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.

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.

A series of five population-specific Indian brain templates and atlases spanning ages 6-60 years.

Anatomical brain templates are commonly used as references in neurological MRI studies, for bringing data into a common space for group-level statistics and coordinate reporting. Given the inherent variability in brain morphology across age and geography, it is important to have templates that are as representative as possible for both age and population. A representative-template increases the accuracy of alignment, decreases distortions as well as potential biases in final coordinate reports. In this study, we developed and validated a new set of T1w Indian brain templates (IBT) from a large number of brain scans (total n = 466) acquired across different locations and multiple 3T MRI scanners in India. A new tool in AFNI, make_template_dask.py, was created to efficiently make five age-specific IBTs (ages 6-60 years) as well as maximum probability map (MPM) atlases for each template; for each age-group's template-atlas pair, there is both a "population-average" and a "typical" version. Validation experiments on an independent Indian structural and functional-MRI dataset show the appropriateness of IBTs for spatial normalization of Indian brains. The results indicate significant structural differences when comparing the IBTs and MNI template, with these differences being maximal along the Anterior-Posterior and Inferior-Superior axes, but minimal Left-Right. For each age-group, the MPM brain atlases provide reasonably good representation of the native-space volumes in the IBT space, except in a few regions with high intersubject variability. These findings provide evidence to support the use of age and population-specific templates in human brain mapping studies.

Does Yoga Have a Role in Schizophrenia Management?

PURPOSE OF REVIEW: To review the efficacy of add-on yoga therapy in improving symptoms of schizophrenia and quality of life and examine the possible underlying biological mechanisms of yoga in schizophrenia. RECENT FINDINGS: Quality of life, cognitive symptoms, and negative symptoms have been found to improve with add-on yoga therapy in schizophrenia (pooled mean effect size 0.8, 0.6, and 0.4, respectively). Yoga also seems to have a small effect on improving positive symptoms. Less explored areas include adverse effects of yoga itself as well as its effects on antipsychotic-induced complications. Preliminary findings suggest that the effects of yoga may be mediated by neurohormonal mechanisms and functional changes in brain activity. Add-on yoga therapy is a potential treatment option for improving quality of life, cognitive symptoms, and negative symptoms in schizophrenia. Future studies should explore efficacy in multicentric trials as well as possible neurobiological changes underlying the effects.

Effect of gender and clinical-financial vulnerability on mental distress due to COVID-19.

The COVID-19 pandemic has had an enormous impact on people's mental health. This study examines whether gender influences the mental distress in people from at-risk populations (clinically high risk and financially vulnerable). A cross-sectional survey was administered between the 23rd and 28th of April 2020 to 15,691 individuals from 32,596 households in the UK. Our findings confirmed that individuals who are clinically high risk or financially vulnerable or a combination of both experience significantly higher levels of mental distress. Additionally, we also found that females experienced higher levels of mental distress than males across various categories.

Retinal vascular abnormalities in schizophrenia and bipolar disorder: A window to the brain.

OBJECTIVES: The examination of retinal microvascular abnormalities through fundus photography is currently the best available non-invasive technique for assessment of cerebral vascular status. Several studies in the last decade have reported higher incidences of adverse cerebrovascular events in Schizophrenia (SCZ) and bipolar disorder (BD). However, retinal microvasculature abnormalities in SCZ and BD have remained under-explored, and no study has compared this aspect of SCZ and BD till date. METHODS: Retinal Images of 100 SCZ patients, BD patients, and healthy volunteers each were acquired by trained individuals using a non-mydriatic camera with a 40-degree field of view. The retinal images were quantified using a valid semi-automated method. The average of left and right eye diameters of the venules and arterioles passing through the extended zone between 0.5 and 2 disc diameters from the optic disc were calculated. RESULTS: The groups differed significantly with respect to average diameters of both retinal venules (P < 0.001) and retinal arterioles (P < 0.001), after controlling for age and sex. Both SCZ and BD patients had significantly narrower arterioles and wider venules compared to HV. There were also significant differences between SCZ and BD patients; patients with BD had narrower arterioles and wider venules. CONCLUSION: Considering the affordability and easy accessibility of the investigative procedure, retinal microvascular examination could serve as a potential screening tool to identify individuals at risk for adverse cerebrovascular events. The findings of the current study also provide a strong rationale for further systematic examination of retinal vascular abnormalities in SCZ and BD.

Examination of retinal vascular trajectory in schizophrenia and bipolar disorder.

AIM: Evidence suggests microvascular dysfunction (wider retinal venules and narrower arterioles) in schizophrenia (SCZ) and bipolar disorder (BD). The vascular development is synchronous with neuronal development in the retina and brain. The retinal vessel trajectory is related to retinal nerve fiber layer thinning and cerebrovascular abnormalities in SCZ and BD and has not yet been examined. Hence, in this study we examined the retinal vascular trajectory in SCZ and BD in comparison with healthy volunteers (HV). METHODS: Retinal images were acquired from 100 HV, SCZ patients, and BD patients, respectively, with a non-mydriatic fundus camera. Images were quantified to obtain the retinal arterial and venous trajectories using a validated, semiautomated algorithm. Analysis of covariance and regression analyses were conducted to examine group differences. A supervised machine-learning ensemble of bagged-trees method was used for automated classification of trajectory values. RESULTS: There was a significant difference among groups in both the retinal venous trajectory (HV: 0.17 ± 0.08; SCZ: 0.25 ± 0.17; BD: 0.27 ± 0.20; P < 0.001) and the arterial trajectory (HV: 0.34 ± 0.15; SCZ: 0.29 ± 0.10; BD: 0.29 ± 0.11; P = 0.003) even after adjusting for age and sex (P < 0.001). On post-hoc analysis, the SCZ and BD groups differed from the HV on retinal venous and arterial trajectories, but there was no difference between SCZ and BD patients. The machine learning showed an accuracy of 86% and 73% for classifying HV versus SCZ and BD, respectively. CONCLUSION: Smaller trajectories of retinal arteries indicate wider and flatter curves in SCZ and BD. Considering the relation between retinal/cerebral vasculatures and retinal nerve fiber layer thinness, the retinal vascular trajectory is a potential marker for SCZ and BD. As a relatively affordable investigation, retinal fundus photography should be further explored in SCZ and BD as a potential screening measure.

Discovery biology of neuropsychiatric syndromes (DBNS): a center for integrating clinical medicine and basic science.

BACKGROUND: There is emerging evidence that there are shared genetic, environmental and developmental risk factors in psychiatry, that cut across traditional diagnostic boundaries. With this background, the Discovery biology of neuropsychiatric syndromes (DBNS) proposes to recruit patients from five different syndromes (schizophrenia, bipolar disorder, obsessive compulsive disorder, Alzheimer's dementia and substance use disorders), identify those with multiple affected relatives, and invite these families to participate in this study. The families will be assessed: 1) To compare neuro-endophenotype measures between patients, first degree relatives (FDR) and healthy controls., 2) To identify cellular phenotypes which differentiate the groups., 3) To examine the longitudinal course of neuro-endophenotype measures., 4) To identify measures which correlate with outcome, and 5) To create a unified digital database and biorepository. METHODS: The identification of the index participants will occur at well-established specialty clinics. The selected individuals will have a strong family history (with at least another affected FDR) of mental illness. We will also recruit healthy controls without family history of such illness. All recruited individuals (N = 4500) will undergo brief clinical assessments and a blood sample will be drawn for isolation of DNA and peripheral blood mononuclear cells (PBMCs). From among this set, a subset of 1500 individuals (300 families and 300 controls) will be assessed on several additional assessments [detailed clinical assessments, endophenotype measures (neuroimaging- structural and functional, neuropsychology, psychophysics-electroencephalography, functional near infrared spectroscopy, eye movement tracking)], with the intention of conducting repeated measurements every alternate year. PBMCs from this set will be used to generate lymphoblastoid cell lines, and a subset of these would be converted to induced pluripotent stem cell lines and also undergo whole exome sequencing. DISCUSSION: We hope to identify unique and overlapping brain endophenotypes for major psychiatric syndromes. In a proportion of subjects, we expect these neuro-endophenotypes to progress over time and to predict treatment outcome. Similarly, cellular assays could differentiate cell lines derived from such groups. The repository of biomaterials as well as digital datasets of clinical parameters, will serve as a valuable resource for the broader scientific community who wish to address research questions in the area.

Prevalence and clinical correlates of obsessive-compulsive disorder in schizophrenia.

Obsessive compulsive symptoms frequently occur in a substantial proportion of patients with schizophrenia. The term schizoobsessive has been proposed to delineate this subgroup of schizophrenia patients who present with obsessive-compulsive symptoms/disorder. However, whether this co-occurrence is more than just co-morbidity and represents a distinct subgroup remains controversial. A striking variation is noted across studies examining prevalence of obsessive-compulsive symptoms/disorder in schizophrenia patients and their impact on clinical profile of schizophrenia. Hence, in this study, we examined the prevalence of obsessive-compulsive symptoms/disorder in a large sample of consecutively hospitalized schizophrenia patients and compared the clinical and functional characteristics of schizophrenia patients with and without obsessive-compulsive symptoms/disorder. We evaluated 200 consecutive subjects with the DSM-IV diagnosis of schizophrenia using the Structured Clinical Interview for DSM-IV Axis I disorders, Positive and Negative Syndrome Scale, Yale-Brown Obsessive-Compulsive Scale, Brown Assessment of Beliefs Scale, Clinical Global Impression-Severity scale, Global Assessment of Functioning Scale, Family Interview for Genetic Studies and World Health Organization Quality of Life scale. The prevalence of obsessive-compulsive symptoms in patients with schizophrenia was 24% (n=48); 37 of them had obsessive-compulsive disorder (OCD) and 11 had obsessive-compulsive symptoms not amounting to a clinical diagnosis of OCD (OCS). Schizophrenia patients with OCS/OCD had an earlier age at onset of schizophrenia symptoms, lower positive symptoms score, higher co-morbidity with Axis II disorders, higher occurrence of OCD in family and better quality of life. Findings of the study indicate a higher prevalence of OCS/OCD in schizophrenia. Schizophrenia patients with and without OCS/OCD have comparable clinical profile with few exceptions. High rates of OCD in first degree relatives suggest possible genetic contributions and differences in neurobiology. Finally, evidence to consider schizoobsessive as a distinct diagnostic entity is inconclusive and warrants further studies.

Hyperprolactinemia with aripiprazole: understanding the paradox.

Aripiprazole, due to its partial agonist activity at the D2 receptors, is often recommended as the drug of choice in patients who develop antipsychotic-induced hyperprolactinemia. We report a case of a female patient who developed hyperprolactinemia while on treatment with aripiprazole. This partial D2 agonistic activity of aripiprazole could be dose related, and hence, at higher doses, aripiprazole by itself can have dopamine antagonistic properties and hence cause prolactin system abnormalities.

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.

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.

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.

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].

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.

Beneficial effects of add-on raloxifene in schizophrenia.

The role of estrogens in schizophrenia has been proposed from the observation of schizophrenia occurring later and with symptom severity being lesser in women. Utility of estrogens in treatment of psychoses, though seen to be useful, comes with inherent risks of neoplasias, given its agonistic action on breast and endometrium. This risk can be overcome with use of selective estrogen receptor modulators, like raloxifene. Raloxifene has been used in schizophrenia, with improvement in symptoms and cognitive functions. We report the use of raloxifene as an adjunctive treatment, with risperidone, in treatment-resistant form of schizophrenia. The patient, a 29-year-old woman, over a 7-month followup period, showed significant improvement in sociooccupational functioning, with reduction in symptom severity.

Has Kahlbaum syndrome disappeared or is it underdiagnosed? Reexamining the nosology of catatonia.

In contemporary psychiatric classification such as the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, and International Classification of Diseases, 10th Revision, catatonia is classified as a subtype of schizophrenia and not as an independent disorder. However, catatonia does not seem to obey nosological boundaries and is seen with both affective and nonaffective psychoses. We conducted a chart review of patients to examine the nosological status of catatonia. Our data suggest that catatonia is a syndrome of varied manifestation possibly related to both affective and nonaffective psychoses with a subgroup independent of both. Further prospective studies examining the natural course are needed, which could have significant implications on future classificatory systems.

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.

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.