depression associated with chronic stressors like social isolation.

Objectives: This study employed a chronic unpredictable mild stress (CUMS) model to examine the antidepressant properties of SEP-363856.

Methods: The sucrose preference test (SPT) was employed to evaluate anhedonia, the open field test (OFT) to measure locomotor activity and exploratory behaviour, the elevated plus-maze (EPM) to assess anxiety-like behaviour, and the tail suspension test (TST) and forced swimming test (FST) to determine despair behaviour. qRT-PCR was implemented to evaluate gene expression levels in the hippocampus. Western blot, and ELISA were implemented to evaluate hippocampal protein expression, and Nissl staining was implemented to identify hippocampal neuronal injury.

Results: The 10 mg/kg dosage of SEP-363856 and fluoxetine significantly improved depressive-like behaviours as assessed by the SPT, OFT, EPM, TST, and FST. This was associated with improved hippocampal neuronal damage, enhanced mRNA expression of brain-derived neurotrophic factor, synaptophysin, and postsynaptic density 95. SEP-363856 increased the levels of insulin-like growth factor-1 (IGF-1), IGF-1 receptor β, phospho-phosphatidylinositide 3-kinase, and phospho-protein kinase B in the brain.

Conclusions: The antidepressant-like effects of SEP-363856 are linked to increased hippocampal neurotrophic factors, decreased hippocampus neuronal lesions, and activation of the IGF-1Rβ/PI3K/AKT signalling pathway. The latter may serve as a novel drug target for the treatment of depression.

Objectives: The primary objective in managing depression is achieving full recovery, but some patients experience ongoing symptoms that affect daily life, with residual hypersomnia being notably prevalent. Understanding its extent, frequency, and potential treatments is limited.

Methods: This systematic review consolidates existing knowledge on the prevalence and treatment of residual hypersomnia in depression, drawing from PubMed, Web of Science, and Scopus databases. The protocol was registered in PROSPERO (CRD42023392062).

Results: Residual hypersomnia is highly prevalent in depression. Modafinil is the only pharmacological intervention studied, showing short-term effectiveness in randomised placebo-controlled trials. For patients with comorbid obstructive sleep apnoea (OSA), continuous positive airway pressure (CPAP) appears promising for reducing excessive sleepiness. Challenges arise from ambiguous definitions of 'residual symptoms', 'partial response', and 'hypersomnia', and the use of various scales to assess hypersomnia. The scarcity of placebo-controlled randomised trials complicates evaluating treatment efficacy and standardising management approaches.

Conclusions: Given its high prevalence, managing residual hypersomnia is a significant challenge with current treatments appearing ineffective long-term. Data suggest benefits from modafinil augmentation and CPAP treatment, but more research is needed.

Background: India currently accounts for a majority of global suicide deaths. Research in European ancestry has established that suicide mortality has a significant genetic component, and suggests that inflammation may play a crucial role in the pathophysiology of suicide. Inflammation is also highly relevant in regions of increased pollution exposure, such as the megacities of India. To address the existing gaps in genetic research on suicide and possible association with inflammatory biomarkers, we examined genetic polymorphism and clinical risk phenotypes in a population-based suicide-death cohort, India.

Material and methods: Genotyping of IL-1β(rs16944) & (rs1143627), IL-4(rs2070874), IL-6(rs1800795) and IL-10(rs1800896) was done in 234 post-mortem suicide-death cases and 256 post-mortem controls (N = 490) using PCR RFLP method.

Results: Our analyses identified three significant (p < 0.001) associations of cytokine variants with suicide death, including IL-1β(rs16944), OR = 0.627; IL-4(rs2070874), OR = 0.524; and IL-6(rs1800795), OR = 2.509. Cases were more likely female and were more likely to have a history of psychiatric illness, though rate of psychiatric illness was low in suicide cases(9%).

Conclusion: Our genetic results are generally consistent with previous research on risk for depression and suicidal behaviour, and both genetic and phenotypic results provide new insights into risk factors that may contribute to suicide in India.

Objectives: Ketamine exerts rapid antidepressant effects by enhancing neuroplasticity, particularly in the amygdala and hippocampus-regions involved in fear processing and learning. While the role of ketamine's dissociative effects in its antidepressant response is debated, anxiety experienced during infusion has been negatively correlated with treatment outcomes.

Methods: In this single-blind, placebo-controlled study, a subset of 17 healthy volunteers (6 males, 23.12 ± 1.9 years) received intravenously a placebo in the first and 0.5 mg/kg racemic ketamine in the second session. Anxiety-related experiences were assessed by the 5D-ASC score obtained post-infusion, structural magnetic resonance imaging scans were acquired 4 h post-infusion. An anxiety-score was obtained from the 5D-ASC. Relation between post-placebo amygdala volume, hippocampal volume, and its subfields with the anxiety-score were assessed using linear regression models.

Results: Results showed a statistically significant negative relation between hippocampal head volume and the anxiety score (β = -0.733, p = 0.006), with trending negative association for each subfield's head and the score.

Conclusion: These findings suggest that anxiety-related experiences during ketamine infusion may be mediated by the hippocampus, with smaller hippocampal volumes leading to more anxiety-related experiences. Thus, hippocampal subfield volumes may be used as a predictor for anxiety-related events during ketamine use and might predict treatment outcome in future approaches.

Objectives: To report an observational case series study of sustained, once-weekly continuation transcranial magnetic stimulation (TMS) provided with the aim of maintaining remission in patients with major depressive disorder (MDD).

Methods: Once-weekly TMS treatments were provided to 7 patients (median age of 54 years) with chronic relapsing MDD: 4 of these patients entered the study in remission according to the six-item Hamilton depression rating scale (HAM-D6) and were followed for more than 12 months, and 3 patients entered the study in HAM-D6 partial remission/relapse and were followed for more than 6 months.

Results: All patients remained clinically well throughout the study. The 4 patients who entered in remission were maintained in HAM-D6 remission or partial remission. The 3 patients who entered the study in HAM-D6 partial remission/relapse were maintained free of clinical depression.

Conclusions: Seven patients with a history of relapsing MDD were provided with once-weekly continuation TMS and remained free of clinical relapse for more than 6 or 12 months. While the study had a small sample size, the clear, real-world outcomes warrant further investigation.

This study aims to elucidate the neuroimaging changes associated with major depressive disorder (MDD) and their relationship with genetic characteristics. We conducted a global-brain functional connectivity (GFC) and genetic-neuroimaging correlation analysis on 42 MDD patients and 42 healthy controls (HCs), exploring the correlation between GFC abnormalities and clinical variables. Results showed that compared to HCs, MDD patients had significantly decreased GFC values in the bilateral posterior cingulate cortex/precuneus and increased GFC values in the left and right cerebellum Crus I/II. Additionally, a negative correlation was observed between the GFC values of the left cerebellum Crus I/II and subjective support scores, as well as social support revalued scale total scores. We identified genes associated with GFC changes in MDD, which are enriched in biological processes such as synaptic transmission and ion transport. Our findings indicate the presence of abnormal GFC values in severe depression, complementing the pathological research on the condition. Furthermore, this study provides preliminary evidence for the correlation between social support levels and brain functional connectivity, offering insights into the potential association between GFC changes and gene expression in MDD patients.

Background: For psychotic disorders (i.e. schizophrenia), pharmacotherapy plays a key role in controlling acute and long-term symptoms. To find the optimal individual dose and dosage strategy, specialised tools are used. Three tools have been proven useful to personalise drug treatments: therapeutic drug monitoring (TDM) of drug levels, pharmacogenetic testing (PG), and molecular neuroimaging.

Methods: In these Guidelines, we provide an in-depth review of pharmacokinetics, pharmacodynamics, and pharmacogenetics for 45 antipsychotics. Over 30 international experts in psychiatry selected studies that have measured drug concentrations in the blood (TDM), gene polymorphisms of enzymes involved in drug metabolism, or receptor/transporter occupancies in the brain (positron emission tomography (PET)).

Results: Study results strongly support the use of TDM and the cytochrome P450 (CYP) genotyping and/or phenotyping to guide drug therapies. Evidence-based target ranges are available for titrating drug doses that are often supported by PET findings.

Conclusion: All three tools discussed in these Guidelines are essential for drug treatment. TDM goes well beyond typical indications such as unclear compliance and polypharmacy. Despite its enormous potential to optimise treatment effects, minimise side effects and ultimately reduce the global burden of diseases, personalised drug treatment has not yet become the standard of care in psychiatry.