Faculty Bibliography

Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.

BACKGROUND:Disruptive Behavioral Disorders (DBDs) and Attention Deficit/Hyperactivity Disorder (ADHD) are chronic, impairing, and costly child and adolescent mental health challenges which, when untreated, can result in disruptions in school performance, friendships and family relations. Yet, there is dearth of prevalence data on child and adolescent behavioral challenges within sub-Saharan Africa, including Uganda. This study aims to estimate the prevalence rate of behavioral challenges and ADHD among young school going children and early adolescents (ages 8-13 at study enrollment), utilizing a school-based sample in southwest Uganda. METHODS:We present screening results from a 5-year scale-up study titled SMART Africa-Uganda (2016-2021), set across 30 public primary schools located in the greater Masaka region in Uganda, a region heavily impacted by poverty and HIV/AIDS. Specifically, we draw on screening data from caregivers of 2434 children that used well-established standardized measures that had been pre-tested in the region. These were: 1) oppositional defiant disorder (ODD) and conduct disorder (CD) subscales of the Disruptive Behavior Disorders (DBD) scale; and 2) the Iowa Connors and Impairment scales. Slightly over half of the children in the sample were female (52%), with a mean age of 10.27 years. RESULTS:Of the 2434 participants screened for disruptive behaviors: 1) 6% (n = 136) scored positive on ODD and 2% (n = 42) scored positive on CD subscales of the DBD scale; 2) 9.61% (n = 234), and 2.67% (n = 65) were reported to have elevated symptoms of ODD and ADHD on the Iowa Connors caregiver report scale respectively. Twenty-five percent (n = 586) of children were described by their caregivers as having experienced some form of impairment in at least four domains of the Impairment scale. CONCLUSION/CONCLUSIONS:The results indicate the presence of behavioral challenges and ADHD among school going children, aged 8-13 years, in Uganda. Given the negative outcomes associated with behavioral challenges as children transition to adolescence and adulthood, detecting these emerging behavioral challenges early is critical in developing appropriate interventions. School settings could be considered as one of the contextually-relevant, culturally-appropriate, and non-stigmatizing venues to implement screening procedures and to detect emerging behavioral challenges and to make necessary referrals.

Active avoidance is the prototypical paradigm for studying aversively-motivated instrumental behavior. However, avoidance research stalled amid heated theoretical debates and the hypothesis that active avoidance is essentially Pavlovian flight. Here I reconsider key "avoidance problems" and review neurobehavioral data collected with modern tools. Although the picture remains incomplete, these studies strongly suggest that avoidance has an instrumental component and is mediated by brain circuits that resemble appetitive instrumental actions more than Pavlovian fear reactions. Rapid progress may be possible if investigators consider important factors like safety signals, response-competition, goal-directed vs. habitual control and threat imminence in avoidance study design. Since avoidance responses likely contribute to active coping, this research has important implications for understanding human resilience and disorders of control.

Introduction/UNASSIGNED:Agitation in children and adolescents in the emergency department (ED) can be dangerous and distressing for patients, family and staff. We present consensus guidelines for management of agitation among pediatric patients in the ED, including non-pharmacologic methods and the use of immediate and as-needed medications. Methods/UNASSIGNED:Using the Delphi method of consensus, a workgroup comprised of 17 experts in emergency child and adolescent psychiatry and psychopharmacology from the the American Association for Emergency Psychiatry and the American Academy of Child and Adolescent Psychiatry Emergency Child Psychiatry Committee sought to create consensus guidelines for the management of acute agitation in children and adolescents in the ED. Results/UNASSIGNED:Consensus found that there should be a multimodal approach to managing agitation in the ED, and that etiology of agitation should drive choice of treatment. We describe general and specific recommendations for medication use. Conclusion/UNASSIGNED:These guidelines describing child and adolescent psychiatry expert consensus for the management of agitation in the ED may be of use to pediatricians and emergency physicians who are without immediate access to psychiatry consultation.

The purpose of this chapter is to briefly describe the long history of gender diversity; address difficulties in estimating the number of gender diverse people worldwide and the challenges for researchers and medical and mental health professionals, who wish to define and count this population; to look at the history and utility of Gender Dysphoria as a diagnosis in the DSM-5 and the International Classification of Diseases (ICD); and to provide some historical perspective on the evolution of standards of care over time. It seeks to describe how we got here, how the history of diagnoses has influenced where we are, and how we move forward in the care and management of gender dysphoria. The chapter is divided into four sections: A Short History of Gender Diversity, Being Counted, A Brief Review of Diagnostic Changes over Time, and An Evolution of Guidelines. Each section ends with thoughts on future directions and the need for further work.

OBJECTIVE:Meta-analytic evidence shows alterations of peripheral inflammatory cytokines in adults with depressive disorders. By contrast, no evidence synthesis on alterations of peripheral inflammatory cytokines in children/adolescents with depressive disorders is available to date. To fill this gap, we conducted a systematic review and meta-analysis of case-control studies comparing serum cytokine levels in children/adolescents with depressive disorders and healthy controls. METHODS:Based on a preregistered protocol (PROSPERO-CRD42018095418), we searched PubMed, Ovid, and Web of Knowledge from inception through July 21, 2018, with no language restrictions, and contacted study authors for unpublished data/information. Random-effects model was used to compute effect size for each cytokine. The Newcastle-Ottawa Scale was used to asses study bias. RESULTS:From a pool of 4231 nonduplicate, potentially relevant references, 8 studies were retained for the qualitative synthesis and 5 for the meta-analysis. TNF-α was higher in participants with depressive disorders versus controls, falling short of statistical significance. CONCLUSIONS:Overall, due to the small number of studies, in contrast to the literature in adults, further evidence is needed to confirm possible inflammatory alterations associated with depression in youth.

Perceptual learning is an enhancement in discriminability of similar stimuli following experience with those stimuli. Here, we examined the efficacy of adding additional active training following a standard training session, compared with additional stimulus exposure in the absence of associated task performance. Mice were trained daily in an odor-discrimination task, and then, several hours later each day, received 1 of 3 different manipulations: 1) a second active-training session, 2) non-task-related odor exposure in the home cage, or 3) no second session. For home-cage exposure, odorants were presented in small tubes that mice could sniff and investigate for a similar period of time as in the active discrimination task each day. The results demonstrate that daily home-cage exposure was equivalent to active odor training in supporting improved odor discrimination. Daily home-cage exposure to odorants that did not match those used in the active task did not improve learning, yielding outcomes similar to those obtained with no second session. Piriform cortical local field potential recordings revealed that both sampling in the active learning task and investigation in the home cage evoked similar beta band oscillatory activity. Together the results suggest that odor-discrimination learning can be significantly enhanced by addition of odor exposure outside of the active training task, potentially because of the robust activity evoked in the olfactory system by both exposure paradigms. They further suggest that odorant exposure alone could enhance or maintain odor-discrimination abilities in conditions associated with olfactory impairment, such as aging or dementia.

Increased reaction time variability (RTV) is one of the most replicable behavioral correlates of attention-deficit/hyperactivity disorder (ADHD). However, this may not be specific to ADHD but a more general marker of psychopathology. Here we compare RT variability in individuals with ADHD and those with other childhood internalizing and externalizing conditions both in terms of standard (i.e., the standard deviation of reaction time) and alternative indices that capture low-frequency oscillatory patterns in RT variations over time thought to mark periodic lapses of attention in ADHD. A total of 667 participants (6-12 years old) were classified into non-overlapping diagnostic groups consisting of children with fear disorders (n = 91), distress disorders (n = 56), ADHD (n = 103), oppositional defiant or conduct disorder (ODD/CD; n = 40) and typically developing controls (TDC; n = 377). We used a simple two-choice reaction time task to measure reaction time. The strength of oscillations in RTs across the session was extracted using spectral analyses. Higher RTV was present in ADHD compared to all other disorder groups, effects that were equally strong across all frequency bands. Interestingly, we found that lower RTV to characterize ODD/CD relative to TDC, a finding that was more pronounced at lower frequencies. In general, our data support RTV as a specific marker of ADHD. RT variation across time in ADHD did not show periodicity in a specific frequency band, not supporting that ADHD RTV is the product of spontaneous periodic lapses of attention. Low-frequency oscillations may be particularly useful to differentiate ODD/CD from TDC.

The search for objective biological tests, sufficiently reliable, and predictive enough to be diagnostic of psychiatric disorders, continues apace - yet their discovery remains a distant dream. It seems increasingly unlikely that current diagnostic structures and concepts map biologically in a straight forward way - with heterogeneity within, and sharing across, existing diagnostic boundaries being the biological rule rather than the exception. Indeed, it now appears that the science of biological psychiatry is more likely to redraw those boundaries than it is to confirm and mark them (Sonuga-Barke, Journal of Child Psychology and Psychiatry, 2016, 57, 1). Clinical identification of childhood psychiatric disorders therefore remains, for the foreseeable future at least, an exercise in regulated social perception - reliant on the fallible and subjective judgements of parents, teachers and clinicians. Social perception of this sort is an active and motivated process and therefore prone, like all social perception, to bias and distortions - both systematic and idiosyncratic. Progress has certainly been made over the last 50 years in reducing such judgement bias by, for instance filtering perceptions through the lens of standardised instruments (questionnaires and interviews) with carefully operationalised items and a degree of reliability and validity. However, such instruments often play only a peripheral role in actual diagnostic encounters and when they are used, there is still sufficient ambiguity to leave open plenty of room for interpretation. When we acknowledge that psychiatric diagnoses are social constructions - we are not saying that symptoms of inattention, impulsivity and hyperactivity are not real or do not cluster together in meaningful ways or that they do not cause real distress and disability but that their interpretation and meaning are often informed by social constructs such as ethnic or gender norms and stereotypes (Meyer, Stevenson, & Sonuga-Barke, Journal of Attention Disorders, 2019).

BACKGROUND:Juvenile justice-involved youth have high rates of trauma exposure, physical and sexual abuse and PTSD. Several factors have been found to be related to PTSD symptoms in youth including number and chronicity of traumatic events. OBJECTIVE:To simultaneously examine the relationships between allostatic load (defined here as number of traumatic experiences), poly-victimization (exposure to two or more forms of victimization based on 5 of the 6 categories in Ford et al.'s 2010 study), physical/sexual abuse and PTSD in justice-involved youth. PARTICIPANTS AND SETTING/METHODS:The sample consisted of 1984 youth in juvenile detention in a Northeastern city. The sample was 73.4% male and the majority of youth were either African American or Hispanic. METHODS:Clinicians collected demographic and psychosocial information, and measured symptoms of PTSD, depression, and problematic substance use. RESULTS:Results showed that youth with more traumas, those who experienced poly-victimization and those who experienced physical/sexual assault/abuse were not only more likely to have PTSD, but also more likely to have depression, thoughts of suicide/self-harm, and problematic substance use (as indicated by the presence of 2 or more of 6 possible indicators). Poly-victimization was a stronger correlate of PTSD than number of traumas or physical/sexual assault/abuse. However, among youth with PTSD, number of traumas was associated with co-occurring problems while poly-victimization and physical/sexual assault/abuse were not. CONCLUSIONS:Findings can be used to help direct resources to juvenile justice-involved youth who are most in need of treatment.