World Journal of Biological Psychiatry最新文献

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.

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.

Objectives: Hair cortisol concentration (HCC) indicates chronic stress exposure, which is a risk factor in the pathogenesis of burnout and depression. However, findings on HCC are inconsistent. Similarly, intervention studies show mixed effects on HCC. The present study aimed to shed light on these inconsistencies, by additionally considering also hair cortisone.

Methods: Twenty-five patients with a burnout-related depressive disorder receiving a multimodal inpatient treatment for clinical burnout and 17 matched healthy controls participated in this study. All participants provided 1 cm long hair samples at the beginning and end of the treatment. HCC and hair cortisone levels (HCNC) were determined. Meteorological data and duration of sick leave were considered as potential covariates. Burnout and depression were assessed with self-ratings, the latter also with examiner ratings.

Results: There were no significant group differences in glucocorticoid levels. Treatment led to a decrease in both depression severity and hair glucocorticoid concentration in inpatients, while lower HCNC in particular predicted a greater reduction in depression severity. Moreover, meteorological data and the duration of sick leave were also found to have an effect on hair glucocorticoid concentrations.

Conclusions: These results suggest that multimodal inpatient treatment of clinical burnout considerably reduced stress on both a psychological and biological level. In parallel, hair glucocorticoids appear to be sensitive biomarkers for the evaluation of treatment success and prediction. Examining both HCC and HCNC in intervention studies may provide clearer results than the usual examination of HCC alone.

Objectives: ULK4 is an established candidate gene for mental disorders and antipsychotic treatment response. We investigated the association of functional genetic variation at the ULK4 locus with the human extended dopaminergic reward system using fMRI during the performance of a well-established reward paradigm.

Methods: Two hundred and thirty-four patients were included in this study. Association of genetic variation in the ULK4 gene with reward system functioning were determined using the Desire-Reason-Dilemma (DRD) paradigm which allows to assess brain activation in response to conditioned reward stimuli.

Results: Variant prioritisation revealed the strongest functional signatures for the ULK4 variant rs17215589, coding for amino acid exchange Ala715Thr. For rs17215589 minor allele carriers, we detected increased activation responses to conditioned reward stimuli in the ventral tegmental area, nucleus accumbens and several cortical brain regions of the extended reward system.

Conclusions: Our findings provide further evidence in humans that genetic variation in ULK4 may increase the vulnerability to mental disorders, by modulating the extended reward system function. Future studies are needed to confirm the modulation of the extended reward system by ULK4 and to specify the role of this mechanism in the pathogenesis of psychiatric disorders.

Objectives: We aimed to review and summarise the existing human literature on the association between lithium and hyperparathyroidism.

Methods: A systematic literature search was carried out according to PRISMA guidelines (last search 27 February 2024), using MEDLINE, Web of Science, Embase and the Cochrane Library. A meta-analysis was performed to determine the prevalence of lithium-associated hypercalcemia (LAH_ca) in lithium-treated patients.

Results: The pooled prevalence of LAH_ca based on total calcium and ionised calcium was comparable, at 3.17% and 4.23%, respectively. Calcium, and PTH if the patient is hypercalcaemic, is insufficiently measured in lithium-treated patients in clinical practice. Lithium use is associated with higher calcium and PTH levels, as well as a higher incidence of hyperparathyroidism. There is a high prevalence of multiglandular disease in lithium-associated hyperparathyroidism (LAH), with a pooled prevalence of 51.28%. Parathyroid surgery and cinacalcet are effective treatments for LAH. Regarding lithium discontinuation, there is anecdotal but conflicting evidence suggesting that it can result in the resolution of LAH in selected cases.

Conclusions: Lithium treatment increases the risk of hyperparathyroidism, a treatable complication with a pooled prevalence of around 4%, compared to 0.5% in the healthy population.

Objective: Syzygium aromaticum and Coffea canephora are acknowledged for their outstanding antioxidant, anti-inflammatory, and nerve-stimulant properties, showcasing potential in brain protection. Therefore, this study aims to quantitatively review existing literature and assess the potential of using it to formulate a herbal tea blend for managing stress and anxiety.

Methods: Data was retrieved from the Scopus database, and a bibliometric analysis was performed using VOSviewer software.

Results: Following a screening process, a total of 121 articles were identified, with S. aromaticum yielding a higher number compared to C. canephora. A detailed exploration of each plant revealed active components such as eugenol, β-caryophyllene, α-humulene, caffeine, mangiferin, and chlorogenic acids, each exhibiting stimulatory effects alongside antioxidant and anti-inflammatory properties. The neuroprotective effects were attributed to the reduction of oxidative stress and inflammation, coupled with the stimulation of neurotransmitters and hormones like dopamine, serotonin, cortisol, and adrenaline.

Conclusions: The review showed that these plants positively affect mood and cognition by influencing the brain's pleasure system. This suggests the need for further research to combine these plant extracts for developing 'Tenang tea', a potential herbal blend for managing stress and anxiety.