Event related potentials indexing the influence of emotion on cognitive processing in veterans with comorbid post-traumatic stress disorder and traumatic brain injury.

OBJECTIVE: Emotion regulation and cognitive executive control are significantly impaired in both post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI). These illnesses are increasingly common in veterans and their co-occurrence may exacerbate symptoms and recovery. The current study sought to investigate neural correlates of these impairments via event-related potentials (ERPs) and examined the association of PTSD symptom severity and impulsivity with these correlates. METHODS: Electroencephalographic data from seventy-nine veterans with PTSD and TBI and 17 control participants were recorded during a visual emotional oddball task and analyzed for the N2 and P3b ERPs. RESULTS: Results revealed that veterans showed a reduced P3b ERP in response to both target images and standard images. However, for standard images that followed a negative emotional distractor, the veterans showed a heightened N2 amplitude while the controls did not. In addition, impulsivity predicted modulation of the P3b across stimulus conditions, with a greater P3b amplitude associated with an increase in impulsivity. CONCLUSIONS: These findings suggest that veterans showed hyper-responsivity to background information and reduced ERPs to task-relevant information. SIGNIFICANCE: These findings may reflect heightened internal states that create neural noise and a reduced ability to modulate relevant responses.

Rationale, design, and methods of the Autism Centers of Excellence (ACE) network Study of Oxytocin in Autism to improve Reciprocal Social Behaviors (SOARS-B).

OBJECTIVE: To describe the rationale, design, and methods of the Autism Centers of Excellence (ACE) network Study of Oxytocin in Autism to improve Reciprocal Social Behaviors (SOARS-B). METHOD: This phase 2 clinical trial was designed to evaluate the use of intranasal oxytocin treatment to improve social difficulties in individuals with autism spectrum disorder (ASD). In total, 290 participants ages 3 to 17 years with a DSM-5 diagnosis of ASD were enrolled to receive 24 weeks of treatment with either oxytocin or a matched placebo at one of seven collaborating sites. Participants were subsequently treated with open-label oxytocin for 24 additional weeks. Post-treatment assessments were done approximately 4 weeks after treatment discontinuation. Plasma oxytocin and oxytocin receptor gene (OXTR) methylation level were measured at baseline, and week 8, 24 and 36 to explore potential relationships between these biomarkers and treatment response. RESULTS: This report describes the rationale, design, and methods of the SOARS-B clinical trial. CONCLUSIONS: There is a tremendous unmet need for safe and effective pharmacological treatment options that target the core symptoms of ASD. Several studies support the hypothesis that intranasal oxytocin could improve social orienting and the salience of social rewards in ASD, thereby enhancing reciprocal social behaviors. However, due to conflicting results from a number of pilot studies on the prosocial effects of exogenous oxytocin, this hypothesis remains controversial and inconclusive. SOARS-B is the best powered study to date to address this hypothesis and promises to improve our understanding of the safety and efficacy of intranasal oxytocin in the treatment of social deficits in children with ASD.

Metformin add-on vs. antipsychotic switch vs. continued antipsychotic treatment plus healthy lifestyle education in overweight or obese youth with severe mental illness: results from the IMPACT trial.

Antipsychotics are used for many psychiatric conditions in youth. Although developmentally inappropriate weight gain and metabolic abnormalities, which are risk factors for premature cardiovascular mortality, are especially frequent in youth, optimal strategies to reduce pediatric antipsychotic-induced overweight/obesity are unclear. The Improving Metabolic Parameters in Antipsychotic Child Treatment (IMPACT) was a randomized, parallel group, 24-week clinical trial which enrolled overweight/obese, psychiatrically stable youth, aged 8-19 years, with a DSM-IV diagnosis of severe mental illness (schizophrenia spectrum disorder, bipolar spectrum disorder or psychotic depression), at four US universities. All of them had developed substantial weight gain following treatment with a second-generation antipsychotic. The centralized, computer-based randomization system assigned participants to unmasked treatment groups: metformin (MET); antipsychotic switch (aripiprazole or, if already exposed to that drug, perphenazine or molindone; SWITCH); or continued baseline antipsychotic (CONTROL). All participants received healthy lifestyle education. The primary outcome was body mass index (BMI) z-score change from baseline, analyzed using estimated least squares means. Altogether, 127 participants were randomized: 49 to MET, 31 to SWITCH, and 47 to CONTROL. BMI z-score decreased significantly with MET (week 24: -0.09±0.03, p=0.002) and SWITCH (week 24: -0.11±0.04, p=0.003), while it increased non-significantly with CONTROL (week 24: +0.04±0.03). On 3-way comparison, BMI z-score changes differed significantly (p=0.001). MET and SWITCH were each superior to CONTROL (p=0.002), with effect sizes of 0.68 and 0.81 respectively, while MET and SWITCH did not differ. More gastrointestinal problems occurred in MET than in SWITCH or CONTROL. The data safety monitoring board closed the perphenazine-SWITCH arm because 35.2% of subjects discontinued treatment due to psychiatric worsening. These data suggest that pediatric antipsychotic-related overweight/obesity can be reduced by adding metformin or switching to a lower risk antipsychotic. Healthy lifestyle education is not sufficient to prevent ongoing BMI z-score increase.

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.

Cost-Effectiveness of Internet-Based Cognitive-Behavioral Treatment for Bulimia Nervosa: Results of a Randomized Controlled Trial.

OBJECTIVE: To evaluate the cost-effectiveness of Internet-based cognitive-behavioral therapy for bulimia nervosa (CBT-BN) compared to face-to-face delivery of CBT-BN. METHODS: This study is a planned secondary analysis of data from a randomized clinical trial. Participants were 179 adults (98% female, mean age = 28 years) meeting DSM-IV criteria for bulimia nervosa who were randomized to group face-to-face or group Internet-based CBT-BN for 16 sessions during 20 weeks. The cost-effectiveness analysis was conducted from a third-party payor perspective, and a partial societal perspective analysis was conducted to investigate cost-utility (ie, cost per gain in quality-adjusted life-years) and patient out-of-pocket travel-related costs. Net health care costs were calculated from protocol and nonprotocol health care services using third-party payor cost estimates. The primary outcome measure in the clinical trial was abstinence from binge eating and purging, and the trial start and end dates were 2008 and 2016. RESULTS: The mean cost per abstinent patient at posttreatment was $7,757 (95% confidence limit [CL], $4,515, $13,361) for face-to-face and $11,870 (95% CL, $6,486, $22,188) for Internet-based CBT-BN, and at 1-year follow-up was $16,777 (95% CL, $10,298, $27,042) for face-to-face and $14,561 (95% CL, $10,165, $21,028) for Internet-based CBT-BN. There were no statistically significant differences between treatment arms in cost-effectiveness or cost-utility at posttreatment or 1-year follow-up. Out-of-pocket patient costs were significantly higher for face-to-face (mean [95% CL] = $178 [$127, $140]) than Internet-based ($50 [$50, $50]) therapy. CONCLUSIONS: Third-party payor cost-effectiveness of Internet-based CBT-BN is comparable with that of an accepted standard. Internet-based dissemination of CBT-BN may be a viable alternative for patients geographically distant from specialist eating disorder services who have an unmet need for treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00877786​.

A 12-week randomized controlled trial of twice-daily intranasal oxytocin for social cognitive deficits in people with schizophrenia.

Social cognition is impaired in people with schizophrenia and these deficits are strongly correlated with social functioning. Oxytocin is a hypothalamic peptide that contributes to maternal infant bonding and has diverse pro-social effects in adults. This study tested the hypothesis that 12weeks of intranasal oxytocin will improve social cognitive function in outpatients with schizophrenia and schizoaffective disorder. Sixty-eight eligible participants were randomized to oxytocin (24IU twice daily) or placebo. Social cognitive function was assessed using the Emotion Recognition-40, Brüne Theory of Mind, Reading the Mind in the Eyes test, Trustworthiness task and Ambiguous Intentions Hostility Questionnaire at baseline, 6weeks and 12weeks. In addition, social function was assessed using the Specific Levels of Functioning Scale and a role-play test, and psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Fifty-five participants completed the 12-week trial. The study found no evidence for a differential advantage of oxytocin over placebo on social cognition. Among secondary outcomes, there was a modest advantage for oxytocin over placebo on a component of social functioning, although there was also evidence that the placebo group outperformed the oxytocin group on the role-play task. No between-group differences emerged on measures of psychopathology in pre-specified comparisons, but oxytocin showed significant within-group reduction in PANSS negative symptoms and significant between-group improvement in negative symptoms in the schizophrenia subgroup. Further testing is needed to clarify whether oxytocin has therapeutic potential for social cognitive deficits and/or negative symptoms in people with schizophrenia.

A Double-Blind, Randomized Pilot Trial of Chromium Picolinate for Overweight Individuals with Binge-Eating Disorder: Effects on Glucose Regulation.

PURPOSE: Chromium treatment has been shown to improve glucose regulation in some populations. The purpose of this study was to evaluate whether chromium picolinate (CrPic) supplementation improves glucose regulation in overweight individuals with binge-eating disorder (BED). METHODS: In this double-blinded randomized pilot trial, participants (N = 24) were randomized to high (HIGH, 1000 mcg/day, n = 8) or moderate (MOD, 600 mcg/day, n = 9) dose of CrPic or placebo (PL, n = 7) for 6 months. Participants completed an oral glucose tolerance test (OGTT) at baseline, 3 months, and 6 months. Fixed effects models were used to estimate mean change in glucose area under the curve (AUC), insulinAUC, and insulin sensitivity index (ISI). RESULTS: Results revealed a significant group and time interaction (p < 0.04) for glucoseAUC, with glucoseAUC increasing significantly in the PL group (p < 0.02) but decreasing significantly in the MOD group (p < 0.03) at 6 months. InsulinAUC increased significantly over time (main effect, p < 0.02), whereas ISI decreased significantly over time (main effect, p < 0.03). CONCLUSION: As anticipated, a moderate dose of CrPic was associated with improved glycemic control, whereas PL was associated with decreased glycemic control. It was unexpected that the improved glycemic control seen in the MOD dose group was not seen in the HIGH dose group. However, although participants randomized to the HIGH dose group did not have improved glycemic control, they had better glycemic control than participants randomized to the PL group. These findings support the need for larger trials.

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).

An exploratory pilot investigation of neurosteroids and self-reported pain in female Iraq/Afghanistan-era Veterans.

Female Veterans are the most rapidly growing segment of new users of the Veterans Health Administration (VHA), and a significant proportion of female Veterans receiving treatment from VHA primary care providers report persistent pain symptoms. Currently, available data characterizing the neurobiological underpinnings of pain disorders are limited. Preclinical data suggest that neurosteroids may be involved in the modulation of pain symptoms, potentially via actions at gamma-aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) receptors. Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) are neurosteroids that modulate inhibitory GABA receptors and excitatory NMDA receptors, producing complex neuronal effects. Emerging evidence from male Iraq/Afghanistan-era Veterans suggests that reductions in neurosteroid levels are associated with increased pain symptoms and that neurosteroids may be promising biomarker candidates. The current exploratory study thus examined associations between self-reported pain symptoms in 403 female Iraq/Afghanistan-era Veterans and serum DHEAS and DHEA levels. Serum DHEAS levels were inversely correlated with low back pain in female Veterans (Spearman r = -0.103; p = 0.04). Nonparametric analyses indicate that female Veterans reporting moderate/extreme low back pain demonstrated significantly lower DHEAS levels than those reporting no/little low back pain (|Z| = 2.60; p = 0.009). These preliminary findings support a role for DHEAS in pain physiology of low back pain and the rationale for neurosteroid therapeutics in pain analgesia.

Antenatal depression, treatment with selective serotonin reuptake inhibitors, and neonatal brain structure: A propensity-matched cohort study.

The aim of this propensity-matched cohort study was to evaluate the impact of prenatal SSRI exposure and a history of maternal depression on neonatal brain volumes and white matter microstructure. SSRI-exposed neonates (n=27) were matched to children of mothers with no history of depression or SSRI use (n=54). Additionally, neonates of mothers with a history of depression, but no prenatal SSRI exposure (n=41), were matched to children of mothers with no history of depression or SSRI use (n=82). Structural magnetic resonance imaging and diffusion weighted imaging scans were acquired with a 3T Siemens Allegra scanner. Global tissue volumes were characterized using an automatic, atlas-moderated expectation maximization segmentation tool. Local differences in gray matter volumes were examined using deformation-based morphometry. Quantitative tractography was performed using an adaptation of the UNC-Utah NA-MIC DTI framework. SSRI-exposed neonates exhibited widespread changes in white matter microstructure compared to matched controls. Children exposed to a history of maternal depression but no SSRIs showed no significant differences in brain development compared to matched controls. No significant differences were found in global or regional tissue volumes. Additional research is needed to clarify whether SSRIs directly alter white matter development or whether this relationship is mediated by depressive symptoms during pregnancy.

Cost-Effectiveness of Long-Acting Injectable Paliperidone Palmitate Versus Haloperidol Decanoate in Maintenance Treatment of Schizophrenia.

OBJECTIVE: This study assessed the relative cost-effectiveness of haloperidol decanoate (HD), a first-generation long-acting injectable (LAI) antipsychotic, and paliperidone palmitate (PP), a second-generation LAI antipsychotic. METHODS: A double-blind, randomized 18-month clinical trial conducted at 22 clinical research sites in the United States compared the cost-effectiveness of HD and PP among 311 adults with schizophrenia or schizoaffective disorder who had been clinically assessed as likely to benefit from an LAI antipsychotic. Patients were randomly assigned to monthly intramuscular injections of HD (25-200 mg) or PP (39-234 mg) for up to 24 months. Quality-adjusted life years (QALYs) were measured by a schizophrenia-specific algorithm based on the Positive and Negative Syndrome Scale and side-effect assessments; total health care costs were assessed from the perspective of the health system. RESULTS: Mixed-model analysis showed that PP was associated with .0297 greater QALYs over 18 months (p=.03) and with $2,100 more in average costs per quarter for inpatient and outpatient services and medication compared with HD (p<.001). Bootstrap analysis with 5,000 replications showed an incremental cost-effectiveness ratio for PP of $508,241 per QALY (95% confidence interval=$122,390-$1,582,711). Net health benefits analysis showed a .98 probability of greater cost-effectiveness for HD compared with PP at an estimated value of $150,000 per QALY and a .50 probability of greater cost-effectiveness at $500,000 per QALY. CONCLUSIONS: HD was more cost-effective than PP, suggesting that PP's slightly greater benefits did not justify its markedly higher costs, which are likely to fall once the medication's patent expires.

A Randomized Clinical Trial of a Money Management Intervention for Veterans With Psychiatric Disabilities.

OBJECTIVE: The study evaluated an intervention to help veterans with psychiatric disabilities, who face a unique set of challenges concerning money management. METHODS: A randomized clinical trial was conducted of a brief (one to three hours) psychoeducational, recovery-oriented money management intervention called $teps for Achieving Financial Empowerment ($AFE). RESULTS: Analyses revealed no main effects on outcomes of random assignment to $AFE (N=67) or a control condition consisting of usual care (N=77). Veterans who reported using $AFE skills showed significantly lower impulsive buying, more responsible spending, higher rates of engaging in vocational activities, and greater number of work hours compared with veterans in the control condition. CONCLUSIONS: Findings have clinical implications for case management services involving informal money management assistance. Offering veterans with psychiatric disabilities a one-time money management intervention is unlikely to lead to substantial changes. Results imply that efforts to improve psychosocial outcomes among veterans must not only teach but also increase use of money management skills.

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.

Double-blind, placebo-controlled pilot study of adjunctive quetiapine SR in the treatment of PMS/PMDD.

OBJECTIVE: Premenstrual dysphoric disorder (PMDD), a more severe form of premenstrual syndrome (PMS), afflicts 5-8% of reproductive age women and results in significant functional impairment. We conducted a double-blind, placebo-controlled trial of adjunctive quetiapine in patients with PMS/PMDD who had inadequate response to selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor therapy for their symptoms. METHODS: A PMS/PMDD diagnosis was confirmed by 2-month prospective diagnostic assessment of PMS/PMDD using the Prospective Record of the Impact and Severity of Premenstrual Symptoms (PRISM) calendar. Women were randomized equally to receive quetiapine sustained-release (SR) or placebo (25-mg starting dose) during the luteal phase for 3 months. Outcome variables included the Hamilton Depression and Anxiety Scales, Clinical Global Impression Scale, and PRISM. RESULTS: Twenty women were enrolled in the treatment phase. Although the study was underpowered, greater reductions in luteal phase mood ratings were observed in the quetiapine group on the 17-item Hamilton Depression Rating Scale, Clinical Global Impression improvement rating, and PRISM daily score. The quetiapine group showed most improvement in symptoms of mood lability, anxiety, and irritability. CONCLUSION: This small double-blind study suggests that adjunctive treatment with quetiapine SR may be a useful addition to selective serotonin reuptake inhibitor therapy in women with PMS/PMDD by reducing symptoms and improving quality of life.

A pilot randomized placebo-controlled trial of adjunctive aripiprazole for chronic PTSD in US military Veterans resistant to antidepressant treatment.

Many individuals with post-traumatic stress disorder (PTSD) experience persistent symptoms despite pharmacological treatment with antidepressants. Several open-label monotherapy and adjunctive studies have suggested that aripiprazole (a second-generation antipsychotic) may have clinical utility in PTSD. However, there have been no randomized placebo-controlled trials of aripiprazole use for PTSD. We thus conducted a pilot randomized controlled trial of adjunctive aripiprazole versus placebo among Veterans with chronic PTSD serving in the US military since 11 September 2001 to assess the feasibility, safety, tolerability, and therapeutic potential of aripiprazole. Sixteen Veterans were randomized, and 14 completed at least 4 weeks of the study; 12 completed the entire 8-week trial. Outcome measures included the Clinician-Administered PTSD Scale (CAPS), PTSD Checklist, Beck Depression Inventory, Second Edition, and Positive and Negative Syndrome Scale scores. Aripiprazole was well-tolerated in this cohort, and improvements in CAPS, PTSD Checklist, Beck Depression Inventory, Second Edition, and Positive and Negative Syndrome Scale scores were as hypothesized. Although CAPS change scores did not reach statistical significance, aripiprazole outperformed placebo by 9 points on the CAPS in the last observation carried forward analysis compared with the placebo group (n = 7 per group), and by 20 points in the group randomized to aripiprazole that completed the entire study (n = 5) compared with the placebo group (n = 7). Results suggest promise for aripiprazole as an adjunctive strategy for the treatment of PTSD.

Exploratory investigation of biomarker candidates for suicide in schizophrenia and bipolar disorder.

BACKGROUND: Clozapine and lithium increase neurosteroids in rodents, and both drugs demonstrate antisuicidal actions. We therefore hypothesized that neurosteroid levels may be reduced in patients with schizophrenia or bipolar disorder who completed suicide. AIMS: To investigate neurosteroid levels in the parietal cortex and posterior cingulate in schizophrenia and bipolar patients who died by suicide, and compare them with patients with these disorders who died of other causes. METHOD: Neurosteroid levels were quantified by gas chromatography/mass spectrometry in the parietal cortex and posterior cingulate. Mann-Whitney analyses were conducted in exploratory post hoc analyses to investigate neurosteroids as possible biomarker candidates for suicide. RESULTS: The study showed that pregnenolone was significantly decreased in the parietal cortex in the combined group of patients with schizophrenia or bipolar disorder who died by suicide (n = 13) compared with patients with these disorders who died of other causes (n = 17, p = .02). Pregnenolone levels were also lower in the parietal cortex in the individual group of schizophrenia patients who died by suicide (n = 4) compared with schizophrenia patients who died of other causes (n = 11) p = .04). CONCLUSION: Pregnenolone alterations may be relevant to the neurobiology of suicide in schizophrenia and bipolar disorder.

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. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.

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.