Faculty Bibliography

BACKGROUND: Lisdexamfetamine (LDX) is a prodrug and consists of an active moiety, d-amphetamine, bound to lysine. Clinically, d-amphetamine becomes available postcleavage of the prodrug in the blood stream. Clinical effects of LDX in attention-deficit/hyperactivity disorder (ADHD) have been shown to persist up to 14 hours; however, pharmacokinetic (PK) data of LDX and amphetamine in ADHD adults are not currently available. OBJECTIVES: (1) To examine PK data of LDX and d-amphetamine in plasma and (2) to compare such PK data with Time-Sensitive ADHD Symptom Scale (TASS) ratings (PK vs. pharmacodynamic [PD]). METHODS: Plasma d-amphetamine/LDX levels and TASS ratings were obtained immediately before morning dosing and then 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdosing in 21 adults with ADHD treated with 5 weeks of single-blind LDX up to 70 mg/day (after 1 week single-blind placebo). ADHD Rating Scale scores were obtained at the beginning of the visit, before morning dosing. RESULTS: LDX levels peaked at 1.5 hours after administration (Tmax) and then rapidly declined (levels were negligible at 6 hours and area under the plasma concentration versus time curve, AUC = 45.9, Cmax = 25.0, and half-life [t1/2] = 0.5 hours). Levels of d-amphetamine peaked at (Tmax) 4.4 hours and then slowly declined (AUC = 641.6, Cmax = 67.9, and t1/2 = 17.0 hours). No statistically significant correlations were seen between d-amphetamine levels and TASS scores. CONCLUSIONS: (1) Prodrug LDX levels peaked fairly rapidly and declined, while d-amphetamine levels peaked 3 hours later than LDX levels and persisted throughout the day and (2) the absence of PK/PD correlations between PK data and TASS ratings may be due to the subjects being tested in a controlled nonattention demanding environment.

Although DSM-5 stipulates that symptoms of attention-deficit hyperactivity disorder (ADHD) are the same for adults as children, clinical observations suggest that adults have more diverse deficits than children in higher-level executive functioning and emotional control. Previous psychometric analyses to evaluate these observations have been limited in ways addressed in the current study, which analyzes the structure of an expanded set of adult ADHD symptoms in three pooled US samples: a national household sample, a sample of health plan members, and a sample of adults referred for evaluation at an adult ADHD clinic. Exploratory factor analysis found four factors representing executive dysfunction/inattention (including, but not limited to, all the DSM-5 inattentive symptoms, with non-DSM symptoms having factor loadings comparable to those of DSM symptoms), hyperactivity, impulsivity, and emotional dyscontrol. Empirically-derived multivariate symptom profiles were broadly consistent with the DSM-5 inattentive-only, hyperactive/impulsive-only, and combined presentations, but with inattention including executive dysfunction/inattention and hyperactivity-only limited to hyperactivity without high symptoms of impulsivity. These results show that executive dysfunction is as central as DSM-5 symptoms to adult ADHD, while emotional dyscontrol is more distinct but nonetheless part of the combined presentation of adult ADHD.

Default mode network (DMN) deactivation has been shown to be functionally relevant for goal-directed cognition. In this study, the DMN's role during olfactory processing was investigated using two complementary functional magnetic resonance imaging (fMRI) paradigms with identical timing, visual-cue stimulation, and response monitoring protocols. Twenty-nine healthy, non-smoking, right-handed adults (mean age = 26 +/- 4 years, 16 females) completed an odor-visual association fMRI paradigm that had two alternating odor + visual and visual-only trial conditions. During odor + visual trials, a visual cue was presented simultaneously with an odor, while during visual-only trial conditions the same visual cue was presented alone. Eighteen of the twenty-nine participants (mean age = 27.0 +/- 6.0 years, 11 females) also took part in a control no-odor fMRI paradigm that consisted of a visual-only trial condition which was identical to the visual-only trials in the odor-visual association paradigm. Independent Component Analysis (ICA), extended unified structural equation modeling (euSEM), and psychophysiological interaction (PPI) were used to investigate the interplay between the DMN and olfactory network. In the odor-visual association paradigm, DMN deactivation was evoked by both the odor + visual and visual-only trial conditions. In contrast, the visual-only trials in the no-odor paradigm did not evoke consistent DMN deactivation. In the odor-visual association paradigm, the euSEM and PPI analyses identified a directed connectivity between the DMN and olfactory network which was significantly different between odor + visual and visual-only trial conditions. The results support a strong interaction between the DMN and olfactory network and highlights the DMN's role in task-evoked brain activity and behavioral responses during olfactory processing. Hum Brain Mapp, 2016. (c) 2016 Wiley Periodicals, Inc.

To identify various biopsychosocial risk factors associated with suicidality in juvenile detention facilities and the effectiveness of suicide prevention protocols currently in use. Medical literature searches were conducted using databases like Pub Med, Ovid, and Google Scholar to identify studies conducted in and outside of United States. The prevalence of suicide among youth imprisoned at detention facilities has risen. Psychiatric disorders are common among such population, making them vulnerable to suicidal tendencies. Suicide risk screening within first 24 h of admission to the detention facility has shown to lower the risk of suicide. Identification of high risk individuals and their further psychiatric assessment is advocated. Much of work with regards to screening tools and instruments is underway and further study is required to get a better understanding.

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.

The New Forest Parenting Programme (NFPP) is a parenting program developed for parents who have a child with attention-deficit hyperactivity disorder (ADHD). It is a manualized program that is delivered in a parent's home over 8 weeks, or in a group format, or through a self-help manual. Three randomized controlled trials have been carried out in the United Kingdom. The NFPP group has adapted the program according to feedback from parents and therapists, and for use with different populations, both within the United Kingdom and internationally. The first international trial took place in New York, United States. Trials in Denmark, Hong Kong, and Japan followed. More recently, a trial of the self-help manual has been carried out in mainland China. This paper will outline the adaptions that were needed in order to be able to deliver the program in different countries with their own expectations of parenting, culture, and language. Training had to be differently focused; manuals and handouts had to be revised, translated and back-translated; and supervision had to be delivered at a distance to maintain the fidelity of the program. The international group will outline their experience of running trials in their own countries with the NFPP in a face-to-face format (Denmark), a group format (Hong Kong and Japan), and a self-help format (mainland China).

Infants become increasingly helpful during the second year. We investigated experimentally whether adults' explicit scaffolding influences this development. Infants (N = 69, 13-18 months old) participated in a series of simple helping tasks. Half of infants received explicit scaffolding (encouragement and praise), whereas the other half did not. Among younger infants (below 15 months), infants who received explicit scaffolding helped twice as often as infants in the control group, and also helped more on several subsequent trials when no scaffolding was provided. As predicted, older infants were not affected by explicit scaffolding. These results demonstrate the influence of social experiences in early helping, but also how the effects of scaffolding may depend on the developmental level of the child. Less explicit forms of scaffolding may be effective when children are older. (PsycINFO Database Record

OBJECTIVES: We examined whether the cut-point 10 for the Patient Health Questionnaire-9 (PHQ9) depression screen used in primary care populations is equally valid for Mexicans (M), Ecuadorians (E), Puerto Ricans (PR) and non-Hispanic whites (W) from inner-city hospital-based primary care clinics; and whether stressful life events elevate scores and the probability of major depressive disorder (MDD). METHODS: Over 18-months, a sample of persons from hospital clinics with a positive initial PHQ2 and a subsequent PHQ9 were administered a stressful life event questionnaire and a Structured Clinical Interview to establish an MDD diagnosis, with oversampling of those between 8 and 12: (n=261: 75 E, 71 M, 51 PR, 64 W). For analysis, the sample was weighted using chart review (n=368) to represent a typical clinic population. Receiver Operating Characteristics analysis selected cut-points maximizing sensitivity (Sn) plus specificity (Sp). RESULTS: The optimal cut-point for all groups was 13 with the corresponding Sn and Sp estimates for E=(Sn 73%, Sp 71%), M=(76%, 81%), PR=(81%, 63%) and W=(80%, 74%). Stressful life events impacted screen scores and MDD diagnosis. CONCLUSIONS: Elevating the PHQ9 cut-point for inner-city Latinos as well as whites is suggested to avoid high false positive rates leading to improper treatment with clinical and economic consequences.

PURPOSE/OBJECTIVE:Our study aimed to examine psychometric properties and cross-cultural utility of the Behavior Assessment System for Children-2, Parent Rating Scale-Child (BASC-2 PRS-C) in Korean children. MATERIALS AND METHODS/METHODS:Two study populations were recruited: a general population sample (n=2115) of 1st to 6th graders from 16 elementary schools and a clinical population (n=219) of 6-12 years old from 5 child psychiatric clinics and an epidemiological sample of autism spectrum disorder. We assessed the validity and reliability of the Korean version of BASC-2 PRS-C (K-BASC-2 PRS-C) and compared subscales with those used for US populations. RESULTS:Our results indicate that the K-BASC-2 PRS-C is a valuable instrument with reliability and validity for measuring developmental psychopathology that is comparable to those in Western population. However, there were some differences noted in the mean scores of BASC-2 PRS-C between Korean and US populations. CONCLUSION/CONCLUSIONS:K-BASC-2 PRS-C is an effective and useful instrument with psychometric properties that permits measurement of general developmental psychopathology. Observed Korean-US differences in patterns of parental reports of children's behaviors indicate the importance of the validation, standardization and cultural adaptation for tools assessing psychopathology especially when used in populations different from those for which the instrument was originally created.