Association Between Post-COVID Pulmonary Dysfunction and New-Onset Anxiety and Depression and the Impact of Incentive Spirometer-Based Exercises.

Objective: To determine the rates of new-onset anxiety and depression in patients with restrictive or obstructive lung disease after COVID-19 infection and to assess the improvement in pulmonary functions and anxiety/depression scores after prescribing incentive spirometer-based breathing exercises.Methods: A 2-phase study with a cross-sectional and open-label randomized interventional design evaluated anxiety (Generalized Anxiety Disorder-7 [GAD-7] and Hamilton Anxiety Rating Scale [HARS]), depression (Patient Health Questionnaire-9 [PHQ-9]), and pulmonary function tests (PFTs) of 100 COVID-19 patients within 8 weeks of acute illness. Patients with pulmonary dysfunction were randomized (incentive spirometry vs controls), and anxiety/depression scores and lung function were reevaluated after 4 weeks.Results: The results revealed 35% (35/100) of mild-moderate COVID-19 patients had abnormal PFTs. Anxiety/depression was higher in patients with abnormal PFTs than in those with normal lung function (prevalence ratio: 1.8 [20% vs 11%]). The median HARS, GAD-7, and PHQ-9 scores decreased significantly with 4 weeks of incentive spirometry exercises (2 [0-5.5, P = .013], 2 [0-3.5, P = .006], and 2 [0-3.5, P = .006], respectively) compared to standard of care alone. More patients with incentive spirometry had normalization of pulmonary functions compared to controls (50% [8/16] vs 33% [6/18]). The mean age of patients with anxiety/depression was significantly higher than those without anxiety/depression (42 ± 11 vs 30 ± 7, P = .04).Conclusions: While the rates of new-onset anxiety/depression were higher in patients with pulmonary dysfunction, these rates were reduced with incentive spirometer-based exercises. Greater age may be a risk factor for abnormal pulmonary functions and greater anxiety or depression.Trials Registry: Clinical Trials Registry-India identifier: CTRI/2022/11/047183.Prim Care Companion CNS Disord 2023;25(5):23m03490. Author affiliations are listed at the end of this article.

Cognitive impairment in 'non-user' first-degree relatives of persons with cannabis dependence syndrome: A pilot, endophenotype study.

INTRODUCTION: Cannabis use disorders are global emerging problem nowadays, with high prevalence and morbidity. Cognitive impairments, and also corresponding genetic vulnerability, has been fairly replicated in individuals with cannabis dependence. However, there are few studies that assess cognitive functioning as an endophenotype or a trait marker for cannabis dependence. While the primary objective of this study was to assess the endophenotype pattern of cognitive dysfunction in cannabis dependence, assessing the association between the degree of cognitive functioning, and their socio-demographic and clinical variables in the cannabis dependence patients and their first-degree relatives was the secondary objective. METHODOLOGY: We compared cognitive functioning across three groups- patients with cannabis dependence syndrome, their 'non-user' first-degree relatives and healthy controls, with 30 participants in each group. Five cognitive domains- attention and concentration, verbal fluency, memory, visuospatial ability and executive functions were assessed. We assessed for endophenotype pattern of statistical significance in pairwise analyses of Kruskal-Wallis test, which was corrected for multiple comparisons. Subsequently, correlation analysis to assess association of cognitive impairment with socio-demographic and clinical variables was conducted. RESULTS: Although impairment in attention and executive functions also was seen in patients with cannabis dependence, endophenotype pattern of statistical significance in pairwise analyses, with impairment in first-degree relatives too, was seen in all sub-scores of verbal fluency and verbal memory. None of the correlations were significant. CONCLUSION: 'Non-user' first-degree relatives of patients with cannabis dependence too show significant cognitive impairment. Verbal fluency and verbal memory are possible endophenotypes or trait markers for cannabis dependence syndrome.

Brief intervention to enhance cessation of smokeless tobacco use in newly diagnosed patients with head and neck cancers: A randomized controlled trial in patient-relative dyads.

Introduction: Tobacco use is a major causative factor for head and neck cancers (HNC). Continued use of tobacco even after cancer diagnosis is common and is associated with all-cause and cancer-specific mortality, cancer recurrence and poor treatment response. Evidence suggests that behavioral interventions, help achieve greater smoking cessation rates in HNC patients. However, intervention studies focussed on HNC patients using smokeless tobacco, which is more common than smoking in India, are sparse. Materials and Methods: We conducted a parallel arm randomized controlled trial (RCT) on dyads of patients with recently diagnosed HNC and a close relative. The experimental arm received a brief tobacco cessation intervention (BTCI) and the control arm received treatment as usual (TAU); 27 and 25 dyads in each arm completed the trial. Results: Overall for the dyads using SLT, the relative risk of continuing to use SLT was 3.23 times higher (odds ratio = 7.01) if BTCI was not undertaken at one-month follow-up and 4.43 times higher (odds ratio = 8.65) at 3-months follow-up. For patients only, the relative risk of continuing to use SLT at one-month and 3-months follow-ups was 4.99 and 12.04 times higher, respectively, if BTCI was not undertaken. For relatives only, the corresponding relative risk values were 2.14 and 2.2. Conclusion: We conclude that BTCI delivered to patient-relative dyads, compared to TAU, is effective in enhancing the discontinuation rates of the use of SLT in newly diagnosed patients with HNC. This form of intervention is significantly effective for discontinuing SLT use in the relatives too.

Indian research on transcranial magnetic stimulation: A bibliometric analysis.

Background: A significant body of evidence on the role of TMS in neurology and psychiatry has emerged from Indian studies. Aims: We aimed to assess the existing and emerging trends of research on TMS as a diagnostic or therapeutic tool in India using bibliometric analysis. Results: A total of 146 publications, retrieved from various databases, were analyzed using Microsoft Excel and VOSviewer. We found a linear positive growth of publications in India in the field of TMS and neuropsychiatry, with about 3000 citations so far. The most researched diagnosis was schizophrenia. NIMHANS, Bengaluru, had the highest number of publications. The journal with the highest number of publications was the Asian Journal of Psychiatry, and that with the highest citations was the Journal of Affective disorders. Conclusion: The growth of Indian research in the field of TMS corresponds to that of the global one but also suggests the need for more studies to match the research output from other countries.

Retinal microvasculature in schizophrenia: A meta-analysis with trial sequential analysis of studies assessing vessel density using Optical Coherence Tomography Angiography.

We performed a series of random-effects meta-analyses on cross-sectional studies assessing vessel density (VD) using Optical Coherence Tomography Angiography (OCTA) in schizophrenia. Five studies with a total sample size of 410 (schizophrenia-192;healthy-218) were analysed. Supplementary Trial Sequential Analyses (TSA) was also performed. Meta-analyses revealed significantly lower VD in schizophrenia patients compared to healthy controls in the peripapillary region of the optic disc, including both superior hemisphere and inferior hemisphere. TSA validated these significant effects. We conclude that reduced VD at the peripapillary region of the optic disc as measured by OCTA may have the potential to be a schizophrenia biomarker.

Evidence from Indian studies on safety and efficacy of therapeutic transcranial magnetic stimulation across neuropsychiatric disorders- A systematic review and meta-analysis.

Repetitive transcranial magnetic stimulation (rTMS) is potentially effective as an augmentation strategy in the treatment of many neuropsychiatric conditions. Several Indian studies have been conducted in this regard. We aimed to quantitatively synthesize evidence from Indian studies assessing efficacy and safety of rTMS across broad range of neuropsychiatric conditions. Fifty two studies- both randomized controlled and non-controlled studies were included for a series of random-effects meta-analyses. Pre-post intervention effects of rTMS efficacy were estimated in "active only" rTMS treatment arms/groups and "active vs sham" (sham-controlled) studies using pooled Standardized Mean Differences (SMDs). The outcomes were 'any depression', depression in unipolar/bipolar depressive disorder, depression in obsessive compulsive disorder (OCD), depression in schizophrenia, schizophrenia symptoms (positive, negative, total psychopathology, auditory hallucinations and cognitive deficits), obsessive compulsive symptoms of OCD, mania, craving/compulsion in substance use disorders (SUDs) and migraine (headache severity and frequency). Frequencies and odds ratios (OR) for adverse events were calculated. Methodological quality of included studies, publication bias and sensitivity assessment for each meta-analyses was conducted. Meta-analyses of "active only" studies suggested a significant effect of rTMS for all outcomes, with moderate to large effect sizes, at both end of treatment as well as at follow-up. However, except for migraine (headache severity and frequency) with large effect sizes at end of treatment only and craving in alcohol dependence where moderate effect size at follow-up only, rTMS was not found to be effective for any outcome in the series of "active vs sham" meta-analyses. Significant heterogeneity was seen. Serious adverse events were rare. Publication bias was common and the sham controlled positive results lost significance in sensitivity analysis. We conclude that rTMS is safe and shows positive results in 'only active' treatment groups for all the studied neuropsychiatric conditions. However, the sham-controlled evidence for efficacy is negative from India. Conclusion: rTMS is safe and shows positive results in "only active" treatment groups for all the studied neuropsychiatric conditions. However, the sham-controlled evidence for efficacy is negative from India.

Safety and Efficacy of Continuous Theta Burst "Intensive" Stimulation in Acute-Phase Bipolar Depression: A Pilot, Exploratory Study.

OBJECTIVES: Repetitive transcranial magnetic stimulation efficacy in unipolar depression is known, but its efficacy in acute-phase bipolar depression is at best modest. Citing differential right dorsolateral prefrontal cortex hyperconnectivity implicated in BD, we aimed to study the effect of novel continuous theta burst stimulation (cTBS) targeting right dorsolateral prefrontal cortex in a randomized rater blinded placebo control design. MATERIAL AND METHODS: Nineteen patients aged 18 to 59 years (baseline Hamilton Depression Rating Scale [HAM-D] 17 severity score >18) were randomly allocated to active cTBS (n = 11) and sham cTBS (n = 9) groups using block randomization method. They received 15 cTBS sessions (burst of 3 pulses delivered at 50 Hz, repeated every 200 ms at 5 Hz, 600 pulses per session), 3 sessions per day (total of 1800 pulses) for 5 days in a week at 80% resting motor threshold. The HAM-D, Beck Depression Inventory, Hamilton Anxiety Rating Scale, World Health Organization's abbreviated quality of life assessment, and Changes in Sexual Functioning Questionnaire were assessed at baseline, after the last session, and at 2 weeks after repetitive transcranial magnetic stimulation. Intention-to-treat analysis was conducted and missing values (2 patients) were replaced using the last observation carried forward method. RESULTS: On repeated measures analysis of variance, a significant within-group time effect (from pretreatment to 2 weeks after TBS) for HAM-D ( F = 15.091, P < 0.001), Beck Depression Inventory ( F = 22.376, P < 0.001), Hamilton Anxiety Rating Scale ( F = 18.290, P < 0.001), Changes in Sexual Functioning Questionnaire ( F = 9.281, P = 0.001), and World Health Organization's abbreviated quality of life assessment ( F = 24.008, P < 0.001). The integrity of the blind assessed by the guess matrix was good. When significant between group*time effect was compared, none of the variables retained statistical significance. No major adverse effects were reported, and none of the patients discontinued the trial because of adverse effects. CONCLUSIONS: Our trial concludes that although safe and well tolerated, the therapeutic efficacy of intensive intermittent TBS in acute-phase bipolar depression is inconclusive. Choice of lower total number to sessions and smaller intersession interval along with small sample size limit the study findings.

Pragmatic issues and prescribing patterns in bipolar disorder: A mental health professional's survey.

Background: There is substantial treatment gap between the suggested guidelines and pragmatic clinical practice for psychotropic usage in bipolar disorder (BD) due to the lack of naturalistic studies and not taking into account the transcultural differences and diverse background. We intend to study this treatment gap and elucidate the preference of psychotropics and prescription patterns, critical clinical issues faced and related pragmatics in BD by conducting the mental health professionals survey. Methodology: After focused discussions, Canadian Network for Mood and Anxiety Treatments guidelines being the primary anchor, a 46-item online survey questionnaire was prepared. With 25.4% response rate, 127 psychiatrists were evaluated using Survey Monkey® electronic platform on the demographics, predominant polarity; usage of antipsychotics, antidepressants, and electroconvulsive therapy, psychotropic's preference (monotherapy vs. polytherapy) in the acute and maintenance phase of BD. Results: Majority of the participants were males (70.9%) and placed in government institute or medical colleges. Majority agreed that child and adolescent and old age bipolar probands are not routinely seen but subthreshold BD cases are frequent; did not prefer mood stabilizer in pregnancy (61.4%) and antidepressants, preferred polytherapy in acute but monotherapy in maintenance phase (after 3rd episode), seldom preferred ECT as an option (more in suicidality), agreed to a subset of BD being refractory and neuroprogressive. Conclusion: This study elucidates the importance of treatment preferences, prescribing patterns and pragmatic issues faced by the clinicians. These patterns if studied longitudinally in a systematic manner would help in modifying the potential treatment strategies and reduce treatment gap.

SARS-CoV-2 infection is associated with increased odds of insomnia, RLS and dream enactment behavior.

Background: Literature suggests that the COVID-19 pandemic has resulted in poor sleep quality, especially among the infected population. However, literature regarding the effect of COVID-19 pandemic and SARS-CoV-2 infection on occurrence of insomnia, restless legs syndrome and dream enactment behavior is either scarce or unavailable. Methods: This study was planned to assess the effect of SARS-CoV-2 infection on the occurrence of insomnia, restless legs syndrome (RLS) and dream enactment behavior (DEB). For this cross-sectional study, a questionnaire comprising of items related to demographic details, past medical history, and information related to SARS-CoV-2 infection was distributed through social media. Insomnia was diagnosed using clinical criteria. RLS, DEB, sleep quality, depression and anxiety were assessed using a validated questionnaire. Information regarding the use of hypnotic medications was also gathered. Results: Of the 1596 respondents, 37.2% reported disturbed sleep while insomnia was reported by 22.6% respondents. 27.3% of respondents reported RLS and 17.4% suffered DEB. The odds of insomnia were greater among males (OR = 1.27; 95% CI: 1.03-1.58; P < 0.02) and among those who had SARS-CoV-2 infection (OR = 1.76; 95% CI = 1.42-2.19; P < 0.001). Similarly, SARS-CoV-2 infection was also associated with increased odds of RLS (OR = 2.48; 95% CI = 1.98-3.11; P < 0.001) and DEB (OR = 1.58; 95%CI = 1.21-2.06; P < 0.001). Insomnia, RLS and DEB were more frequent among respondents who required oxygen therapy, those who experienced loss of taste and/or smell, depression and anxiety. Prevalence of insomnia, DEB and RLS was higher than said prevalence among respondents with no history of SARS-CoV-2 infection, but lower than that of those with positive history of SARS-CoV-2 infection. 5.3% of respondents reported taking hypnotic medications before infection, 7% during infection and 5.3% after infection. Conclusion: SARS-CoV-2-infection-related factors in association with environmental factors have increased the prevalence of insomnia, DEB and RLS among subjects having infection. SARS-CoV-2-associated immunological changes, hypoxia and neurotropism may play a role in occurrence of insomnia, DEB and RLS.

Motor cortical plasticity in adolescents with early onset schizophrenia: A TMS-EMG study assessing the perturbation effect of intermittent and continuous theta burst stimulation.

BACKGROUND: Neuroplasticity in adolescents is distinct from that of adults. Literature pertaining to neuroplasticity in schizophrenia is limited to adult populations. AIM: We aimed to assess baseline (or resting) cortical excitability and cortical plasticity in adolescents with schizophrenia using the transcranial magnetic stimulation-electromyography (TMS-EMG) protocol. METHODS: Twenty adolescent cases with schizophrenia and 20 age and gender matched healthy controls were studied using a crossover design. Single pulse TMS elicited resting motor threshold (RMT) and motor evoked potentials (MEPs) were assessed. Cortical plasticity was determined by tracking MEPs after a single session continuous theta burst stimulation (cTBS) and intermittent theta burst stimulation (iTBS) up to 120 min at 12 intervals. RESULTS: Baseline (or resting) cortical excitability was found to be significantly lower in cases compared with controls. Response patterns to cTBS and iTBS were similar between the crossover. While cTBS led to inhibitory response, iTBS had an excitatory effect in both the groups. In the cases, while cTBS led to significantly greater initial inhibitory response, iTBS led to significantly lower excitatory response, compared with controls. The time taken to return to baseline excitability was significantly longer after receiving cTBS for cases, compared with controls. CONCLUSIONS: iTBS and cTBS lead to excitatory and inhibitory response, representing classical long-term depression and long-term potentiation effects, respectively, in both cases and controls. We conclude that adolescents with schizophrenia have significantly lower baseline (resting) cortical excitability as well as significantly greater inhibitory plasticity; excitatory plasticity is significantly lower.

Factor Structure of the Telugu Version of the COVID-19 Pandemic-Related Perceived Stress Scale (PSS-10-C) Administered on Grassroots Frontline Health Care Workers of Rural Telangana.

Background: During the COVID-19 pandemic, perceived stress is an important determinant of mental health problems, especially in health care workers (HCW). By and large, regional language tools to assess perceived stress in the context of the pandemic have not been validated in India. We aim to explore the factor structure of the Telugu translated version of the COVID-19 pandemic-related Perceived Stress Scale (PSS-10-C) administered on grassroots frontline HCW of rural Telangana, India. Methods: Data relating to 311 grassroots frontline HCW consisting of accredited social health activists (ASHA), multipurpose health workers (MPHW), and auxiliary nurse and midwives (ANMs) working in rural primary health centers (PHC) in five districts of Telangana were analyzed. An exploratory factor analysis was conducted to identify latent factors. Convergent validity was assessed by computing Pearson product-moment correlations between the scores of PSS-10-C and Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) scales. Results: The principal component analysis showed that the 10 items of the scale were significantly loaded by two latent factors with eigen values of 2.792 and 2.009, respectively. Factor solution showed that six and four items correlated with each of the two factors, respectively. Significant correlations between PSS-10-C, GAD-7, and PHQ-9 scores showed convergent validity. The two factors may represent substantive factors "perceived self-efficacy" and "perceived helplessness." There may be an influence of the reverse-coded method on the factor solution. Conclusion: The Telugu translated version of PSS-10-C holds fair-to-good psychometric properties.

"Efficacy of intensive bilateral Temporo-Parietal Continuous theta-burst Stimulation for Auditory VErbal hallucinations (TPC-SAVE) in schizophrenia: A randomized sham-controlled trial"☆.

Transcranial magnetic stimulation (TMS) is a non-invasive tool that moderates specific brain regions to ameliorate auditory verbal hallucinations (AVH) in schizophrenia. Citing the critical involvement of temporoparietal cortex (TPC) in AVH, our study aimed to evaluate the effect of continuous theta burst stimulation (cTBS) targeting bilateral TPC in schizophrenia subjects with AVH, on a randomized rater blinded placebo control trial. 59 patients were randomly allocated to active and sham groups. They received 20 cTBS sessions (2 per day: first right TPC, then left TPC) 5 days a week for 2 weeks. PANSS (Positive and Negative Syndrome Scale), AVHRS (Auditory vocal hallucination rating scale), PSYRAT-AH (Psychiatric symptoms rating scale- Auditory hallucinations scale), CDSS (Calgary depression scale for schizophrenia), SCoRS (Schizophrenia cognition rating scale) and CGI-S (Clinical global impression-severity) were rated at baseline, immediately post 20th session and 2 weeks post-TBS. 50 patients (25-active, 25-sham) completed the study. Conducting an intention to treat analysis, we found a significant group*time effect for PANSS, AVHRS, PSYRAT-AH, CDSS, SCoRS, CGI-S but when controlled for confounding variables and multiple comparisons, only PANSS-PS (F=26.617, p < 0.001), PANSS-TOTAL (F=23.671, p < 0.001), AVHRS (F=17.779, p < 0.001), PSYRAT-AH (F=11.385, p < 0.001) and CGI-S (F=28.462, p < 0.001) retained significance. We conclude that cTBS over TPC is safe and has efficacy in treating AVH in schizophrenia. Limited sample size and lack of integrity assessment for blinding in the study participants are major limitations of the study.