Faculty Bibliography

OBJECTIVE:The purpose of this open-label study was to examine the effects of long-acting methylphenidate (MPH) treatment on irritability and related emotional symptoms associated with disruptive mood dysregulation disorder (DMDD) in youth with comorbid attention-deficit/hyperactivity disorder (ADHD). METHODS:), with weekly dosing increases until a therapeutic dose was reached. Repeated measures t-tests were used to compare pre- and posttreatment ratings of primary and secondary measures. The primary outcome was self-report irritability. Secondary outcomes included parent and child ratings of emotional frequency, emotional lability, and negative affect (NA). Multiple regression was used to examine the impact baseline hyperactivity, age, gender, race, socioeconomic status, or comorbid diagnosis had on treatment outcomes. RESULTS:Significant improvements (medium to large effect sizes) in child-rated irritability as well as parent and child ratings of emotional lability, NA, and anger were found. As anticipated, ADHD symptoms also improved. While a majority of the sample saw improvement in child-rated irritability (71%), symptoms worsened a small proportion (19%), and an even smaller portion experienced no change (10%). No demographics, psychiatric comorbidities, or severity of ADHD symptoms influenced treatment outcomes. CONCLUSIONS:Study findings suggest that MPH treatment significantly improved mood and emotional symptoms associated with DMDD comorbid with ADHD. These findings, coupled with good tolerability in this open-label pilot study supports further research into the use of MPH as a first-line treatment for DMDD. Future work examining MPH treatment of youth with DMDD with and without comorbid ADHD is needed.

Repeated presentations of a previously conditioned stimulus lead to a new form of learning known as extinction, which temporarily alters the response to the original stimulus. Previous studies have shown that the consolidation of extinction memory requires de novo protein synthesis. However, the role of specific nodes of translational control in extinction is unknown. Using auditory threat conditioning in mice, we investigated the role of mechanistic target of rapamycin complex 1 (mTORC1) and its effector p70 S6 kinase 1 (S6K1) in the extinction of auditory threat conditioning. We found that rapamycin attenuated the consolidation of extinction memory. In contrast, genetic deletion and pharmacological inhibition of S6K1, a downstream effector of mTORC1, blocked within-session extinction, indicating a role for S6K1 independent of protein synthesis. Indeed, the activation of S6K1 during extinction required extracellular signal-regulated kinase (ERK) activation in the basolateral nucleus of the amygdala (BLA) and was necessary for increased phosphorylation of the GluA1 (Thr840) subunit of the AMPA receptor following extinction training. Mice exposed to brief uncontrollable stress showed impaired within-session extinction as well as a downregulation of ERK and S6K1 signaling in the amygdala. Finally, using fiber photometry we were able to record calcium signals in vivo, and we found that inhibition of S6K1 reduces extinction-induced changes in neuronal activity of the BLA. These results implicate a novel ERK-S6K1-GluA1 signaling cascade critically involved in extinction.

To investigate the effect of the count of traumatizing event (TE) types on post-trauma mental health, several studies have compared posttraumatic stress disorder (PTSD) severity between individuals experiencing one versus multiple TE types. However, the validity of these studies depends on the establishment of measurement invariance of the construct(s) of interest. The current study examined the stability of the most optimal PTSD Model symptom cluster constructs (assessed by the PTSD Checklist for DSM-5 [PCL-5]) across subgroups experiencing one versus multiple TE types. The sample included university students (n = 556) endorsing at least one TE (Stressful Life Events Screening Questionnaire). Using data from the entire sample, results suggest that the PCL-5-assessed Hybrid Model provided a significantly better fit compared to other models. Results also indicated invariance of factor loadings (metric), and intercepts (scalar) for the PCL-5-assessed Hybrid Model factors across subgroups endorsing one (n = 191) versus multiple TE types (n = 365). Our findings thus support the stability, applicability, and meaningful comparison of the PCL-assessed Hybrid Model factor structure (including subscale severity scores) across subgroups experiencing one versus multiple TE types.

The objective of this study is to compare the efficacy and cost of specialised individually delivered parent training (PT) for preschool children with attention-deficit/hyperactivity disorder (ADHD) against generic group-based PT and treatment as usual (TAU). This is a multi-centre three-arm, parallel group randomised controlled trial conducted in National Health Service Trusts. The participants included in this study were preschool children (33-54 months) fulfilling ADHD research diagnostic criteria. New Forest Parenting Programme (NFPP)-12-week individual, home-delivered ADHD PT programme; Incredible Years (IY)-12-week group-based, PT programme initially designed for children with behaviour problems were the interventions. Primary outcome-Parent ratings of child's ADHD symptoms (Swanson, Nolan & Pelham Questionnaire-SNAP-IV). Secondary outcomes-teacher ratings (SNAP-IV) and direct observations of ADHD symptoms and parent/teacher ratings of conduct problems. NFPP, IY and TAU outcomes were measured at baseline (T1) and post treatment (T2). NFPP and IY outcomes only were measured 6 months post treatment (T3). Researchers, but not therapists or parents, were blind to treatment allocation. Analysis employed mixed effect regression models (multiple imputations). Intervention and other costs were estimated using standardized approaches. NFPP and IY did not differ on parent-rated SNAP-IV, ADHD combined symptoms [mean difference - 0.009 95% CI (- 0.191, 0.173), p = 0.921] or any other measure. Small, non-significant, benefits of NFPP over TAU were seen for parent-rated SNAP-IV, ADHD combined symptoms [- 0.189 95% CI (- 0.380, 0.003), p = 0.053]. NFPP significantly reduced parent-rated conduct problems compared to TAU across scales (p values < 0.05). No significant benefits of IY over TAU were seen for parent-rated SNAP, ADHD symptoms [- 0.16 95% CI (- 0.37, 0.04), p = 0.121] or parent-rated conduct problems (p > 0.05). The cost per family of providing NFPP in the trial was significantly lower than IY (£1591 versus £2103). Although, there were no differences between NFPP and IY with regards clinical effectiveness, individually delivered NFPP cost less. However, this difference may be reduced when implemented in routine clinical practice. Clinical decisions should take into account parental preferences between delivery approaches.

Previous studies have associated Attention-Deficit/Hyperactivity Disorder (ADHD) with a maturational lag of brain functional networks. Functional connectivity of the human brain changes from primarily local to more distant connectivity patterns during typical development. Under the maturational lag hypothesis, we expect children with ADHD to exhibit increased local connectivity and decreased distant connectivity compared with neurotypically developing (ND) children. We applied a graph-theory method to compute local and distant connectivity levels and cross-sectionally compared them in a sample of 120 children with ADHD and 120 age-matched ND children (age range = 7-17 years). In addition, we measured if potential group differences in local and distant connectivity were stable across the age range considered. Finally, we assessed the clinical relevance of observed group differences by correlating the connectivity levels and ADHD symptoms severity separately for each group. Children with ADHD exhibited more local connectivity than age-matched ND children in multiple brain regions, mainly overlapping with default mode, fronto-parietal and ventral attentional functional networks (p < .05- threshold free-cluster enhancement-family-wise error). We detected an atypical developmental pattern of local connectivity in somatomotor regions, that is, decreases with age in ND children, and increases with age in children with ADHD. Furthermore, local connectivity within somatomotor areas correlated positively with clinical severity of ADHD symptoms, both in ADHD and ND children. Results suggest an immature functional state of multiple brain networks in children with ADHD. Whereas the ADHD diagnosis is associated with the integrity of the system comprising the fronto-parietal, default mode and ventral attentional networks, the severity of clinical symptoms is related to atypical functional connectivity within somatomotor areas. Additionally, our findings are in line with the view of ADHD as a disorder of deviated maturational trajectories, mainly affecting somatomotor areas, rather than delays that normalize with age.

Despite high rates of exposure to community violence among Latino youth in urban communities, there is considerable variability in individual outcomes. This study examined (a) associations between coping and indices of Latino culture, (b) main effects of active/avoidant coping on psychopathology, and (c) whether coping moderates the impact of violence exposure on mental health in Latino youth. Participants included 168 Latino youth (56% female; ages 11-14) that took part in a short-term longitudinal study. Results indicate that youth acculturation was positively associated with active coping, but enculturation level and immigrant status were not associated with coping. Structural equation models suggested that active coping was negatively associated with internalizing problems (p = .046) while avoidant coping was positively associated with internalizing problems (p = .013) and posttraumatic stress symptoms (p = .024). Moderation analyses revealed that violence exposure was more strongly associated with internalizing problems as reliance on avoidance coping increased. However, at high levels of violence exposure, a greater reliance on active coping was related to increased posttraumatic stress problems. Findings suggest that consideration of the specific stressor, level of stress exposure, and mental health problem-type may be crucial in determining the effectiveness of a coping strategy. Implications for future research and intervention are discussed.

Sleep alterations associated with adulthood ADHD are poorly understood. Here, we conducted the first meta-analysis of sleep studies in adults with ADHD. Based on a pre-registered protocol (PROSPERO-CRD42017065407), we searched Pubmed, Ovid and Web of Knowledge databases through August 3rd, 2017, with no language or publication type restrictions, and contacted study authors for unpublished data/information. From a pool of 8812 references, we retained 13 studies. Random-effects models were performed and study quality was rated using the Newcastle-Ottawa Scale. Compared to adults without ADHD, those with ADHD significantly differed in seven out of nine subjective parameters (Standardized Mean Difference, SMD, ranging from 0.56 to 1.55) and two out of five actigraphic parameters [SMD (95% CI): sleep onset latency: 0.80 (0.46-1.14); sleep efficiency: -0.68 (-1.03, -0.34)]. No significant differences were detected for polysomnographic parameters. We conclude that, whereas subjectively reported sleep problems are significantly associated with ADHD in adults and should be systematically screened during the clinical interview, additional research is needed to understand if they are underpinned by objective sleep alterations.

INTRODUCTION/BACKGROUND:Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder, characterized by age inappropriate and impairing levels of inattention and/or hyperactivity/impulsivity. Pharmacotherapy is an important part of the ADHD multimodal treatment. The extent to which ADHD is pharmacologically over or under treated worldwide is controversial. We aimed to estimate the pooled worldwide rate of ADHD pharmacological treatment in individuals with and without the disorder. METHOD AND ANALYSIS/UNASSIGNED:We will include published or unpublished studies reporting the rates of ADHD pharmacological treatment in participants with and without ADHD of any age group. Population-based, cohort, or follow-up studies, as well as data from insurance health system and third-party reimbursements will be eligible. Searches will be performed in a large number of electronic databases, including Medline, Embase, CINAHL, Cochrane, PsycINFO, Web of Science, and Scopus. The primary outcome will be the prevalence of ADHD pharmacological treatment in individuals with ADHD and without ADHD. Two independent reviewers will perform the screening, and data extraction process. Study quality/bias will be assessed with the Newcastle-Ottawa scale by 2 independent reviewers. To test the robustness of the findings, we will perform a series of sensitivity and meta-regression analysis. Analyses will be performed with R and STATA software. ETHICS AND DISSEMINATION/UNASSIGNED:No IRB approval will be necessary. The results of this systematic review and meta-analysis will be presented at international conferences and published in peer-reviewed journals. REGISTRATION AND STATUS/UNASSIGNED:PROSPERO 2018 CRD42018085233.

BACKGROUND:The contents of traditional communication media and new internet social media reflect the interests of society. However, certain barriers and a lack of attention towards mental disorders have been previously observed. OBJECTIVE:The objective of this study is to measure the relevance of influential American mainstream media outlets for the distribution of psychiatric information and the interest generated in these topics among their Twitter followers. METHODS:We investigated tweets generated about mental health conditions and diseases among 15 mainstream general communication media outlets in the United States of America between January 2007 and December 2016. Our study strategy focused on identifying several psychiatric terms of primary interest. The number of retweets generated from the selected tweets was also investigated. As a control, we examined tweets generated about the main causes of death in the United States of America, the main chronic neurological degenerative diseases, and HIV. RESULTS:In total, 13,119 tweets about mental health disorders sent by the American mainstream media outlets were analyzed. The results showed a heterogeneous distribution but preferential accumulation for a select number of conditions. Suicide and gender dysphoria accounted for half of the number of tweets sent. Variability in the number of tweets related to each control disease was also found (5998). The number of tweets sent regarding each different psychiatric or organic disease analyzed was significantly correlated with the number of retweets generated by followers (1,030,974 and 424,813 responses to mental health disorders and organic diseases, respectively). However, the probability of a tweet being retweeted differed significantly among the conditions and diseases analyzed. Furthermore, the retweeted to tweet ratio was significantly higher for psychiatric diseases than for the control diseases (odds ratio 1.11, CI 1.07-1.14; P<.001). CONCLUSIONS:American mainstream media outlets and the general public demonstrate a preferential interest for psychiatric diseases on Twitter. The heterogeneous weights given by the media outlets analyzed to the different mental health disorders and conditions are reflected in the responses of Twitter followers.