Developmental undernutrition, offspring obesity and type 2 diabetes.

The Developmental Origins of Health and Disease (DOHaD) paradigm posits that a mismatch between circumstances at or around conception and in later life leads to metabolic dysregulation and the development of obesity and diabetes. In this review we highlight three strands of evidence: prospective studies of patterns of growth from birth to adulthood, historical studies of exposure to famine at defined points during gestation and early life, and nutrition intervention studies. We conclude that, while much is still unknown, it is becoming clearer that the combination of early-life undernutrition and later development of obesity is associated with increased risk of diabetes. There is a need to support public health programmes aimed at intergenerational (primordial) prevention of diabetes and other non-communicable disease.

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.

Psychiatric specialization as an option for medical students in the Indian context.

There is a shortage of psychiatrists in India and psychiatry as a subject of specialization is not a preferred option among medical undergraduates. There is inadequate exposure to psychiatry during the medical undergraduate training in India which might contribute towards it. There are attempts to overcome the negative attitudes towards psychiatry and mental illness among medical undergraduates by changes in the curriculum. In this paper we attempt to review studies on attitudes of undergraduate students towards psychiatry and compare the results with findings from our own survey done as a part of International Study of Student Career Choice in Psychiatry (ISoSCCiP) project.

Robust determinants of neurocognitive development in children: evidence from the Pune Maternal Nutrition Study.

Neurocognitive development is a dynamic process over the life course and is influenced by intrauterine factors as well as later life environment. Using data from the Pune Maternal Nutrition Study from 1994 to 2008, we investigate the association of in utero, birth, and childhood conditions with offspring neurocognitive development in 686 participants of the cohort, at age 12 years. The life course exposure variables in the analysis include maternal pre-pregnancy size and nutrition during pregnancy, offspring birth measurements, nutrition and physical growth at age 12 years along with parental education and socio-economic status. We used the novel Bayesian Model Averaging (BMA) approach; which has been shown to have better predictive performance over traditional tests of associations. Our study employs eight standard neurocognitive tests that measure intelligence, working memory, visuo-conceptual and verbal learning, and decision-making/attention at 12 years of age. We control for nutritional-metabolic information based on blood measurements from the pregnant mothers and the children at 12 years of age. Our findings highlight the critical role of parental education and socio-economic background in determining child neurocognitive performance. Maternal characteristics (pre-pregnancy BMI, fasting insulin during pregnancy) and child height at 12 years were also robust predictors on the BMA. A range of early factors - such as maternal folate and ferritin concentrations during pregnancy, and child's head circumference at birth - remained important determinants of some dimensions of child's neurocognitive development, but their associations were not robust once we account for model uncertainty. Our results suggest that intrauterine influences on long- term neurocognitive outcomes may be potentially reversible by post-birth remediation. In addition to the current nutritional interventions, public health policy should also consider social interventions in children born into families with low socio-economic status to improve human capital.

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.

Emotional Threat Perception and Its Association with Neurocognition in Social Anxiety Disorder.

Background: The negative appraisal of emotional stimuli is a feature of social anxiety disorder (SAD). People with SAD demonstrate deficits in neurocognitive performance while performing tasks of attention. However, the relationship between attentional control, working memory, and threat perception in SAD has not been studied well. The present study aimed to identify patterns of threat perception in relation to performance on attention and visuospatial working memory tasks in individuals with SAD. Methods: Subjects with SAD (n = 27) and a healthy comparative (HC) group (n = 26) completed tasks of sustained and focused attention, visuospatial working memory, computerized emotion identification, and pictorial emotional Stroop. Results: The SAD group had decreased performance in the domains of sustained (P = 0.001) and focused attention (P = 0.04). They also had an enhanced threat perception as demonstrated by greater reaction time to anger (P = 0.03), lower emotion recognition accuracy (P = 0.05), and higher over-identification of the threat to neutral and nonthreatening faces. However, the Stroop effect was not demonstrated across the groups. No group difference was seen in the performance on the visuospatial working memory tasks. Lower focused attention was significantly correlated with higher emotional threat perception (ETP; P = 0.001) in the SAD group. Conclusion: People with SAD have greater deficits in attention processing and ETP. The attention deficits were associated with enhanced ETP in social anxiety. The link between threat perception and cognitive functions would aid in a better understanding of SAD and in planning appropriate intervention.

Corrigendum: Pre-conceptional Maternal Vitamin B12 Supplementation Improves Offspring Neurodevelopment at 2 Years of Age: PRIYA Trial.

[This corrects the article DOI: 10.3389/fped.2021.755977.].

Physical deformity as sequela of chronic catatonia and response to electroconvulsive therapy: a case report.

Chronic catatonia with posturing can cause joint contractures leading to greater morbidity associated with the physical deformity. We report a case of a young man with chronic catatonic schizophrenia with posturing of bilateral upper limbs in flexion leading to fixed flexion contracture of left metacarpophalangeal joints. Initiation of electroconvulsive therapy along with physical rehabilitation measures helped him regain full range of motion in the right upper limb. The fixed flexion contracture, however, remained resistant to intensive treatment efforts. Early interventions in the form of electroconvulsive therapy and physical rehabilitation can be useful in reversing such potentially disabling complications.

Successful use of maintenance electroconvulsive therapy in the treatment of clozapine-associated obsessive-compulsive symptoms in schizophrenia: a case report.

Denovo obsessive-compulsive (OC) symptoms are associated with the use of atypical antipsychotics, clozapine in particular. Treatment of clozapine-associated OC symptoms is challenging and often difficult because continuation of clozapine can result in worsening of OC symptoms, whereas discontinuation may result in worsening of psychosis. We report, for the first time, the use of maintenance electroconvulsive therapy, in clozapine-associated OC symptoms, in a patient with schizophrenia.

Thought Disorder on Object Sorting Test Is Associated with Executive Dysfunction in Schizophrenia.

BACKGROUND: Thought disorder is considered to be central to the core disturbances in schizophrenia and was described by Goldstein as aberrant "concept formation." Executive dysfunction is another core deficit in schizophrenia. With a greater emphasis on psychopathology in nosological systems, the classical thought disorder receives less prominence. The present study aimed to understand the association between classical thought disorder (aberrant concept formation and concrete abstraction) and executive dysfunction. METHODS: Thirty patients with schizophrenia and thirty healthy subjects, matched on age, gender, education, and socioeconomic status, were screened using MINI 5.0, following which they were assessed on object sorting test (OST) and selected tests for executive functions (EFs). RESULTS: Individuals with schizophrenia were found to have significantly decreased performance on all domains of EFs and OST. Total peculiar scores on OST were significantly associated with mental speed, focused attention, and divided attention. Total impoverished scores on OST was significantly associated with focused attention, sustained attention, planning, set shifting, perseveration, and concept formation. CONCLUSION: Several correlations, among performance on OST and neuropsychological tests, suggest that patterns of responses on OST can point to underlying executive dysfunction. Both thought disorder and executive dysfunction mirror similar constructs. This similarity represents a conceptual bridge between the classical and contemporary descriptions of the core deficits in schizophrenia.

Maternal vitamin B12, folate during pregnancy and neurocognitive outcomes in young adults of the Pune Maternal Nutrition Study (PMNS) prospective birth cohort: study protocol.

INTRODUCTION: The Developmental Origins of Health and Disease (DOHaD) hypothesis proposes that intrauterine and early life exposures significantly influence fetal development and risk for disease in later life. Evidence from prospective birth cohorts suggests a role for maternal B12 and folate in influencing neurocognitive outcomes in the offspring. In the Indian setting, B12 deficiency is common during the pregnancy while rates of folate deficiency are lower. The long-term influences of maternal nutrition during the pregnancy on adult neurocognitive outcomes have not been examined. The Pune Maternal Nutrition Study (PMNS) is a preconceptional birth cohort into its 24th year and is considered a unique resource to study the DOHaD hypothesis. We found an association between maternal B12 status in pregnancy and child's neurocognitive status at 9 years of age. We now plan to assess neurocognitive function and MRI measurements of brain structural-functional connectivity at young adult age to study its association with maternal nutritional exposures during the pregnancy. METHODS AND ANALYSIS: As part of ongoing prospective follow-up in young adults of the PMNS at the Diabetes Unit, KEM Hospital Research Center, Pune India, the following measurements will be done: neurocognitive performance (Standardised Tests of Intelligence, Verbal and Visual Memory, Attention and Executive Functions), temperament (Adult Temperament Questionnaire), psychopathology (Brief Symptom Inventory and Clinical Interview on Mini Neuropsychiatric Interview 7.0). Brain MRI for structural T1, resting-state functional connectivity and diffusion tensor imaging will be performed on a subset of the cohort (selected based on exposure to a lower or higher maternal B12 status at 18 weeks of pregnancy). ETHICS AND DISSEMINATION: The study is approved by Institutional ethics committee of KEM Hospital Research Center, Pune. The results will be shared at national and international scientific conferences and published in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT03096028.

Maternal Vitamin B12 Status During Pregnancy and Its Association With Outcomes of Pregnancy and Health of the Offspring: A Systematic Review and Implications for Policy in India.

Background: Vitamins B12 and folate participate in the one-carbon metabolism cycle and hence regulate fetal growth. Though vitamin B12 deficiency is widely prevalent, the current public health policy in India is to supplement only iron and folic acid for the prevention of anaemia. Prompted by our research findings of the importance of maternal vitamin B12 status for a healthy pregnancy, birth and offspring health outcomes, we evaluated available literature evidence using a systematic review approach, to inform policy. Methods: A systematic search was performed for relevant Indian studies in the MEDLINE/PubMed and IndMed databases. We selected studies reporting maternal vitamin B12 status (dietary intake or blood concentrations), and/or metabolic markers of vitamin B12 deficiency (homocysteine, methylmalonic acid) or haematological indices during pregnancy and their associations with outcomes of pregnancy, infancy or in later life. Intervention trials of vitamin B12 during pregnancy were also included. Quality of evidence was assessed on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Of the 635 articles identified, 46 studies met the inclusion criteria (cohort studies-26, case-control studies-13, RCT's -7). There is a high prevalence of vitamin B12 deficiency in Indian women during pregnancy (40-70%) (3 studies). Observational studies support associations (adjusted for potential sociodemographic confounders, maternal body size, postnatal factors) of lower maternal B12, higher homocysteine or an imbalance between vitamin B12-folate status with a higher risk of NTDs (6 studies), pregnancy complications (recurrent pregnancy losses, gestational diabetes, pre-eclampsia) (9 studies), lower birth weight (10 studies) and adverse longer-term health outcomes in the offspring (cognitive functions, adiposity, insulin resistance) (11 studies). Vitamin B12 supplementation (7 RCT's) in pregnancy showed a beneficial effect on offspring neurocognitive development and an effect on birth weight was inconclusive. There is a high quality evidence to support the role of low maternal vitamin B12 in higher risk for NTD and low birth weight and moderate-quality evidence for higher risk of gestational diabetes and later life adverse health outcomes (cognitive functions, risk for diabetes) in offspring. Conclusion: In the Indian population low maternal vitaminB12 status, is associated with adverse maternal and child health outcomes. The level of evidence supports adding vitamin B12 to existing nutritional programs in India for extended benefits on outcomes in pregnancy and offspring health besides control of anaemia. Systematic Review Registration: [website], identifier [registration number].

Facial emotion recognition and its association with quality of life and socio-occupational functioning in patients with bipolar disorder and their first-degree relatives.

INTRODUCTION: Facial emotion recognition deficits (FERD) are common even in the remitted phase of bipolar disorder (BD). Research regarding FERD in first-degree relatives is inconclusive. This study aimed to assess the facial emotion recognition in remitted patients of bipolar disorder and first-degree relatives(FDR) in comparison with healthy controls. Correlation between FERD and quality of life and socio-occupational functioning was also assessed. METHODS: It was an observational, cross-sectional study done at a tertiary hospital in India. Study population (n = 75) included remitted patients of bipolar disorder (n = 27), first-degree relatives of BD patients (FDR) (n = 20) and healthy controls (HC) (n = 28). Facial emotion recognition, social and occupational functioning, and quality of life (QoL) was measured using Tool for Recognition of Emotions in Neuropsychiatric Disorders, Social & Occupational Functioning Assessment Scale and World Health Organization Quality of Life-Bref, respectively, in all the participants. RESULTS: The BD group did significantly worse in facial emotion recognition in comparison to FDR and HC groups (p < 0.001). Emotion recognition of fear, anger, surprise, and happy were most affected. FDR did not vary significantly from HC in facial emotion recognition. Lower scores on facial emotion recognition were associated with lower QoL in the social domain(p = 0.006) and poorer socio- occupational functioning scores (p = 0.01), but it was not significant within the BD group. CONCLUSION: FERD is seen in remitted patients of bipolar disorder but not in the first -degree relatives. FERD affects social quality of life and functioning. Poorer social functioning in remitted patients of bipolar disorder might be multifactorial and cannot be attributed solely to FERD.

A combined stimuli presentation for assessing facial emotion related N170, N250 and visual mismatch negativity in neuropsychiatric disorders.

Event-related potential (ERP) is a useful approach to assess the neurophysiological correlates of facial emotion processing. Previous studies examined the facial emotion recognition (FER) related ERPs (N170, N250, visual MisMatch Negativity) individually using ERP specific paradigms. This approach can be time-consuming and may not resemble real-life scenarios where an individual must process multiple stimuli simultaneously. The aim of the study was to assess the utility of a combined paradigm when compared to individual paradigms to measure N170, N250 and visual MisMatch Negativity (vMMN) in healthy controls (HC), utilizing emotion stimuli standardized in the Indian population. Further, the combined paradigm was examined in patients with schizophrenia (SCZ) to detect the differences in ERPs compared to HC. Within paradigms, ERPs showed higher amplitudes for emotion compared to neutral stimuli suggesting that the paradigms were able to detect valence associated with emotional stimuli. The combined paradigm was able to elicit decipherable peaks of N170, N250 and vMMN similar to individual paradigms. ERP data quality as assessed by analytic Standardized Measurement Error (aSME) showed a satisfactory aggregate score of above 2 for all the three paradigms. Combined paradigm approaches to record ERPs in neuropsychiatric conditions has the advantage of reducing the time required for task administration, avoiding practice effects, better subject cooperation and participation.

Pre-conceptional Maternal Vitamin B12 Supplementation Improves Offspring Neurodevelopment at 2 Years of Age: PRIYA Trial.

Background: The first thousand days window does not include the pre-conceptional period. Maternal pre-conceptional health has a profound influence on early embryonic development (implantation, gastrulation, placentation etc). Nutrition provided by B-complex vitamins is important for fetal growth, especially neural development. We report effects of a maternal pre-conceptional vitamin B12 and multi micronutrient (MMN) supplementation on offspring neurodevelopmental performance. Methods: In the Pune Rural Intervention in Young Adolescents trial (PRIYA), adolescents (N = 557, 226 females) were provided with vitamin B12 (2 µg/day) with or without multiple micronutrients, or a placebo, from preconception until delivery. All groups received mandatory iron and folic acid. We used the Bayley's Scale of Infant Development (BSID-III) at 24-42 months of age to investigate effects on offspring neurodevelopment. Results: Participants had similar baseline B12 levels. The levels improved in the B12 supplemented groups during pre-conception and pregnancy (28 weeks gestation), and were reflected in higher cord blood holotranscobalamin (holo-TC) levels compared to the placebo group. Neurodevelopmental outcomes in the B12 alone group (n = 21) were better than the placebo (n = 27) in cognition (p = 0.044) and language (p = 0.020) domains (adjusted for maternal baseline B12 levels). There was no difference in neurodevelopmental outcomes between the B12 + MMN (n = 26) and placebo group. Cord blood Brain Derived Neurotrophic Factor (BDNF) levels were highest in the B12 alone group, though not significant. Conclusion: Pre-conceptional vitamin B12 supplementation improved maternal B12 status and offspring neurodevelopment at 2 years of age. The usefulness of cord BDNF as a marker of brain development needs further investigation. Our results highlight the importance of intervening during pre-conception.

Inverse relationship between serum high density lipoprotein and negative syndrome in antipsychotic-naive schizophrenia.

BACKGROUND: Recent literature suggests a role for apolipoprotein L (apoL) aberrations in the pathogenesis of schizophrenia. ApoL is almost exclusively associated with apolipoprotein A-I in high-density lipoproteins (HDLs). The objective of this study was to examine the correlation between symptom scores and serum HDL in antipsychotic-naive schizophrenia patients. METHODS: In this cross-sectional study, 60 antipsychotic-naive schizophrenia patients were systematically examined for their symptom scores, with good inter-rater reliability. Concurrently, an overnight fasting serum lipid profile from these patients was assessed. RESULTS: Serum HDL had a significant inverse correlation with a total negative syndrome score (rho=-0.43; p=0.001). CONCLUSIONS: The study observation supports the potential role for HDL abnormalities in the genesis of negative symptoms in schizophrenia.

Electroconvulsive therapy in the treatment of delirious mania: a report of 2 patients.

Delirious mania also known as Bell mania is a syndrome of excitement, delirium, and psychosis, of acute onset. We report 2 patients who presented with acute onset of disorientation, aggressive behavior, double incontinence, grandiose ideas, and auditory hallucinations. Results of investigations to rule out organic etiology such as computed tomographic scan of brain, cerebrospinal fluid examination, and biochemical parameters were normal. Creatine kinase levels were only moderately elevated. A provisional diagnosis of delirious mania was made, and patients were empirically started on electroconvulsive therapy (ECT) session. Delirium resolved by the second ECT session, unmasking manic symptoms, and recovered completely at the end of sixth ECT session. Prophylactic lithium was started, and both patients continue to be in remission after 1 year. Differential diagnosis of the above clinical presentation includes neuroleptic malignant syndrome and malignant catatonia. Delirious mania is clinically important owing to the potential for diagnostic confusion and good response to ECTs.