Sensory gating, neurocognition, social cognition and real-life functioning: a 2-year follow-up of early psychosis.

BACKGROUND: Diminished sensory gating (SG) is a robust finding in psychotic disorders, but studies of early psychosis (EP) are rare. It is unknown whether SG deficit leads to poor neurocognitive, social, and/or real-world functioning. This study aimed to explore the longitudinal relationships between SG and these variables. METHODS: Seventy-nine EP patients and 88 healthy controls (HCs) were recruited at baseline. Thirty-three and 20 EP patients completed 12-month and 24-month follow-up, respectively. SG was measured using the auditory dual-click (S1 & S2) paradigm and quantified as P50 ratio (S2/S1) and difference (S1-S2). Cognition, real-life functioning, and symptoms were assessed using the MATRICS Consensus Cognitive Battery, Global Functioning: Social (GFS) and Role (GFR), Multnomah Community Ability Scale (MCAS), Awareness of Social Inference Test (TASIT), and the Positive and Negative Syndrome Scale (PANSS). Analysis of variance (ANOVA), chi-square, mixed model, correlation and regression analyses were used for group comparisons and relationships among variables controlling for potential confounding variables. RESULTS: In EP patients, P50 ratio (p < 0.05) and difference (p < 0.001) at 24-month showed significant differences compared with that at baseline. At baseline, P50 indices (ratio, S1-S2 difference, S1) were independently associated with GFR in HCs (all p < 0.05); in EP patients, S2 amplitude was independently associated with GFS (p = 0.037). At 12-month and 24-month, P50 indices (ratio, S1, S2) was independently associated with MCAS (all p < 0.05). S1-S2 difference was a trending predictor of future function (GFS or MCAS). CONCLUSIONS: SG showed progressive reduction in EP patients. P50 indices were related to real-life functioning.

Dynamic and progressive changes in thalamic functional connectivity over the first five years of psychosis.

The early stage of psychosis (ESP) is a critical period where effective intervention has the most favorable impact on outcomes. Thalamic connectivity abnormalities have been consistently found in psychosis, and are associated with clinical symptoms and cognitive deficits. However, most studies consider ESP patients as a homogeneous population and fail to take the duration of illness into account. In this study, we aimed to capture the progression of thalamic connectivity changes over the first five years of psychosis. Resting-state functional MRI scans were collected from 156 ESP patients (44 with longitudinal data) and 82 healthy controls (24 with longitudinal data). We first performed a case-control analysis comparing thalamic connectivity with 13 networks in the cortex and cerebellum. Next, we modelled the shape (flat, linear, curvilinear) of thalamic connectivity trajectories by comparing flexible non-linear versus linear models. We then tested the significance of the duration of illness and diagnosis in trajectories that changed over time. Connectivity changed over the ESP period between the thalamus and default mode network (DMN) and fronto-parietal network (FPN) nodes in both the cortex and cerebellum. Three models followed a curvilinear trajectory (early increase followed by a subsequent decrease), while thalamo-cerebellar FPN connectivity followed a linear trajectory of steady reductions over time, indicating different rates of change. Finally, diagnosis significantly predicted thalamic connectivity. Thalamo-cortical and thalamo-cerebellar connectivity change in a dynamic fashion during the ESP period. A better understanding of these changes may provide insights into the compensatory and progressive changes in functional connectivity in the early stages of illness.

Is birth weight the major confounding factor in the study of gestational weight gain?: an observational cohort study.

BACKGROUND: Much interest has been focussed on both maternal obesity and gestational weight gain (GWG), particularly on their role in influencing birth weight (BW). Several large reviews have reported that excessive GWG is associated with an increase in BW. However recent large, well-designed, randomized controlled trials studying interventions aimed at reducing GWG have all consistently failed to show a reduction in BW despite achieving a reduction in GWG. The aim of this longitudinal prospective study was to examine the relationship between GWG and birth weight in women where GWG and Body Mass Index (BMI) were measured accurately in a strictly standardized way. METHODS: Women were enrolled at their convenience before 18 weeks gestation. Height and weight were measured accurately at the first antenatal visit and BMI calculated. Maternal weight was measured again after 37 weeks gestation. The weight of the baby was measured at birth. Relationships were tested using linear regression analysis, chi-squared tests and t-tests as appropriate. RESULTS: Of the 522 women studied, the mean BMI was 25.3 kg/m2 and 15.7% were obese. The mean BW at term was 3576 g (2160-5120) and 2.7% (n = 14) weighed ≥4500 g. The mean GWG overall was 12.3 kg (4.6 to 28.4) and GWG decreased as BMI increased. The mean GWG was less in obese women, at 8.7 kg (- 4.6 to 23.4), compared to non-obese,13.0 kg (0.6-28.4) (p < 0.001). Mean BW in obese women was 3630 g vs 3565 g in non-obese (p = 0.27). The total GWG correlated positively with BW (p < 0.001). When BW was subtracted from total GWG, GWG no longer correlated with BW (p = 0.12). CONCLUSIONS: The positive correlation between GWG in pregnancy and BW can be accounted for by the contribution of fetal weight to GWG antenatally without a contribution from increased maternal adiposity. There was a wide range of BW irrespective of the degree of GWG and obese women had a lower GWG than non-obese women. These findings help explain why Randomized Controlled Trials (RCTs) designed to reduce GWG have failed to decrease BW and suggest there is no causative link between excessive GWG and increased BW.

Maternal nutrient intakes from food and drinks consumed in early pregnancy in Ireland.

Background: The aim of this observational study was to measure food, macronutrient and micronutrient intakes of women presenting for antenatal care and assess compliance with current nutritional recommendations. Methods: Women were recruited in the first trimester of pregnancy. Maternal weight and height were measured and body mass index (BMI) calculated. Body composition was measured using bioelectrical impedance analysis. Maternal energy and nutrient intakes were estimated using a validated Willett Food Frequency Questionnaire and misreporting of energy intakes (EI) determined. Results: Plausible EIs were reported in 402 women. Mean age, weight and BMI were 30.8 years, 67.1 kg and 24.6 kg/m2 respectively. Median EIs were 2111 kcal, and median protein, carbohydrate and fat intakes were 17.3, 48.1 and 36.2 g/MJ/day, respectively. More than 90% of women exceeded the recommended daily allowance for saturated fat. Nearly all of the women (99%) did not meet estimated average requirements (EAR) for vitamin D. One in three women failed to achieve a dietary folate intake of 400 µg/day. Over one in five women failed to meet the EAR for iron, and 14% failed to achieve the EAR for calcium. Conclusions: Our findings highlight concerning deficits in nutrient intakes among women and will help guide professional dietary advice to women attending for future obstetric care in Ireland.

Breast-feeding and postpartum maternal weight trajectories.

OBJECTIVE: We examined whether breast-feeding, and in particular exclusive breast-feeding, was associated with maternal weight and body composition changes at 4 months postpartum independently of other maternal variables. DESIGN: Prospective longitudinal study. Women were recruited in the first trimester after an ultrasound examination confirmed an ongoing singleton pregnancy. Weight and body composition were measured using advanced bio-electrical impedance analysis at the first antenatal visit and 4 months postpartum. Detailed questionnaires were completed on breast-feeding, socio-economic status, diet and exercise in addition to routine clinical and sociodemographic details. SETTING: Large Irish university maternity hospital. SUBJECTS: Women who delivered a baby weighing ≥500 g between November 2012 and March 2014. RESULTS: At the postpartum visit, the mean weight was 70·9 (sd 14·2) kg (n 470) and the mean BMI was 25·9 (sd 5·0) kg/m2. 'Any breast-feeding' was reported by 65·1 % of women (n 306). Irish nativity (OR=0·085, P<0·001), current smoking (OR=0·385, P=0·01), relative income poverty (OR=0·421, P=0·04) and deprivation (OR=0·458, P=0·02) were negatively associated with exclusive breast-feeding. At 4 months postpartum there was no difference in maternal weight change between women who exclusively breast-fed and those who formula-fed (+2·0 v. +1·1 kg, P=0·13). Women who exclusively breast-fed had a greater increase in percentage body fat at 4 months postpartum compared with women who formula-fed (+1·0 v. -0·03 %, P=0·02), even though their dietary quality was better. Exclusive breast-feeding was not associated with postpartum maternal weight or body fat percentage change after adjusting for other maternal variables. CONCLUSIONS: There are many reasons why breast-feeding should be strongly promoted but we found no evidence to support postpartum weight management as an advantage of breast-feeding.

Maternal arterial elasticity in the first trimester as a predictor of birthweight.

The early detection of foetal growth restriction and macrosomia is an important goal of modern obstetric care. Aberrant foetal growth is an important cause of perinatal morbidity and mortality. Current modalities for detecting the abnormal foetal growth are often inadequate. Pulse wave analysis using applanation tonometry is a simple and non-invasive test that provides information about the cardiovascular system. Arterial elasticity has previously been implicated in the pathophysiology of pre-eclampsia and cardiovascular disease. Our study examined the relationship between maternal arterial elasticity and birthweight by using pulse wave analysis. We discovered that increased large artery elasticity predicted a larger baby at birth. Large artery elasticity therefore has the potential to act as a useful screening tool which may help in the prediction of women who are at risk of aberrant foetal growth.

An estimation of periconceptional under-reporting of dietary energy intake.

BACKGROUND: The purpose of this cross-sectional study was to examine periconceptional misreporting of energy intake (EI) using the Willet food frequency questionnaire (WFFQ). METHODS: Women were recruited in the first trimester. Women completed a semi-quantitative WFFQ. Maternal body composition was measured using eight-electrode bioelectrical impedance analysis. Under-reporters were those whose ratio of EI to their calculated basal metabolic rate fell below the calculated plausible threshold for their physical activity category. RESULTS: The mean age was 30.1 ± 5.3 years (n = 524). The mean body mass index (BMI) was 25.4 ± 5.6 kg/m(2), and 16.6% were obese (BMI ≥ 30.0 kg/m(2)). Under-reported EI was observed in 122 women (23.3%) with no over-reporters in the sample. Under-reporters were younger (P < 0.001), less likely to have a normal BMI (P = 0.002) and more likely to be obese (P < 0.001) than plausible reporters. Under-reporters had higher percentage of body-fat and lower percentage of body fat-free mass (P < 0.001), were more likely to be at risk of relative deprivation (P = 0.001) and reported a higher percentage of EI from carbohydrate (P = 0.02) than plausible reporters. CONCLUSIONS: Observed differences between under-reporters and plausible reporters suggest that the exclusion of these under-reporters represents an important potential source of bias in obesity research among women in the periconceptional period.

The interplay between maternal obesity and gestational diabetes mellitus.

There is a strong epidemiological association between maternal obesity and gestational diabetes mellitus (GDM). Since the publication of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study on women with mild hyperglycemia in 2008, new criteria have been introduced in maternity services internationally for the diagnosis of GDM. As a result, the diagnosis of GDM may be made in one-third of obese women (n=68). The aim of this review was to examine the interplay between maternal obesity and GDM in light of the HAPO study and the subsequent revised diagnostic criteria. Obesity and GDM are important obstetric risk factors because they both are potentially modifiable. However, the new international criteria for the diagnosis of GDM have serious resource implications for maternity services provided to the large number of women attending for care in developed countries. Further consideration needs to be given as to whether obese women with mild hyperglycemia need to be referred to a multidisciplinary team antenatally if they do not require insulin treatment.

Interpregnancy changes in maternal weight and body mass index.

OBJECTIVE: This longitudinal study compared changes in maternal weight and body mass index (BMI) in early pregnancy in the time interval between when a woman first attended for antenatal care with her first child and when she next attended for antenatal care. STUDY DESIGN: We studied women with a singleton pregnancy who delivered their first baby weighing ≥ 500 g in 2009 and who attended again for antenatal care with an ongoing pregnancy before January 1, 2012. Maternal weight and height were measured before 18 weeks' gestation in both pregnancies and BMI was calculated. RESULTS: Of the 3,284 primigravidas, the mean weight at the first visit in 2009 was 66.4 kg (standard deviation [SD] 12.7). The mean BMI was 24.5 kg/m(2) (SD 4.6), and 11.3% (n = 370) were obese. Of the 3,284 women, 1,220 (37.1%) re-attended for antenatal care before 2012 after sonographic confirmation of an ongoing pregnancy. Of the 1,220 women who re-attended, 788 (64.6%) had gained weight (mean 4.6 kg [SD 3.9]), 402 (33%) had lost weight (mean 3 kg [SD 2.9]), and 30 (2.4%) had maintained their weight. CONCLUSION: The birth of a first baby was associated with an increase in maternal weight in two-thirds of women when they next attended for antenatal care.

The relationship between unplanned pregnancy and maternal body mass index 2009-2012.

OBJECTIVE: To analyse the relationship between unplanned pregnancy and maternal Body Mass Index (BMI). METHODS: A prospective case-control study of planned vs. unplanned pregnancies among women who delivered an infant weighing ≥ 500 g during the four years 2009-2012 in a large maternity hospital in Ireland. Maternal weight and height were measured at the first antenatal visit before calculation of BMI. Clinical and sociodemographic details were computerised. BMI was categorised according to the World Health Organization. The epidemiological associations were examined using logistic regression, adjusted for confounding variables. RESULTS: Between 2009 and 2012, 34,377 women were included, 31.7% (n = 10,894) reported an unplanned pregnancy and 16.6% (n = 5647) were obese. The odds ratios of unplanned pregnancy were greater among obese women compared with those of normal BMI (unadjusted Odds Ratio (OR) 1.3; 95% Confidence Interval (CI) 1.3-1.4 p < 0.001). These ratios increased with increasing BMI (mild unadjusted OR 1.3; CI 1.2-1.4 p < 0.001; moderate unadjusted OR 1.4; CI 1.2-1.6 p < 0.001; severe obesity unadjusted OR 1.7; CI 1.4-2.0 p < 0.001). The higher rate of unplanned pregnancy among obese women was associated with a lower rate of contraception usage and a higher rate of contraceptive failure. Only 37.6% (n = 2112) of obese women took preconceptional folic acid to prevent neural tube defects compared with 46.1% (n = 8176) of women with a normal BMI (p < 0.001). CONCLUSION: Higher rates of unplanned pregnancy among obese women compared with women with a normal BMI is associated with compromised prepregnancy care in this high-risk population.

Fetal subcutaneous tissue measurements in pregnancy as a predictor of neonatal total body composition.

OBJECTIVE: The purpose of this study was to examine the relationship between prenatal measures of subcutaneous tissue as surrogate markers of fetal nutritional status and correlate them with neonatal total body composition. METHODS: This prospective longitudinal study of 62 singleton pregnancies obtained serial biometry and subcutaneous tissue measurements at 28, 33 and 38 weeks gestation. These measurements were then correlated with neonatal body composition, which was analysed using the PEAPOD™ Infant Body Composition System (Cosmed USA, Concord, CA, USA). RESULTS: At 38 weeks gestation, fetal abdominal subcutaneous tissue (FAST) in millimetres was significantly associated with infant fat mass at delivery (+64 g per mm of FAST, p < 0.001). Thigh fat (TF) at 28 weeks gestation was associated with infant fat mass at delivery (+79 g/mm TF, p = 0.023). TF at 38 weeks gestation was associated with infant fat mass (+63/mm TF, p = 0.004). TF and FAST at 38 weeks were also predictive of both birth weight and increased abdominal circumference (AC) (p = 0.001) with FAST measurement predicting an additional 5.7 mm in AC per millimetre of FAST (p = 0.002) and TF predicting an additional 6.9 mm per mm of TF (p = 0.002). CONCLUSION: We believe that this study further validates the use of prenatal measures of subcutaneous tissue and may help to highlight fetuses at risk of newborn adiposity and metabolic syndrome.

The relationship between gestational weight gain and fetal growth: time to take stock?

The aim of this article is to review the current evidence on gestational weight gain (GWG). Maternal obesity has emerged as one of the great challenges in modern obstetrics as it is becoming increasingly common and is associated with increased maternal and fetal complications. There has been an upsurge of interest in GWG with an emphasis on the relationship between excessive GWG and increased fetal growth. Recent recommendations from the Institute of Medicine in the USA have revised downwards the weight gain recommendations in pregnancy for obese mothers. We believe that it is time to take stock again about the advice that pregnant women are given about GWG and their lifestyle before, during, and after pregnancy. The epidemiological links between excessive GWG and aberrant fetal growth are weak, particularly in obese women. There is little evidence that intervention studies decrease excessive GWG or improve intrauterine fetal growth. Indeed, there is a potential risk that inappropriate interventions during the course of pregnancy may lead to fetal malnutrition that may have adverse clinical consequences, both in the short- and long-term. It may be more appropriate to shift the focus of attention from monitoring maternal weight to increasing physical activity levels and improving nutritional intakes.

Birth weight and neonatal adiposity prediction using fractional limb volume obtained with 3D ultrasound.

INTRODUCTION: The objective of this investigation was to study fetal thigh volume throughout gestation and explore its correlation with birth weight and neonatal body composition. This novel technique may improve birth weight prediction and lead to improved detection rates for fetal growth restriction. MATERIALS AND METHODS: Fractional thigh volume (TVol) using 3D ultrasound, fetal biometry and soft tissue thickness were studied longitudinally in 42 mother-infant pairs. The percentages of neonatal body fat, fat mass and fat-free mass were determined using air displacement plethysmography. Correlation and linear regression analyses were performed. RESULTS: Linear regression analysis showed an association between TVol and birth weight. TVol at 33 weeks was also associated with neonatal fat-free mass. There was no correlation between TVol and neonatal fat mass. Abdominal circumference, estimated fetal weight (EFW) and EFW centile showed consistent correlations with birth weight. Thigh volume demonstrated an additional independent contribution to birth weight prediction when added to the EFW centile from the 38-week scan (p = 0.03). CONCLUSION: Fractional TVol performed at 33 weeks gestation is correlated with birth weight and neonatal lean body mass. This screening test may highlight those at risk of fetal growth restriction or macrosomia.

Advanced optical photothermal infrared spectroscopy for comprehensive characterization of microplastics from intravenous fluid delivery systems.

Growing attention is being directed towards exploring the potential harmful effects of microplastic (MP) particles on human health. Previous reports on human exposure to MPs have primarily focused on inhalation, ingestion, transdermal routes, and, potentially, transplacental transfer. The intravenous transfer of MP particles in routine healthcare settings has received limited exploration in existing literature. Standard hospital IV system set up with 0.9 % NaCl in a laminar flow hood with MP contamination precautions. Various volumes of 0.9 % NaCl passed through the system, some with a volumetric pump. Fluid filtered with Anodisc filters washed with isopropyl alcohol. The IV cannula was immersed in Mili-Q water for 72 h to simulate vein conditions. Subsequently, the water was filtered and washed. Optical photothermal infrared (O-PTIR) microspectroscopy is used to examine filters for MP particles. All filters examined from the IV infusion system contained MP particles, including MPs from the polymer materials used in the manufacture of the IV delivery systems (polydimethylsiloxane, polypropylene, polystyrene, and polyvinyl chloride) and MP particles arising from plastic resin additives (epoxy resin, polyamide resin, and polysiloxane-containing MPs). The geometric mean from the extrapolated result data indicated that approximately 0.90 MP particles per mL of 0.9 % NaCl solution can be administered through a conventional IV infusion system in the absence of a volumetric pump. However, with the implementation of a pump, this value may increase to 1.57 particles per mL. Notably, over 72 h, a single cannula was found to release approximately 558 MP particles including polydimethylsiloxane, polysiloxane-containing MPs, polyamide resin, and epoxy resin. Routine IV infusion systems release microplastics. MP particles are also released around IV cannulas, suggesting transfer into the circulatory system during standard IV procedures.

Longitudinal measurement of fetal thigh soft tissue parameters and its role in the prediction of birth weight.

OBJECTIVE: The aim of this study was to profile longitudinal changes in thigh muscle and fat with gestation and to determine whether thigh measurements can improve the prediction of birth weight (BW). METHODS: A prospective longitudinal study of subcutaneous soft tissue measurements was conducted in 328 singleton fetuses at 28 and 37 weeks gestation. Estimated fetal weight (EFW) was calculated using abdominal circumference, femur length, biparietal diameter, and head circumference. RESULTS: The fetal abdominal subcutaneous tissue (FAST) and thigh muscle and fat show an increase with gestation. At 28 weeks gestation, the abdominal circumference, thigh fat, FAST, and EFW percentile were found to be significant predictors of BW. A combination of EFW percentile and thigh fat were found to be the optimal multivariate model at 28 weeks for predicting BW. At 37 weeks, BW prediction using EFW percentile, FAST, and thigh fat was the most accurate. The results revealed acceptable reproducibility for fetal thigh muscle and fat. CONCLUSION: This study provides reference ranges for thigh fat and muscle at 28 and 37 weeks gestation. The inclusion of fetal thigh fat in the algorithm improves the predictive power for birth weight. This information is important to explore the role of fetal thigh in the detection of aberrant growth.

Management of obesity across women's life course: FIGO Best Practice Advice.

Obesity is a chronic, progressive, relapsing, and treatable multifactorial, neurobehavioral disease. According to the World Health Organization, obesity affects 15% of women and has long-term effects on women's health. The focus of care in patients with obesity should be on optimizing health outcomes rather than on weight loss. Appropriate and common language, considering cultural sensitivity and trauma-informed care, is needed to discuss obesity. Pregnancy is a time of significant physiological change. Pre-, ante-, and postpartum clinical encounters provide opportunities for health optimization for parents with obesity in terms of, but not limited to, fertility and breastfeeding. Pre-existing conditions may also be identified and managed. Beyond pregnancy, women with obesity are at an increased risk for gastrointestinal and liver diseases, impaired kidney function, obstructive sleep apnea, and venous thromboembolism. Gynecological and reproductive health of women living with obesity cannot be dismissed, with accommodations needed for preventive health screenings and consideration of increased risk for gynecologic malignancies. Mental wellness, specifically depression, should be screened and managed appropriately. Obesity is a complex condition and is increasing in prevalence with failure of public health interventions to achieve significant decrease. Future research efforts should focus on interprofessional care and discovering effective interventions for health optimization.

Longitudinal relationships between mismatch negativity, cognitive performance, and real-world functioning in early psychosis.

BACKGROUND: Reduced mismatch negativity (MMN) is observed in early psychosis (EP) and correlated with cognition and functioning, but few studies have examined their longitudinal relationships and diagnostic specificity. We examined MMN, neuro- and social-cognition, and functional measures in EP patients with schizophrenia-spectrum (SZ) or bipolar disorder (BD) over a 1-year follow-up. METHODS: 54 EP patients (SZ: n = 24; BD: n = 30) and 42 healthy controls completed baseline measures: MMN, neuro- and social-cognition, and functional assessments. 30 EP patients completed 12-month follow-up assessments. Patients and controls were compared on MMN at baseline and follow-up, and diagnostic subgroup analyses were performed. Associations amongst MMN, neuro- and social cognition, and clinical measures were examined and predictive models of follow-up outcomes were conducted. RESULTS: EP patients showed significantly reduced MMN compared to controls at baseline (p = 0.023). MMN was impaired in SZ patients at baseline (p = 0.017) and follow-up (p = 0.003); BD patients did not differ from controls at either timepoint. MMN was associated with symptom severity and functioning at baseline, and with social cognition and functioning at follow up, but was not predictive of functional outcomes at follow-up. CONCLUSIONS: MMN abnormalities were evident in EP SZ-spectrum disorders at both timepoints, but not in BD at either timepoint. MMN was associated with functioning cross-sectionally, but did not predict future functional outcomes. However, deficits in MMN were associated with social cognition, which may have downstream effects on community functioning. Implications for targeted interventions to improve social processing and community outcomes are discussed.

Heterogeneity of Outcomes and Network Connectivity in Early-Stage Psychosis: A Longitudinal Study.

Imaging studies in psychotic disorders typically examine cross-sectional relationships between magnetic resonance imaging (MRI) signals and diagnosis or symptoms. We sought to examine changes in network connectivity identified using resting-state functional MRI (fMRI) corresponding to divergent functional recovery trajectories and relapse in early-stage psychosis (ESP). Prior studies have linked schizophrenia to hyperconnectivity in the default mode network (DMN). Given the correlations between the DMN and behavioral impairments in psychosis, we hypothesized that dynamic changes in DMN connectivity reflect the heterogeneity of outcomes in ESP. Longitudinal data were collected from 66 ESP patients and 20 healthy controls. Longitudinal cluster analysis identified subgroups of patients with similar trajectories in terms of symptom severity and functional outcomes. DMN connectivity was measured in a subset of patients (n = 36) longitudinally over 2 scans separated by a mean of 12 months. We then compared connectivity between patients and controls, and among the different outcome trajectory subgroups. Among ESP participants, 4 subgroups were empirically identified corresponding to: "Poor," "Middle," "Catch-up," and "Good" trajectory outcomes in the complete dataset (n = 36), and an independent replication (n = 30). DMN connectivity changes differed significantly between functional subgroups (F3,32 = 6.06, P-FDR corrected = .01); DMN connectivity increased over time in the "Poor" outcome cluster (ß = +0.145) but decreased over time in the "Catch-up" cluster (ß = -0.212). DMN connectivity is dynamic and correlates with a change in functional status over time in ESP. This approach identifies a brain-based marker that reflects important neurobiological processes required to sustain functional recovery.

Identifying Clinically and Functionally Distinct Groups Among Healthy Controls and First Episode Psychosis Patients by Clustering on EEG Patterns.

OBJECTIVE: The mismatch negativity (MMN) is considered as a promising biomarker that can inform future therapeutic studies. However, there is a large variability among patients with first episode psychosis (FEP). Also, most studies report a single electrode site and on comparing case-control group differences. Few have taken advantage of the full wealth of multi-channel EEG signals to examine observable patterns. None, to our knowledge, have used machine learning (ML) approaches to investigate neurophysiological derived subgroups with distinct cognitive and functional outcome characteristics. In this study, we applied ML to empirically stratify individuals into homogeneous subgroups based on multi-channel MMN data. We then characterized the functional, cognitive, and clinical profiles of these neurobiologically derived subgroups. We also explored the underlying low frequency range responses (delta, theta, alpha) during MMN. METHODS: Clinical, neurocognitive, functioning data of 33 healthy controls and 20 FEP patients were collected. 90% of the patients had 6-month follow-up data. Neurocognition, social cognition, and functioning measures were assessed using the NCCB Cognitive Battery, the Awareness of Social Inference Test, UCSD Performance-Based Skills Assessment, and Multnomah Community Ability Scale. Symptom severity was collected using the PANSS. MMN amplitude and single-trial derived low frequency activity across 24 frontocentral channels were used as main variables in the ML k-means clustering analyses. RESULTS: We found a consistent pattern of two distinctive subgroups. We labeled them as "better functioning" and "poorer functioning" clusters, respectively. Each subgroup can be mapped onto either better or poorer clinical, cognitive, and functioning profiles. Also, we identified two subgroups of patients: one showed improved MMN and one showed worsening of MMN over time. Patients with improved MMN had better follow-up clinical, cognitive, and functioning profile than those with worsening MMN. Among the low frequency bands, delta frequency appeared to be the most relevant to the observed MMN responses in all individuals. However, higher delta responses were not necessarily associated with a better functioning profile, suggesting that delta frequency alone may not be useful in clinical characterization. CONCLUSIONS: The ML approach could be a robust tool to explore heterogeneity and facilitate the identification of neurobiological homogeneous subgroups in FEP.