Neuropsychopharmacology Reports最新文献

We report a case of a 61-year-old female with 22q11.2 deletion syndrome (22q11.2DS) and a novel heterozygous nonsense variant in MAP1A, identified through whole-genome sequencing (WGS). The patient presented with intellectual developmental disorder, treatment-resistant schizophrenia (SCZ), and multiple congenital anomalies. Despite aggressive pharmacotherapy, she experienced persistent auditory hallucinations and negative symptoms. WGS revealed a 3 Mb deletion at 22q11.2 and a nonsense variant in MAP1A (c.4652T>G, p.Leu1551*). MAP1A, encoding microtubule-associated protein 1A, is crucial for axon and dendrite development and has been implicated in autism spectrum disorder and SCZ. The MAP1A variant may contribute to the severe psychiatric phenotype, as it is thought to influence synaptic plasticity, a process also affected by 22q11.2 deletion. This case highlights the importance of WGS in identifying additional pathogenic variants that may explain phenotypic variability in 22q11.2DS. Thus, WGS can lead to a better understanding of the genetic architecture of 22q11.2DS. However, further studies are needed to elucidate the role of secondary genetic contributors in the diverse clinical presentations of 22q11.2DS.

Aim: Postmortem brain studies offer enormous opportunities to study molecular mechanisms associated with suicide. In the present study, conventional [³⁵S]GTPγS binding assay and its version-up method ([³⁵S]GTPγS binding/immunoprecipitation assay) were applied to postmortem human hippocampal membranes prepared from suicide victims and control subjects.

Methods: By using conventional [³⁵S]GTPγS binding assay, functional activations of G_i/o proteins coupled with multiple GPCRs (5-HT_1A receptor, α_2A-adrenoceptor, M₂/M₄ mAChRs, adenosine A₁ receptor, histamine H₃ receptor, group II mGlu, GABA_B receptor, μ-opioid receptor, δ-opioid receptor, and NOP receptor) were detected by using 15 different agonists. Furthermore, 5-HT_2A receptor- and M₁ mAChR-mediated Gα_q/11 activation and adenosine A₁ receptor-mediated Gα_i-3 activation were detectable by means of [³⁵S]GTPγS binding/immunoprecipitation assay.

Results: No significant differences in pharmacological parameters of all concentration-response curves investigated were found between suicide victims and control subjects. Significant correlations were obtained for the maximal percent increases between some distinct signaling pathways.

Conclusion: Although only preliminary and auxiliary results were obtained as to the potential differences between suicide victims and control subjects because of the limited number of subjects as well as unmatched age and postmortem delay, adenosine A₁ receptor-mediated Gα_i/o activation and 5-HT_2A receptor-mediated Gα_q/11 activation appear worth focusing on in the future investigations. This study also indicates the possibility that some distinct signaling pathways are interrelated with each other, for example, functional activations of G_i/o proteins coupled to M₂/M₄ mAChR and 5-HT_1A receptor, NOP receptor, and GABA_B receptor, and NOP receptor and δ-opioid receptor.

Aims: Women may experience unique mental disorders due to hormone shifts. Rates of schizophrenia and bipolar disorder are similar between genders, but onset and symptoms may differ. Women tend to use more psychotropic drugs due to limited therapeutic options. This study was aimed to estimate the prevalence of psychotropic polypharmacy among females of childbearing potential and factors impacting prescribing patterns.

Methods: This was a quantitative retrospective chart review for patients admitted to inpatient units at the Mental Health Hospital in Qatar. SPSS® Statistics was used for data analysis. In addition to descriptive statistics applied, linear regression and binary logistic regression models were used to examine the clinical and sociodemographic factors associated with polypharmacy and full therapeutic response upon discharge, respectively. An alpha value of 0.05 was used.

Results: Of the 347 patients, 52.7% of the patients received a prescription of at least two psychotropic drugs upon discharge. Around two-thirds (63.1%) were prescribed at least one antipsychotic. Potential predictors of polypharmacy were age (p = 0.027), longer hospital stay (p = 0.003), family history (p < 0.001), absence of suicidal history (p = 0.005), and a diagnosis of a mood disorder (p = 0.009), or a diagnosis of a psychotic disorder (p = 0.015). A full response upon discharge was less likely to occur in patients with a longer stay (OR = 0.940; p = 0.029) and in those with a substance use disorder (OR = 0.166; p = 0.035).

Conclusion: There is a notably high prevalence of total polypharmacy upon discharge. Some identified factors are modifiable. Evidence-based prescription practices through hospital guidelines and education should be emphasized to avoid unreasonable polypharmacy.

Amada N, Hirose T, Suzuki M, Kakumoto Y, Futamura T, Maeda K, et al. Synergistic anti-depressive effect of combination treatment of Brexpiprazole and selective serotonin reuptake inhibitors on forced swimming test in mice. Neuropsychopharmacol Rep. 2023;43:132-136. In the 'Methods' section of the Abstract, the second sentence is as follows: "Escitalopram (10 mg/kg), fluoxetine (75 mg/kg), paroxetine (10 mg/kg), or sertraline (15 mg/kg) were orally administered to mice 60 min before testing." The amount listed for escitalopram is incorrect. It should be: 60 mg/kg. We apologize for this error.

Aims: Eating disorders represent an aspect of mental illness involving failure to control eating behaviors. Food valence plays a regulatory role in eating behaviors and changes with eating experiences. Failure to control food valence may be associated with eating disorders. This study presents a newly developed behavior task-food reservation task, which assesses changes in food valence.

Methods: Over three consecutive days, mice were fed a regular diet for 30 min and subsequently were offered either palatable or low-palatable foods for 30 min.

Results: Mice decreased regular diet consumption on the days that it was followed by a palatable food-sweet chocolate (SC) or cheese (CH) and increased it when it was followed by a low-palatable food-bitter (dark) chocolate (BC). Our findings indicate that mice can change regular diet consumption by learning whether it will be followed by a palatable or low-palatable food. This suggests that palatable food devaluated the food valence of regular diet, whereas low-palatable food evaluated it.

Conclusion: We developed a new food reservation task, which allows to assess experience-dependent change in the food valence of a regular diet. This task will contribute to a better understanding of the neural mechanisms underlying those changes.

Aim: Real-world data (RWD) for paliperidone palmitate (PP) three-monthly (PP3M) is lacking based on Japan label requirements. This study evaluated the clinical effectiveness of PP3M versus PP once-monthly (PP1M) in patients with schizophrenia administered according to Japan label requirements.

Methods: Retrospective analyses were conducted using RWD from Merative™ MarketScan® Multi-State Medicaid (MDCD) claims database (June 2015-December 2022). Adult patients with schizophrenia switching from PP1M to PP3M were included. Patients transitioning to PP3M were matched with patients who continued with PP1M using propensity score matching (PSM) at 1:1 ratio. Primary hypothesis aimed to investigate non-inferiority of PP3M versus PP1M in terms of relapse-free status at 24 months from index PP injection. Outcome measures were proportions of relapse-free patients at 24 months, time to relapse, treatment persistence, and adherence.

Results: Total 4252 eligible adult schizophrenia patients on PP (PP3M:582; PP1M:3670) were identified. After PSM, each PP cohort comprised 562 matched individuals. Estimated proportion of relapse-free patients was higher in PP3M (85.7%) versus PP1M (77.9%), per Japan PP label. PP3M demonstrated superiority to PP1M after testing for non-inferiority in terms of achieving relapse-free status at 24 months, with an estimated difference of 7.8% (95% CI: 1.7%-13.9%). PP3M cohort had lower risk of relapse (HR: 0.605; CI: 0.427-0.856), longer treatment persistence, and higher treatment adherence versus PP1M cohort.

Conclusions: Findings suggests that patients who switched to PP3M might be able to reduce risk of relapse compared to those who continued PP1M after aligning particularly with Japan's label requirements.

The current literature on the effects of clozapine on pregnancy is limited, and no cases of pregnant Japanese women have been reported. Decreased variability in the fetal heart rate due to clozapine exposure has been reported in countries other than Japan, but its association with serum concentrations of clozapine has not been documented. In this case, a 29-year-old Japanese primipara with treatment-resistant schizophrenia taking clozapine 250 mg/day experienced pregnancy. The pregnancy progressed without complications. At 40 weeks and 2 days of gestation, the patient developed premature rupture of membranes, and decreased variability in the fetal heart rate and variable deceleration were observed, leading to an emergency cesarean section. The neonate had no congenital malformations, metabolic disorders, seizures, floppy infant syndrome, leukopenia, or neutropenia. Serum concentrations of clozapine and norclozapine (N-desmethylclozapine), measured in the mother and in the neonate immediately after birth, suggested that clozapine and norclozapine were transported to the fetus during pregnancy. Based on these observations, the present case suggests that high fetal serum concentrations of clozapine and norclozapine may affect fetal heart rate. This case report concludes that, with careful monitoring, Japanese women taking clozapine can deliver successfully and emphasizes the importance of monitoring serum clozapine concentrations and fetal cardiac function throughout pregnancy, with particular attention to the later stages.

Background: Stressors induce depression together with parenting experienced in childhood, personality traits, and sleep. In this study, we investigated factors associated with the development of depression in a long-term stressful environment, namely, the Antarctic Research Expedition wintering party, by comparing 2 groups, the depression and nondepression groups.

Methods: A self-administered questionnaire was used to survey 91 members of the Japanese Antarctic Research Expedition who spent winters in the Antarctic base. Psychological evaluations of depression, anxiety, and sleep were performed using a questionnaire every 3 months during the participants' stay in Antarctica. The primary endpoint was the occurrence of minor or major depression, as evaluated by the PHQ-9 score.

Results: Participants with a PHQ-9 score of 5 or more during their stay in Antarctica were defined as the depression group (25 subjects), and participants with a PHQ score of 4 or less were defined as the nondepression group (43 subjects). Compared with the nondepression group, the depression group had significantly higher scores for predeparture PHQ-9, state and trait anxiety, sleep disturbance, and neuroticism. Multivariable logistic regression analyses showed that higher predeparture scores of subthreshold depressive symptoms and neuroticism were found to be significant predictors of the occurrence of depression during their stay in Antarctica.

Conclusions: This study prospectively showed that subthreshold depressive symptoms and neuroticism, which were suggested as risk factors in previous studies, were confirmed to be risk factors for depression. The results of our study are expected to contribute to the understanding of depression in harsh environments.

Background: Post-traumatic stress disorder (PTSD) is a mental health disorder resulting from exposure to traumatic events, manifesting in various debilitating symptoms. Despite available treatments, many individuals experience inadequate response or significant side effects. Previous reviews suggest promising outcomes with MDMA-assisted psychotherapy (MDMA-AT), but limitations prompt the need for a comprehensive evaluation.

Methods: We searched various online databases and registries such as MEDLINE (via PubMed), Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov to retrieve RCTs that fit our inclusion criteria. We performed meta-analyses using Review Manager by applying a random-effects model. Dichotomous and continuous outcomes were pooled as risk ratios (RR) and standard mean difference (SMD), respectively.

Results: Nine studies with a total of 297 participants with PTSD were included in our meta-analysis. The control group consisted of inactive doses of MDMA (25-40 mg) or placebo. Our meta-analysis showed that MDMA-AT led to a significant reduction in the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) severity scores as compared to the control group (SMD -1.10, 95% CI: -1.62 to -0.59). More patients in the MDMA-AT group exhibited significant response (RR 1.59, 95% CI: 1.22, 2.08) and remission (RR 2.32, 95% CI: 1.47 to 3.66) as compared to patients in the control group. There was no significant difference regarding the incidence of ≥1 treatment-emergent adverse events (TEAE), ≥1 severe TEAE, and suicidal ideation between the two groups.

Conclusion: MDMA-AT demonstrates significant efficacy in improving PTSD symptoms, enhancing both response and remission rates in individuals with chronic, treatment-resistant PTSD, while maintaining a favorable safety profile.

Aim: Social anxiety disorder (SAD) is a common disorder characterized by excessive fear of scrutiny and embarrassment, leading to severe distress and avoidance behaviors or dysfunctions. SAD and other relevant diseases have been reported to be associated with a higher risk of aging-related diseases, such as Alzheimer's disease, Parkinson's disease, and diabetes mellitus. Recently, epigenetic clock analysis, which measures biological aging based on comprehensive DNA methylation (DNAm) status, has been widely conducted. We conducted epigenetic clock analyses in patients with SAD and controls, examining various epigenetic age acceleration and DNAm-based predictive values of aging-related proteins (GrimAge components and GrimAge2 components), including leptin level.

Methods: We used the publicly available DNAm dataset, GSE164056, which consists of 66 patients with SAD and 77 controls of Caucasian descent aged between 18 and 50 years. We conducted regression analyses investigating the association between SAD and various indices of epigenetic aging, using age and sex as covariates.

Results: None of the epigenetic clocks showed significant differences in age acceleration. Of the DNAm-based predictive values of aging-related proteins, leptin level in GrimAge components (q = 0.0123) and GrimAge2 components (q = 0.0123) were significantly lower in patients with SAD than in controls.

Conclusions: The results of this study suggested that leptin may be involved in SAD pathogenesis as an aging-related protein. Therefore, further studies with different designs are required.