Negative symptoms represent an unmet need for schizophrenia treatment. The effect of theta frequency transcranial alternating current stimulation (theta-tACS) applied during working memory (WM) tasks on negative symptoms has not been demonstrated as of yet. We conducted a randomized, double-blind, sham-controlled trial of 36 stabilized schizophrenia patients, randomized to receive either twice daily, 6 Hz 2 mA, 20 min sessions of in-phase frontoparietal tACS or sham for five consecutive weekdays. Participants were concurrently engaged in WM tasks during stimulation. The primary outcome measure was the change over time in the Positive and Negative Syndrome Scale (PANSS) negative subscale score measured from baseline through to the 1-month follow-up. Secondary outcome measures were other symptom clusters, neurocognitive performance, and relevant outcomes. The intention-to-treat analysis demonstrated greater reductions in PANSS negative subscale scores at the end of stimulation in the active (−13.84%) than the sham (−3.78%) condition, with a large effect size (Cohen’s d = 0.96, p = 0.006). The positive effect endured for at least one month. Theta-tACS also showed efficacies for cognitive symptoms, WM capacity, and psychosocial functions. Online theta-tACS offers a novel approach to modulate frontoparietal networks to treat negative symptoms of schizophrenia. The promising results require large-scale replication studies in patients with predominantly negative symptoms.

Reduced health-related quality of life in the physical domain (HRQOLphysical) has been reported to increase risks for cardiovascular disease (CVD); however, the mechanism underlying this phenomenon is still unclear. The autonomic nervous system (ANS) that connects the body and mind is a biologically plausible candidate to investigate this mechanism. The aim of our study is to examine whether the HRQOLphysical independently contributes to heart rate variability (HRV), which reflects ANS activity. We recruited 329 physically and mentally healthy adults. All participants completed Beck Anxiety Inventory, Beck Depression Inventory and World Health Organization Questionnaire on Quality of Life: Short Form-Taiwanese version (WHOQOL-BREF). They were divided into groups of individuals having high or low scores of HRQOLphysical as discriminated by the quartile value of WHOQOL-BREF. We obtained the time and frequency-domain indices of HRV, namely variance (total HRV), the low-frequency power (LF; 0.05–0.15 Hz), which may reflect baroreflex function, the high-frequency power (HF; 0.15–0.40 Hz), which reflects cardiac parasympathetic activity, and the LF/HF ratio. There was an independent contribution of HRQOLphysical to explaining the variance in HRV after excluding potential confounding factors (gender, age, physical activity, alcohol use, depression and anxiety). Compared with the participants with high levels of HRQOLphysical, those with low levels of HRQOLphysical displayed significant reductions in variance and LF. This study highlights the independent role of low HRQOLphysical in contributing to the reduced HRV in healthy adults and points to a potential underlying mechanism for HRQOLphysical to confer increased risks for CVD.

The valine⁶⁶methionine (Val⁶⁶Met) polymorphism (rs6265) of the brain-derived neurotrophic factor (BDNF) gene has been shown to influence autonomic arousal pathways, which in turn predict elevated syndromal anxiety in healthy humans. We examined whether the BDNF variant is associated with an increased risk of generalized anxiety disorder (GAD), one of the most prevalent anxiety disorders, through altering parasympathetic stress/relaxation reactivity. A total of 2,250 Han Chinese adults (750 GAD patients and 1,500 healthy controls) were included in the genotyping. High-frequency heart rate variability, an index of vagal (parasympathetic) activity, was measured during the supine-standing-supine test (5 min in each position); vagal withdrawal and vagal activation were calculated as baseline supine minus standing and recovery supine minus standing, respectively. Analysis of healthy participants indicated that Val/Val homozygotes displayed significantly blunted vagal withdrawal and vagal activation compared with Met allele carriers. After analyzing the entire sample, these effects remained significant. Furthermore, both attenuated vagal response patterns were found to be significantly associated with a higher incidence of GAD. Lastly, the path analysis identified a significant indirect effect of BDNF on the risk of GAD via diminishing vagal response to either orthostatic stress or supine relaxation. Even when further testing the subsample comprising only comorbidity- and medication-free GAD patients and healthy controls to minimize the confounding bias, the results still remained. Our findings demonstrate that individuals carrying the BDNF Val/Val genotype, compared to Met-carriers, may be at higher risk of GAD due to blunted vagal reactivity in response to both stress and relaxation. (PsycInfo Database Record (c) 2020 APA, all rights reserved).