Neuropsychopharmacology Reports最新文献

Bipolar disorder is the fourth most debilitating psychiatric illness in the world regarding Disability Adjusted Life Years and manic episodes frequently lead to lengthy hospitalizations which restricts the freedom of patients. Therefore, decreasing the length of hospitalization with safer agents is of utmost importance in the treatment of manic episodes. Aripiprazole is a medication known for its efficacy in managing mania associated with bipolar disorder. Aripiprazole long-acting injection is approved for the treatment of mania associated with bipolar disorder in adults and found efficacious as a maintenance treatment. In the treatment of schizophrenia, European Medicines Agency has approved a simplified starting strategy of aripiprazole once a month, with two 400 mg injections and a single oral 20 mg dose of aripiprazole. To the best of our knowledge, no previous study has reported the safety, tolerability, and efficacy of this regimen in adult bipolar disorder patients. We present a case series of eight patients who were admitted to the hospital in a manic episode with psychotic features. We observed that the double injection start regimen was effective in treating manic symptoms with no specific severe adverse events. We conclude from a small sample of manic patients that a double injection start regimen has good efficacy and tolerability.

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.

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.

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.

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.

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.

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.

Non-pharmacological interventions include physical activity, biofield energy therapy, reiki, Tai chi, and therapeutic touch. However, no reports analyzed the effectiveness of biofield therapy on cognition and motor function performance in adult subjects. The study aimed to investigate the impact of remote biofield energy healing therapy on cognition and motor functioning in adults with self-perceived neuropsychological impairments. This was a randomized double-blind clinical trial that involved 114 participants with self-perceived neuropsychological impairments. The participants were divided into three groups (control, sham control, and biofield intervention). Cognitive and motor function scores were assessed using the NIH Toolbox at baseline (day 0), day 90, and day 180. The biofield treatment group showed significant improvements in language function (p < 0.0001), working memory (p < 0.0001), and episodic memory (p < 0.0001) scores. Other cognitive functions also improved, although not statistically significant. The biofield intervention group also demonstrated significant enhancements (p < 0.05 to p < 0.0001) in locomotion, standing balance, dexterity, grip strength, and muscle endurance. No adverse effects were reported. The results suggest that remote biofield energy therapy is a safe, noninvasive intervention that improves cognitive and motor functions in adults. Further research is needed to understand its clinical benefits.