Neuropsychopharmacology Reports最新文献

Aim: Photopharmacology is a new technique for modulating biological phenomena through the photoconversion of substances in a specific target region at precise times. Caged compounds are thought to be compatible with photopharmacology as uncaged ligands are released and function in a light irradiation-dependent manner. Here, we investigated whether a microscale light-emitting diode (MicroLED) probe is applicable for the photoconversion of caged-glutamate (caged-Glu) in vivo.

Methods: A needle-shaped MicroLED probe was fabricated and inserted into the mouse hippocampal dentate gyrus (DG) with a cannula for drug injection and a recording electrode for measuring the local field potential (LFP). Artificial cerebrospinal fluid (ACSF) or caged-Glu was infused into the DG and illuminated with light from a MicroLED probe.

Results: In the caged-Glu-injected DG, the LFP changed in the 10-20 Hz frequency ranges after light illumination, whereas there was no change in the ACSF control condition.

Conclusion: The MicroLED probe is applicable for photopharmacological experiments to modulate LFP with caged-Glu in vivo.

Aim: This study aimed to identify subgroups of alcohol use disorder (AUD) based on a multidimensional combination of alexithymia, depression, and diverse drinking behavior.

Method: We recruited 176 patients with AUD, which were initially divided into non-alexithymic (n = 130) and alexithymic (n = 46) groups using a cutoff score of 61 on the Toronto Alexithymia Scale (TAS-20). Subsequently, the profiles of the two groups were compared. Thereafter, a two-stage cluster analysis using hierarchical and K-means methods was performed with the Z-scores from the TAS-20, the Quick Inventory of Depressive Symptomatology Self-Report Japanese Version, the 12-item questionnaire for quantitative assessment of depressive mixed state, and the 20-item questionnaire for drinking behavior pattern.

Results: In the first analysis, Alexithymic patients with AUD showed greater depressive symptoms and more pathological drinking behavior patterns than those without alexithymia. Cluster analysis featuring alexithymia, depression, and drinking behavior identified three subtypes: Cluster 1 (core AUD type) manifesting pathological drinking behavior highlighting automaticity; Cluster 2 (late-onset type) showing relatively late-onset alcohol use and fewer depressive symptoms or pathological drinking behavior; and Cluster 3 (alexithymic type) characterized by alexithymia, depression, and pathological drinking behavior featuring greater coping with negative affect.

Conclusion: The multidimensional model with alexithymia, depression, and diverse drinking behavior provided possible practical classification of AUD. The alexithymic subtype may require more caution, and additional support for negative affect may be necessary due to accompanying mood problems and various maladaptive drinking behaviors.

Anticholinergic toxicity is a common occurrence in the emergency room, making it crucial for emergency clinicians to have a good understanding of this toxidrome. The neuropsychiatric effects of anticholinergic agents and anabolic steroids (ASs) can manifest as symptoms like anxiety, agitation, dysarthria, confusion, seizures, visual hallucinations, bizarre behavior, delirium, psychosis, and coma. When dealing with a conscious patient who has ingested an anticholinergic substance, a detailed history of ingestion can aid clinicians in making an accurate diagnosis. However, the lack of information about the substances consumed can complicate diagnosis. In cases where the exposure is unknown, clinicians should consider anticholinergic poisoning in patients showing signs of altered mental status and physical examination findings consistent with anticholinergic toxicity. We report four cases presenting a range of symptoms, including neuropsychiatric manifestations, following the ingestion of the same bodybuilding powders with anticholinergic properties. All four patients consumed yellow and white powders at the same time and in the same place. Laboratory analysis revealed that yellow powder and white powder contained ASs and cyproheptadine, respectively.

Aim: Bipolar disorder (BD) has a significant impact on global health, yet its neurophysiological basis remains poorly understood. Conventional treatments have limitations, highlighting the need for a better understanding of the neurophysiology of BD for early diagnosis and novel therapeutic strategies.

Design: Employing a systematic review approach of the PRISMA guidelines, this study assessed the usefulness and validity of transcranial magnetic stimulation (TMS) neurophysiology in patients with BD.

Methods: Databases searched included PubMed, MEDLINE, Embase, and PsycINFO, covering studies from January 1985 to January 2024.

Results: Out of 6597 articles screened, nine studies met the inclusion criteria, providing neurophysiological insights into the pathophysiological basis of BD using TMS-electromyography and TMS-electroencephalography methods. Findings revealed significant neurophysiological impairments in patients with BD compared to healthy controls, specifically in cortical inhibition and excitability. In particular, short-interval cortical inhibition (SICI) was consistently diminished in BD across the studies, which suggests a fundamental impairment of cortical inhibitory function in BD. This systematic review corroborates the potential utility of TMS neurophysiology in elucidating the pathophysiological basis of BD. Specifically, the reduced cortical inhibition in the SICI paradigm observed in patients with BD suggests gamma-aminobutyric acid (GABA)-A receptor-mediated dysfunction, but results from other TMS paradigms have been inconsistent. Thus, complex neurophysiological processes may be involved in the pathological basis underlying BD. This study demonstrated that BD has a neural basis involving impaired GABAergic function, and it is highly expected that further research on TMS neurophysiology will further elucidate the pathophysiological basis of BD.

Background: Persistent cognitive impairment is a serious consequence of the post-COVID condition. However, there have been no established effective treatments for this pathophysiology supported by sufficient evidence.

Case presentation: A 32-year-old woman became aware of difficulty in word recalling, reading, and writing as well as difficulty in completing various household multitasks 3 weeks after the COVID-19 infection. Although blood tests, magnetic resonance imaging, electroencephalography, and Kohs block design test were all within normal limits, completion time by trail making test (TMT) A or B was markedly delayed. Finally, she was referred to our hospital 3 months after the infection. At baseline, the THINC integrated tool (THINC-it), a digital battery consisting of the five-item version of the perceived deficit questionnaire (PDQ-5), choice reaction time (CRT), 1-back test, digit symbol substitution test (DSST), and TMT-B, revealed poor capability in attention, working memory, and executive function. Also, near-infrared spectroscopy (NIRS) demonstrated no activation in frontal or temporal regions during verbal fluency task. Extended-release guanfacine (GXR) 2 mg/day was initiated and a month later was elevated up to 4 mg/day as a maintenance dose. The PDQ-5, CRT, 1-back test, DSST, and TMT-B were dramatically improved 1 month after GXR treatment. NIRS finding was also normalized after 2 months of treatment. These effects were successfully maintained throughout the 6-month follow-up period.

Conclusion: GXR may be helpful in improving subjective/objective cognitive functioning and frontotemporal brain activity in long-COVID patients manifesting apparent cognitive impairment.

The prevalence of obesity is increasing worldwide, resulting in various health issues such as hypertension, dyslipidemia, diabetes mellitus, heart disease, and a lower life expectancy. Importantly, several psychiatric disorders and the use of psychotropic medications have been linked to obesity, and the possible risk factors need further investigation. This study examined the prevalence of obesity and its associated factors using a self-administered questionnaire. Participants were recruited from three outpatient clinics and individuals who met one or more of the ICD-10 F0-F9, G4 diagnoses were included. In total, 1384 participants completed the questionnaire about their lifestyle. Statistical analysis compared the demographic and clinical characteristics of the individuals who were obese (Body Mass Index: BMI ≥25) and those who were non-obese (BMI <25). The results revealed that the factors associated with obesity in psychiatric outpatients were being male, prolonged treatment duration, eating out frequently, and use of both second- and first-generation antipsychotics. The study emphasized the importance of closely monitoring BMI in individuals with multiple obesity-related factors.

Aim: Brexpiprazole is the first FDA-approved treatment for agitation associated with dementia due to Alzheimer's disease. Agitation in Alzheimer's dementia (AAD) occurs in high prevalence and is a great burden for patients and caregivers. Efficacy, safety, and tolerability of brexpiprazole were demonstrated in the AAD clinical trials. To demonstrate the agitation-ameliorating effect of brexpiprazole in animals, we evaluated brexpiprazole in two AAD mouse models.

Methods: The resident-intruder test was conducted in 5- to 6-month-old Tg2576 mice, given vehicle or brexpiprazole (0.01 or 0.03 mg/kg) orally 1 h before the test. Locomotor activity was measured in 6-month-old APPSL-Tg mice given vehicle or brexpiprazole (0.01 or 0.03 mg/kg) orally the evening before the start of locomotor measurement for 3 days.

Results: In the resident-intruder test, Tg2576 mice showed significantly higher attack number and shorter latency to first attack compared to non-Tg mice. In the Tg mice, brexpiprazole treatment (0.03 mg/kg) significantly delayed the latency to first attack and showed a trend toward a decrease in attack number. APPSL-Tg mice (≧6 months old) showed significantly higher locomotion during dark period Phase II (Zeitgeber time [ZT] 16-20) and Phase III (ZT20-24) compared to non-Tg mice, correlating with the clinical observations of late afternoon agitation in Alzheimer's disease. Brexpiprazole treatment (0.01 and 0.03 mg/kg) significantly decreased hyperlocomotion during the Phase III in APPSL-Tg mice.

Conclusion: The suppression of attack behavior and the reduction of nocturnal hyperlocomotion in these Tg mice may be indicative of the therapeutic effect of brexpiprazole on AAD, as demonstrated in the clinical trials.

Aim: Yokukansan is one of the most frequently used herbal medicines that can improve the behavioral and psychological symptoms of dementia. In this exploratory study, we investigated whether yokukansan affects the steady-state blood concentrations of donepezil, risperidone, and the major metabolites of both drugs in a real-world clinical setting.

Methods: A non-randomized, open-label, single-arm study examining drug-drug interactions was conducted. Fifteen dementia patients taking donepezil for at least 4 weeks and eight schizophrenia patients taking risperidone for at least 2 weeks were orally administered 2.5 g of yokukansan three times a day before or between meals, and blood samples were collected before and 8 weeks after starting co-treatment with yokukansan. Plasma concentrations of donepezil, risperidone, and each metabolite were measured using high-performance liquid chromatography-tandem mass spectrometry and compared before and after the 8-week administration of yokukansan.

Results: The plasma concentrations of donepezil and its metabolites (6-O-desmethyl-donepezil, 5-O-desmethyl-donepezil, and donepezil-N-oxide), risperidone, and its metabolite paliperidone did not differ before and after the 8-week treatment with yokukansan.

Conclusions: The findings of this study show that the concomitant use of yokukansan may have little clinical impact on the steady-state blood levels of donepezil and risperidone in patients with dementia or schizophrenia.

Neurodegenerative diseases (NDs) such as Alzheimer disease (AD) and Parkinson disease (PD) are group of diseases affecting the central nervous system (CNS) characterized by progressive neurodegenerations and cognitive impairment. Findings from different studies highlighted the beneficial and detrimental effects of serum uric acid on the development and progression of NDs. Therefore, this mini-review aims to discuss the beneficial and detrimental effects of uric on NDs. The neuroprotective effect of uric acid is mainly related to the antioxidant effect of uric acid which alleviates oxidative stress-induced neurodegeneration in AD and PD. However, long-term effect of hyperuricemia prompts for the development and progression of cognitive impairment. Hyperuricemia is associated with cognitive impairment and dementia, and gout increases dementia risk. In addition, hyperuricemia can cause cerebral vascular injury which is a risk factor for vascular dementia and cognitive impairment. Taken together, the relationship between uric acid and NDs risk remains conflicting. Hence, preclinical and clinical studies are indicated in this regard.

Background: In patients with schizophrenia, violent behavior is a clinically important factor that prevents their discharge. Clozapine is an effective antipsychotic medication for treatment-resistant schizophrenia, and its usefulness for aggressive behavior has also been suggested.

Case presentation: We present the case of a 38-year-old male patient diagnosed with schizophrenia who was successfully treated with clozapine after recurrent violent behavior. He was diagnosed with schizophrenia during his adolescence. He was hospitalized for treatment in his teens, but his hallucinations and delusions persisted even after discharge. In his 30s, he became noticeably emotionally unstable, and despite being treated for an adequate period with sufficient doses of several antipsychotics, his symptoms did not improve. This led to repeated hospitalizations triggered by violent behavior toward his parents and siblings within the home. During his fourth hospitalization, clozapine was initiated due to multiple incidents of violence toward nursing staff secondary to hallucinations and delusions. As the dose of clozapine was gradually increased with therapeutic drug monitoring, the patient's hostility, uncooperativeness, and suspiciousness markedly improved, and his aggressive behavior disappeared. He was discharged to a facility on day 194 after starting clozapine and has continued outpatient visits.

Conclusion: Clozapine was suggested to be effective for aggressive behavior in patients with treatment-resistant schizophrenia and should be actively considered. In such cases, regular measurement of blood concentration is useful for adjusting the dosage of clozapine.