BACKGROUND:The relationship of facial emotion recognition deficits (FERD) with the stage, severity, and treatment of schizophrenia is unclear. This study aimed to assess FERD across acute drug-free, chronic symptomatic, and asymptomatic stages of schizophrenia and its correlation with attention deficits, positive, and negative symptoms. METHODS:This was a cross-sectional study with 132 subjects. The patient group (n = 99) was divided into three groups: Group A: drug-free symptomatic acute schizophrenia (n = 33), Group B: chronic symptomatic schizophrenia (n = 33), Group C: chronic asymptomatic schizophrenia (n = 33), and compared with Group D: healthy controls (n = 33). FERD was assessed using The Tool for Recognition of Emotions in Neuropsychiatric Disorders using the TRENDS Accuracy score (TRACS). Additional assessments included Psychotic Symptom Rating Scales (PSYRATS), Negative Symptom Assessment (NSA-16), and Digit Vigilance Test (DVT). RESULTS:A significant difference was noted in TRACS among the groups (H (3) = 17.36; p = 0.001). The acute group did worse in TRACS than chronic asymptomatic group and healthy control group (A<C, D). Worse TRACS was noted in acute group (A) than chronic groups B & C (U= 671; p = 0.002; r = 0.31). Symptomatic patients (Groups A & B) did significantly worse than the asymptomatic patients in Group C (U= 763.5; p = 0.01; r = 0.24). TRACS showed significant negative correlations with PSYRATS delusion score, total BPRS, DVT total time, and DVT omission errors. CONCLUSION:The acute drug-free stage of illness had highest FERD and chronic asymptomatic medicated patients had FERD comparable to the general population. Symptom remission was helpful, suggesting a state association instead of a trait.

Background:Facial emotion recognition (FER) deficits are being considered as core features of social cognitive deficits in schizophrenia, associated with socio-occupational dysfunction. Social cognition intervention programs have been shown to improve these deficits; however, there are no such intervention strategies in India. In this study, we aim to examine the efficacy of Training of Affect Recognition - Indian Version (TAR-IV) to enhance the FER abilities of people with schizophrenia. Methods:In an open-label experimental design, 36 participants with schizophrenia underwent 12 sessions of TAR-IV as an add-on to treatment as usual (TAU), while 29 participants with schizophrenia continued TAU (pharmacological treatment with or without occupational therapy and vocational rehabilitation services). Clinical and functional assessments were done using the positive and negative syndrome scale (PANSS) and socio-occupational functioning scale. Emotion recognition abilities were assessed on the tool for recognition of emotions in neuropsychiatric disorders at baseline, post-intervention, and follow-up (two to three months post-intervention). Results:The intervention group showed significant improvements in FER (P = .001) and socio-occupational functioning (P = .008) after receiving the TAR-IV, which remained significant at two months follow-up. A lower age of onset and poorer neurocognitive function at baseline predicted greater changes in emotion recognition ability following the intervention. Conclusions:This study demonstrated the efficacy of TAR-IV, the Indian adaptation of social cognition intervention, in improving emotion recognition abilities and socio-occupational functioning in patients with schizophrenia. These findings need to be replicated in randomized controlled trials.

Social cognition abilities are significantly impaired in serious mental illnesses. Facial emotion recognition deficits (FERD) have been consistently reported in schizophrenia (SCZ), while the respective findings in bipolar disorder (BPD) are mixed. Assessment of FERD using a task that imposes a time restriction on the stimulus presentation and response may be more akin to real-life situations. We examined FERD, misattribution patterns, and response times in SCZ (n=24) and BPD (n=26) patients and healthy controls (HC; n=26) on: (i) a conventional emotion recognition task using a forced-choice response task, and (ii) a computerized task with the time-restricted presentation of stimuli and recording of the response times. Patients with BPD had a lower duration of illness compared to SCZ patients. Both SCZ and BPD groups showed significantly lower emotion recognition accuracy scores in both tasks, as compared to the HC. The BPD group had significantly higher overidentification than the HC one. On imposing the time restriction, both patient groups gave a significantly higher percentage of the erroneous responses. There were no significant differences in the reaction times. The ratio of accuracy scores vs. response time showed a differential pattern, with a significantly lower ratio for fear in SCZ and that for anger in BPD. The BPD group showed FERDs comparable to those in SCZ patients though the duration of illness in the former was shorter than that in the latter. The study highlights the need for early initiation of the social cognition intervention in patients with serious mental illnesses.

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.

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.

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

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.

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 B 12 and folate in influencing neurocognitive outcomes in the offspring. In the Indian setting, B 12 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 B 12 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 B 12 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

Intrauterine nutritional exposures to vitamin B12 and folate are known to influence neurodevelopment. We tested the hypothesis that intrauterine exposure to high folate in presence of low vitamin B12 is associated with poor neurodevelopmental outcomes in young adult offspring. PMNS is a preconceptional birth cohort in its 24th year of follow up. We examined Intelligence Quotient (IQ) and obtained brain structural MPRAGE T1 sequence on a 3T MRI Scanner [participants selected based on exposure to maternal B12 at 18 wk pregnancy <103 PM(Low maternal B12 group n = 97) and >175 pM (high maternal B12 group, n = 93)]. Brain morphometric measurements (cortical volumes, thickness and subcortical volumes) were performed on Freesurfer software. The mean age of participants was 22.3 ± 0.5 years (n = 190, 96 boys). High maternal B12 group showed greater cortical thickness in temporal regions (P < 0.001) and cortical thinning in frontal regions (P < 0.01). Higher maternal folate (median Red Cell Folate at 28 wk pregnancy 420 ng/ml) was associated with greater frontal cortical volumes in the high maternal B12 group but cortical thinning in multiple temporal and parietal cortical areas in the low B12 group(P < 0.05). There was a significant interaction between maternal B12 and folate status in relation to subcortical volumes. Exposure to higher maternal folate was associated with greater subcortical volume in high B12 group but lower volumes in low B12 group (P = 0.02, adjusted for age, education, gender and total intracranial volume). Higher IQ score was associated with larger subcortical brain volume (r = 0.34, P < 0.001) in the offspring. Intrauterine exposure to higher maternal folate in the presence of low vitamin B12 was associated with poorer cortical development in young adult offspring. Higher maternal folate with adequate B12 benefits subcortical brain development which reflects in higher IQ score. Optimizing maternal vitamin B12 and folate concentrations during pregnancy would benefit neurocognitive development in the offspring. DBT Wellcome India Alliance Clinical and Public Health Intermediate Fellowship.

AbstractBackgroundNutritional interventions during the first 1000 days of life improves lifelong health. Better pre-conceptional maternal nutrition improves the nutrition of the early embryo. Vitamins B12 and folate are important for fetal neural development. Vitamin B12 deficiency is common in India.MethodsIn the Pune Rural Intervention in Young Adolescents (PRIYA) adolescents (N=557, 226 females) were provided with vitamin B12 (2µg/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. We examined cord blood concentrations of brain-derived neurotropic factor (BDNF).ResultsParticipants in the three groups had similar baseline B12 levels. These improved in the B12 supplemented groups at pre-conceptional and pregnancy (28 weeks gestation) measurements, reflected in higher cord holo-TC levels compared to the placebo. Neurodevelopmental outcomes are available for 74 children. Offspring in the B12 alone group (n=21) performed better than the placebo (n=27) on cognition (p=0.044) and language (p=0.020) domains (adjusted for maternal baseline B12 levels). There were no differences between the B12+MMN (n=26) and placebo group. Cord blood BDNF levels were highest in the B12 alone group (not statistically significant).ConclusionPre-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 in the pre-conceptional period.

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]

We read with interest the paper by Bailey et al. (1) and the associated editorial by Molloy (2). They report a significant interaction between low vitamin B-12 and high folate status in relation to lower cognitive functioning in elderly participants of the NHANES cohort. There is a suggestion that unmetabolized folic acid might be related to such outcomes, raising a concern about dose of folic acid in fortified foods and supplements. We wish to highlight the possible detrimental effects of maternal imbalance of these 2 vitamins (low vitamin B-12–high folate) on the health of the offspring, both in the short term and long term. Indians are predominantly vegetarian because of multigenerational cultural and socioeconomic influences. Low intake of animal-origin foods in a predominantly vegetarian population contributes to low vitamin B-12–high folate status. The national anemia-control program (now called Intensified-National Iron Plus Initiative) provides iron and folic acid but no vitamin B-12 to children, adolescents, and women of reproductive age. Obstetricians use large-dose folic acid supplements (5 mg) for the prevention of neural tube defects (NTDs) and other purported benefits (although the recommended dose for prevention of a first occurrence of NTDs is only 400 μg). Pune two-thirds had (plasma pmol/L) and 90% had methylmalonic acid (>0.26 folate replete (<1% RBC folate <283 nmol/L) even before iron and folic acid started. erythrocyte

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.

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.

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.

In the identification of facial expressions related to certain emotions, certain parameters of event-related potentials (ERPs) can be interpreted as the respective indices. Patients with schizophrenia exhibit deficits in facial affect recognition at both behavioral and neural levels. We examined face expressionsensitive ERP components, N170 and N250, which are mostly related to encoding and decoding of the facial emotions, respectively, in 10 patients with schizophrenia and 10 healthy adults matched in age and gender. The mean amplitude and peak latency of the N170 and N250 waveforms, induced by visual stimuli in the form of happy, sad, fearful, and neutral face images, were measured and compared in these two groups. In the patient group, the mean amplitude of the N250 was higher in the right hemisphere (–1.402 mV on average) compared to that in the left hemisphere (–0.814 mV). The independent-sample t- test revealed that the N250 latencies were significantly longer in the patient group compared to those in the normal group for all four emotions. We, however, find no significant differences in the mean amplitude and peak latency of the N170 waveform between the two groups. Our study shows that decoding of the facial expressions in patients with schizophrenia is clearly impaired, which may contribute to cognitive and behavioral symptoms of the disease.