Clinical Psychopharmacology and Neuroscience最新文献

Objective: Pan-immune inflammation value (PIV) and systemic immune-inflammation index (SII) have recently been investigated as new inflammatory markers. The aim of this study was to investigate and compare the PIV and SII in different mood episodes in bipolar disorder (BD) and healthy controls (HC).

Methods: In this study, white blood cells, neutrophil, monocyte, lymphocyte, and platelet counts of 339 BD patients (138 manic, 100 depressive, and 101 euthymic patients) along with 117 HC were evaluated. The PIV and the SII were calculated using these parameters and compared between the groups.

Results: PIV (p < 0.001) and SII (p = 0.002) were significantly higher in the manic group than in the HC. A comparison of the HC with the depressed and euthymic groups indicated no significant difference in PIV (p = 0.086, p = 0.139, respectively) and SII (p = 0.555, p = 0.244, respectively), while neutrophil (p = 0.043, p = 0.042, respectively) and monocyte (p = 0.010, p = 0.023, respectively) counts were significantly higher. Compared to the depressed and euthymic patients, the manic patients had significantly higher PIV (p <0.001, p <0.001, respectively) and SII (p = 0.019, p = 0.034, respectively). PIV could to be predictive in distinguishing manic episode patients from the other groups.

Conclusion: Our findings highlight the role of the low-grade systemic inflammation in the pathophysiology of BD, particularly during the manic episode, and suggest that PIV could serve as an inflammation marker to distinguish the manic episode of BD from other phases.

Objective: Human endogenous retroviruses (HERVs) and associated sequences occupy ∼8% of the human genome and dysregulation of HERV transcripts may have significant impacts on human health including psychiatric disorders. HERV-K18 is still active in the human genome and its envelope gene encodes a superantigen (SAg) which may result in deregulation of the immune system. In the study, the possible associations of the two variants localized in the SAg-coding region of HERV-K18 with bipolar disorder type I (BD-I) were evaluated.

Methods: The subjects included 100 patients with BD-I and 100 age- and sex-matched healthy controls. The effects of the two HERV-K18 variants (HERV-8594 and HERV-8914) were analyzed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The possible associations of the genotypes/alleles in BD-I patients with several clinical and demographic data were also evaluated.

Results: HERV-8914 TT genotype had approximately 5.36 times higher risk of BD-I than those with the CC genotype (odds ratio, 5.386; 95% confidence interval, 1.602-18.110). Moreover, the prevalence of the CC genotype in patients with hypomania (31.25%) was found to be higher than that observed in patients without hypomania (10.71%) (Fisher's exact test = 5.931, p = 0.036).

Conclusion: This is the first study implying that HERV-K18 variations may be associated with the pathogenesis of BD-I.

Objective: Pathological anxiety is characterized by dysregulated arousal and lower heart rate variability associated with emotional dysregulation. This study explored the connection between peripheral and central autonomic nervous system activity during emotional processing in social anxiety disorder (SAD).

Methods: Thirty-two patients with SAD and 41 healthy controls engaged in a passive viewing task alternating between neutral and angry faces. The root mean square of successive differences (RMSSD) was measured during the resting state (baseline RMSSD) and emotional processing (task RMSSD). We examined the relationships between brain activation during emotional processing and these RMSSD measures.

Results: Unlike the controls, the SAD group exhibited a trend level toward significant correlations of baseline RMSSD with left anterior insula activity during neutral face processing (p = 0.058) and significant correlations with both left anterior insula and right amygdala activities during angry face processing (p = 0.027 and 0.046, respectively). In the controls, task-related RMSSD correlated with neural activities in the right amygdala and right dorsomedial prefrontal cortex during neutral face processing (p = 0.017 and 0.004, respectively), while in the SAD group, a correlation emerged with the right parahippocampal gyrus (p = 0.044). Notably, only in the control group did RMSSD, measured during neutral face processing, significantly correlate with neural activation during the processing of angry faces (p = 0.035).

Conclusion: This study delineates distinct autonomic and neural response patterns to emotional stimuli in SAD patients, highlighting increased autonomic readiness and diminished flexibility in response to social threats.

Objective: Schizophrenia is a major psychiatric illness which mostly begins in adolescence and leads to impairments of social functioning. Some patients with schizophrenia have been associated with ultra-high risk state for psychosis (UHR), a condition used to operationally represent the prodromal stage of the illness. In previous studies, the UHR and the progression to overt psychosis has been reported to be accompanied with alterations in the quality of sleep and the immune system, as represented by change of blood levels of cytokines. Currently, biomarkers to predict the development of psychosis in persons at UHR have not yet reached a steady consensus. Therefore, we present a study protocol to explore predictors of transitions to psychosis, in the realm of monitoring of sleep condition and cytokine measurement, in subjects with the UHR.

Methods: This is a multicenter, longitudinal cohort study participated by 7 hospitals in Japan. We will recruit 50 UHR people and 30 healthy volunteers as a control group, and measure positive symptom, depressive symptoms, cognitive function, and social function. Blood cytokines levels and sleep indices, as well as actigraphy data will be monitored. After the baseline assessment, clinical symptoms, sleep indices, and cytokine levels will be measured every 12 weeks for 52 weeks. Actigraphy devices will continue to be worn for 52 weeks, while social function will be assessed over 104 weeks. The results of this study are expected to facilitate the development of novel intervention therapies to reduce the risk of psychosis and improve functional outcomes.

Objective: Cholinesterase inhibitors (ChEIs) are effective in treating mild to moderate Alzheimer's disease (AD) dementia by compensating for acetylcholine deficiency. While their use in mild cognitive impairment (MCI) lacks strong trial support, some studies suggest they may delay neurodegeneration. This study aims to investigate ChEIs' neuroprotective effects in individuals with amnestic MCI (aMCI) using multi-modal neuroimaging, and to determine if amyloid-beta (Aβ) deposition influences these effects.

Methods: Longitudinal data from a cohort study were retrospectively analyzed. A total of 118 aMCI patients (ages 55- 90), who underwent baseline evaluations encompassing the assessment of ChEI use and [¹¹C] Pittsburgh compound B-positron emission tomography (PET), were included in the analyses. All participants also received baseline and 2-year follow-up magnetic resonance imaging and [¹⁸F] fluorodeoxyglucose-PET imaging.

Results: The ChEI use group exhibited a significantly lesser decline in AD-signature region cerebral metabolism (AD-CM) over a 2-year period than the ChEI non-use group (B = 0.089, 95% CI: 0.030-0.149). However, there was no significant difference in the 2-year change of AD-signature region cortical thickness (AD-CT) (B = 0.032, 95% CI: -0.075 to 0.138) and hippocampal volume (B = -88.013, 95% CI: -323.900 to 147.874) between the ChEI use and non-use groups. The presence of Aβ pathology did not moderate the effect of ChEI use on AD-CM, AD-CT, or hippocampal volume.

Conclusion: The findings suggest that ChEIs may delay functional neurodegeneration in aMCI individuals, irrespective of the presence of amyloid pathology.

Objective: To investigate the cognitive impairment and peripheral inflammation induced by methamphetamine (METH) and their association in METH abusers.

Methods: The cross-sectional study included 100 METH-dependent patients and 100 healthy controls. Cognitive screening was conducted using the Thai version of the Montreal Cognitive Assessment (MoCA-T). Thirty normal controls and 30 METH-dependent patients were randomly selected for blood collection to measure inflammatory markers, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, using a quantitative enzyme-linked immunosorbent assay method.

Results: METH-dependent patients had significantly poorer MoCA-T scores and higher levels of blood inflammatory markers compared to healthy controls. Demographic characteristics, METH use patterns, and proinflammatory cytokines were associated with cognitive impairment. The MoCA-T score was negatively associated with plasma TNF-α and IL-6 levels.

Conclusion: METH-associated cognitive decline is correlated with elevated plasma levels of TNF-α and IL-6 cytokines, indicating the involvement of specific neuroinflammatory pathways in neurocognitive dysfunction. These insights could pave the way for novel therapeutic strategies aimed at mitigating neuroinflammation, potentially improving outcomes for individuals with METH addiction.

Objective: The present study was to investigate the association of physical activity (PA), relative-handgrip strength (RHGS), depressive symptoms, and cognitive impairment in Korean older adults.

Methods: This study included 512 community-dwelling Korean older adults (417 female, 95 male) aged ≥ 65 years (74.8 ± 5.4 years). PA and RHGS were assessed using an accelerometer and dynamometer, respectively. Depressive symptoms were evaluated by the Korean form of the Center for Epidemiologic Studies Depression (CES-D) Scale. Cognitive impairment was assessed through the Mini-Mental State Examination for Dementia Screening (MMSE-DS).

Results: Multiple logistic regression analysis revealed that depressive symptoms (odds ratio [OR] = 2.676, 95% confidence interval [CI]: 1.594-4.492, p < 0.001) showed a significant association with increased odds of cognitive impairment compared with normal depression status (OR = 1). Depressive symptoms had both direct and indirect effects on cognitive impairment. Both PA and RHGS partially mediated the relationship between depressive symptoms and cognitive impairment (PA: effect [B] = -0.017, 95% CI: -0.028 to -0.009, p < 0.001; RHGS: B = -0.005, 95% CI: -0.007 to -0.003, p < 0.001). Serial mediation analysis further indicated that the association between depressive symptoms and cognitive impairment was sequentially mediated by PA and RHGS (B = -0.004, 95% CI: -0.006 to -0.002, p < 0.001).

Conclusion: Promoting PA among older adults may be crucial, as this helps improve and maintain muscular strength and mitigates the negative impact of depressive symptoms on cognitive impairment.

Objective: Childhood trauma is associated with executive function impairment and an increased risk of methamphetamine (MA) use. MA use itself also compromises executive function. Limited evidence is known about the association between childhood trauma, executive functioning and treatment outcomes among individuals with MA use disorder (MAUD). The study explored whether patients with MAUD who had experienced childhood trauma presented poorer executive function and treatment outcomes.

Methods: The participants were individuals with MAUD and were all recruited from an outpatient-based addiction clinic from 2019 to 2022. Childhood trauma was assessed using Childhood Trauma Questionnaire-Short Form. The Wisconsin Card Sorting Test (WCST), Severity of Dependence Scale (SDS), and Visual Analog Scale for Craving, and urine MA/amphetamine tests were assessed repeatedly during the one-year treatment program. Generalized estimating equations were used to estimate the changes in these outcomes.

Results: In 115 MAUD patients we recruited those with a history of childhood physical neglect (PN) exhibited inferior WCST performance on number of categories completed (p = 0.02), and conceptual level responses (p = 0.046) and were more likely to test positive for MA/amphetamine in urine during the one-year treatment (p = 0.02). Patients with PN also reported significantly more severe cravings (p = 0.002), while those with a history of sexual abuse (SA) had notably higher SDS scores (p = 0.004) during treatment.

Conclusion: Childhood trauma, particularly PN and SA, shows substantial adverse effects on executive function and treatment outcomes among MAUD patients.

Mirtazapine is an antidepressant approved by the FDA whose mechanism of action involves antagonism of alpha-2, H1, 5-HT2A, 5-HT2C, and 5-HT3 receptors. Tics are sudden, rapid, purposeless, recurrent, non-rhythmic motor movements or vocalizations. There have been previous case reports of various medications causing tics. In this article, we report tic symptoms that we thought developed in association with mirtazapine treatment.

Objective: Obstructive sleep apnea syndrome (OSAS) is associated with recurrent apnea episodes. Positive airway pressure (PAP) treatment prevents repeatedly hypoxia in OSAS. Serum nitric oxide (NO) and Nod-like receptor protein 3 (NLRP3), that are involved in inflammation and pyroptotic cell death, may be affected hypoxia in OSAS. If so preventing hypoxia-ischemia episodes by PAP treatment may change serum NLRP3 and NO levels in OSAS. We aimed to determine whether serum levels of NLRP3 and NO change after at least 3 months of treatment with PAP.

Methods: Twenty-five OSAS patients, including 17 men and 8 women, who underwent polysomnography (PSG) and had an apnea-hypopnea index (AHI) of 30 or more and had started treatment at PAP. AHI was recorded. Serum levels NO and NLRP3 were analyzed before and at least 3 months after PAP treatment.

Results: After treatment with the PAP device, serum NO levels were significantly increased, NLRP3 levels were significantly decreased compared to pre-treatment levels (p < 0.001, p = 0.003). No correlation was found between serum NLRP3 and NO levels, AHI, type of the PAP device before or after PAP treatment.

Conclusion: We revealed that PAP treatment which prevents hypoxia, can alter the serum levels of NO and NLRP3 in OSAS, that is not related to the severity of AHI or type of the PAP device. This is the first study to measure NLRP3 levels before and after treatment with PAP in OSAS patients. Prospective studies with large cohorts and longitudinal follow-up evaluation of complications may provide further insights.