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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 [...]

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]

Objectives: To examine heart rate variability (HRV) in unmedicated patients with major depressive disorder (MDD) and its changes after treatment with agomelatine alone and in combination with sedative-hypnotics. Methods: We recruited 152 physically healthy, unmedicated patients with MDD and 472 ageand sex-matched healthy volunteers. Frequency-domain measures of HRV were obtained during enrolment for all participants and again for MDD patients after 6 weeks of treatment with agomelatine alone and combining sedative-hypnotics. Results: Compared to the controls, unmedicated patients exhibited significantly lower mean R-R intervals, low-frequency (LF) HRV, and high-frequency (HF) HRV, but higher LF/HF ratios. Fifty-six and 49 patients successfully completed agomelatine monotherapy and the combination therapy of agomelatine and sedative-hypnotics, respectively. Between-group analyses showed significant treatment-by-group interactions for LF-HRV, HF-HRV and LF/HF ratio. The results showed a significant increase in HF-HRV after agomelatine monotherapy, a significant decrease in LF-HRV and HF-HRV, and a increase in the LF/HF ratio after combination therapy. Conclusions: MDD patients had reduced HRV, and the patterns of HRV changes differed between patients treated with agomelatine alone and in combination with sedative-hypnotics. Clinicians should consider HRV effects when adding sedative-hypnotics to agomelatine, which is important for depressed patients who already have decreased cardiac vagal tone. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Schizophrenia, a debilitating mental disorder, is characterized by persistent negative symptoms such as avolition and anhedonia. Currently, there are no effective treatments available for these symptoms. Thus, our study aims to assess the efficacy of online high‐definition transcranial direct current stimulation (online HD‐tDCS) in addressing the negative symptoms of schizophrenia, utilizing a double‐blind, randomized, sham‐controlled trial design.Fifty‐nine patients with schizophrenia were randomized to receive either active HD‐tDCS or sham stimulation, targeting the left dorsolateral prefrontal cortex. Outcomes were measured by changes in the Positive and Negative Syndrome Scale Factor Score for Negative Symptom (PANSS‐FSNS). Exact low‐resolution electromagnetic tomography was used to assess the functional connectivity.All 59 participants, including 50.84% females with an average age of 43.36 years, completed the trial. In the intention‐to‐treat analysis, patients receiving active HD‐tDCS showed greater improvement in PANSS‐FSNS scores compared to those receiving the sham procedure. The differences were 2.34 (95% confidence interval [CI], 1.28–3.40), 4.28 (95% CI, 2.93–5.62), and 4.91 (95% CI, 3.29–6.52) after the intervention, as well as at 1‐week and 1‐month follow‐ups, respectively. A tingling sensation on the scalp was more common in the active group (63.3%) compared to the sham group (10.3%). Additionally, HD‐tDCS was associated with a decrease in delta‐band connectivity within the default mode network.High‐definition transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia when combined with online functional targeting. [ABSTRACT FROM AUTHOR]

The article presents a case study of a woman patient who was diagnosed with bipolar disorder due to lung atypical carcinoid tumor-induced ectopic Cushing's syndrome. The treatment options, symptoms of bipolar disorder, the role of hypercortisolemia in the development of bipolar disorder and the unfavorable clinical outcomes of atypical carcinoid tumor are discussed.

Background: Compared to functional magnetic resonance imaging (fMRI), source localization of a scalp-recorded electroencephalogram (EEG) provides higher temporal resolution and frequency synchronization to better understand the potential neurophysiological origins of disrupted functional connectivity (FC) in major depressive disorder (MDD). The present study aimed to investigate EEG-sourced measures to examine the FC in drug-free patients with MDD., Method: Resting-state 32-channel EEG were recorded in 84 drug-free patients with MDD and 143 healthy controls, and the cortical source signals were estimated. Exact low-resolution brain electromagnetic tomography (eLORETA) was used to compute the intracortical activity from regions within the default mode network (DMN) and frontoparietal network (PFN). Lagged phase synchronization was used as a measure of functional connectivity., Results: Compared with control subjects, the MDD group showed greater within-DMN alpha 1 and 2 bands and within-FPN alpha 1, 2, and beta 3 bands. Furthermore, the MDD group showed hyperconnectivity between the DMN and the FPN in the alpha 1 and 2 bands. Finally, higher levels of anhedonia were associated with higher between-network DMN and FPN connectivity in the alpha-1 band., Limitations: Due to the inherent limitations of eLORETA with predefined seeds, we could not exclude connectivity between regions of interest (ROIs), which may be related to the activity from regions adjacent to the ROIs., Conclusions: The present findings support the importance of phase-lagged functional dysconnectivity in the neurophysiological mechanisms underlying MDD. Exploring the potential of these patterns as surrogates for treatment responses may advance targeted interventions for depression., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)