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1.  Psychosocial Factors Associated with Bulimia Nervosa during Pregnancy: An Internal Validation Study 
Objective
The aim of this paper was to internally validate previously reported relations (1) between psychosocial factors and bulimia nervosa (BN) outcomes during pregnancy.
Method
This study is based on the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. Participants were women enrolled during pregnancy (N = 69,030). Internal validity was evaluated by way of bootstrapped parameter estimates using the overall sample and a split sample calibration approach.
Results
Bootstrap bias estimates were below the problematic threshold, and extend earlier findings(1) by providing support for the validity of the models at the population level of all pregnant women in Norway. Bootstrap risk ratios indicated that prevalence, incidence, and remission of BN during pregnancy were significantly associated with psychosocial factors. The split sample procedure showed that the models developed on the training sample did not predict risks in the validation sample.
Discussion
This study characterizes associations between psychosocial exposures and BN outcomes among pregnant women in Norway. Women with lifetime and current self-reported psychosocial adversities were at a much higher risk for BN during pregnancy. Psychosocial factors were associated with BN remission during pregnancy, inviting the prospect of enhancing therapeutic interventions. We consider the findings in the context of reproducibility in science.
doi:10.1002/eat.22361
PMCID: PMC4411202  PMID: 25346291
bulimia nervosa; course; eating disorders; incidence; internal validation; MoBa; pregnancy; The Norwegian Mother and Child Cohort Study
2.  Dynamic Development of Regional Cortical Thickness and Surface Area in Early Childhood 
Cerebral Cortex (New York, NY)  2014;25(8):2204-2212.
Cortical thickness (CT) and surface area (SA) are altered in many neuropsychiatric disorders and are correlated with cognitive functioning. Little is known about how these components of cortical gray matter develop in the first years of life. We studied the longitudinal development of regional CT and SA expansion in healthy infants from birth to 2 years. CT and SA have distinct and heterogeneous patterns of development that are exceptionally dynamic; overall CT increases by an average of 36.1%, while cortical SA increases 114.6%. By age 2, CT is on average 97% of adult values, compared with SA, which is 69%. This suggests that early identification, prevention, and intervention strategies for neuropsychiatric illness need to be targeted to this period of rapid postnatal brain development, and that SA expansion is the principal driving factor in cortical volume after 2 years of age.
doi:10.1093/cercor/bhu027
PMCID: PMC4506327  PMID: 24591525
brain development; cerebral cortex; gray matter; human; magnetic resonance imaging
3.  Eating Disorders, Pregnancy, and the Postpartum Period: Findings from the Norwegian Mother and Child Cohort Study (MoBa) 
This review summarizes studies on eating disorders in pregnancy and the postpartum period that have been conducted as part of the broader Norwegian Mother and Child Cohort Study (MoBa). Prior to the 2000s, empirical literature on eating disorders in pregnancy was sparse and consisted mostly of studies in small clinical samples. MoBa has contributed to a new era of research by making population-based and large-sample research possible. To date, MoBa has led to 19 studies on diverse questions including the prevalence, course, and risk correlates of eating disorders during pregnancy and the postpartum. The associations between eating disorder exposure and pregnancy, birth and obstetric outcomes, and maternal and offspring health and well-being, have also been areas of focus. The findings indicate that eating disorders in pregnancy are relatively common and appear to confer health risks to mother and her child related to sleep, birth outcomes, maternal nutrition, and child feeding and eating.
PMCID: PMC4838406  PMID: 27110061
eating disorders; pregnancy; MoBa; The Norwegian Mother and Child Cohort Study
4.  Prevalence of Screening-Detected Eating Disorders in Chinese Females and Exploratory Associations with Dietary Practices 
Objective
China is undergoing dramatic Westernization, hence may be able to provide unique insights into the role of sociocultural factors in disease. The purpose of this exploratory study was two-fold: to describe the prevalence of screening-detected eating disorders and disordered eating in China at the first occasion of assessment in the large-scale China Health and Nutrition Survey (CHNS) and to explore the associations between dietary practices and disordered eating. Regarding the first objective, participants are provincially representative and in subsequent waves will be followed longitudinally.
Method
CHNS participants were recruited using multistage, cluster random sampling, beginning in 1989. In this study, participants comprised 259 female adolescents (12–17 years) and 979 women (18–35 years) who participated in the CHNS 2009 survey, which is the first CHNS survey to assess disordered eating. Dietary practice-disordered eating associations were investigated with logistic regression adjusting for age, body mass index, and urbanization.
Results
Of the participants, 6.3% (95% CI: 4.8, 8.2) of adults and 7.8% (95% CI: 5.0, 12.0) of adolescents had a screening-detected eating disorder. Dietary practices had non-significant associations with disordered eating at the general population level, except for protein consumption among women. There was evidence that skipping meals and a high-fat diet may confer risk.
Discussion
Screening-detected eating disorders in China are lower in prevalence than in developed countries. Dietary practices had fairly limited associations with disordered eating at the general population level; protein consumption, skipping meals, and a high-fat diet are candidate dietary practice exposures for disordered eating.
doi:10.1002/erv.2334
PMCID: PMC4314345  PMID: 25407415
China; China Health and Nutrition Survey; dietary practices; disordered eating; screening; overweight; SCOFF
5.  Gestational and Postpartum Weight Change Patterns in Mothers with Eating Disorders 
Background
Although pregnancy can be associated with adaptive changes in weight and eating behavior for women with eating disorders, less is known about whether these changes are maintained in the postpartum period. We used a longitudinal design to examine gestational and postpartum weight trajectories in mothers with and without eating disorders in the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health.
Methods
Fifty-six women reported anorexia nervosa (AN), 636 bulimia nervosa (BN), 3,327 binge eating disorder (BED), and 69 EDNOS purging type (EDNOS-P). The referent group included 61,233 mothers with no eating disorder. We used a mixed effects model to predict weight change over time by eating disorder subtype.
Results
Mothers with AN, BN, BED and EDNOS had greater increases in BMI during pregnancy and greater decreases in BMI over the first six months postpartum. Women with AN shifted from the underweight BMI range before pregnancy to the normal weight range at 36 months postpartum
Conclusions
Patterns of maternal weight gain and retention during the perinatal period vary across eating disorder subtype and warrant clinical attention.
doi:10.1002/erv.2314
PMCID: PMC4205262  PMID: 25201473
eating disorders; MoBa; The Norwegian Mother and Child Cohort Study; pregnancy; postpartum; weight; anorexia nervosa; bulimia nervosa; binge eating disorder
6.  Impact of Sex and Gonadal Steroids on Neonatal Brain Structure 
Cerebral Cortex (New York, NY)  2013;24(10):2721-2731.
There are numerous reports of sexual dimorphism in brain structure in children and adults, but data on sex differences in infancy are extremely limited. Our primary goal was to identify sex differences in neonatal brain structure. Our secondary goal was to explore whether brain structure was related to androgen exposure or sensitivity. Two hundred and ninety-three neonates (149 males) received high-resolution structural magnetic resonance imaging scans. Sensitivity to androgen was measured using the number of cytosine, adenine, guanine (CAG) triplets in the androgen receptor gene and the ratio of the second to fourth digit, provided a proxy measure of prenatal androgen exposure. There was a significant sex difference in intracranial volume of 5.87%, which was not related to CAG triplets or digit ratios. Tensor-based morphometry identified extensive areas of local sexual dimorphism. Males had larger volumes in medial temporal cortex and rolandic operculum, and females had larger volumes in dorsolateral prefrontal, motor, and visual cortices. Androgen exposure and sensitivity had minor sex-specific effects on local gray matter volume, but did not appear to be the primary determinant of sexual dimorphism at this age. Comparing our study with the existing literature suggests that sex differences in cortical structure vary in a complex and highly dynamic way across the human lifespan.
doi:10.1093/cercor/bht125
PMCID: PMC4153808  PMID: 23689636
androgen; gender; neonate; neuroimaging; sex
7.  Rate of Chiari I Malformation in Children of Mothers with Depression with and without Prenatal SSRI Exposure 
Neuropsychopharmacology  2014;39(11):2611-2621.
Selective serotonin reuptake inhibitors (SSRIs) are frequently prescribed to pregnant women. Therefore, research on in utero exposure to SSRIs can be helpful in informing patients and clinicians. The aim of this retrospective two-cohort study was to determine whether there is a statistically significant increase in Chiari I malformations (CIM) in children exposed to SSRIs during pregnancy. A total of 33 children whose mothers received a diagnosis of depression and took SSRIs during pregnancy (SSRI-exposed cohort) were matched to 66 children with no history of maternal depression and no SSRI exposure. In addition, 30 children whose mothers received a diagnosis of depression, but did not receive antidepressants during pregnancy (history of maternal depression cohort), were matched to 60 children with no history of maternal depression and no SSRI exposure. Main outcome was presence/absence of CIM on MRI scans at 1 and/or 2 years of age. Scans were reviewed by two independent neuroradiologists who were blind to exposure status. The SSRI-exposed children were significantly more likely to be classified as CIM than comparison children with no history of maternal depression and no SSRI exposure (18% vs 2%, p=0.003, OR estimate 10.32, 95% Wald confidence limits 2.04–102.46). Duration of SSRI exposure, SSRI exposure at conception, and family history of depression increased the risk. The history of maternal depression cohort did not differ from comparison children with no history of maternal depression and no SSRI exposure in occurrence of CIM (7% vs 5%, p=0.75, OR estimate 1.44, 95% Wald confidence limits 0.23–7.85). Replication is needed, as is additional research to clarify whether SSRIs directly impact risk for CIM or whether this relationship is mediated by severity of depressive symptoms during pregnancy. We would discourage clinicians from altering their prescribing practices until such research is available.
doi:10.1038/npp.2014.114
PMCID: PMC4207341  PMID: 24837031
8.  A comparison of infant and toddler feeding practices of mothers with and without histories of eating disorders 
Maternal & child nutrition  2012;10(3):360-372.
This preliminary study surveyed the feeding practices of mothers with eating disorder histories through evaluation of mothers’ reported feeding styles, child diet composition, and restrictive special approaches to feeding. For this non-randomized cohort study, 25 mothers with eating disorder histories and 25 mothers with no history of an eating disorder with children ages 6–36 months were selected such that the groups were similar based on child age group and child sex. Mothers were compared on self-reported feeding style using the Infant Feeding Styles Questionnaire and on child diet composition and special feeding approaches using a modified version of the Toddler Diet Questionnaire from the Women, Infants, and Children program. Mothers with eating disorder histories scored lower on the restrictive feeding style subscale than controls. No significant differences were detected between groups in child diet including the percentage of mothers who breastfed, duration of breastfeeding, age at solid food introduction, daily number of meals or snacks, or daily frequency of consumption of fruits, vegetables, or protein foods. Mothers with eating disorder histories were more likely to report taking a restrictive special approach to feeding such as limiting processed foods or feeding organic foods only. Although mothers with eating disorder histories may not differ greatly from control mothers in terms of child diet composition (smaller effects may not have been detected due to limited sample size), they may be more likely to take restrictive special approaches to feeding which mirror dietary rules common in individuals with eating disorders.
doi:10.1111/j.1740-8709.2012.00429.x
PMCID: PMC3473145  PMID: 22784046
eating disorders; feeding behavior; maternal behavior; restrictive feeding; infant; toddler
9.  Weight-for-length trajectories in the first year of life in children of mothers with eating disorders in a large Norwegian cohort 
Objective
To describe weight-for-length (WFL) trajectories in the children (birth-12 months) of mothers with and without eating disorders.
Methods
This study is based on the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. We categorized women (N=57,185) based on diagnosis prior to and during pregnancy: anorexia nervosa (AN), bulimia nervosa (BN), eating disorder not otherwise specified-purging subtype (EDNOS-P), binge eating disorder (BED), or no eating disorder (no-ED). The primary analysis included a shape invariant model fitted with non-linear mixed effects to compare growth rates across eating disorder subtypes.
Results
The children of mothers reporting any eating disorder had a lower WFL growth rate from birth--12 months than the children of mothers without eating disorders, even after adjusting for relative birth weight and some confounders known to affect growth.
Discussion
In this cohort, child WFL was related to maternal eating disorder status before and/or during pregnancy. These differences in growth trajectories warrant further study of long-term health outcomes and, if replicated, tailoring counseling to mothers with eating disorders during pregnancy.
doi:10.1002/eat.22290
PMCID: PMC4482472  PMID: 24782279
10.  Neurocognition in Early-Onset Schizophrenia and Schizoaffective Disorders 
Objective
We examined the neuropsychological functioning of youth enrolled in the NIMH funded trial, Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). We compared the baseline neuropsychological functioning of youth with schizophrenia (SZ, n = 79) to those with schizoaffective disorder (SA, n = 40), and examined the relationship of different variables of illness severity and adaptive behavior to neuropsychological functioning.
Method
Participants ranged in age from 8 to 19 years. Diagnostic status was confirmed via structured interview over multiple time points. Domains of neuropsychological functioning included fine-motor, attention, working memory, problem-solving efficiency, inhibitory control, and social cognition. Other variables included intelligence (IQ), academic achievement skills, adaptive behavior, and different measures of illness severity.
Results
The two groups did not differ on IQ or on any of the neuropsychological domains. The SZ group performed significantly lower in spelling. A high proportion of individuals in both groups reflected significant intellectual and academic achievement skill deficits. Significant correlations were found between the neurocognitive domains and both illness severity and adaptive behavior variables.
Conclusions
There were few differences between the SZ and SA groups on IQ, achievement, or neuropsychological functioning; however, both groups showed significantly high rates of deficits in IQ and basic academic skills. Correlations of the neurocognitive functions with illness severity and adaptive behavior were small to moderate in magnitude. These findings continue to implicate the importance of neurocognitive functioning as a key area of vulnerability in the study of youth with schizophrenia spectrum disorders.
PMCID: PMC4447145  PMID: 20215926
early-onset schizophrenia; childhood schizophrenia; schizoaffective disorder in childhood; neurocognition in schizophrenia
11.  Common Variants in Psychiatric Risk Genes Predict Brain Structure at Birth 
Cerebral Cortex (New York, NY)  2013;24(5):1230-1246.
Studies in adolescents and adults have demonstrated that polymorphisms in putative psychiatric risk genes are associated with differences in brain structure, but cannot address when in development these relationships arise. To determine if common genetic variants in disrupted-in-schizophrenia-1 (DISC1; rs821616 and rs6675281), catechol-O-methyltransferase (COMT; rs4680), neuregulin 1 (NRG1; rs35753505 and rs6994992), apolipoprotein E (APOE; ɛ3ɛ4 vs. ɛ3ɛ3), estrogen receptor alpha (ESR1; rs9340799 and rs2234693), brain-derived neurotrophic factor (BDNF; rs6265), and glutamate decarboxylase 1 (GAD1; rs2270335) are associated with individual differences in brain tissue volumes in neonates, we applied both automated region-of-interest volumetry and tensor-based morphometry to a sample of 272 neonates who had received high-resolution magnetic resonance imaging scans. ESR1 (rs9340799) predicted intracranial volume. Local variation in gray matter (GM) volume was significantly associated with polymorphisms in DISC1 (rs821616), COMT, NRG1, APOE, ESR1 (rs9340799), and BDNF. No associations were identified for DISC1 (rs6675281), ESR1 (rs2234693), or GAD1. Of note, neonates homozygous for the DISC1 (rs821616) serine allele exhibited numerous large clusters of reduced GM in the frontal lobes, and neonates homozygous for the COMT valine allele exhibited reduced GM in the temporal cortex and hippocampus, mirroring findings in adults. The results highlight the importance of prenatal brain development in mediating psychiatric risk.
doi:10.1093/cercor/bhs401
PMCID: PMC3977618  PMID: 23283688
catechol-O-methyltransferase; cortex; disrupted-in-schizophrenia-1; neonate; neuroimaging
12.  A Double-blind, Randomized Pilot Trial of Chromium Picolinate for Binge Eating Disorder: Results of the Binge Eating and Chromium (BEACh) Study 
Objective
Chromium treatment has been shown to improve mood, appetite, and glucose regulation in various psychiatric and medical patient populations. The authors propose that chromium may be useful in the treatment of binge eating disorder (BED).
Method
Twenty-four overweight adults with BED were enrolled in a 6-month double-blind placebo-controlled trial and randomly assigned to receive either 1000mcg chromium/day (“high dose”; n=8) or 600mcg chromium/day (“moderate dose”; n=9) as chromium picolinate or placebo (n=7). Mixed linear regression models were used to estimate mean change in binge frequency and related psychopathology, weight, symptoms of depression, and fasting glucose.
Results
Fasting glucose was significantly reduced in both chromium groups compared to the placebo group; similarly, numerically, but not significantly, greater reductions in binge frequency, weight, and symptoms of depression were observed in those treated with chromium versus placebo, although statistical power was limited in this pilot trial. For fasting glucose, the findings suggest a dose response with larger effects in the high dose compared to moderate dose group.
Conclusion
These initial findings support further larger trials to determine chromium’s efficacy in maintaining normal glucose regulation, reducing binge eating and related psychopathology, promoting modest weight loss, and reducing symptoms of depression in individuals with BED. Studies designed to link the clinical effects of chromium with changes in underlying insulin, serotonin, and dopamine pathways may be especially informative. If efficacious, chromium supplementation may provide a useful, low-cost alternative to or augmentation strategy for selective serotonin reuptake inhibitors, which have partial efficacy in BED. ClinicalTrials.gov NCT00904306.
doi:10.1016/j.jpsychores.2013.03.092
PMCID: PMC4358897  PMID: 23751236
binge eating disorder; chromium; depression; glucose; weight
13.  Behavioral and Psychophysiological Responsiveness During Child Feeding in Mothers with Histories of Eating Disorders: A Pilot Study 
The aim of this pilot project was to describe maternal responsiveness during child feeding in mothers with eating disorder histories through the combined use of observational, self-report, and physiologic methods. For this non-randomized cohort pilot study, 25 mothers with histories of eating disorders and 25 mothers with no history of an eating disorder with children ages 6–36 months were selected such that the groups were similar based on child age group (within 6 months) and child sex. Maternal behavioral responsiveness to child cues was assessed by video-recording and behavioral coding of both a free-play and feeding episode. Physiologic engagement was assessed through measurement of respiratory sinus arrhythmia (RSA) reactivity during free-play and feeding episodes. No differences were detected in observed behavioral responsiveness during feeding or free-play in mothers with eating disorder histories compared with controls. Mothers with eating disorder histories did report more parenting stress, increased anxiety, and exhibited a blunted physiologic stress response (less RSA reactivity) during both feeding and free-play interactions with their children. These results support future larger-scale investigations of RSA reactivity in mothers with eating disorders.
doi:10.1007/s10862-013-9357-2
PMCID: PMC3913224  PMID: 24511180
eating disorders; mothers; feeding behavior; maternal responsiveness; RSA reactivity; infant feeding
14.  Effectiveness of Paliperidone Palmitate vs. Haloperidol Decanoate for Maintenance Treatment of Schizophrenia: A Randomized Clinical Trial 
Importance
Long-acting injectable (LAI) antipsychotics are used to reduce medication non-adherence and subsequent relapse in schizophrenia-spectrum disorders. The relative effectiveness of LAI versions of second-generation (atypical) and older antipsychotics has not been assessed.
Objective
To compare the effectiveness of the second-generation LAI antipsychotic paliperidone palmitate (PP) to the older LAI antipsychotic haloperidol decanoate (HD).
Design, Setting, and Participants
Multisite, double-blind, randomized clinical trial conducted at 22 clinical research sites in the U.S. The 311 randomized patients (PP=157, HD=154) were adults diagnosed with schizophrenia or schizoaffective disorder who were clinically assessed to be at risk of relapse and likely to benefit from a LAI antipsychotic.
Interventions
Intramuscular injections of HD 25–200 mg or PP 39–234 mg every month for up to 24 months.
Main Outcome Measures
Efficacy failure, which reflected inadequate control of psychopathology by the study medication, as determined by a blinded adjudication committee. Key secondary outcomes were common adverse effects of antipsychotic medications.
Results
There was no statistically significant difference in the rate of efficacy failure for PP compared to HD (adjusted hazard ratio 0.98, 95% confidence interval [CI] 0.65–1.47). On average, patients on PP gained and those on HD lost weight; after six months the least squares mean weight change on PP was +2.17 kg (1.25 to 3.09) and on HD was −0.96 kg (−1.88 to −0.04). Patients taking PP had significantly greater increases in serum prolactin (men 34.56 µg/L (29.75 to 39.37) vs. 15.41 (10.73 to 20.08), p<0.001; women 75.19 (63.03 to 87.36) vs. 26.84 (13.29 to 40.40), p<0.001). Patients taking HD had significantly larger increases in global ratings of akathisia (0.73 [0.59 to 0.87] vs. 0.45 [0.31 to 0.59], p=0.006).
Conclusions and Relevance
Among adults with schizophrenia or schizoaffective disorder, treatment with paliperidone palmitate compared with haloperidol decanoate did not result in a statistically significant difference in efficacy failure, but was associated with more weight gain and greater increases in serum prolactin, whereas haloperidol was associated with more akathisia. However, based on the 95% confidence limits, a clinically meaningful difference in efficacy failure between treatments cannot be ruled out.
Trial Registration
clinicaltrials.gov identifier NCT01136772
doi:10.1001/jama.2014.4310
PMCID: PMC4101890  PMID: 24846035
15.  Remission, continuation, and incidence of eating disorders during early pregnancy: A validation study on a population-based birth cohort 
Psychological medicine  2012;43(8):1723-1734.
Background
The objective of this study was to validate previously published rates of remission, continuation, and incidence of broadly defined eating disorders during pregnancy. The previous rate modeling was done by our group (Bulik et al. 2007) and yielded participants halfway into recruitment of the planned 100,000 pregnancies in the Norwegian Mother and Child (MoBa) Cohort at the Norwegian Institute of Public Health. This study aimed to internally validate the findings with the completed cohort.
Methods
77267 pregnant women enrolled at 17 weeks gestation between 2001 and 2009 were included. Participants were split into a “training” sample (n=41243) based on participants in the MoBa version 2 dataset of the original study and a “validation” sample (n=36024) comprising individuals in the MoBa version 5 dataset that were not in the original study (Bulik et al. 2007). Internal validation of all original rate models involved fitting a calibration model to compare model parameters between the “training” and “validation” samples as well as bootstrap estimates of bias in the entire version 5 dataset.
Results
Remission, continuation, and incidence estimates from the “training” sample remained stable when evaluated via a split sample validation procedure. Pre-pregnancy prevalence estimates in the “validation” sample were 0.1% for anorexia nervosa, 1.0% for bulimia nervosa (BN), 3.3% for binge eating disorder (BED), and 0.1% for purging disorder (EDNOS-P). In early pregnancy, estimates were 0.2% for BN, 4.8% for BED, and <0.01% for EDNOS-P. Consistent with the original study, incident BN and EDNOS-P during pregnancy were rare. For BED, the adjusted incidence rate in the “validation” sample was 1.17 per 1000 person-weeks. The highest rates were for full or partial remission for BN and EDNOS-P, and continuation for BED.
Conclusions
This study provides evidence of validity of previously estimated rates of remission, continuation, and incidence of eating disorders during pregnancy. Eating disorders during pregnancy were relatively common, occurring in nearly 1 in every 20 women, although almost all were cases of BED. Pregnancy was a window of remission from BN but a window of vulnerability for onset and continuation of BED. Training to detect the signs and symptoms of eating disorders by obstetricians/gynecologists and interventions to enhance pregnancy and neonatal outcomes warrant attention.
doi:10.1017/S0033291712002516
PMCID: PMC4206832  PMID: 23164164
Eating disorders; epidemiology; incidence; pregnancy; prospective; remission; The Norwegian Mother and Child Cohort Study
16.  Metformin for Weight Loss and Metabolic Control in Overweight Outpatients With Schizophrenia and Schizoaffective Disorder 
The American journal of psychiatry  2013;170(9):10.1176/appi.ajp.2013.12010127.
Objective
The purpose of this study was to determine whether metformin promotes weight loss in overweight out-patients with chronic schizophrenia or schizoaffective disorder.
Method
In a double-blind study, 148 clinically stable, overweight (body mass index [BMI] ≥27) outpatients with chronic schizophrenia or schizoaffective disorder were randomly assigned to receive 16 weeks of metformin or placebo. Metformin was titrated up to 1,000 mg twice daily, as tolerated. All patients continued to receive their prestudy medications, and all received weekly diet and exercise counseling. The primary outcome measure was change in body weight from baseline to week 16.
Results
Fifty-eight (77.3%) patients who received metformin and 58 (81.7%) who received placebo completed 16 weeks of treatment. Mean change in body weight was −3.0 kg (95% CI=−4.0 to −2.0) for the metformin group and −1.0 kg (95% CI= −2.0 to 0.0) for the placebo group, with a between-group difference of −2.0 kg (95% CI=−3.4 to −0.6). Metformin also demonstrated a significant between-group advantage for BMI (−0.7; 95% CI=−1.1 to −0.2), triglyceride level (−20.2 mg/dL; 95% CI=−39.2 to −1.3), and hemoglobin A1c level (−0.07%; 95% CI=−0.14 to −0.004). Metformin-associated side effects were mostly gastrointestinal and generally transient, and they rarely led to treatment discontinuation.
Conclusions
Metformin was modestly effective in reducing weight and other risk factors for cardiovascular disease in clinically stable, overweight outpatients with chronic schizophrenia or schizoaffective disorder over 16 weeks. A significant time-by-treatment interaction suggests that benefits of metformin may continue to accrue with longer treatment. Metformin may have an important role in diminishing the adverse consequences of obesity and metabolic impairments in patients with schizophrenia.
doi:10.1176/appi.ajp.2013.12010127
PMCID: PMC3874085  PMID: 23846733
17.  NURTURE: Development and Pilot Testing of a Novel Parenting Intervention for Mothers with Histories of an Eating Disorder 
Objective
To describe the treatment development and pilot testing of a group parenting intervention, NURTURE (Networking, Uniting, and Reaching out To Upgrade Relationships and Eating), for mothers with histories of eating disorders.
Method
Based on focus group findings, extant research, and expert opinion, NURTURE was designed to be delivered weekly over 16 (1.5 hour) sessions via an interactive web conferencing forum. It comprises four modules: 1) laying the foundation, 2) general parenting skills, 3) eating and feeding, and 4) breaking the cycle of risk. Pilot testing was conducted with three groups of 3–6 mothers (N = 13) who had children ages 0–3 years to determine feasibility (e.g., retention), acceptability (e.g., feedback questionnaire responses), and preliminary efficacy. Maternal satisfaction with NURTURE and changes in mother-child feeding relationship measures, maternal feeding style, maternal self-efficacy, and maternal psychopathology (eating disorder, depression, and anxiety symptoms) across three time points (baseline, post-treatment, 6-month follow-up) were examined. All outcomes were exploratory.
Results
The intervention was well tolerated with a 100% retention rate. Feedback from mothers was generally positive and indicated that the groups provided an engaging, supportive experience to participants. We observed changes suggestive of improvement in self-reported maternal self-efficacy and competence with parenting. There were no notable changes in measures of maternal feeding style or psychopathology.
Discussion
NURTURE is a feasible, acceptable, and potentially valuable intervention for mothers with eating disorder histories. Results of this pilot will inform a larger randomized-controlled intervention to determine efficacy and impact on child outcomes.
doi:10.1002/eat.22178
PMCID: PMC4009482  PMID: 23983082
18.  Effects of switching from olanzapine, quetiapine, and risperidone to aripiprazole on 10-year coronary heart disease risk and metabolic syndrome status: Results from a randomized controlled trial 
Schizophrenia research  2013;146(0):190-195.
Purpose
This study examined the clinical significance of switching from olanzapine, quetiapine, or risperidone to aripiprazole by examining changes in predicted risk of cardiovascular disease (CVD) according to the Framingham Risk Score (FRS) and metabolic syndrome status. FRS estimates 10-year risk of “hard” coronary heart disease (CHD) outcomes (myocardial infarction and coronary death) while metabolic syndrome is associated with increased risk of CVD, stroke, and diabetes mellitus.
Method
Changes in FRS and metabolic syndrome status were compared between patients with BMI ≥ 27 and non-HDL-C ≥ 130 mg/dL randomly assigned to stay on stable current treatment (olanzapine, quetiapine, or risperidone) or switch to treatment with aripiprazole with 24 weeks of follow-up. All study participants were enrolled in a behavioral program that promoted healthy diet and exercise.
Results
The pre-specified analyses included 89 switchers and 98 stayers who had post-baseline measurements needed to assess changes. Least squares mean estimates of 10-year CHD risk decreased more for the switch (from 7.0% to 5.2%) than the stay group (from 7.4% to 6.4%) (p=0.0429). The odds ratio for having metabolic syndrome (stay vs. switch) at the last observation was 1.748 (95% CI 0.919, 3.324, p=0.0885).
Conclusion
Switching from olanzapine, quetiapine, or risperidone to aripiprazole was associated with larger reductions in predicted 10-year risk of CHD than the behavioral program alone. The advantage of switching on metabolic syndrome was not statistically significant. The benefits of switching must be balanced against its risks, which in this study included more discontinuations of the study treatment but no significant increase in symptoms or hospitalizations.
doi:10.1016/j.schres.2013.01.013
PMCID: PMC3622801  PMID: 23434503
Antipsychotics; Metabolic side effects; Randomized clinical trial
19.  Promoviendo una Alimentación Saludable (PAS) Design and Methods: Engaging Latino Families in Eating Disorder Treatment 
Contemporary clinical trials  2013;35(1):52-61.
The use of culturally sensitive intervention could improve mental health care for the eating disorders treatment in the Latino population. The aim of this report is to describe the rationale, design, and methods of the ongoing study entitled “Engaging Latino families in eating disorders treatment.” The primary aim of the study is to compare (a) the combined effect of individual cognitive behavioral therapy for bulimia nervosa (CBT-BN) that has been previously adapted for the Latino population plus Family Enhanced (FE) modules, with (b) the standard adapted individual CBT-BN in a proof-of-principle study with 40 Latina adults with eating disorders and one relative or significant other per patient. We hypothesize that 1) the feasibility, acceptability, and adherence of participants in CBT-BN+ FE will be superior to individual CBT-BN only; 2) relatives in CBT-BN+ FE will report greater treatment satisfaction, greater reduction in family conflict, and greater decreases in caregiver burden than relatives in the individual CBT-BN only condition; and 3) patients who participate in CBT-BN+ FE will show trends towards greater decreases in ED symptoms compared with patients in CBT-BN only; although power will be limited to detect this difference. However, we predict that they will show greater retention in treatment, greater treatment satisfaction, and greater decreases in family conflict than patients in CBT-BN only. The completion of this investigation will yield important information regarding the acceptability and feasibility of a culturally sensitive evidence-based treatment model for Latinos with eating disorders. (Word Count=240)
doi:10.1016/j.cct.2013.01.005
PMCID: PMC3640683  PMID: 23376815
Latinas; Eating disorders; Cultural adaptation; Family intervention; Clinical trial; Cognitive-behavioral therapy
20.  A prospective study of perinatal depression and trauma history in pregnant minority adolescents 
OBJECTIVE
Adolescent pregnancy is common and minority adolescents are at high risk. We sought the following: (1) to prospectively assess prevalence of antenatal depression (AND) and postpartum depression (PPD) in minority adolescents and (2) to examine the association of social support and adjustment, trauma, and stress on depression status.
STUDY DESIGN
A total of 212 pregnant adolescents were recruited from public prenatal clinics and administered a prospective research survey during pregnancy and 6 weeks postpartum. Depression was measured using the Edinburgh Postnatal Depression Scale. Univariate, bivariate, and multivariable analyses were performed using logistic regression to assess predictors of AND and PPD.
RESULTS
In our cohort, 20% screened positive for AND and 10% for PPD. The strongest predictor of PPD was AND (odds ratio [OR], 4.89; P < .001). Among adolescents with trauma history, there was a 5-fold increase (OR, 5.01) in the odds of AND and a 4-fold increase (OR, 3.76) in the odds of PPD. AND was associated with the adolescent’s poor social adjustment (P < .001), perceived maternal stress (P < .001), less social support (P < .001), and a less positive view of pregnancy (P < .001). PPD was significantly associated with primiparity (P = .002), poor social adjustment (P < .001), less social support and involvement of the baby’s father (P < .001), and less positive view of pregnancy (P < .001).
CONCLUSION
Significant independent risk factors for PPD include AND, view of pregnancy, and social support. Trauma history was highly prevalent and strongly predicted AND and PPD. Point prevalence decreased postpartum, and this may be due to transient increased social support following the birth, warranting longer follow-up and development of appropriate interventions in future work.
doi:10.1016/j.ajog.2012.12.020
PMCID: PMC3762981  PMID: 23246315
adolescents; perinatal depression; postpartum depression; pregnancy; trauma
21.  Longitudinal Development of Cortical and Subcortical Gray Matter from Birth to 2 Years 
Cerebral Cortex (New York, NY)  2011;22(11):2478-2485.
Very little is known about cortical development in the first years of life, a time of rapid cognitive development and risk for neurodevelopmental disorders. We studied regional cortical and subcortical gray matter volume growth in a group of 72 children who underwent magnetic resonance scanning after birth and at ages 1 and 2 years using a novel longitudinal registration/parcellation approach. Overall, cortical gray matter volumes increased substantially (106%) in the first year of life and less so in the second year (18%). We found marked regional differences in developmental rates, with primary motor and sensory cortices growing slower in the first year of life with association cortices growing more rapidly. In the second year of life, primary sensory regions continued to grow more slowly, while frontal and parietal regions developed relatively more quickly. The hippocampus grew less than other subcortical structures such as the amygdala and thalamus in the first year of life. It is likely that these patterns of regional gray matter growth reflect maturation and development of underlying function, as they are consistent with cognitive and functional development in the first years of life.
doi:10.1093/cercor/bhr327
PMCID: PMC3464410  PMID: 22109543
amygdala; cerebral cortex; hippocampus; lateral ventricle; magnetic resonace imaging
22.  CBT4BN versus CBTF2F: Comparison of Online versus Face-To-FaceTreatment for Bulimia Nervosa 
Contemporary clinical trials  2012;33(5):1056-1064.
Cognitive-behavioral therapy (CBT) is currently the “gold standard” for treatment of bulimia nervosa (BN), and is effective for approximately 40–60% of individuals receiving treatment; however, the majority of individuals in need of care do not have access to CBT. New strategies for service delivery of CBT and for maximizing maintenance of treatment benefits are critical for improving our ability to treat BN. This clinical trial is comparing an Internet-based version of CBT (CBT4BN) in which group intervention is conducted via therapeutic chat group with traditional group CBT (CBTF2F) for BN conducted via face-to-face therapy group. The purpose of the trial is to determine whether manualized CBT delivered via the Internet is not inferior to the gold standard of manualized group CBT. In this two-site randomized controlled trial, powered for non-inferiority analyses, 180 individuals with BN are being randomized to either CBT4BN or CBTF2F. We hypothesize that CBT4BN will not be inferior to CBTF2F and that participants will value the convenience of an online intervention. If not inferior, CBT4BN may be a cost-effective approach to service delivery for individuals requiring treatment for BN.
doi:10.1016/j.cct.2012.05.008
PMCID: PMC3408767  PMID: 22659072
23.  Feasibility and Pilot Efficacy Results from the Multi-site Cognitive Remediation in the Schizophrenia Trials Network (CRSTN) Study 
The Journal of clinical psychiatry  2012;73(7):1016-1022.
Background
The true benefit of pharmacological intervention to improve cognition in schizophrenia may not be evident without regular cognitive enrichment. Clinical trials assessing the neurocognitive effects of new medications may require engagement in cognitive remediation exercises to stimulate the benefit potential. However, the feasibility of large-scale multi-site studies using cognitive remediation at clinical trials sites has not been established.
Methods
Patients with DSM-IV schizophrenia from nine sites were randomized to a cognitive remediation condition that included the Posit Science Brain Fitness auditory training program with weekly NEAR ‘bridging groups,’ or a control condition of computer games and weekly healthy lifestyles groups. Patients were expected to complete 3–5 one-hour sessions weekly for 40 sessions or 12 weeks, whichever came first.
Results
The primary outcomes were feasibility results as measured by rate of enrollment, retention, and completion rate of primary outcome measures. Within the 3-month enrollment period, 53 of a projected 54 patients were enrolled and 47 completed the study. Thirty-one patients completed all 40 sessions and all patients completed all primary outcome measures. Preliminary efficacy results indicated that after 20 sessions, patients in the cognitive remediation condition demonstrated mean MCCB composite score improvements that were 3.7 (95% CI: 7.34, 0.05) T-score points greater than in patients in the computer games control group (F=4.16, df=1,46, p=0.047). At the end of treatment, a trend favoring cognitive remediation was not statistically significant (F=2.26, df=1,47, p=0.14).
Discussion
Multi-site clinical trials of cognitive remediation using the Posit Science auditory training program with the NEAR method of weekly bridging groups in traditional clinical sites appear feasible.
doi:10.4088/JCP.11m07100
PMCID: PMC3746329  PMID: 22687548
24.  Improving metabolic parameters of antipsychotic child treatment (IMPACT) study: rationale, design, and methods 
Background
Youth with serious mental illness may experience improved psychiatric stability with second generation antipsychotic (SGA) medication treatment, but unfortunately may also experience unhealthy weight gain adverse events. Research on weight loss strategies for youth who require ongoing antipsychotic treatment is quite limited. The purpose of this paper is to present the design, methods, and rationale of the Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) study, a federally funded, randomized trial comparing two pharmacologic strategies against a control condition to manage SGA-related weight gain.
Methods
The design and methodology considerations of the IMPACT trial are described and embedded in a description of health risks associated with antipsychotic-related weight gain and the limitations of currently available research.
Results
The IMPACT study is a 4-site, six month, randomized, open-label, clinical trial of overweight/obese youth ages 8–19 years with pediatric schizophrenia-spectrum and bipolar-spectrum disorders, psychotic or non-psychotic major depressive disorder, or irritability associated with autistic disorder. Youth who have experienced clinically significant weight gain during antipsychotic treatment in the past 3 years are randomized to either (1) switch antipsychotic plus healthy lifestyle education (HLE); (2) add metformin plus HLE; or (3) HLE with no medication change. The primary aim is to compare weight change (body mass index z-scores) for each pharmacologic intervention with the control condition. Key secondary assessments include percentage body fat, insulin resistance, lipid profile, psychiatric symptom stability (monitored independently by the pharmacotherapist and a blinded evaluator), and all-cause and specific cause discontinuation. This study is ongoing, and the targeted sample size is 132 youth.
Conclusion
Antipsychotic-related weight gain is an important public health issue for youth requiring ongoing antipsychotic treatment to maintain psychiatric stability. The IMPACT study provides a model for pediatric research on adverse event management using state-of-the art methods. The results of this study will provide needed data on risks and benefits of two pharmacologic interventions that are already being used in pediatric clinical settings but that have not yet been compared directly in randomized trials.
Trial registration
Clinical Trials.gov NCT00806234
doi:10.1186/1753-2000-7-31
PMCID: PMC3846140  PMID: 23947389
25.  Plasma, Salivary, and Urinary Oxytocin in Anorexia Nervosa: A Pilot Study 
Eating Behaviors  2012;13(3):256-259.
While oxytocin (OT) has the potential to be an informative biomarker of social functioning in patients with eating disorders, the burden of invasive blood draws or lumbar punctures limits OT study. Salivary and urinary OT measurements may be advantageous, as they require less invasive sampling techniques which could be conducted in a wider variety of settings. Yet, the degree to which the concentration of OT in these fluids is correlated with blood levels is uncertain, as is the impact of vomiting on salivary secretion of OT. Therefore, we compared contemporaneously sampled OT concentration in blood, saliva, and urine from twenty women acutely ill with anorexia nervosa. Salivary OT was positively correlated with plasma OT in patients with no history of self-induced vomiting(r=0.89), but correlation was lower in those with recent history of self-induced vomiting(r=0.42). Urinary and plasma OT were not well-correlated(r=0.13), suggesting preliminarily that collection of plasma OT remains the method of choice. Self-induced vomiting in eating disorders may limit the applicability of salivary sampling for OT.
doi:10.1016/j.eatbeh.2012.02.004
PMCID: PMC3368224  PMID: 22664406
oxytocin; plasma; saliva; urine; eating disorder; self-induced vomiting

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