Neuropsychopharmacology Reports最新文献

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.

Mutations in proline-rich transmembrane protein 2 (PRRT2) cause paroxysmal kinesigenic dyskinesia (PKD). Recently, we reported that a Prrt2 mutation exacerbated L-dopa-induced motor deficits in mice, suggesting that the basal ganglia might contribute to PKD pathology. Here, we demonstrated that the Prrt2 mutation enhanced depolarization stimuli-induced extracellular dopamine levels in the mouse striatum, which were attenuated by repeated stimulation. L-dopa administration maintained high dopamine levels in Prrt2-KI mice even during repetitive stimuli but did not affect dopamine levels in wild-type mice. Thus, the enhanced and prolonged responsiveness of dopamine release in nigrostriatal dopaminergic neurons to sequential excitation may be partially implicated in Prrt2-related dyskinesia.

Social dysfunctions are common in various psychiatric disorders, including depression, schizophrenia, and autism, and are long-lasting and difficult to treat. The development of treatments for social impairment is critical for the treatment of several psychiatric disorders. "Amyloban 3399," a product extracted from the mushroom Hericium erinaceus, markedly improves social dysfunctions in patients with treatment-resistant schizophrenia and depression. However, the molecular mechanism(s) through which amyloban ameliorates social impairment remains unclear. To clarify this mechanism, in this study, we aimed to establish a mouse model of social defeat stress (SDS) and investigate the effects of amyloban on social deficits. Amyloban administration ameliorated social deficits and the dopamine system activity in SDS mice. These findings suggest that there is a possibility that amyloban may improve social deficits by suppressing the hyperactivation of the dopaminergic system. Amyloban may be an effective treatment for social dysfunctions associated with various psychiatric disorders.

Aim: To explore the optimal dose of blonanserin transdermal patch (BNS-P) based on baseline psychiatric symptomatic characteristics during acute schizophrenia.

Methods: A post hoc cluster analysis was conducted using data from a 6-week randomized, double-blind, placebo-controlled study of BNS-P (40 or 80 mg/day) in acute schizophrenia. We classified patients into three clusters based on baseline psychiatric symptoms. Efficacy was assessed using the change from baseline to week 6 in the PANSS total score. Safety was assessed by the incidence of adverse events.

Results: Among 577 patients, three clusters were identified, characterized by severe psychiatric (Cluster-S; n = 122), predominant negative (Cluster-N; n = 191), and predominant positive (Cluster-P; n = 264) symptoms. In Cluster-P, both BNS-P 40 and 80 mg/day reduced PANSS total score significantly more than placebo (p = 0.036, effect size = 0.342; p < 0.001, effect size = 0.687, respectively). In Cluster-S and -N, only BNS-P 80 mg/day reduced PANSS total score significantly more than placebo (p = 0.045, effect size = 0.497; p = 0.034, effect size = 0.393, respectively). The effect size was greater at 80 mg/day than at 40 mg/day across all clusters. The most common treatment-emergent adverse events were akathisia and skin-related adverse events in all clusters.

Conclusion: BNS-P exhibited a dose-dependent antipsychotic effect in all clusters, particularly highlighting its efficacy in patients with predominant positive symptoms, even at lower doses. These findings provide novel and valuable insights for determining BNS-P dose tailoring to individual symptomatic characteristics in real-world practice.

Valproic acid or sodium valproate is a widely used drug in the treatment of epilepsy, although it also appears to have anxiolytic and sedative properties derived from its agonistic action on the GABAergic system. To analyze these potential effects of the drug, we conducted three experiments with rats using procedures designed to assess anxiety in rodents. In the first experiment, with a fear conditioning procedure, three groups of male rats were included that received either 100 mg/kg or 300 mg/kg of valproate or an equivalent volume of saline solution. In Experiment 2, recording spontaneous activity in an open field, we compared the effects of valproic acid (300 mg/kg) on male and female rats. In the third experiment, we analyzed the effect of valproic acid using a novelty-induced hypophagia test and tested again for potential differences as a function of the sex of the animals. The results showed an anxiolytic effect restricted to the 300 mg/kg dose of the drug in Experiment 1. Such an effect was restricted to the female sample in Experiment 2, but in the third experiment affected both sexes. As for the sedative effect, it was observed in all experiments irrespective of the sex of the rats. These findings hold significant implications for the treatment of anxiety disorders since valproate may offer a novel therapeutic approach for anxiety-related conditions with distinct benefits and fewer side effects. However, clinical studies are needed to validate the translation of these findings from animal models to human patients.

Background: Self-disturbance has been considered as a core symptomatology of schizophrenia and its emergence from the prodromal phase makes it a crucial target for early detection and intervention in schizophrenia. Currently, the clinical assessment of self-disturbance relies on the self-report of patients, and clinicians have no diagnostic tools in clinical practice. Identifying the neural substrate of self-disturbance would be of great clinical value by shedding light on the core dimension of schizophrenia.

Case presentation: We first introduce an adolescent patient who initially presented self-disturbance, and clinically detectable hypoperfusion in angular gyrus (AG) was observed when early psychosis was suspected. Interestingly, the hypoperfusion in AG may correspond to improvement and exacerbation of self-disturbance. This clinical observation led us to pursue the relationship between the decreased blood flow in the AG and self-disturbance. Among 15 cases with suspected early psychosis in which single photon emission computed tomography was performed to exclude organic factors, we found additional 5 cases, including one prodromal patient, showing hypoperfusion in the AG and self-disturbance with significant correlation (r = 0.79, p = 0.00025).

Discussion: The self-disturbance has been interpreted as a reflection of disturbance of the "Sense of Agency", the ability to attribute their action and/or thoughts to themselves. AG has been shown to play a pivotal role in the sense of agency. These cases suggest that the hypoperfusion in AG associated with the disruption in the sense of agency would be an early clinical sign of schizophrenia. Further longitudinal studies are needed to test this hypothesis.

Aims: To investigate the factors associated with interoception in patients with alcohol use disorder and determine whether treatment causes changes in their interoception.

Methods: The Body Perception Questionnaire-Body Awareness ultra-short version Japanese version (BPQ-BAVSF-J) was used to measure interoception in 50 alcohol-dependent participants (27 in the inpatient group and 23 in the outpatient group). The BPQ-BAVSF-J was administered and data on aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), mean corpuscular volume, platelet count, and Fib-4 index were extracted at admission and immediately before discharge for the inpatient group and at the first outpatient visit and approximately 3 months after the visit for the outpatient group.

Results: The mean age of the 50 participants was 51.0 ± 12.3 years. Significant associations were found between the BPQ-BAVSF-J and Fib-4 index and AST. The BPQ-BAVSF-J score significantly decreased at discharge in the inpatient group. AST, ALT, γ-GTP, and Fib-4 index of liver function were also significantly lower at discharge. In contrast, in the outpatient group, there were no significant changes in the BPQ-BAVSF-J score, AST level, ALT level, γ-GTP level, and Fib-4 index between at the first outpatient visit and approximately 3 months after the visit.

Conclusions: Interoception in patients with alcohol use disorder increased with worsening liver function and decreased with improvement in liver function owing to treatment. This suggests that the BPQ-BAVSF-J score, an easily accessible scale, may be used to detect early deterioration of liver function through regular administration.

Aim: Overweight is associated with low-grade systemic inflammation. However, its effect on neuroinflammation remains unclear. We examined the possible association between overweight and neuroinflammation using cerebrospinal fluid (CSF) in a nonclinical adult population in Japan.

Methods: CSF and plasma levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), plasma levels of C-reactive protein (CRP), and leptin were measured in nonclinical adult participants (35 males and 34 females) who had no current or past history of neuropsychiatric diseases. We performed partial correlation analyses with sex and age as covariates between the body mass index (BMI) and the inflammatory markers and compared them between overweight and nonoverweight participants.

Results: The BMI significantly correlated with CSF levels of IL-6 (rs = 0.32, p = 0.009), plasma levels of CRP (rs = 0.30, p = 0.016), IL-1β (rs = 0.29, p = 0.019), IL-6 (rs = 0.25, p = 0.042), TNF-α (rs = 0.43, p < 0.001), and leptin (rs = 0.72, p < 0.001). Overweight participants (BMI ≧ 25) had significantly higher CSF levels of IL-6 (p < 0.001), plasma levels of IL-1β (p = 0.023), TNF-α (p < 0.001), and leptin (p < 0.001) than the nonoverweight participants.

Conclusion: Overweight is associated with central IL-6, a marker for neuroinflammation, as well as systemic inflammation markers, even in a nonclinical population.

Background: The distance from the patient is a crucial factor in the communication with patients. The distance between patients and pharmacists varies depending on several factors. In this study, we aimed to investigate the relationship between comfort distance and patients' physical condition and mood by measuring this distance at a chemotherapy center.

Methods: A total of 114 patients were surveyed regarding their physical condition and mood. The distance at which the patients were best able to talk to the pharmacists was measured. For comfort distance measurement, the pharmacists were instructed to approach or move away from the patients.

Results: The correlation between physical condition, mood, and comfort distance was examined in both male and female patients, and no significant correlation was found; however, there was a strong correlation between physical condition and mood in female patients. We looked at correlations by further dividing patients into those over and under 65 years of age and found a slight correlation with comfort distance in women under 65. They tended to shorten the distance when they felt well and lengthen the distance when they felt not well.

Conclusions: No correlation was found between physical condition or mood and comfort distance in male or female. A slight correlation was observed when age was included; however, the results were not satisfactory. By directly measuring the distance in actual patients, we obtained an actual measurement of the comfort distance that synthesized the patient's condition and various backgrounds during chemotherapy, providing a foothold for future studies.

Background: Ischemic priapism is a rare pathological condition, and delayed intervention can result in irreversible sequelae. Most cases are attributed to the use of antipsychotics. The blockade of α1-adrenergic receptors is thought to be associated with the disease onset, although data supporting this hypothesis are lacking. No consensus regarding the optimal choice of medication is available.

Case presentation: A 59-year-old man with schizophrenia, who had been receiving long-acting injections of risperidone, developed ischemic priapism after receiving paliperidone treatment. Following improvement in ischemic priapism, we administered a combination of aripiprazole and olanzapine, which improved his psychiatric symptoms. We did not observe any recurrence of ischemic priapism.

Conclusions: Switching the antipsychotic drug causing ischemic priapism to patients having a relatively low affinity for α1-adrenergic receptors may enable the treatment of schizophrenia without recurrence of ischemic priapism. In addition to the affinity for α1-adrenergic receptor, differences in metabolic enzyme types and antipsychotic doses may be involved in the occurrence of ischemic priapism. Accumulating evidence is necessary to establish guidelines for selecting medication of patients with ischemic priapism.