Comparative Analysis of High-Frequency and Low-Frequency Transcutaneous Electrical Stimulation of the Right Median Nerve in the Regression of Clinical and Neurophysiological Manifestations of Generalized Anxiety Disorder.

Background/Objectives: The anxiolytic effect of transcutaneous electrical nerve stimulation (TENS) is associated with the activation of endogenous inhibitory mechanisms in the central nervous system. Both low-frequency, high-amplitude TENS (LF-TENS) and high-frequency, low-amplitude TENS (HF-TENS) are capable of activating opioid, GABA, serotonin, muscarinic, and cannabinoid receptors. However, there has been no comparative analysis of the effectiveness of HF-TENS and LF-TENS in the treatment of GAD. The purpose of our research was to study the effectiveness of direct HF-TENS and LF-TENS of the right median nerve in the treatment of patients with GAD compared with sham TENS. Methods: The effectiveness of direct HF-TENS and LF-TENS of the right median nerve in the treatment of GAD was studied using Generalized Anxiety Disorder 7-item scale (GAD-7) and the Hamilton Anxiety Rating Scale (HAM-A). 40 patients underwent sham TENS, 40 patients passed HF-TENS (50 Hz-50 µs-sensory response) and 41 patients completed LF -TENS (1 Hz-200 µs-motor response) for 30 days daily. After completion of treatment, half of the patients received weekly maintenance therapy for 6 months. Electroencephalography was performed before and after treatment. Results: Our study showed that a significant reduction in the clinical symptoms of GAD as assessed by GAD-7 and HAM-A was observed after HF-TENS and LF-TENS by an average of 42.4%, and after sham stimulation only by 13.5% for at least 2 months after the end of treatment. However, LF-TENS turned out to be superior in effectiveness to HF-TENS by 51% and only on electroencephalography leads to an increase in PSD for the alpha rhythm in the occipital regions by 24% and a decrease in PSD for the beta I rhythm in the temporal and frontal regions by 28%. The prolonged effect of HF-TENS and LF-TENS was maintained without negative dynamics when TENS treatment was continued weekly throughout the entire six-month observation period. Conclusions: A prolonged anxiolytic effect of direct TENS of the right median nerve has been proven with greater regression of clinical and neurophysiological manifestations of GAD after LF-TENS compared to HF-TENS. Minimal side effects, low cost, safety, and simplicity of TENS procedures are appropriate as a home treatment modality.

Amelioration of Anxiety Associated with Opioid Withdrawal by Activation of Spinal Mechanoreceptors Via Novel Heterodyned Whole Body Vibration.

Objectives: Opioid use disorder (OUD)-associated overdose deaths have reached epidemic proportions worldwide. An important driving force for relapse is anxiety associated with opioid withdrawal. We hypothesized that our new technology, termed heterodyned whole-body vibration (HWBV) would ameliorate anxiety associated with OUD. Methods: Using a randomized, placebo (sham)-controlled, double-blind study design in an NIH-sponsored Phase 1 trial, we evaluated 60 male and 26 female participants diagnosed with OUD and undergoing treatment at pain and rehabilitation clinics. We utilized the Hamilton Anxiety Scale (HAM-A) and a daily visual analog scale anxiety rating (1-10) to evaluate anxiety. Subjects were treated for 10 min 5X/week for 4 weeks with either sham vibration (no interferential beat or harmonics) or HWBV (beats and harmonics). The participants also completed a neuropsychological test battery at intake and discharge. Results: In OUD subjects with moderate anxiety, there was a significant improvement in daily anxiety scores in the HWBV group compared to the sham treatment group (p=3.41 × 10-7). HAM-A scores in OUD participants at intake showed moderate levels of anxiety in OUD participants (HWBV group: 15.9 ± 1.6; Sham group: 17.8 ± 1.6) and progressively improved in both groups at discharge, but improvement was greater in the HWBV group (p=1.37 × 10-3). Furthermore, three indices of neuropsychological testing (mental rotations, spatial planning, and response inhibition) were significantly improved by HWBV treatment. Conclusions: These findings support HWBV as a novel, non-invasive, non-pharmacological treatment for anxiety associated with OUD.

Anxiety level among students of different college and universities in India during lock down in connection to the COVID-19 pandemic.

Objectives: COVID-19 incidence became a pandemic immediately after its origin and spread. Apart from death because of coronavirus infection, the pandemic brought unbearable psychological pressure to all. We assessed the psychological pressure on college and university students in India through cluster sampling. Methods: The students responded (n = 209) to an online questionnaire following the Generalized Anxiety Disorder Scale (GAD-7) and Hamilton Anxiety Rating Scale (HAM-A) with some other basic information. Results: According to GAD-7 scoring, we found the respondent students had severe anxiety (1.44%), moderately severe anxiety (14.35%), moderate anxiety (36.36%) and mild anxiety (47.85%). Following HAM-A scoring, anxiety level among the students could be scaled as severe (0.96%), high (4.31%), moderate (13.40%) and mild anxiety (34.93%) level. Age of the students was a confounding factor (p = 0.049, HAM-A) of experiencing anxiety, students <20 years of age were more anxious. We found female students to be more anxious than the males following the HAM-A scoring tool. Academic delays (R2 = 0.996, p = 0.036) and impact on daily life (R2 = 0.996, p = 0.117) were positively associated with anxiety symptoms, while social support was marginally correlated (R2 = 0.726, p = 0.069) with the anxiety level. Conclusions: As the study found almost all the students are experiencing anxiety because of the current pandemic situation, continuous observation of psychological health for all is recommended as well as establishing psychological intervention during the preparedness phase.

Evaluation of comparative efficacy of Celastrus paniculatus (Jyotishmati) capsule versus sertraline capsule in the management of Chittodvega (generalized anxiety disorder): protocol for a randomized controlled trial.

Background: Generalized anxiety disorder (GAD) (Chittodvega) is one among many types of mental disorders explained in Ayurveda. It can be defined as a Chitta (mind) + Udvega (anxiety)= Chittodvega- Anxious status of a mind. Celastrus paniculatus also known as Jyotishmati. stimulates and improves the digestive fire and metabolism at a cellular level ( Jatharagni and Majja dhatwagni). It can be correlated to GAD. GAD is characterized by feelings of threat, restlessness, irritability, sleep disturbance, and tension, and symptoms such as palpitations, dry mouth, and sweating. It affects women more frequently than men and prevalence rates are high in midlife (prevalence in females over age 35: 10%) and older subjects. In modern medicine the first-line psychological and pharmaceutical treatments are selective serotonin reuptake inhibitors (SSRIs) like sertraline (SNRIs). Aim and objectives: To evaluate the comparative efficacy of Jyotishmati versus sertraline in the management of Chittodvega. Methods: In this randomized active controlled double blind equivalence trial a total of 70 patients will be enrolled and divided into two equal groups. Patients between 20-50 years age of either gender having symptoms of Chittodvega and a Hamilton anxiety rating (HAM-A) scale score less than 24 (i.e., mild to moderate) will be selected for the study. In Group A, sertraline capsules 25 mg for first 7 days and then dose increased to 50 mg at bedtime for next 53 days and in Group B Jyotishmati Capsules 500 mg will be given twice a day after food with water for 60 days. Result and observation: The patients will be assessed on the HAM-A scale, serum cortisol and WHO Quality of Life on day 0, 30, 60 and 90 and data will be analyzed using paired and unpaired t-tests for continuous variables and chi-square tests for categorical variables to evaluate whether treatments are equivalent. Trial registration: CTRI No. REF/2023/07/069880 Date - 15/09/2023.

Consistency checks to improve measurement with the Hamilton Rating Scale for Anxiety (HAM-A).

BACKGROUND: Mitigating rating inconsistency can improve measurement fidelity and detection of treatment response. METHODS: The International Society for CNS Clinical Trials and Methodology convened an expert Working Group that developed consistency checks for ratings of the Hamilton Anxiety Rating Scale (HAM-A) and Clinical Global Impression of Severity of anxiety (CGIS) that are widely used in studies of mood and anxiety disorders. Flags were applied to 40,349 HAM-A administrations from 15 clinical trials and to Monte Carlo-simulated data as a proxy for applying flags under conditions of inconsistency. RESULTS: Thirty-three flags were derived these included logical consistency checks and statistical outlier-response pattern checks. Twenty-percent of the HAM-A administrations had at least one logical scoring inconsistency flag, 4 % had two or more. Twenty-six percent of the administrations had at least one statistical outlier flag and 11 % had two or more. Overall, 35 % of administrations had at least one flag of any type, 19 % had one and 16 % had 2 or more. Most of administrations in the Monte Carlo- simulated data raised multiple flags. LIMITATIONS: Flagged ratings may represent less-common presentations of administrations done correctly. Conclusions-Application of flags to clinical ratings may aid in detecting imprecise measurement. Flags can be used for monitoring of raters during an ongoing trial and as part of post-trial evaluation. Appling flags may improve reliability and validity of trial data.

Diagnostic Value in Screening Severe Depression of the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Beck Depression Inventory Scale, and Zung's Self-Rating Anxiety Scale Among Patients with Recurrent Depression Disorder.

Background: Depression is a widespread and incapacitating mental health disorder that impacts millions of people worldwide, playing a substantial role in the overall global health challenges. Depression has a big impact on a person's quality of life, cognitive and social functioning, risk of suicide, risk of heart disease and other illnesses, as well as death from all causes. Objective: It may be challenging to choose the best tools to screen for severe depression in patients with recurrent depression disorder (PRD) considering the diversity of psychological scales in Vietnam. The aim of this study was to evaluate diagnostic value for detect severe depression of four psychological scales including Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory Scale (BECK), and Zung's Self-Rating Anxiety Scale (SAS) by genders and age groups among PRD in Vietnam. Methods: This study was conducted at National Institute of Mental Health, Bach Mai Hospital, Vietnam, from 2020 to 2021. There were 109 PRD evaluated with HAM-D, HAM-A, BECK, and SAS by qualified psychiatrists. By analysing Area Under the Curve (AUC) of Receiver Operating Characteristic (ROC) curve, we determined sensitivity, specificity and cut points of four above scales. Results: Among four scales, the BECK scale had the best diagnostic effect with the most optimal sensitivity and specificity (61.64% and 75%, respectively). We proposed the new cut-off of HAM-D, HAM-A, BECK, and SAS for detecting severe depression among PRD were 20, 34, 30, and 45, respectively. By genders, the cut points for the HAM-D, HAM-A, BECK, and SAS in males were 20, 27, 34, and 44, respectively, while those figure in females were 14, 34, 30, and 46, respectively. By age groups, adults had cut values for four above scales of 20, 34, 27, and 45, respectively, whereas those for the elderly were 16, 17, 35, and 44, respectively. Conclusion: We highly recommended that BECK is the most optimal method to screen severe depression in PRD in Vietnam. It is essential to utilize varied cut values of HAM-D, HAM-A, BECK, and SAS for different genders and age groups.

Application of Comfort Therapy under eCASH Concept in Acute and Chronic Wound Treatment.

INTRODUCTION: Given the new ideas on wound care offered by the eCASH (early Comfort using Analgesia, minimal Sedatives, and maximal Humane care) and the substantial differences in clinical treatment between acute and chronic wounds, we aimed to investigate the effect of comfort therapy under the eCASH concept on analgesic sedation and accelerated wound healing in patients with acute or chronic wounds. METHODS: This randomized clinical study was conducted in two parts: acute wounds and chronic wounds. Patients with acute wounds were allocated into the acute wound control group (AWCG) and the acute wound experimental group (AWEG). Patients with chronic wounds were allocated into the chronic wound control group (CWCG) and two experimental groups, in which they received intermittent negative pressure therapy (IPTEG) and continuous negative pressure therapy (CPTEG). On the basis of the standard treatment for patients in the control group, eCASH therapy was used in the experimental groups. In addition, pain intensity and procedural anxiety were evaluated using the visual analogue score (VAS) and the Hamilton Anxiety Scale (HAM-A). In addition, clinical effects were assessed on the basis of the size of the surface area, rate of healing, and concentration of pro-inflammatory factors (IL-1, IL-6, TNF-α) and growth factors (VEGF, bFGF, TGF-ß1). RESULTS: Compared with the control group, the VAS score and HAM-A score in the experimental groups were significantly decreased after intervention (P < 0.05). After intervention, the levels of IL-1ß, IL-6, and TNF-α in AWEG, IPTEG, and CPTEG were significantly lower than those in AWCG. In addition, the levels of VEGF, bFGF, and TGF-ß1 in IPTEG and CPTEG were significantly higher than those in CWCG (P < 0.05). CONCLUSION: These results indicated that comfort therapy under the eCASH concept has a significant effect on ameliorating the pain and anxiety of patients, reducing the inflammatory reaction during the period of wound healing in the treatment of acute and chronic wounds. CLINICAL TRIAL REGISTRY: The trial has been registered in the Chinese Clinical Trial Registry (ChiCTR2200057981).

Psycho-Social Effects of Pet Dog Ownership on Mentally Challenged Children.

AIM: Mental retardation is a social stigma and children affected by this condition always require love and compassion. Pets have a positive role in human life to relieve stress and anxiety. Pets are therefore considered to be a very important aspect of psychological therapy. Those children who are suffering from mental retardation have to be given regular stress and anxiety-relieving sessions. Hence this study aims to analyze the psychosocial effects of pet dog ownership on mentally challenged children. METHODOLOGY: A total of 112 children were included in the study and were counseled at the Department of Pediatrics, District Hospital, Amritsar. Twenty patients were lost to follow up and pet ownership materialized in 52 patients. The study was divided into 2 groups, the compliant group (n=52) and the non-compliant group (n=40). Hamilton anxiety scale (HAM-A) was applied to all the children before pet dog ownership (PRE) and after 3-6 months with a pet dog (POST). The pre and post-scores of all the children were recorded and subjected to statistical analysis. RESULTS: The HAM-A score before pet ownership was comparable, before pet ownership (p=.825), but after 3-6 months of pet ownership significant difference was observed between compliant and non-compliant groups (p<.001). Also, the HAM-A score in children with mild mental retardation (mild MR) and moderate mental retardation (moderate MR) was significantly less than the non-compliant group after 3-6 months. We also observed that the decrease in the anxiety levels was comparable in children who owned local breeds and foreign breeds. CONCLUSION: This short-term follow-up research highlights the potential advantages of keeping a companion dog for youngsters with mental problems in terms of improving their lives. Many of these long-term gains might be attributed to lessening tensions within families.

H-FABP Levels and Psycho-Emotional Improvement of CABG Patients during Cardiac Rehabilitation.

(1) Background: The heart-type fatty acid-binding protein (H-FABP) is a specific myocardial biomarker and high levels indicate ischemia regardless of patient-reported symptoms. Concurrently, major adverse cardiovascular events and surgery such as coronary artery by-pass grafting (CABG) cause substantial psycho-emotional distress e.g., depression and anxiety. Comprehensive cardiac rehabilitation is, therefore, essential to both physical and psychological recovery. (2) Methods: This is a unicentric, prospective study on 120 consecutive post-CABG patients undergoing a 6-month cardiac rehabilitation program based on physical exercise, Mediterranean diet principles, and Q10 coenzyme antioxidant supplements. H-FABP levels, depression, and anxiety scores (Hamilton HAM-D and HAM-A scales) were monitored after surgery and at 6 months. (3) Results: Mean H-FABP dropped from 60.56 to 4.81. Physical ability increased from 1-2 to 4-5 METS. Mean depression and anxiety improved from 15.88 to 6.96 and from 25.13 to 15.68, respectively. Median scores went down 50% for depression and 9% for anxiety. Explored associations between H-FABP and psycho-emotional status were statistically insignificant. (4) Conclusions: patients adhered to the program and improved significantly in all studied aspects. Clinical significance is discussed in the context of countries like Romania, where such programs are limited by systemic and financial constraints. Further research directions are identified.

The potency of psychiatric questionnaires to distinguish major mental disorders in Chinese outpatients.

Background: Considering the huge population in China, the available mental health resources are inadequate. Thus, our study aimed to evaluate whether mental questionnaires, serving as auxiliary diagnostic tools, have efficient diagnostic ability in outpatient psychiatric services. Methods: We conducted a retrospective study of Chinese psychiatric outpatients. Altogether 1,182, 5,069, and 4,958 records of Symptom Checklist-90 (SCL-90), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D), respectively, were collected from March 2021 to July 2022. The Mann-Whitney U test was applied to subscale scores and total scores of SCL-90, HAM-A, and HAM-D between the two sexes (male and female groups), different age groups, and four diagnostic groups (anxiety disorder, depressive disorder, bipolar disorder, and schizophrenia). Kendall's tau coefficient analysis and machine learning were also conducted in the diagnostic groups. Results: We found significant differences in most subscale scores for both age and gender groups. Using the Mann-Whitney U test and Kendall's tau coefficient analysis, we found that there were no statistically significant differences in diseases in total scale scores and nearly all subscale scores. The results of machine learning (ML) showed that for HAM-A, anxiety had a small degree of differentiation with an AUC of 0.56, while other diseases had an AUC close to 0.50. As for HAM-D, bipolar disorder was slightly distinguishable with an AUC of 0.60, while the AUC of other diseases was lower than 0.50. In SCL-90, all diseases had a similar AUC; among them, bipolar disorder had the lowest score, schizophrenia had the highest score, while anxiety and depression both had an AUC of approximately 0.56. Conclusion: This study is the first to conduct wide and comprehensive analyses on the use of these three scales in Chinese outpatient clinics with both traditional statistical approaches and novel machine learning methods. Our results indicated that the univariate subscale scores did not have statistical significance among our four diagnostic groups, which highlights the limit of their practical use by doctors in identifying different mental diseases in Chinese outpatient psychiatric services.

Correlations Between Inflammatory Biomarkers in Tuberculosis-Associated Obstructive Pulmonary Disease Patients With Anxiety and Depression.

Introduction Tuberculosis-associated obstructive pulmonary disease (TOPD), anxiety, and depression are significant public health problems worldwide and their prevalence is common. These diseases interfere with physical, psychosocial, and economic well-being, resulting in unemployment, prolonged hospitalization, abstinence from working, and isolation. Subjects and methods This is a single-center, cross-sectional cohort, observational study conducted in a tertiary care hospital over six years to understand spirometry, laboratory profiles, as well as the impact on overall health, daily life, and perceived well-being in patients with TOPD. Result The sample size of the study was 73 patients. A total of 43 (58.5%) patients had depression with an average St. George's Respiratory Questionnaire for chronic obstructive pulmonary disease (SGRQ-C) score of 67.5, and 16 (21.9%) patients had anxiety with an average SGRQ-C score of 78.9. In the patients who scored higher on the Hamilton Depression Rating Scale (HAM-D), there was a significant correlation between Hamilton Anxiety Rating Scale (HAM-A) and HAM-D scores, as well as C-reactive protein (CRP) levels and WBC counts. In 16 (21.9%) of the patients with moderate to severe anxiety, there was a statistically significant negative correlation between higher HAM-A scores and lower WBC counts. Anxiety, depression, CRP level, WBC count, and serum fibrinogen did not show a significant correlation with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups-based assessment of TOPD severity. A high serum fibrinogen level did not correlate with a high HAM-D score, nor did a high CRP level correlate with a high HAM-A score. Conclusion Psychiatric comorbidities like depression are associated with increased inflammation in chronic diseases like TOPD, but no definitive biomarker has been identified and further studies are required to identify suitable biomarkers.

Efficacy and Safety of Escitalopram Oral Drops to Treat Major Depressive Disorder and Generalized Anxiety Disorder in Adolescent, Adult and Geriatric Patients: A Prospective Multicenter Observational Study in Pakistan.

Background  Escitalopram is widely used for the management of the major depressive disorder and generalized anxiety disorder, but there is no to very limited data available regarding efficacy and safety in Pakistani patients. This study was conducted to evaluate the efficacy and safety of escitalopram oral drops to manage the major depressive disorder and generalized anxiety disorder in a local cluster within Pakistan. Methods This prospective multicenter observational study was conducted in the department of psychiatry from August 2018 - August 2019. Eighty-five patients meeting the selection criteria were included in the study. Adolescent, adult, and geriatric patients of either gender with generalized anxiety disorder having Hamilton Anxiety Rating Scale (HAM-A) rate ≥ 10 and major depressive disorder having Montgomery-Asberg Depression Rating Scale (MADRS) rate ≥ 7 or patients with co-morbid generalized anxiety disorder (GAD), major depressive disorder (MDD) were selected for the study. We are reporting patients' improvement from baseline, response rate, and remission rate. Data analysis is performed by using SPSS version 21 (IBM Inc, Armonk, USA). Results Among enrolled patients, 42 were adolescents, 22 were adults, and 21 were geriatric. The mean age of an adolescent, adult, and geriatric patients was 14.92 ± 2.04, 44.54 ± 12.08, and 64.61 ± 3.16 years, respectively. Among enrolled patients, the mean change in a total score of HAM-A for anxiety and MADRS for depression were -10.04 ± 4.32 and -17.67 ± 14.42, respectively. At the end of the study, the remission rate and response rate for depression were 82 % and 75%, respectively. Similarly, the remission rate and the response for anxiety were 76% and 81%, respectively. Mean HAM-A and MADRS scores were significantly improved for adolescent, adult, and geriatric patients. Adverse events were reported in eight (9.41%) patients with six having gastrointestinal (GI) disturbance and two having to worsen anxiety. All reported adverse events were of mild severity.  Conclusion  Escitalopram oral drops are found effective and tolerable in reducing both anxiety and depression over the duration of study in all age groups, including adolescents, adults, and geriatrics.

Influence of covariates on heterogeneity in Hamilton Anxiety Scale ratings in placebo-controlled trials of benzodiazepines in generalized anxiety disorder: Systematic review and meta-analysis.

BACKGROUND: Generalized anxiety disorder is a common psychiatric condition that is associated with decreased quality of life and significant disability. Benzodiazepines are anti-anxiety drugs used widely in the treatment of generalized anxiety disorder. This study examines the influence of several variables on benzodiazepine efficacy in generalized anxiety disorder. METHOD: We performed a systematic review of placebo-controlled randomized controlled trials with benzodiazepines in generalized anxiety disorder. Fifty-eight studies were deemed eligible to include in the meta-analysis. The studies dated from 1977 to 2013 and included over 5400 participants. From each paper, we extracted: benzodiazepine name and dose, dosing regimen, baseline Hamilton Anxiety Scale (HAM-A) score, change in HAM-A score at study endpoint, drop-out rate, year of study publication, diagnostic criteria used, study size, study duration, location, any conflicts of interest and side-effect profile. We then assessed the influence, direct and indirect, of individual variables on the primary outcome (mean difference at endpoint, HAM-A score). RESULTS: Three factors were shown to be associated statistically with change in HAM-A; baseline HAM-A for benzodiazepine arm, baseline HAM-A for the placebo arm, and duration of the study. A higher baseline HAM-A in both arms was associated with a greater mean difference in HAM-A. A shorter study length was also associated with a greater mean difference. DISCUSSION: The major factors determining benzodiazepine response was baseline anxiety level for the benzodiazepine arm and study duration. In any design of further meta-analyses and clinical trials for generalized anxiety disorder we suggest that these should be considered these as confounding factors.

[Mental disorders, social maladaptation and quality of life of patients with acne and post-acne symptoms]. / Psikhicheskie rasstroistva, sotsial'naia dezadaptatsiia i kachestvo zhizni patsientov s akne i simptomami postakne.

AIM: A comparative analysis of the psycho-emotional status and quality of life of patients with acne and post-acne. MATERIAL AND METHODS: There were 147 patients included in the study, 84 (57%) women and 63 (43%) men, aged from 14 to 48 years. The following parameters were studied: CADI score, APSEA score, DLQI score. Anxiety and depression were assessed with HAM-D and HAM-A. RESULTS: Higher scores on CADI, APSEA and DLQI and dissatisfaction with the results of therapy were noted in older patients. Significant changes in CADI, APSEA and DLQI scores in patients with post-acne symptoms were recorded later compared to patients with acne. Anxiety and depression symptoms measured with HAM-D and HAM-A reached the level of depressive disorder of moderate severity and moderate anxiety in patients over 20 years old. Mental disorders were qualified within the nosogenic anxiety-phobic reactions developing in connection with dermatosis manifestation. CONCLUSION: Acnes substantially better give in to correction than post-acne symptom complex. Regardless of age, post-acne symptoms considerably reduce quality of life of patients, sometimes causing more expressed changes (anxiety and depression) than dermatosis.

Impaired emotion processing in functional (psychogenic) tremor: A functional magnetic resonance imaging study.

BACKGROUND: Despite its high prevalence and associated disability, the neural correlates of emotion processing in patients with functional (psychogenic) tremor (FT), the most common functional movement disorder, remain poorly understood. METHODS: In this cross sectional functional magnetic resonance imaging (fMRI) study at 4T, 27 subjects with FT, 16 with essential tremor (ET), and 25 healthy controls (HCs) underwent a finger-tapping motor task, a basic-emotion task, and an intense-emotion task to probe motor and emotion circuitries. Anatomical and functional MRI data were processed with FSL (FMRIB Software Library) and AFNI (Analysis of Functional Neuroimages), followed by seed-to-seed connectivity analyses using anatomical regions defined from the Harvard-Oxford subcortical atlas; all analyses were corrected for multiple comparisons. RESULTS: After controlling for depression scores and correcting for multiple comparisons, the FT group showed increased activation in the right cerebellum compared to ET during the motor task; and increased activation in the paracingulate gyrus and left Heschl's gyrus compared with HC with decreased activation in the right precentral gyrus compared with ET during the basic-emotion task. No significant differences were found after adjusting for multiple comparisons during the intense-emotion task but increase in connectivity between the left amygdala and left middle frontal gyrus survived corrections in the FT subjects during this task, compared to HC. CONCLUSIONS: In response to emotional stimuli, functional tremor is associated with alterations in activation and functional connectivity in networks involved in emotion processing and theory of mind. These findings may be relevant to the pathophysiology of functional movement disorders.

Neurobiological and clinical effects of fNIRS-controlled rTMS in patients with panic disorder/agoraphobia during cognitive-behavioural therapy.

BACKGROUND: A relevant proportion of patients with panic disorder (PD) does not improve even though they receive state of the art treatment for anxiety disorders such as cognitive-behavioural therapy (CBT). At the same time, it is known, that from a neurobiological point of view, PD patients are often characterised by prefrontal hypoactivation. Intermittent Theta Burst Stimulation (iTBS) is a non-invasive type of neurostimulation which can modulate cortical activity and thus has the potential to normalise prefrontal hypoactivity found in PD. We therefore aimed at investigating the effects of iTBS as an innovative add-on to CBT in the treatment for PD. METHODS: In this double-blind, bicentric study, 44 PD patients, randomised to sham or verum stimulation, received 15 sessions of iTBS over the left prefrontal cortex (PFC) in addition to 9 weeks of group CBT. Cortical activity during a cognitive as well as an emotional (Emotional Stroop) paradigm was assessed both at baseline and post-iTBS treatment using functional near-infrared spectroscopy (fNIRS) and compared to healthy controls. RESULTS: In this manuscript we only report the results of the emotional paradigm; for the results of the cognitive paradigm please refer to Deppermann et al. (2014). During the Emotional Stroop test, PD patients showed significantly reduced activation to panic-related compared to neutral stimuli for the left PFC at baseline. Bilateral prefrontal activation for panic-related stimuli significantly increased after verum iTBS only. Clinical ratings significantly improved during CBT and remained stable at follow-up. However, no clinical differences between the verum- and sham-stimulated group were identified, except for a more stable reduction of agoraphobic avoidance during follow-up in the verum iTBS group. LIMITATIONS: Limitations include insufficient blinding, the missing control for possible state-dependent iTBS effects, and the timing of iTBS application during CBT. CONCLUSION: Prefrontal hypoactivity in PD patients was normalised by add-on iTBS. Clinical improvement of anxiety symptoms was not affected by iTBS.

Repetitive transcranial magnetic stimulation in the treatment of obsessive-compulsive disorders: Double blind randomized clinical trial.

Repetitive transcranial magnetic stimulation (rTMS) has become widely used as a therapeutic tool in psychiatric research. The aim of this study was to evaluate the impact of different frequencies of rTMS over right dorsolateral prefrontal cortex (DLPFC) in OCD. Forty five patients with OCD participated in the study. Patients were evaluated using: Yale-Brown obsessive compulsive scale (Y-BOCS), Hamilton Anxiety Rating Scale (HAM-A), and Clinical Global Impression-Severity scale (CGI-S). They were randomly classified into three groups: 1st group received 1Hz rTMS; 2nd group received 10Hz rTMS; and 3rd group received sham stimulation all at 100% of the resting motor threshold for 10 sessions. They were followed up after the last treatment session and 3 months later. There was a significant "time"×"group" interaction for 1Hz versus Sham but not for 10Hz versus Sham. 1Hz versus 10Hz groups showed a significant interaction for Y-BOCS and HAM-A (P=0.001 and 0.0001 respectively). 1Hz rTMS has a greater clinical benefit than 10Hz or Sham. There was also a significantly larger percentage change in GCI-S in the 1Hz group versus either 10Hz or sham. We conclude that 1Hz-rTMS, targeting right DLPFC is a promising tool for treatment of OCD.

Investigation of the relationship between anxiety and heart rate variability in fibromyalgia: A new quantitative approach to evaluate anxiety level in fibromyalgia syndrome.

BACKGROUND: Fibromyalgia syndrome (FMS) is identified by widespread musculoskeletal pain, sleep disturbance, nonrestorative sleep, fatigue, morning stiffness and anxiety. Anxiety is very common in Fibromyalgia and generally leads to a misdiagnosis. Self-rated Beck Anxiety Inventory (BAI) and doctor-rated Hamilton Anxiety Inventory (HAM-A) are frequently used by specialists to determine anxiety that accompanies fibromyalgia. However, these semi-quantitative anxiety tests are still subjective as the tests are scored using doctor-rated or self-rated scales. METHOD: In this study, we investigated the relationship between heart rate variability (HRV) frequency subbands and anxiety tests. The study was conducted with 56 FMS patients and 34 healthy controls. BAI and HAM-A test scores were determined for each participant. ECG signals were then recruited and 71 HRV subbands were obtained from these ECG signals using Wavelet Packet Transform (WPT). The subbands and anxiety tests scores were analyzed and compared using multilayer perceptron neural networks (MLPNN). RESULTS: The results show that a HRV high frequency (HF) subband in the range of 0.15235Hz to 0.40235Hz, is correlated with BAI scores and another HRV HF subband, frequency range of 0.15235Hz to 0.28907Hz is correlated with HAM-A scores. The overall accuracy is 91.11% for HAM-A and 90% for BAI with MLPNN analysis. CONCLUSION: Doctor-rated or self-rated anxiety tests should be supported with quantitative and more objective methods. Our results show that the HRV parameters will be able to support the anxiety tests in the clinical evaluation of fibromyalgia. In other words, HRV parameters can potentially be used as an auxiliary diagnostic method in conjunction with anxiety tests.

Tryptophan hydroxylase 2 gene polymorphism in anxiety and depressive disorder in kashmiri population.

BACKGROUND: The gene of tryptophan hydroxylase is widely recognized as a major candidate gene in many psychiatric disorders. However, no study has been done which investigates tryptophan hydroxylase 2 gene polymorphism in anxiety and depressive disorders in Kashmiri population (India). OBJECTIVES: To study tryptophan hydroxylase 2 (TPH2) C 11993 A gene polymorphism in anxiety and depressive disorders. METHOD: Sixty patients of depression disorder, 60 patients of anxiety disorder and 40 unrelated healthy volunteers (control) were studied in a case control design. Polymorphism was determined using polymerase chain reaction (PCR) and agarose gel electrophoresis after digestion with HAP II enzyme. Genotypes and allele frequencies were compared using Chi-square tests, Fischer's exact test, odds ratio, 95% confidence interval (C.I) and p-value of <0.05 was considered to be statistical significant. RESULTS: The mean age ± SD of anxiety, depression and control group was 32.73±10.99, 32.20±10 and 29.75±10.12 respectively and the difference was found to be statistically non significant (p=0.349).The mean HAM-A (Hamilton rating scale for anxiety) score and HAM-D (Hamilton rating scale for depression) score was high in both groups (anxiety and depression) and found to be statistically significant (p=0.001).Depression group had AA genotype (55.2%) than control (37.5%) and was found to be statistically non significant (p=0.890).Comparison of allelic frequency revealed no association of A allele in anxiety group (76.67%) compared with control (75.5%) and was found to be statistically non significant (p= 0.866), OR 1.09 (0.56-2.11). CONCLUSION: TPH2C 11993 A gene was not found to be associated with major depressive disorder (MDD) and anxiety disorder in Kashmiri population.

Deep-brain stimulation for anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) is a complex and severe, sometimes life-threatening, psychiatric disorder with high relapse rates under standard treatment. After decades of brain-lesioning procedures offered as a last resort, deep-brain stimulation (DBS) has come under investigation in the last few years as a treatment option for severe and refractory AN. METHODS AND RESULTS: In this jointly written article, Sun et al. (the Shanghai group) report an average of 65% increase in body weight in four severe and refractory patients with AN after they underwent the DBS procedure (average follow-up: 38 months). All patients weighed greater than 85% of expected body weight and thus no longer met the diagnostic criteria of AN at last follow-up. Nuttin et al. (the Leuven group) describe other clinical studies that provide evidence for the use of DBS for AN and further discuss patient selection criteria, target selection, and adverse event of this evolving therapy. CONCLUSION: Preliminary results from the Shanghai group and other clinical centers showed that the use of DBS to treat AN may be a valuable option for weight restoration in otherwise-refractory and life-threatening cases. The nature of this procedure, however, remains investigational and should not be viewed as a standard clinical treatment option. Further scientific investigation is essential to warrant the long-term efficacy and safety of DBS for AN.