Neuropsychopharmacology Reports最新文献

Objective: The use of serotonin 5-HT_1A receptor partial agonists (5-HT_1A-PAs) as an add-on therapy has been associated with the enhancement of attention/processing speed in patients with schizophrenia. Also, 5-HT_1A receptors have been shown to play a role in the pathophysiology of mood disorders. There is compelling evidence supporting that stimulation of 5-HT_1A receptors accelerates antidepressant effects. Accordingly, this systematic review examines the ability of adjunctive treatment with 5-HT_1A-PAs to improve cognitive function in patients with depressive symptoms.

Methods: A literature search using PubMed, the Cochrane Library, and Web of Science databases was performed from 1987 to January 2024 to identify randomized controlled trials (RCTs) corresponding to the following inclusion criteria: (1) RCTs, (2) human studies; studies that (3) targeted patients with a psychiatric disorder (except for schizophrenia or schizoaffective disorder), (4) evaluated the effect of cognitive functions, (5) were written in English.

Results: From the 80 studies initially screened, three met the inclusion criteria. Two of these studies dealt with vascular depression while one focused on major depressive disorder (MDD). In MDD, combined treatment with buspirone and melatonin was more efficacious in ameliorating subjective cognitive disturbances compared to the use of buspirone alone or the use of a placebo. Likewise, the combination of escitalopram-tandospirone was more advantageous than escitalopram alone for improving executive function and verbal fluency in patients with vascular depression.

Conclusions: Further studies with novel 5-HT_1A receptor agonists are warranted to examine their potentially more robust benefits on cognitive performance in subjects suffering from mood deficits.

Background: In 2003, contamination of drinking well water with diphenylarsinic acid (DPAA), an organoarsenic compound not naturally found in the environment, was reported in Kamisu City, Ibaraki Prefecture, due to suspected illegal dumping. Residents in the surrounding area, including pregnant women, were exposed to DPAA, leading to health issues primarily affecting the central nervous system. However, the extent of DPAA transfer from pregnant women to their fetuses remains unknown.

Methods: The concentration of DPAA in preserved dried umbilical cords from pregnant women who had consumed DPAA-contaminated well water was measured using liquid chromatography-tandem mass spectrometry. Additionally, pregnant rats (n = 9) were orally administered DPAA (0.25, 0.5, or 1.0 mg/kg/day) for 13 days. Fetuses (five per mother, n = 45) were delivered, and the DPAA concentrations in maternal and fetal blood, as well as in the brain, were measured.

Results: The DPAA concentration in fetal blood was 30.0%-40.1% of that in maternal blood, regardless of the administered dose. On the other hand, the DPAA concentration in the fetal brain was 8.31%-9.00% of that in the maternal brain, independent of the administered DPAA dose.

Conclusion: The analysis of umbilical cords from pregnant women who drank water containing DPAA revealed that DPAA could transfer from the mother to the fetus through the placenta. Additionally, experiments using rodents confirmed that DPAA could also reach the fetal brain through placental transfer, but the transfer rate was low.

The surge in online gaming's popularity has raised concerns regarding excessive engagement particularly among younger generations. Internet gaming disorder (IGD) is increasingly recognized as a clinical concern, underscoring the necessity for early detection and intervention. Although facial expressions provide key emotional insights, their link to symptoms associated with internet gaming addiction remains largely unexplored. In this preliminary study, we investigated facial emotional expressions in response to internet gaming videos among 28 young adults who casually play online games, utilizing the automated facial expression recognition system for analysis. Participants watched internet gaming and neutral (nongaming) videos while their facial expressions were recorded. We measured the intensity of each facial expression (happy, sad, angry, surprised, scared, disgusted, and neutral) and explored their correlation with symptoms related to internet gaming addiction. Participants exhibited a higher intensity of neutral expression and a lower intensity of sad expression in internet gaming videos compared to neutral ones; however, the findings were only nominally significant and did not survive correction for multiple comparisons. Moreover, participants with higher symptoms of internet gaming addiction displayed reduced facial intensity of sadness in response to internet gaming videos. Additionally, we noted a positive correlation between the facial intensity of surprise and levels of gaming desire. Furthermore, the intensity of disgusted facial expressions showed a negative correlation with participants' familiarity levels with the online games. These preliminary and exploratory findings hold promise for deepening our understanding of individuals' emotional responses and internet gaming behavior. Future research with larger samples, including patients with IGD, will be crucial to validate these findings and to inform the development of preventive strategies and effective interventions in this field.

Aim: To examine treatment persistence rates of paliperidone palmitate 3-month (PP3M) for schizophrenia in Japan because evidence in real-world settings is limited.

Methods: A retrospective population-based cohort study was conducted using the Japan Medical Data Center claims database. The overall cohort comprised schizophrenia patients aged ≥ 18 years, who received paliperidone palmitate 1-month (PP1M) within 180 days before initiating PP3M. Of patients in the overall cohort, those who received PP1M ≥ 4 times within 180 days at 21-42-day intervals with the same dosage strength as the last two PP1M doses before switching to PP3M initiated PP3M with a dose equivalent to 3.5-fold the last PP1M dose and took no other concomitant antipsychotics within 112 days before initiating PP3M were included in the per protocol cohort (PPC). The Kaplan-Meier method was used to calculate PP3M persistence rates in the overall cohort and PP3M monotherapy persistence rates in the PPC.

Results: In the overall cohort and PPC, 121 patients and 87 patients, with a mean age of 41.5 years and 48%-53% being employed, were followed up for ≤ 27 months. At 365 days and 730 days, the PP3M persistence rate was 76.9% and 71.7% in the overall cohort, and that for PP3M monotherapy was 73.1% and 64.6% in the PPC.

Conclusion: Treatment persistence rates for PP3M in Japan were relatively high among schizophrenia patients transitioned from PP1M. High persistence rates can be achieved with PP3M monotherapy in patients who have been sufficiently stabilized with PP1M monotherapy prior to initiating PP3M.

Aim: This study estimated the prevalence of over-the-counter (OTC) drug abuse among high school students in Japan and clarified the predictors related to their school and home life.

Methods: A nationwide cross-sectional survey was conducted between September 2021 and March 2022. The survey included 41 357 valid responses from 202 randomly selected regular high schools in Japan. Respondents were asked about their history of OTC drug abuse within the past year, which was the primary outcome of this study. Multivariate logistic regression analyses were performed to identify the predictors of OTC drug abuse.

Results: The estimated prevalence of OTC drug abuse over the past year was 1.5% (95% CI: 1.4-1.6). Dissatisfaction with school life (AOR = 2.57, 95% CI = 1.80-3.66), hours spent in a day without parents (AOR = 1.59, 95% CI = 1.27-2.00), and COVID-19-related stress (AOR = 1.53, 95% CI = 1.14-2.05) significantly increased the risk of OTC drug abuse. Conversely, positive extracurricular activities (AOR = 0.80, 95% CI = 0.63-1.00), close communication with the mother (AOR = 0.66, 95% CI = 0.51-0.87), and high drug-refusal skills (AOR = 0.57, 95% CI = 0.41-0.79) significantly reduced the risk.

Conclusions: OTC drug abuse is widespread among high school students in Japan, and attention should be paid to students who are isolated at school and home. Therefore, it is important to develop effective prevention, education, and treatment programs for adolescents that consider the risks and protective factors associated with OTC drug abuse.

Identifying genes involved in anxiety is important to elucidate the mechanisms of anxiety disorders. Hatano high avoidance animals (HAA) and low avoidance animals (LAA) are inbred strains that are selected based on their performance in an active avoidance test. HAA shows a higher level of anxiety-like behavior than LAA. The present study focuses on the hippocampus, which is associated with anxiety-like behavior, and used microarray analysis and RT-qPCR to select genes with differential expression in the hippocampus between HAA and LAA (Experiment 1). The microarray analysis revealed differences in 498 gene expressions between HAA and LAA, of which 21 genes were ligand-receptor related in the nervous system. We selected nine genes based on p value and conducted RT-qPCR, which identified seven genes whose expressions were higher in LAA than in HAA. We focused on the gene, neuromedin U receptor 2 (Nmur2), which showed significantly different expression levels between HAA and LAA. Further, we conducted a behavioral test to evaluate anxiety levels by administering neuromedin U (NmU), an agonist for NmUR2, into the hippocampus (Experiment 2). NmU treatment did not affect the results of the open field test or the elevated plus maze test, which are unconditioned response models of anxiety. However, in the passive avoidance test, a conditioned response model of anxiety, the NmU group showed less anxiety-like behavior than the control group. This is the first study to show that NmU suppresses the conditioned response model of anxiety via the hippocampus, indicating that NmUR2 in the hippocampus may be involved in anxiety-like behavior.

Aim: This study aimed to investigate the association between blood fatty acid fractions and posttraumatic stress disorder (PTSD) judgment in individuals who have experienced physical trauma.

Methods: Patients admitted to the emergency department for trauma, excluding those with brain damage or serious psychiatric disorders, were enrolled. Blood samples were collected on admission, and PTSD symptoms were assessed using a questionnaire 1 and 3 months after the injury. Multiple regression analysis was used to evaluate the association between fatty acids and Posttraumatic Diagnostic Scale severity scores, adjusting for age, sex, the Childhood Trauma Questionnaire (CTQ), and the use of psychotropic medications.

Results: A significant association was observed between certain fatty acids and PTSD judgment. Mann-Whitney U test results revealed that arachidonic acid was associated with PTSD judgment at 1 month and palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, eicosenoic acid, and eicosadiene acid with PTSD judgment at 3 months. Multiple regression analysis revealed that stearic acid, linoleic acid, arachidic acid, docosatetraenoic acid, lignoceric acid, docosahexaenoic acid, and total omega-6 fatty acids (ω6) were associated with PTSD judgment after 1 month after trauma. In contrast, only linoleic acid and total ω6 were associated with PTSD judgment 3 months after trauma.

Conclusions: This study is the first to enroll patients with general physical trauma and examine the relationship between fatty acids and PTSD. The findings suggest a potential relationship between blood fatty acid fractions and the development of PTSD symptoms in individuals who have experienced physical trauma. However, further research is needed to confirm and expand on these findings.

Background: Contactin-5 (CNTN5), a neural adhesion molecule involved in synaptogenesis and synaptic maturation in the auditory pathway, has been associated with the pathophysiology of autism spectrum disorder (ASD), particularly hyperacusis. To investigate the role of rare CNTN5 variants in ASD susceptibility, we performed resequencing and association analysis in a Japanese population.

Methods: We resequenced the CNTN5 coding regions in 302 patients with ASD and prioritized rare putatively damaging variants. The prioritized variants were then genotyped in 313 patients with ASD and 1065 controls. Subsequently, we conducted an association study of selected variants with ASD in 614 patients with ASD and 61 057 controls. Clinical data were reviewed for patients carrying prioritized variants.

Results: Through resequencing, we prioritized three rare putatively damaging missense variants (W69G, I227L, and L1000S) in patients with ASD. Although we found a nominally significant association between the I227L variant and ASD, it did not remain significant after post hoc correction. Hyperacusis was found in three out of nine patients carrying prioritized variants.

Conclusion: This study does not provide evidence for the contribution of rare CNTN5 variants to the genetic etiology of ASD in the Japanese population.

Background: Schizotypy refers to a personality type characterized by behavioral and cognitive abnormalities similar in nature but less severe than those of schizophrenia. Schizotypy often progresses to schizophrenia, so identifying risk factors may facilitate early schizophrenia diagnosis and improve treatment. Psychological distress may be associated with schizotypy, highlighting its importance. However, the link between psychological distress and schizotypy remains unclear.

Methods: This cross-sectional study examined the relationship between schizotypy and psychological distress in a Japanese adult population using internet-based questionnaires. Schizotypy was assessed using the Schizotypal Personality Questionnaire-Brief and psychological distress was measured using the Kessler Screening Scale for Psychological Distress. Multivariate logistic regression analysis was used to assess the relationship between psychological distress and schizotypy after adjusting for numerous potential confounding variables.

Results: Among 6632 participants, 225 were classified with schizotypy (3.39%, 89 females [39.6%]). Multivariate logistic regression analysis adjusting for confounding factors revealed that participants with psychological distress were significantly more likely to exhibit signs of schizotypy than those without psychological distress (adjusted odd ratio, 2.91; 95% confidence interval, 1.85-4.59).

Conclusions: The emergence of schizotypy in adults is strongly associated with psychological distress. This finding emphasizes the need for physicians to carefully, thoroughly, and routinely assess psychological distress in adults. Longitudinal studies are warranted to investigate the causal relationship between schizotypy and psychological distress.