Faculty Bibliography

OBJECTIVE:To promote integrated general medical care for individuals with serious mental illness, the New York State Office of Mental Health (OMH) established regulations allowing specialty mental health clinics to provide Medicaid-reimbursable health monitoring (HM) and health physicals (HP). This study examined clinics' enrollment in this program to understand its potential to reach individuals with serious mental illness. METHODS:Information on enrollment and characteristics of clinics (N=500) was obtained from OMH administrative databases. Clinic enrollment in the HM/HP program was examined for the program's first five years (2010-2015). Logistic regression models accounting for the clustering of multiple clinics within agencies were used to examine characteristics associated with enrollment. RESULTS:A total of 291 of 500 (58%) licensed clinics in New York State in 2015 enrolled in the HM/HP program, potentially reaching 62% of all Medicaid enrollees with serious mental illness seen in specialty mental health clinics in the state. State-operated clinics were required to participate, and had 91% enrollment. Over half of hospital-affiliated and freestanding mental health clinics elected to enroll (53% and 54%, respectively). In adjusted models, enrollment was higher among freestanding clinics compared with hospital-affiliated clinics, higher in larger than smaller clinics, and higher in county-operated than in private nonprofit clinics. CONCLUSIONS:The high level of enrollment in the HM/HP program indicates strong interest among mental health clinics in providing general medical care services. However, supplemental policies may be needed to extend the program to areas of the mental health system where barriers to general medical care services are highest.

BACKGROUND:Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) are frequently co-occurring and highly heritable mental health conditions. We hypothesized that BPD cases with an early age of onset (≤21 years old) would be particularly likely to show genetic covariation with ADHD. METHODS:Genome-wide association study data were available for 4609 individuals with ADHD, 9650 individuals with BPD (5167 thereof with early-onset BPD), and 21,363 typically developing controls. We conducted a cross-disorder genome-wide association study meta-analysis to identify whether the observed comorbidity between ADHD and BPD could be due to shared genetic risks. RESULTS:) on chromosome 5 in the ADCY2 gene. Additional nominally significant regions identified contained known expression quantitative trait loci with putative functional consequences for NT5DC1, NT5DC2, and CACNB3 expression, whereas functional predictions implicated ABLIM1 as an allele-specific expressed gene in neuronal tissue. CONCLUSIONS:The single nucleotide polymorphism-based genetic correlation between ADHD and BPD is substantial, significant, and consistent with the existence of genetic overlap between ADHD and BPD, with potential differential genetic mechanisms involved in early and later BPD onset.

The newly introduced Mixed Features Specifier of Major Depressive Episode and Disorder (MDE/MDD) is especially challenging in terms of pharmacological management. Prior to the publication of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, the symptoms of the mixed features specifier were intradepressive hypomanic symptoms, always and only associated with bipolar disorder (BD). Intradepressive hypomanic symptoms, mostly referred to as depressive mixed states (DMX), have been poorly characterized, and their treatment offers significant challenges. To understand the diagnostic context of DMX, we trace the nosological changes and collocation of intradepressive hypomanic symptoms, and examine diagnostic and prognostic implications of such mixed features. One of the reasons so little is known about the treatment of DMX is that depressed patients with rapid cycling, substance abuse disorder, and suicidal ideation/attempts are routinely excluded from clinical trials of antidepressants. The exclusion of DMX patients from clinical trials has prevented an assessment of the safety and tolerability of short- and long-term use of antidepressants. Therefore, the generalization of data obtained in clinical trials for unipolar depression to patients with intradepressive hypomanic features is inappropriate and methodologically flawed. A selective review of the literature shows that antidepressants alone have limited efficacy in DMX, but they have the potential to induce, maintain, or worsen mixed features during depressive episodes in BD. On the other hand, preliminary evidence supports the effective use of some atypical antipsychotics in the treatment of DMX.

Studies have demonstrated inefficient use of antecedent-focused emotion regulation strategies in children with ADHD attention-deficit/hyperactivity disorder (ADHD). In the current study we tested for the first time if ADHD is also associated with difficulties in response-focused strategies by measuring the ability to override action tendencies induced by emotional information. Performance data on a computer-based approach-avoidance paradigm of 28 children with ADHD and 38 typically developing children between 8 and 15 years of age were analyzed, by comparing a congruent condition in which they were instructed to approach positive and avoid negative pictures and an incongruent condition where they had to override these automatic reactions and approach negative and avoid positive pictures. Children also rated the valence and salience of the pictures. Children with ADHD and typically developing children rated the emotional valence of the pictures appropriately and similarly, while positive pictures were rated as more arousing by children with ADHD. Solid congruency effects were found indicating that the task measured response-focused emotion regulation; however groups did not differ in this respect. Our findings do not support a deficit in emotion regulation in ADHD in terms of the ability to override natural tendencies to approach positive and avoid negative pictures.

Specific treatments targeting adolescents with substance use disorders (SUDs) have been developed over the last couple of decades. Despite these developmentally tailored treatments, long-term abstinence rates remain relatively low among adolescents receiving care. Research over the last decade has increasingly focused on adolescents with comorbid substance use and psychiatric disorders, in recognition of the barriers caused by inadequate treatment of co-occurring psychiatric disorders. Treatments targeting dually diagnosed youth are now regarded as essential to improving SUD treatment outcomes, but remain underutilized. A variety of treatment modalities such as behavioral therapy, family therapy, 12-step groups, motivational interviewing, contingency management, and combinations of these interventions have been modified for adolescents. In this article, we review the research on these treatments, as they apply to dually diagnosed youth. Furthermore, we explore the evidence for various treatments targeting comorbid SUD, specific to the presence of externalizing or internalizing disorders. The current evidence base supports the importance of integrated treatment targeting both SUD and psychiatric disorders simultaneously. High-quality treatment programs offering combinations of behavioral and family therapy, particularly with motivational interviewing and contingency management, are particularly well supported. In addition, we review various psychotropic medication treatments that have also been studied in conjunction with adolescent SUD treatment. Finally, we review research on post-treatment, supportive care that has been shown to improve long-term SUD outcomes. Recently conceptualized modular treatments, which offer personalized combinations of evidence-based treatments for specific disorders, have been proposed as a means of improving outcomes. Future research on modular programs must test the efficacy of individualized treatments when applied to combinations of psychiatric and SUDs in adolescents.

Psychophysiological interaction (PPI) is a widely used regression-based method to study connectivity changes in different experimental conditions. A PPI effect is generated by point-by-point multiplication of a psychological variable (experimental design) and a physiological variable (time series of a seed region). If the psychological variable is non-centered with a constant component, the constant component will add a physiological variable to the PPI term. The physiological component would in theory be accounted for by the physiological main effect in the model. But due to imperfect deconvolution and convolution with hemodynamic response function, the physiological component in PPI may no longer be exactly the same as the physiological main effect. This issue was illustrated by analyzing two block-designed fMRI datasets, one simple visual checkerboard task and a set of different tasks designed to activate different hemispheres. When PPI was calculated with deconvolution but without centering, significant results were usually observed between regions that are known to have baseline functional connectivity. These results could be suppressed by simply centering the psychological variable when calculating the PPI term or adding a deconvolve-reconvolved version of the physiological covariate. The PPI results with centering and with deconvolve-reconvolved physiological covariate are consistent with an explicit test for differences in coupling between conditions. It was, therefore, suggested that centering of the psychological variable or the addition of a deconvolve-reconvolved covariate is necessary for PPI analysis. Hum Brain Mapp 38:1723-1740, 2017. © 2017 Wiley Periodicals, Inc.

Antidepressant medications are commonly used to treat depression, but only about 30% of patients reach remission with any single first-step antidepressant. If the first-step treatment fails, response and remission rates at subsequent steps are even more limited. The literature on biomarkers for treatment response is largely based on secondary analyses of studies designed to answer primary questions of efficacy, rather than on a planned systematic evaluation of biomarkers for treatment decision. The lack of evidence-based knowledge to guide treatment decisions for patients with depression has lead to the recognition that specially designed studies with the primary objective being to discover biosignatures for optimizing treatment decisions are necessary. Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) is one such discovery study. Stage 1 of EMBARC is a randomized placebo controlled clinical trial of 8 week duration. A wide array of patient characteristics is collected at baseline, including assessments of brain structure, function and connectivity along with electrophysiological, biological, behavioral and clinical features. This paper reports on the data analytic strategy for discovering biosignatures for treatment response based on Stage 1 of EMBARC.

BACKGROUND:Time-limited, early-life exposures to institutional deprivation are associated with disorders in childhood, but it is unknown whether effects persist into adulthood. We used data from the English and Romanian Adoptees study to assess whether deprivation-associated adverse neurodevelopmental and mental health outcomes persist into young adulthood. METHODS:The English and Romanian Adoptees study is a longitudinal, natural experiment investigation into the long-term outcomes of individuals who spent from soon after birth to up to 43 months in severe deprivation in Romanian institutions before being adopted into the UK. We used developmentally appropriate standard questionnaires, interviews completed by parents and adoptees, and direct measures of IQ to measure symptoms of autism spectrum disorder, inattention and overactivity, disinhibited social engagement, conduct or emotional problems, and cognitive impairment (IQ score <80) during childhood (ages 6, 11, and 15 years) and in young adulthood (22-25 years). For analysis, Romanian adoptees were split into those who spent less than 6 months in an institution and those who spent more than 6 months in an institution. We used a comparison group of UK adoptees who did not experience deprivation. We used mixed-effects regression models for ordered-categorical outcome variables to compare symptom levels and trends between groups. FINDINGS:Romanian adoptees who experienced less than 6 months in an institution (n=67 at ages 6 years; n=50 at young adulthood) and UK controls (n=52 at age 6 years; n=39 at young adulthood) had similarly low levels of symptoms across most ages and outcomes. By contrast, Romanian adoptees exposed to more than 6 months in an institution (n=98 at ages 6 years; n=72 at young adulthood) had persistently higher rates than UK controls of symptoms of autism spectrum disorder, disinhibited social engagement, and inattention and overactivity through to young adulthood (pooled p<0·0001 for all). Cognitive impairment in the group who spent more than 6 months in an institution remitted from markedly higher rates at ages 6 years (p=0·0001) and 11 years (p=0·0016) compared with UK controls, to normal rates at young adulthood (p=0·76). By contrast, self-rated emotional symptoms showed a late-onset pattern with minimal differences versus UK controls at ages 11 years (p=0·0449) and 15 years (p=0·17), and then marked increases by young adulthood (p=0·0005), with similar effects seen for parent ratings. The high deprivation group also had a higher proportion of people with low educational achievement (p=0·0195), unemployment (p=0·0124), and mental health service use (p=0·0120, p=0·0032, and p=0·0003 for use when aged <11 years, 11-14 years, and 15-23 years, respectively) than the UK control group. A fifth (n=15) of individuals who spent more than 6 months in an institution were problem-free at all assessments. INTERPRETATION:Notwithstanding the resilience shown by some adoptees and the adult remission of cognitive impairment, extended early deprivation was associated with long-term deleterious effects on wellbeing that seem insusceptible to years of nurturance and support in adoptive families. FUNDING:Economic and Social Research Council, Medical Research Council, Department of Health, Jacobs Foundation, Nuffield Foundation.

Disgust plays a crucial role in the avoidance of pathogen threats. In many species, body odors provide important information related to health and disease, and body odors are potent elicitors of disgust in humans. With this background, valid assessments of body odor disgust sensitivity are warranted. In the present article, we report the development and psychometric validation of the Body Odor Disgust Scale (BODS), a measure suited to assess individual differences in disgust reaction to a variety of body odors. Collected data from 3 studies (total n = 528) show that the scale can be used either as a unidimensional scale or as a scale that reflects two hypothesized factors: sensitivity to one's own body odors versus those of others. Guided by our results, we reduced the scale to 12 items that capture the essence of these 2 factors. The final version of the BODS shows an excellent internal consistency (Cronbach's αs > 0.9). The BODS subscales show convergent validity with other general disgust scales, as well as with other olfactory functions measures and with aspects of personality that are related to pathogen avoidance. A fourth study confirmed the construct validity of the BODS and its measurement invariance to gender. Moreover, we found that, compared with other general disgust scales, the BODS is more strongly related to perceived vulnerability to disease. The BODS is a brief and valid assessment of trait body odor disgust sensitivity.