Association between urban upbringing and functional brain connectivity in schizophrenia.

Background: Environmental factors considerably influence the development of the human cortex during the perinatal period, early childhood, and adolescence. Urban upbringing in the first 15 years of life is a known risk factor for schizophrenia (SCZ). Though the risk of urban birth and upbringing is well-examined from an epidemiological perspective, the biological mechanisms underlying urban upbringing remain unknown. The effect of urban birth and upbringing on functional brain connectivity in SCZ patients is not yet examined. Methods: This is a secondary data analysis of three studies that included 87 patients with SCZ and 70 healthy volunteers (HV) aged 18 to 50 years. We calculated the developmental urbanicity index using a validated method in earlier studies. Following standard pre-processing of resting functional magnetic resonance imaging (fMRI) scans, seed-return on investment (ROI) functional connectivity analysis was performed. Results: The results showed a significant association between urban birth and upbringing on functional connectivity in SCZ patients and HV (P < 0.05). In SCZ patients, connections from the right caudate, anterior cingulate cortex, left and right intracalcarine cortices, left and right lingual gyri, left posterior parahippocampal cortex to the cerebellum, fusiform gyri, lateral occipital cortex, and amygdala were significantly associated with the urbanicity index (P < 0.05). Conclusions: These study findings suggest a significant association between urban birth and upbringing on functional brain connectivity in regions involved in reward processing and social cognition in SCZ. Assessment of social cognition could have implications in developing an in-depth understanding of this impairment in persons with SCZ.

A systematic review and meta-analysis of optical coherence tomography studies in schizophrenia, bipolar disorder and major depressive disorder.

OBJECTIVES: Due to the common neurodevelopmental origin and easy accessibility, the retina serves as a surrogate marker for changes in the brain. Hence, Optical Coherence Tomography (OCT), a tool to examine the neuronal layers of retina has gained importance in investigating psychiatric disorders. Several studies in the last decade have reported retinal structural alterations in schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). However, the findings are inconsistent. Hence, we conducted a meta-analysis to investigate alterations in OCT parameters in patients with SCZ, BD and MDD. METHODS: We searched electronic databases for studies that examined OCT parameters in patients with SCZ, BD and MDD published up to January 2023. The primary outcome measures were thickness and volumes of the retinal Nerve Fibre Layer (RNFL). We conducted meta-analysis using a random effects model. RESULTS: The searches yielded 2638 publications of which 43 studies were included in the final analysis across all disorders. Compared to controls, the RNFL was thinner in SCZ patients (SMD = -0.37, p = <0.001) and BD patients (SMD = -0.67, p = < 0.001), but not in MDD patients (SMD = -0.08, p = 0.54). On quadrant wise analysis, temporal quadrant RNFL was thinner in SCZ but not in BD, while all other quadrants were thinner in both SCZ and BD. CONCLUSION: We found significant reductions in RNFL thickness in SCZ and BD, but not in MDD. The differential involvement in various quadrants and parameters across the disorders has potential implications for using retinal parameters as a diagnostic biomarker.

Composition of yoga-philosophy based mental traits (Gunas) in major psychiatric disorders: A trans-diagnostic approach.

Yoga philosophy includes the theory of Tri-guna (three mental traits): sattva (signifies a tendency to 'goodness'), rajas (tendency towards 'activity'), and tamas (tendency towards "inertia"). This cross-sectional study aimed to understand the differences in the expression of gunas in patients suffering from major psychiatric disorders (n = 113, 40 females) and age-gender-education-matched healthy controls (HCs; n = 113, 40 females). Patients were diagnosed by a psychiatrist using DSM 5 criteria and suffered from the following disorders: depression (n = 30), schizophrenia (SCZ; n = 28), obsessive-compulsive disorder (OCD; n = 23), anxiety (n = 16), and bipolar affective disorder (BPAD; n = 16). Tri-gunas were assessed using a validated tool (Vedic Personality Inventory) and symptoms were assessed using standard scales as per the diagnosis. Multi-variate analysis of variance (MANOVA) was used to assess the differences in guna scores between HCs and patients, and between patients with different diagnoses. A two-tailed Pearson correlation was performed between the gunas and psychometric scales. Results revealed that HCs had significantly higher sattva traits as compared to patients (except those with OCD). Each psychiatric diagnosis also showed a specific guna configuration: (1) Anxiety disorders and OCD: High sattva-rajas, low tamas; (2) Depression: High sattva-tamas, low rajas; (3) Psychotic disorders (SCZ/BPAD): High tamo-rajas, low sattva. Significant positive correlations were observed between rajas traits and anxiety/OC/positive psychotic symptoms, negative psychotic symptoms and tamas traits, and sattva traits and OC symptoms. This finding has clinical implications, both to develop ways of predicting outcomes of psychiatric disorders, as well as to develop psycho-therapeutic and lifestyle interventions targeting the gunas.

Successful use of ketamine to treat severe depression with suicidality post-COVID-19 - A case report.

Every second patient who suffers from COVID-19 experiences is at risk for depression. The treatment of severe depression with suicidal risk is challenging in patients with COVID-19 given the restrictions in access to and safety concerns with the use of electroconvulsive therapy during the COVID pandemic. Although ketamine is effective in treating depression, especially in presence of acute suicidality, to date, there are no reports on ketamine use to treat severe depression in the context of COVID-19. In this case report, we describe the success of ketamine to treat a person with severe depression and suicidality following COVID-19 infection.

Trust and psychosis: a systematic review and meta-analysis.

BACKGROUND: Impaired trust in other humans is commonly seen in psychosis and it leads to poor societal functioning. However, examining trust behavior in an experimental setting is challenging. Investigators have used the trust game, a neuro-economic game to assess trust behavior in psychosis. However, the findings are inconsistent. Hence, we systematically reviewed the existing literature and conducted a meta-analysis to examine trust behavior in patients with psychosis, their relatives, and those at high risk for psychosis. METHODS: We searched electronic databases for studies that have examined trust game in patients with psychosis, published up to November 2021. The primary outcome measure was the baseline trust in a trust game by patients and controls. The meta-analysis was performed if at least three data sets of control and patient groups were available for that measure/design. We conducted meta-analyses with a random-effects model. The results were described narratively wherever meta-analysis was not possible due to paucity of studies. RESULTS: The searches across the databases including cross-references yielded 465 publications of which 10 studies were included in the final analysis. Baseline trust in the trust game was significantly lower in patients with psychosis compared to controls (SMD 0.39, 95% CI -0.14 to 0.64, p -0.002). However, a similar decrease in baseline trust was not present in relatives of patients (SMD 0.08, 95% CI -0.20 to 0.36, p -0.58). CONCLUSIONS: The current meta-analysis suggests significant trust deficits in patients with psychosis. Future studies with a bigger sample size are required to understand the nature of trust deficits and factors affecting this impairment.

Treatment strategies for serotonin reuptake inhibitor-resistant obsessive-compulsive disorder: A network meta-analysis of randomised controlled trials.

OBJECTIVES: Treatment-resistant obsessive-compulsive disorder is a chronic debilitating illness. We conducted a network meta-analysis [NMA] to compare the efficacy of all interventions in SRI-resistant OCD from published Randomised controlled trials [RCT]. METHODS: We performed an NMA of RCTs in SRI resistant OCD from all modalities of treatments; pharmacological, psychological, neuromodulation, neurosurgery including deep brain stimulation. The design-by-treatment interaction inconsistency model within the frequentist framework was adopted with a change in Yale-Brown Obsessive-Compulsive Scale score as the primary outcome. We conducted sensitivity analyses excluding studies examining neurosurgical interventions, deep brain stimulation, studies in the paediatric population, and studies from a single geographical region. We also conducted analyses of interventions categorised into treatment groups. RESULTS: 55 RCTs examining 19 treatments or placebo involving 2011 participants were included in the NMA. Ondansetron [Standardised mean difference -2.01 (95% CI: -3.19, -0.83)], deep TMS [- 1.95 (-3.25, -0.65)], therapist administered Cognitive Behavioural Therapy [CBT-TA] [-1.46 (-2.93, 0.01)] and aripiprazole [-1.36 (-2.56, -0.17)] were ranked as the best four treatments on using the Surface Under the Cumulative Ranking [SUCRA] percentage values (85.4%, 83.2%, 80.3%, 67.9% respectively). While all four interventions had large effect sizes, CBT[TA] narrowly missed statistical significance in our analysis. In sensitivity analyses, deep TMS was ranked as the best treatment strategy for SRI-resistant OCD. The small number of subjects in individual studies, higher confidence interval limits, and wider prediction interval for most agents warrant a cautious interpretation. CONCLUSIONS: Considering the principal analysis and sensitivity analyses together, deep TMS, ondansetron, CBT[TA], and aripiprazole may be considered a first-line intervention for SRI-resistant OCD in adults. OTHER: This work was not funded. The NMA has been registered with PROSPERO, [Registration number: CRD42020173589].

Neurohemodynamic correlates of BDNF gene expression in schizophrenia patients with working memory deficits: A functional MRI study.

INTRODUCTION: Brain-derived neurotrophic factor (BDNF) is involved in neuroplasticity underlying cognitive deficits, including working memory deficits (WMD), in schizophrenia. Methodological challenges and inconsistencies are reported with peripheral BDNF levels. Left dorsolateral prefrontal cortex (DLPFC) is proposed to underlie WMD, though inconsistently. We aimed to explore the correlations between brain activation during working memory task-based functional Magnetic Resonance Imaging (fMRI) and BDNF gene expression in schizophrenia patients with WMD. METHODS: 26 patients with schizophrenia with established WMD were recruited for the study. Blood samples were collected to study lymphocyte BDNF gene expression. Patients underwent task-based fMRI to examine the working memory performance and related brain activation. Whole-brain analysis was performed with 2-back > 0-back and 2-back > rest contrast. The peak intensity values of the activation were used for correlation analysis. RESULTS: Whole brain analysis with 2-back > rest contrast revealed maximum activation in left DLPFC, Brodmann area 9 (t = 10.54, FWE corrected p < 0.05). The baseline BDNF gene expression correlated positively with the peak intensity of brain activation in left DLPFC (r = 0.365, p = 0.033). Negative symptom score negatively correlated with BDNF gene expression (r = -0.499, p = 0.005) and left DLPFC fMRI activation (r = -0.393, p = 0.023) respectively. CONCLUSION: We found a significant positive association between BDNF gene expression and the activation of the DLPFC during the working memory task. This novel observation needs further systematic evaluation to establish the potential role of peripheral BDNF expression in WMD in schizophrenia.

Montreal Cognitive Assessment (MoCA) and Digit Symbol Substitution Test (DSST) as a screening tool for evaluation of cognitive deficits in schizophrenia.

Cognitive deficit is one of the core features of schizophrenia and is associated with poor functional outcomes. There is a lack of validated criteria to screen and monitor cognitive deficits in schizophrenia. This study aimed to evaluate the concurrent validity and sensitivity of MoCA (Montreal Cognitive Assessment) and DSST (Digit Symbol Substitution Test) in identifying cognitive deficits in Schizophrenia comparing with a comprehensive MCCB [MATRICS (Measurement And Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery] equivalent battery. We did clinical and cognitive assessments on 30 patients with schizophrenia and 30 age and gender-matched healthy controls. The Cronbach's Alpha of MoCA was 0.839, and on adding the DSST, it increased to 0.859. In stepwise binary logistic regression, adding DSST to MoCA improved the prediction of cognitive impairment as defined by a comprehensive battery with 86.7% classification accuracy. Receiver operating characteristic curve analysis suggested a score of 25 of MoCA and 59 of DSST as an optimal cut-off in identifying severe cognitive deficits with an additional MoCA cut-off of 27 for identifying mild cognitive deficits. Combined MoCA and DSST is a sensitive and quick method to screen for neurocognitive deficits in schizophrenia.

Relation between frontal pole volumes and cognitive insight in Schizophrenia.

OBJECTIVE: Cognitive insight comprising self-reflection and self-certainty is an important determinant of functional outcomes in Schizophrenia. The neural correlates of cognitive insight in Schizophrenia are underexamined. The frontal pole (FP) is implicated in metacognitive function in healthy individuals, but its role is not well examined in Schizophrenia. We had earlier reported the relationship between Frontal pole volumes and cognitive insight in a small sample of only male patients. Hence, we studied this relationship in an independent sample of schizophrenia patients and healthy controls. METHODS: We examined 41 healthy volunteers (HV) and 57 patients with Schizophrenia (SCZ). We used a previously validated manual morphometric method to perform FP parcellation on images obtained from a 3 T scanner and calculated the volumes. Cognitive insight was measured using Beck's Cognitive insight scale (BCIS). To assess the relationship between FP volumes and BCIS scores, multiple linear regression analyses were performed. RESULTS: In the overall sample, age, years of education, and intracranial volume were significant predictors of BCIS scores. Within the SCZ group, age and left FP volume were significant predictors of BCIS composite scores and age, ICV for BCIS-self certainty. There was no significant relationship between age and FP volumes in either SCZ or HV group. DISCUSSION: The current study in an independent sample further supports the critical role of the frontal pole in cognitive insight, earlier reported by us. As cognitive insight has a vital role in functional outcome, our findings have potential clinical implications.

Effect of Intranasal Oxytocin on Resting-state Effective Connectivity in Schizophrenia.

OBJECTIVES: Evidence from several lines of research suggests the critical role of neuropeptide oxytocin in social cognition and social behavior. Though a few studies have examined the effect of oxytocin on clinical symptoms of schizophrenia, the underlying neurobiological changes are underexamined. Hence, in this study, we examined the effect of oxytocin on the brain's effective connectivity in schizophrenia. METHODS: 31 male patients with schizophrenia (SCZ) and 21 healthy male volunteers (HV) underwent resting functional magnetic resonance imaging scans with intra-nasal oxytocin (24 IU) and placebo administered in counterbalanced order. We conducted a whole-brain effective connectivity analysis using a multivariate vector autoregressive granger causality model. We performed a conjunction analysis to control for spurious changes and canonical correlation analysis between changes in connectivity and clinical and demographic variables. RESULTS: Three connections, sourced from the left caudate survived the FDR correction threshold with the conjunction analysis; connections to the left supplementary motor area, left precentral gyrus, and left frontal inferior triangular gyrus. At baseline, SCZ patients had significantly weaker connectivity from caudate to these three regions. Oxytocin, but not placebo, significantly increased the strength of connectivity in these connections. Better cognitive insight and lower negative symptoms were associated with a greater increase in connectivity with oxytocin. CONCLUSIONS: These findings provide a preliminary mechanistic understanding of the effect of oxytocin on brain connectivity in schizophrenia. The study findings provide the rationale to examine the potential utility of oxytocin for social cognitive deficits in schizophrenia.

Effect of national cultural dimensions and HIV prevalence rates on stigma towards people living with HIV/AIDS.

This paper examines the main and interactive effects of national culture dimensions and HIV prevalence rates on stigma towards people living with HIV/AIDS (PLHIVA). We examined these various relationships using data from a sample of 68,041 individuals from 49 countries, obtained from the World Values Survey. We used Hierarchical Linear Modeling to conduct our cross-level analyses. Our results indicated that collectivistic societies were positively associated while egalitarian and performance-oriented societies were negatively associated with stigma towards PLHIVA. Additionally, HIV prevalence rates interact with several cultural dimensions to worsen stigma towards PLHIVA. Our findings indicate the need to tailor stigma reduction strategies by taking the national culture dimensions of a given society into consideration when designing and implementing programs.

Deep learning model using retinal vascular images for classifying schizophrenia.

Contemporary psychiatric diagnosis still relies on the subjective symptom report of the patient during a clinical interview by a psychiatrist. Given the significant variability in personal reporting and differences in the skill set of psychiatrists, it is desirable to have objective diagnostic markers that could help clinicians differentiate patients from healthy individuals. A few recent studies have reported retinal vascular abnormalities in patients with schizophrenia (SCZ) using retinal fundus images. The goal of this study was to use a trained convolution neural network (CNN) deep learning algorithm to detect SCZ using retinal fundus images. A total of 327 subjects [139 patients with Schizophrenia (SCZ) and 188 Healthy volunteers (HV)] were recruited, and retinal images were acquired using a fundus camera. The images were preprocessed and fed to a convolution neural network for the classification. The model performance was evaluated using the area under the receiver operating characteristic curve (AUC). The CNN achieved an accuracy of 95% for classifying SCZ and HV with an AUC of 0.98. Findings from the current study suggest the potential utility of deep learning to classify patients with SCZ and assist clinicians in clinical settings. Future studies need to examine the utility of the deep learning model with retinal vascular images as biomarkers in schizophrenia with larger sample sizes.

Association between retinal vascular measures and brain white matter lesions in schizophrenia.

OBJECTIVE: Recent studies have examined retinal vascular abnormalities in schizophrenia as retinal vascular imaging is a non-invasive proxy to cerebral microvasculature. However, relation between retinal vascular abnormalities and brain structure is not well examined in schizophrenia. Hence in this study, for the first time, we examined the relationship between retinal vascular measures and brain white matter lesions in schizophrenia. We examined brain white matter lesions as they are considered a predictive marker for future adverse cerebrovascular event. METHODS: We acquired retinal vascular images of both eyes using a non-mydriatic camera and calculated retinal vascular diameter, tortuosity, trajectory and fractal dimension using validated methods. All patients underwent Magnetic Resonance Imaging of bran and we computed white matter hypo-intensities using Freesurfer software. We performed a linear regression analysis to examine the relationship between white matter hypo-intensities and retinal vascular measures controlling for age, sex, fasting blood sugar, creatinine, whole-brain volume, and antipsychotic dose. RESULTS: The regression model was significant in Schizophrenia patients (R=0.983;R2 =0.966;-F=10.849;p = 0.008) but not in healthy volunteers (R=0.828;R2 =0.686;F=0.182; p = 0.963). Among the retinal vascular measures, arterial tortuosity (ß = 0.963;p-0.002), tortuosity (ß = -1.002;p = 0.001) and fractal dimension (ß = -0.688;p = 0.014) were significant predictors of white matter lesions. DISCUSSION: The current study's findings support the conclusion that retinal vascular fractal dimension and tortuosity are associated with changes in cerebral white matter and may be considered proxy markers for cerebral microvasculature in schizophrenia. Considering the relationship between white matter lesions and stroke, these observations could have important clinical implications to screen schizophrenia patients for risk of adverse cerebrovascular event.

Effect of antipsychotic dose reduction on cognitive function in schizophrenia.

Cognitive deficits are predictors of social functioning but remain an unmet therapeutic challenge. While lowering the antipsychotics carries a risk of relapse, it possibly has a beneficial effect on cognitive function. However, this has not been examined in a real-world setting. A prospective naturalistic 6-month follow-up study (n = 71) was conducted with patients between 18 and 45 years in their first five years of illness and the maintenance phase of the treatment. Brief Assessment of Cognition in Schizophrenia (BACS) was administered to assess cognitive functions. Patients were divided into three groups based on the change in dose of antipsychotics. The data were analyzed using linear mixed-effects modeling (LMEM) to examine the group differences. At the end of six months, those with decreased antipsychotic dose had significant improvement in BACS total score, token test, and symbol coding compared to those with no change in the dose of antipsychotic. Reducing the dose of antipsychotics during the maintenance phase was associated with improved cognitive functions without an increased risk of relapse. Antipsychotic dose reduction may be better than discontinuation as the relapse risk is higher with the discontinuation strategy. Clinicians must balance the improvements in cognitive functions and relapse risk.

Effect of national cultural dimensions and consumption rates on stigma toward alcohol and substance use disorders.

BACKGROUND: Despite the notion of stigma as a socio-cultural process with the concept rooted in social space rather than in individual space, global studies examining impact of cultural differences on stigma toward substance use disorders are lacking. AIM: In this study, we aim to study the influence of national culture differences on stigma toward alcohol and substance use disorders. METHODS: We analyzed individual-level data from 68,041 respondents from 49 countries on stigma toward alcohol and substance use disorders. We examined the effect of the national culture dimensions and national alcohol and substance consumption rates on stigma toward alcohol and substance use disorders using hierarchical linear modeling. RESULTS: Our hierarchical linear modeling results indicate that cultural dimensions and consumption rates significantly influence stigma. We found significant positive associations between stigma toward AUD and institutional collectivism and assertiveness, but a negative association with future orientation dimension. Like AUD, stigma toward SUD was also positively associated with institutional collectivism and assertiveness, but negatively associated with power distance. CONCLUSIONS: The study findings have immense implications for national interventions to decrease stigma and influence policy making.

Evaluation of Psychological Impact of COVID-19 on Health-Care Workers.

BACKGROUND: Little information is available from India about the psychological impact of COVID-19 on helath-care workers. AIM: The current study aimed to evaluate the psychological issues among the health-care workers (HCW) during the COVID-19 pandemic. MATERIALS AND METHODS: An online survey using Survey Monkey® platform was carried out to evaluate depression (using Patient Health Questionnaire-9), anxiety (using Generalized Anxiety Disorder Questionnaire-7), and other psychological issues (using a self-designed questionnaire). RESULTS: The study sample comprised 303 participants with a mean age of 41.2 (standard deviation: 11.1) years. A majority of them were male (69%) and married (79.9%). Nearly half (46.2%) of the participants had either anxiety disorder or depression or both and 12.9% of HCW had suicidal behavior. Higher level of anxiety and depression scores were associated with being female, having undergone quarantine, directly involved in the care of COVID-19 patients, and younger age (<30 years). Higher prevalence of depression and anxiety disorder was seen in younger (<30 years) age group, being a doctor (compared to paramedics). In addition, higher prevalence of depression was seen in those who were directly involved in the care of patients with COVID-19 infection. CONCLUSION: About half of the HCWs are suffering from psychiatric morbidity, specifically anxiety, in the wake of the COVID-19 pandemic. There is a need to assess all the HCWs for psychiatric morbidity and provide them with psychological support.

Association between retinal vascular caliber and brain structure in schizophrenia.

OBJECTIVE: Several lines of research in the last decade have indicated the potential utility of retina as a window to the brain. Emerging evidence suggests abnormalities in retinal vascular caliber in schizophrenia. However, the relationship between retinal vascular measures and brain structure has not been examined in schizophrenia to date. Hence, we examined the relationship between retinal vasculature measured using fundus photography and brain structure measured using magnetic resonance imaging. METHOD: We recruited 17 healthy volunteers and 20 patients with schizophrenia. Using a non-mydriatic camera, we captured the images for left and right eyes separately and retinal vascular calibers were calculated using a semi-automated software package. Whole-brain anatomical T1 MPRAGE images were acquired using a 3-Tesla MRI scanner. Whole-brain and regional volume and cortical thickness were calculated using the Freesurfer software package. We used FreeSurfer's QDEC interface to compute vertex-by-vertex for analysis of the volume and cortical thickness. The relation between brain volume, cortical thickness, and retinal vascular caliber was examined using partial correlation and regression analysis. RESULTS: There was a significant negative correlation between average CRVE and global cortical mean thickness in schizophrenia but not in healthy. In schizophrenia patients, there was a significant negative correlation between average CRVE and cortical thickness in frontal regions - left rostral middle frontal, left superior frontal, and right caudal middle frontal gyri and posterior brain regions - left lateral occipital gyrus and left posterior cingulate cortex. DISCUSSION: The findings of the study suggest potential utility of retinal venular diameter as a proxy marker to abnormal neurodevelopment in schizophrenia.