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Background: Neuroticism personality trait is recognized as an important endophenotypic predictor of generalized anxiety disorder (GAD). Furthermore, endophenotype-based pathway approaches have recently been shown to have greater advantages for gene-finding strategies than traditional case-control studies. In the present study, in addition to conventional case-control methods, we used pathway analyses to test whether the tri-allelic serotonin transporter promoter polymorphism (combining 5-HTTLPR and rs25531) is associated with risk of GAD through its effects on trait neuroticism. Methods: We included 2236 Han Chinese adults in this study, including 736 patients with GAD and 1500 healthy participants. We genotyped the 5-HTTLPR and rs25531 polymorphisms using the polymerase chain reaction restriction fragment length polymorphism method. We used the Neuroticism scale of the Maudsley Personality Inventory (MPI) short version (MPI-Neuroticism) to measure participants' tendency toward neuroticism. Results: Using endophenotype-based path analyses, we found significant indirect effects of the tri-allelic genotype on risk of GAD, mediated by MPI-Neuroticism in both men and women. Compared to women carrying the S'S' genotype, women carrying the L' allele had higher levels of MPI-Neuroticism, which in turn were associated with higher risk of GAD. Men, however, showed the opposite pattern. Using traditional case-control comparisons, we observed that the effect of tri-allelic genotype on GAD was significant, but only in women. Limitations: Participants were restricted to Han Chinese, and we used only 1 questionnaire to assess neuroticism. Conclusion: These findings are the first to show that the triallelic 5-HTTLPR polymorphism is associated with elevated risk of GAD, and that this effect is mediated via increased trait neuroticism, a sex-dependent risk pathway., Introduction Generalized anxiety disorder (GAD) is characterized by persistent worry associated with a variety of symptoms, including concentration problems, difficulty sleeping, fatigue, irritability, muscle tension and restlessness. It is a [...]

Objective: Although the physiological mechanisms contributing to the development of major depression remain unclear, several lines of evidence suggest that the catecholaminergic system involving the norepinephrine transporter (NET) is implicated [...]

Background We previously showed the efficacy of bi-anodal transcranial direct current stimulation (tDCS) over the prefrontal cortex (PFC) regions with extracephalic reference placement in improving negative symptoms in schizophrenia. In this ancillary investigation, the effects of this intervention on insight levels, other clinical outcomes, and cardio-respiratory and autonomic functions were examined and the potential of biomarkers for treatment response was explored. Methods Schizophrenia patients were randomly allocated to receive 10 sessions of bi-anodal tDCS over the PFC regions with extracephalic reference placement (2 mA, 20 minutes, twice daily for 5 weeks) or sham stimulation. We examined, in 60 patients at baseline, immediately after stimulation and at follow-up visits, the insight levels, other clinical outcomes, blood pressure, respiratory rate, heart rate, and heart rate variability. Results Insight levels as assessed by the abbreviated version of the Scale to Assess Unawareness in Mental Disorder in schizophrenia awareness of the disease, positive and negative symptoms dimensions, and beliefs about medication compliance as assessed by Medication Adherence Rating Scale were significantly enhanced by active stimulation relative to sham. No effects were observed on cognitive insight, other clinical outcomes, or cardio-respiratory and autonomic functions. Heart rate variability indices as biomarkers were not associated with the clinical response to the intervention. Conclusions Our results provide evidence for bi-anodal tDCS over the PFC regions with extracephalic reference placement in heightening the levels of insight into the disease and symptoms, as well as beliefs about medication compliance in schizophrenia, without impacting other clinical outcomes and cardio-respiratory/autonomic functions. [ABSTRACT FROM AUTHOR]

Background: Altered heart rate variability (HRV), an index of autonomic nervous system function, has been reported in generalized anxiety disorder (GAD), but the results have been mixed. Thus, the present study, using a large sample size and better methodology, aims to examine whether GAD is associated with impaired HRV, both at rest and in response to posture challenges. Methods: In total, 1832 participants were recruited in this study, consisting of 682 patients with GAD (including 326 drug- and comorbidity-free GAD patients) and 1150 healthy controls. Short-term HRV was measured during the supine-standing-supine test (5-min per position). Propensity score matching (PSM), a relatively novel method, was used to control for potential confounders. Results: After PSM algorithm, drug- and comorbidity-free GAD patients had reductions in resting (baseline) high-frequency power (HF), an index for parasympathetic modulation, and increases in the low-frequency/HF ratio (LF/HF), an index for sympathovagal balance as compared to matched controls. Furthermore, the responses of HF and LF/HF to posture changes were all attenuated when compared with matched controls. Effect sizes, given by Cohen's d, for resting HF and HF reactivity were 0.42 and 0.36–0.42, respectively. Conclusions: GAD is associated with altered sympathovagal balance, characterized by attenuation in both resting vagal modulation and vagal reactivity, with an almost medium effect size (Cohen's d ≈ 0.4), regardless of medication use or comorbidity status. [ABSTRACT FROM AUTHOR]