Cognitive Rehabilitation With Mobile Technology and Social Support for Veterans With TBI and PTSD: A Randomized Clinical Trial.

OBJECTIVE: To investigate effects of cognitive rehabilitation with mobile technology and social support on veterans with traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD). PARTICIPANTS: There were 112 dyads, comprised by a veteran and a family member or friend (224 participants in total). DESIGN: Dyads were randomized to the following: (1) a novel intervention, Cognitive Applications for Life Management (CALM), involving goal management training plus mobile devices for cueing and training attentional control; or (2) Brain Health Training, involving psychoeducation plus mobile devices to train visual memory. MAIN MEASURES: Executive dysfunction (disinhibition, impulsivity) and emotional dysregulation (anger, maladaptive interpersonal behaviors) collected prior to randomization and following intervention completion at 6 months. RESULTS: The clinical trial yielded negative findings regarding executive dysfunction but positive findings on measures of emotion dysregulation. Veterans randomized to CALM reported a 25% decrease in anger over 6 months compared with 8% reduction in the control (B = -5.27, P = .008). Family/friends reported that veterans randomized to CALM engaged in 26% fewer maladaptive interpersonal behaviors (eg, aggression) over 6 months compared with 6% reduction in the control (B = -2.08, P = .016). An unanticipated result was clinically meaningful change in reduced PTSD symptoms among veterans randomized to CALM (P < .001). CONCLUSION: This preliminary study demonstrated effectiveness of CALM for reducing emotional dysregulation in veterans with TBI and PTSD.

Neuropsychological correlates of self-reported impulsivity and informant-reported maladaptive behaviour among veterans with posttraumatic stress disorder and traumatic brain injury history.

OBJECTIVE: Frontal lobe deficits resulting from traumatic brain injury (TBI) and/or posttraumatic stress disorder (PTSD) have been linked to impulsive behaviour. We sought to examine whether neuropsychological performance predicted self-reported impulsivity and informant-reported maladaptive behaviour. METHOD: We administered the Delis-Kaplan Executive Function System (D-KEFS) to 116 Iraq/Afghanistan-era veterans diagnosed with a history of TBI and PTSD. RESULTS: Poorer performance on D-KEFS Stroop Task (both colour and word, separately) and Trail making (letter sequencing and motor speed) tasks and higher PTSD symptom severity were associated with higher self-reported impulsivity. Trail making letter sequencing performance was negatively associated with informant-reported maladaptive behaviour. Regression analyses revealed PTSD symptom severity and Trail making letter sequencing best predicted self-reported impulsivity, even when accounting for age, sex, and education. Only Trail making letter sequencing predicted informant-reported maladaptive behaviour when accounting for other variables in the model. CONCLUSIONS: Attention and processing speed impairments and PTSD symptom severity appear to be important predictors of impulsivity and problematic behaviour among veterans. Findings have implications for theoretical models of aggression and violence and inform the assessment and treatment of individuals with TBI and PTSD.

CBT4BN: A Randomized Controlled Trial of Online Chat and Face-to-Face Group Therapy for Bulimia Nervosa.

OBJECTIVE: Although cognitive-behavioral therapy (CBT) represents the first-line evidence-based psychotherapy for bulimia nervosa (BN), most individuals seeking treatment do not have access to this specialized intervention. We compared an Internet-based manualized version of CBT group therapy for BN conducted via a therapeutic chat group (CBT4BN) to the same treatment conducted via a traditional face-to-face group therapy (CBTF2F). METHOD: In a two-site, randomized, controlled noninferiority trial, we tested the hypothesis that CBT4BN would not be inferior to CBTF2F. A total of 179 adult patients with BN (2.6% males) received up to 16 sessions of group CBT over 20 weeks in either CBT4BN or CBTF2F, and outcomes were compared at the end of treatment and at the 12-month follow-up. RESULTS: At the end of treatment, CBT4BN was inferior to CBTF2F in producing abstinence from binge eating and purging. However, by the 12-month follow-up, CBT4BN was mostly not inferior to CBTF2F. Participants in the CBT4BN condition, but not CBTF2F, continued to reduce their binge-eating and purging frequency from the end of treatment to the 12-month follow-up. CONCLUSIONS: CBT delivered online in a group chat format appears to be an efficacious treatment for BN, although the trajectory of recovery may be slower than face-to-face group therapy. Online chat groups may increase accessibility of treatment and represent a cost-effective approach to service delivery. However, barriers in service delivery such as state-specific license and ethical guidelines for online therapists need to be addressed.

Predictors of dropout in face-to-face and internet-based cognitive-behavioral therapy for bulimia nervosa in a randomized controlled trial.

OBJECTIVE: We sought to identify predictors and moderators of failure to engage (i.e., pretreatment attrition) and dropout in both Internet-based and traditional face-to-face cognitive-behavioral therapy (CBT) for bulimia nervosa. We also sought to determine if Internet-based treatment reduced failure to engage and dropout. METHOD: Participants (N = 191, 98% female) were randomized to Internet-based CBT (CBT4BN) or traditional face-to-face group CBT (CBTF2F). Sociodemographics, clinical history, eating disorder severity, comorbid psychopathology, health status and quality of life, personality and temperament, and treatment-related factors were investigated as predictors. RESULTS: Failure to engage was associated with lower perceived treatment credibility and expectancy (odds ratio [OR] = 0.91, 95% CI: 0.82, 0.97) and body mass index (BMI) (OR = 1.10; 95% CI: 1.03, 1.18). Dropout was predicted by not having a college degree (hazard ratio [HR] = 0.55; 95% CI: 0.37, 0.81), novelty seeking (HR = 1.02; 95% CI: 1.01, 1.03), previous CBT experience (HR = 1.77; 95% CI: 1.16, 2.71), and randomization to the individual's nonpreferred treatment format (HR = 1.95, 95% CI: 1.28, 2.96). DISCUSSION: Those most at risk of failure to engage had a higher BMI and perceived treatment as less credible and less likely to succeed. Dropout was associated with less education, higher novelty seeking, previous CBT experience, and a mismatch between preferred and assigned treatment. Contrary to expectations, Internet-based CBT did not reduce failure to engage or dropout. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:569-577).

Dynamic Development of Regional Cortical Thickness and Surface Area in Early Childhood.

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.

Allopregnanolone Levels Are Inversely Associated with Self-Reported Pain Symptoms in U.S. Iraq and Afghanistan-Era Veterans: Implications for Biomarkers and Therapeutics.

BACKGROUND AND OBJECTIVES: Pain symptoms are common among Iraq/Afghanistan-era veterans, many of whom continue to experience persistent pain symptoms despite multiple pharmacological interventions. Preclinical data suggest that neurosteroids such as allopregnanolone demonstrate pronounced analgesic properties, and thus represent logical biomarker candidates and therapeutic targets for pain. Allopregnanolone is also a positive GABAA receptor modulator with anxiolytic, anticonvulsant, and neuroprotective actions in rodent models. We previously reported inverse associations between serum allopregnanolone levels and self-reported pain symptom severity in a pilot study of 82 male veterans. METHODS: The current study investigates allopregnanolone levels in a larger cohort of 485 male Iraq/Afghanistan-era veterans to attempt to replicate these initial findings. Pain symptoms were assessed by items from the Symptom Checklist-90-R (SCL-90-R) querying headache, chest pain, muscle soreness, and low back pain over the past 7 days. Allopregnanolone levels were quantified by gas chromatography/mass spectrometry. RESULTS: Associations between pain ratings and allopregnanolone levels were examined with Poisson regression analyses, controlling for age and smoking. Bivariate nonparametric Mann­Whitney analyses examining allopregnanolone levels across high and low levels of pain were also conducted. Allopregnanolone levels were inversely associated with muscle soreness [P = 0.0028], chest pain [P = 0.032], and aggregate total pain (sum of all four pain items) [P = 0.0001]. In the bivariate analyses, allopregnanolone levels were lower in the group reporting high levels of muscle soreness [P = 0.001]. CONCLUSIONS: These findings are generally consistent with our prior pilot study and suggest that allopregnanolone may function as an endogenous analgesic. Thus, exogenous supplementation with allopregnanolone could have therapeutic potential. The characterization of neurosteroid profiles may also have biomarker utility.

Impact of sex and gonadal steroids on neonatal brain structure.

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.

Common variants in psychiatric risk genes predict brain structure at birth.

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; ε3ε4 vs. ε3ε3), 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.

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 (Knoph Berg et al., Aust N Z J Psychiatry, 42, 396-404, 2008) 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 (Knoph Berg et al., Aust N Z J Psychiatry, 42, 396-404, 2008) 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.

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. METHOD: 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, bulimia nervosa, eating disorder not otherwise specified-purging subtype, binge eating disorder, or no eating disorder. The primary analysis included a shape invariant model fitted with nonlinear 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 to 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.