Faculty Bibliography

Serotonergic medications can mitigate the negative affective biases in disorders such as depression or anxiety, but the neural mechanism by which this occurs is largely unknown. In line with recent advances demonstrating that negative affective biases may be driven by specific medial prefrontal-amygdala circuitry, we asked whether serotonin manipulation can alter affective processing within a key dorsal medial prefrontal-amygdala circuit: the putative human homologue of the rodent prelimbic-amygdala circuit or 'aversive amplification' circuit. In a double-blind, placebo-controlled crossover pharmaco-fMRI design, subjects (N=19) performed a forced-choice face identification task with word distractors in an fMRI scanner over two separate sessions. On one session subjects received dietary depletion of the serotonin precursor tryptophan while on the other session they received a balanced placebo control diet. Results showed that dorsal medial prefrontal responding was elevated in response to fearful relative to happy faces under depletion but not placebo. This negative bias under depletion was accompanied by a corresponding increase in positive dorsal medial prefrontal-amygdala functional connectivity. We therefore conclude that serotonin depletion engages a prefrontal-amygdala circuit during the processing of fearful relative to happy face stimuli. This same 'aversive amplification' circuit is also engaged during anxiety induced by shock anticipation. As such, serotonergic projections may inhibit engagement of the 'aversive amplification' circuit and dysfunction in this projection may contribute to the negative affective bias in mood and anxiety disorders. These findings thus provide a promising explanation for the role of serotonin and serotonergic medications in the neurocircuitry of negative affective bias.

OBJECTIVE: To better understand how heterogeneity in attention-deficit hyperactivity disorder (ADHD) symptoms relates to heterogeneity in functional impairment domains in children with ADHD after accounting for demographic variables and comorbidities, in particular oppositionality and internalizing symptoms. METHODS: Parents and teachers (n = 5663) rated child/adolescent impairments across impairment domains in the International Classification of Functioning, Disability and Health as well as symptoms of ADHD and comorbidities. Hierarchical regressions were conducted to assess the relationship between parent and teacher ratings of ADHD symptom domains and functional impairments after accounting for personal factors and comorbid disorders. RESULTS: Symptoms of inattention were the strongest predictors of ratings of academic (math, writing, and so on) functioning, while hyperactivity/impulsivity symptoms were the strongest predictor of classroom disruption even after accounting for the presence of learning disorders and oppositional symptoms. Symptoms of ADHD accounted for minimal variance in interpersonal functioning or participation in organized activities after controlling oppositional symptoms. CONCLUSION: The ADHD symptom domains demonstrate domain-specific relations with various ADHD-related functional impairments. In addition, the results highlight the role of oppositionality in interpersonal relationship difficulties and participation in organized activities.

Optimistic bias (OB) is seen when individuals underestimate their probability of experiencing negative life events and overestimate their probability of experiencing positive life events. A reduced OB has been linked with increased depression symptoms. However, given the relevance of this information to mood and anxiety disorders, little is currently known regarding the neurobiology of OB. In the current study, we examine the neural basis of OB in healthy individuals (n=33) during probability estimation of future positive and negative events occurring to themselves relative to other, comparable individuals. In line with previous work, subjects showed significant OB; they considered themselves significantly more likely to experience future positive and significantly less likely to experience future negative events relative to comparable others. Positive, relative to negative events, un-modulated by subjects' probability estimates, were associated with significantly greater activity within the ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC). Moreover, responses within both regions to positive events negatively related to the healthy subjects' self reports of depression symptoms. However, there was no significant modulation of activity in either region by the subject's OB, objectified as the level to which they thought the event was more likely [positive events] or less likely [negative events] to occur to them relative to comparable others. In contrast, activity within the rostral anterior cingulate cortex (rACC) was positively modulated by OB for positive events and activity within the anterior insula and dorsomedial prefrontal cortex (dmPFC) was negatively modulated by OB for negative events. However, there was no significant relationship between responsiveness within these regions and self reports of depression symptoms. The data are discussed with reference to current models of vmPFC, rACC and anterior insula functioning.

Verbal initiations, such as questions, are essential components of social conversation often lacking in children with autism. Building on research showing that single questions can be taught in isolation, this study used a multiple baseline design to investigate whether a self-management intervention was effective for teaching concurrent acquisition and discrimination of three social questions in the context of conversation. Following intervention, participants rapidly increased their appropriate use of all three questions in a conversational context and maintained these gains over time. The participants also used questions appropriately with partners uninvolved in treatment. Additionally, the occasional presence of appropriate questions during baseline coupled with rapid improvement during intervention support theories that a lack of question-asking may be motivation-based rather than ability-based.

BACKGROUND: Training has been identified as an important barrier to implementation of clinical decision support systems (CDSSs), but little is known about the effectiveness of different training approaches. METHODS: Using an observational retrospective cohort design, we examined the impact of four training conditions on physician use of a CDSS: (1) computer lab training with individualized follow-up (CL-FU) (n=40), (2) computer lab training without follow-up (CL) (n=177), (3) lecture demonstration (LD) (n=16), or (4) no training (NT) (n=134). Odds ratios of any use and ongoing use under training conditions were compared to no training over a 2-year follow-up period. RESULTS: CL-FU was associated with the highest percent of active users and odds for any use (90.0%, odds ratio (OR)=10.2, 95% confidence interval (CI): 3.2-32.9) and ongoing use (60.0%, OR=6.1 95% CI: 2.6-13.7), followed by CL (any use=81.4%, OR=5.3, CI: 2.9-9.6; ongoing use=28.8%, OR=1.7, 95% CI: 1.0-3.0). LD was not superior to no training (any use=47%, ongoing use=22.4%). CONCLUSION: Training format may have differential effects on initial and long-term follow-up of CDSSs use by physicians.

Despite evidence for its efficacy and effectiveness, the use of medication for the treatment of ADHD remains controversial. Little is known about the factors that influence clinicians' decisions to use medication for ADHD. Here, we present initial data on the attitudes of prescribing clinicians from the Influences on Prescribing for ADHD Questionnaire (IPAQ)-a new clinician-completed, 40-item scale. The eight IPAQ subscales cover attitudes towards (1) treatment outcome optimisation, (2) the use of rule based over more informal approaches, (3) side effects, (4) symptoms control as the primary goal of treatment, (5) the influence of external pressure on medication-related decisions, (6) the value of taking the child's views into account, (7) long-term medication use and (8) the value of psychosocial approaches for the treatment of ADHD. Sixty-eight clinicians from Belgium and the UK took part. All subscales had acceptable levels of internal reliability (Chronbach's alpha = 0.62-0.78). Overall, clinicians reported taking a rule-based approach to prescribing with a focus on treatment optimisation, taking the child's view into account and valuing psycho-social approaches. They focused on treating broader patterns of impairment, but were wary of the potential side effects and long-term treatment. Psychiatrists scored high on their focus on symptom control and preference for long-term medication use, while paediatricians reported using more rule-based approaches. We identified four distinctive response profiles: (1) pro-psychosocial; (2) medication focused; (3) unsystematic; and (4) response optimizers. Future larger scale studies are required to replicate these profiles and to explore their relationship with prescribing behaviour and treatment outcomes.

OBJECTIVES: The Longitudinal Assessment of Manic Symptoms (LAMS) study was designed to investigate phenomenology and establish predictors of functional outcomes in children with elevated manic symptoms. The purpose of this series of analyses was to determine whether the participants demonstrated different trajectories of parent-reported manic and biphasic symptoms over the first 24 months of follow-up and to describe the clinical characteristics of the trajectories. METHODS: The 707 participants were initially aged 6-12 years and ascertained from outpatient clinics associated with the four university-affiliated LAMS sites. There were 621 children whose parents/guardians' ratings scored >/= 12 on the Parent General Behavior Inventory-10-item Mania Form (PGBI-10M) and a matched random sample of 86 children whose parents/guardians' ratings scored