World Journal of Biological Psychiatry最新文献

Objectives: This systematic review and meta-analysis focussed on insights into the relationship between CACNA1C-rs1006737 and ZNF804A-rs1344706 polymorphisms and cognitive performance in schizophrenia (SCZ) spectrum and bipolar disorder (BD) and provide some contributions for clinical practice.

Methods: We searched the websites databases (PubMED, PsycINFO, Web of Science, EMBASE and Cochrane Library) using eligibility and exclusion criteria to capture all potential studies, based on PICO model and according to the PRISMA.

Results: Eight articles were included in this systematic review (five referring to CACNA1C-rs1006737 and three related to ZNF804A-rs1344706 polymorphisms), with a total of 5759 participants (1751 SCZ patients, 348 BD patients, 3626 controls and 34 first-degree relatives). The results demonstrated that the pooled effect of CACNA1C-rs1006737 (risk difference RD = 0.08; 95% CI 0.02-0.15) was associated with altered cognitive function in patients with severe mental disorders, but not ZNF804A-rs1344706 polymorphism (RD = 0.19; 95% CI 0.09-0.48.

Conclusion: The present meta-analysis provides evidence regarding slight association between CACNA1C-rs1006737 polymorphisms and cognitive performance in severe mental disorders, indicating that cognitive impairment in severe mental disorders associated with the CACNA1C rs1006737 risk variants could only be expressed when interacting with environmental exposures. This study is registered with PROSPERO, number CRD42021246726.

Objectives: The habenula is a brain structure implicated in depression, yet with unknown molecular mechanisms. Several phosphodiesterases (PDEs) have been associated with a risk of depression. Although the role of PDE7A in the brain is unknown, it has enriched expression in the medial habenula, suggesting that it may play a role in depression.

Methods: We analysed: (1) habenula volume assessed by 3-T magnetic resonance imaging (MRI) in 84 patients with major depressive disorder (MDD) and 41 healthy controls; (2) frequencies of 10 single nucleotide polymorphisms (SNPs) in PDE7A gene in 235 patients and 41 controls; and (3) both indices in 80 patients and 27 controls. The analyses considered gender, age, body mass index and season of the MRI examination.

Results: The analysis did not reveal habenula volumetric changes in MDD patients regardless of PDE7A SNPs. However, in the combined group, the carriers of one or more mutations among 10 SNPs in the PDE7A gene had a lower volume of the left habenula (driven mainly by rs972362 and rs138599850 mutations) and consequently had the reduced habenular laterality index in comparison with individuals without PDE7A mutations.

Conclusions: Our findings suggest the implication of the PDE7A gene into mechanisms determining the habenula structure.

Objectives: Based on previous research, it has been proposed that the development of depressive disorders is related to altered functioning of the serotonergic systems as well as the personality style, including narcissism. However, it is unclear to date how personality style, especially narcissism, depressive disorders and serotonergic activity are related.

Methods: We included 74 patients with a depressive disorder (DP) and 74 healthy controls (HC) in the study. All participants completed the Personality Style and Disorder Inventory (PSDI) and the Beck Depression Inventory (BDI II). Moreover, we conducted EEG recordings for analysis of serotonergic neurotransmission by using the so-called intensity or loudness dependence of the auditory evoked potentials (LDAEP).

Results: Significantly higher LDAEP results emerged for the DP group compared to the HC group, which indicated lower serotonergic activity in the patient's group. In addition, the positive correlation between ambitious-narcissistic personality and LDAEP reached significance in depressive patients.

Limitations: There was only a monocentric cross-sectional study with only one scale having differences between the two groups due to age and education.

Conclusions: Our data supports the theory of lower serotonergic activity in patients with depressive disorders and further suggests that high narcissistic personality traits are related to lower serotonergic neurotransmission in patients.

Objectives: Because alcohol use disorder (AUD) is often accompanied by mood disorder (MD) and both alcoholism and depression result in activation of the immune system, this study compares serum cytokine levels in the presence of co-morbidity with those in either AUD or MD alone.

Methods: In this naturalistic prospective study the levels of 15 different cytokines were measured in serum samples of patients with MD (n = 43), participants with combined AUD-MD (n = 44) and AUD without MD (n = 42). The levels were compared cross-sectionally among themselves and with those in 50 healthy volunteers.

Results: Pro-inflammatory IFN-2α levels were consistently significantly higher and anti-inflammatory IL-1RA significantly lower in all study groups in comparison to healthy volunteers. In the MD only group we found increased IL-6 (p = 0.001), IL-7 (p = 0.001) and IL-13 (p = 0.006) levels, and decreased TNFα (p = 0.0001), IL-1RA (p = 0.012), IL-10 (p = 0.002) compared with group MD + AUD. Patients with AUD only showed elevated levels of IL-1β (p = 0.046), IL-2 (p = 0.004), IL-7 (p = 0.0001), IL-4 (p = 0.049) and IL-13 (p = 0.015) in contrast with MD + AUD group.

Conclusions: Because the interactions of alcohol with peripheral and cerebral immune systems are multifaceted, the pertinent connection to the mechanism how alcohol consumption contributes to the development of mood disorders cannot be properly explored.

Objectives: Methamphetamine (METH) as a potent psychostimulant drug with a high potency of dependence rate that results in neurotoxicity has become a major drug of abuse in many parts of the world. Unfortunately, there is limited evidence regarding treatment of METH withdrawal syndrome. Therefore, we aimed to investigate whether metformin mitigate the methamphetamine (METH) withdrawal syndrome in male mice. Based on the literature, depression and anxiety are the major METH withdrawal symptoms.

Methods: Here, METH (2 mg/kg) was administered to mice twice a day for 14 constitutive days to induce animal model of METH-induced withdrawal syndrome. To do this, mice in control group and those with METH withdrawal syndrome were divided into treatment (receiving metformin in 3 doses of 50, 100 and 200 mg/kg for 10 days) and non-treatment sub-groups. Following the behavioural test, the animals were sacrificed; their hippocampus was dissected to measure oxidative stress parameters and expression of cellular energy homeostasis and immune-inflammatory genes.

Results: Our data revealed that metformin provoked antidepressant effects in behavioural tests through AMPK overexpression as an important mitochondrial energetic sensor and inhibition of Tlr4 overexpression in the immune system gene expression. In addition, metformin was able to improve oxidative stress biomarkers and neuronal damage in the hippocampus and restore cellular energy homeostasis and immune system gene expression.

Conclusions: The data suggested that metformin can influence the hippocampus through targeting mitochondria and their performance, and consequently, neuroinflammation responses and brain metabolic changes. It is supposed to be a new therapeutic option in clinical trials of depression and anxiety following METH withdrawal treatment.

Objectives: Recent studies have reported altered methylation levels at disorder-relevant DNA sites in people who are ill with Anorexia Nervosa (AN) compared to findings in people with no eating disorder (ED) or in whom AN has remitted. The preceding implies state-related influences upon gene expression in people with AN. This study further examined this notion.

Methods: We measured genome-wide DNA methylation in 145 women with active AN, 49 showing stable one-year remission of AN, and 64 with no ED.

Results: Comparisons revealed 205 differentially methylated sites between active and no ED groups, and 162 differentially methylated sites between active and remitted groups (Q < 0.01). Probes tended to map onto genes relevant to psychiatric, metabolic and immune functions. Notably, several of the genes identified here as being differentially methylated in people with AN (e.g. SYNJ2, PRKAG2, STAT3, CSGALNACT1, NEGR1, NR1H3) have figured in previous studies on AN. Effects also associated illness chronicity and lower BMI with more pronounced DNA methylation alterations, and remission of AN with normalisation of DNA methylation.

Conclusions: Findings corroborate earlier results suggesting reversible DNA methylation alterations in AN, and point to particular genes at which epigenetic mechanisms may act to shape AN phenomenology.

Aim: This is the third version of the guideline of the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Posttraumatic Stress Disorders which was published in 2002 and revised in 2008.

Method: A consensus panel of 34 international experts representing 22 countries developed recommendations based on efficacy and acceptability of the treatments. In this version, not only medications but also psychotherapies and other non-pharmacological interventions were evaluated, applying the same rigorous methods that are standard for the assessment of medication treatments.

Result: The present paper (Part II) contains recommendations based on published randomised controlled trials (RCTs) for the treatment of OCD (n = 291) and PTSD (n = 234) in children, adolescents, and adults. The accompanying paper (Part I) contains the recommendations for the treatment of anxiety disorders.For OCD, first-line treatments are selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT). Internet-CBT was also superior to active controls. Several second-line medications are available, including clomipramine. For treatment-resistant cases, several options are available, including augmentation of SSRI treatment with antipsychotics and other drugs.Other non-pharmacological treatments, including repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS) and others were also evaluated.For PTSD, SSRIs and the SNRI venlafaxine are first-line treatments. CBT is the psychotherapy modality with the best body of evidence. For treatment-unresponsive patients, augmentation of SSRI treatment with antipsychotics may be an option.

Conclusion: OCD and PTSD can be effectively treated with CBT and medications.

Objectives: Treatment-resistant obsessive-compulsive disorder is a chronic debilitating illness. We conducted a network meta-analysis [NMA] to compare the efficacy of all interventions in SRI-resistant OCD from published Randomised controlled trials [RCT].

Methods: We performed an NMA of RCTs in SRI resistant OCD from all modalities of treatments; pharmacological, psychological, neuromodulation, neurosurgery including deep brain stimulation. The design-by-treatment interaction inconsistency model within the frequentist framework was adopted with a change in Yale-Brown Obsessive-Compulsive Scale score as the primary outcome. We conducted sensitivity analyses excluding studies examining neurosurgical interventions, deep brain stimulation, studies in the paediatric population, and studies from a single geographical region. We also conducted analyses of interventions categorised into treatment groups.

Results: 55 RCTs examining 19 treatments or placebo involving 2011 participants were included in the NMA. Ondansetron [Standardised mean difference -2.01 (95% CI: -3.19, -0.83)], deep TMS [- 1.95 (-3.25, -0.65)], therapist administered Cognitive Behavioural Therapy [CBT-TA] [-1.46 (-2.93, 0.01)] and aripiprazole [-1.36 (-2.56, -0.17)] were ranked as the best four treatments on using the Surface Under the Cumulative Ranking [SUCRA] percentage values (85.4%, 83.2%, 80.3%, 67.9% respectively). While all four interventions had large effect sizes, CBT[TA] narrowly missed statistical significance in our analysis. In sensitivity analyses, deep TMS was ranked as the best treatment strategy for SRI-resistant OCD. The small number of subjects in individual studies, higher confidence interval limits, and wider prediction interval for most agents warrant a cautious interpretation.

Conclusions: Considering the principal analysis and sensitivity analyses together, deep TMS, ondansetron, CBT[TA], and aripiprazole may be considered a first-line intervention for SRI-resistant OCD in adults.

Other: This work was not funded. The NMA has been registered with PROSPERO, [Registration number: CRD42020173589].