Faculty Bibliography
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Department/Unit:Child and Adolescent Psychiatry
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11618
Trajectories of emotional and behavioral problems from childhood to early adult life
LAY ABSTRACT/UNASSIGNED:Although mental health problems are common in autism, relatively little is known about their stability and the factors that influence their persistence or change over the life-course. To address this, we use data from the Special Needs and Autism Project (SNAP) cohort studied at three time-points from 12 to 23 years. Using the parent-reported Strengths and Difficulties Questionnaire (SDQ) domains of conduct, emotional, and ADHD symptoms, we evaluated the role of child, family, and contextual characteristics on these three trajectories. Symptoms decreased significantly over time for all three domains, but many participants still scored above the published disorder cutoffs. Individuals showed high levels of persistence. Higher initial adaptive function and language levels predicted a greater decline in conduct and ADHD symptoms. In contrast, higher language functioning was associated with higher levels of emotional symptoms, as was lower levels of autism symptom severity and higher parental education. Those with higher neighborhood deprivation had higher initial conduct problems but a steeper decline over time. Our findings highlight that it may be possible to accurately predict mental health trajectories over this time period, which could help parents and carers in planning and help professionals target resources more efficiently.
PMID: 32191121
ISSN: 1461-7005
CID: 4485962
Dissemination Strategies to Accelerate the Policy Impact of Children's Mental Health Services Research
The United States is in the midst of a children's mental health crisis, with rates of depression, anxiety, and suicide increasing precipitously. Evidence produced by children's mental health services research can help address this crisis by informing public policy decisions about service delivery, system design, and investments in the social determinants of mental health. Unfortunately, the policy impact of children's mental health services research is limited because evidence often fails to reach policy makers, be responsive to their needs, resonate with their worldview, or reflect the contexts in which they make decisions. Dissemination strategies-defined as the development and targeted distribution of messages and materials about research evidence pertaining to a specific issue or intervention-can help address these challenges. Yet, limited integrated guidance exists to inform the design of such strategies. This article addresses this need by synthesizing the results of empirical studies to provide guidance about how to enhance the dissemination of children's mental health services research to policy makers. The article provides four recommendations about the content of policy maker-focused dissemination materials, discusses how strategic framing and message tailoring can increase the chances that evidence is persuasive to policy makers, and highlights strategies to ensure that evidence reaches policy makers.
PMID: 32517640
ISSN: 1557-9700
CID: 4489592
Thoughtful feelings
In this My Word, Joseph LeDoux describes how his four-decade career exploring how non-conscious processes involving the amygdala detect and respond to danger has contributed to the 'amygdala fear center' meme, a view he does not endorse. The conscious experience of fear, he tells us here, is not wired into the amygdala, but is instead a cognitively assembled understanding that you are in harm's way based on non-conscious memories, schemas, and mental models.
PMID: 32516605
ISSN: 1879-0445
CID: 4489572
Genes Bound by ΔFosB in Different Conditions With Recurrent Seizures Regulate Similar Neuronal Functions
Seizure incidence is increased in Alzheimer's disease (AD) patients and mouse models, and treatment with the antiseizure drug levetiracetam improves cognition. We reported that one mechanism by which seizures can exert persistent effects on cognition is through accumulation of ΔFosB, a transcription factor with a long half-life. Even the infrequent seizures that spontaneously occur in transgenic mice expressing human amyloid precursor protein (APP) lead to persistent increases in ΔFosB in the hippocampus, similar to what we observed in patients with AD or temporal lobe epilepsy. ΔFosB epigenetically regulates expression of target genes, however, whether ΔFosB targets the same genes when induced by seizures in different neurological conditions is not clear. We performed ChIP-sequencing to assess the repertoire of ΔFosB target genes in APP mice and in pilocarpine-treated wildtype mice (Pilo mice), a pharmacological model of epilepsy. These mouse models allowed us to compare AD, in which seizures occur in the context of high levels of amyloid beta, and epilepsy, in which recurrent seizures occur without AD-specific pathophysiology. Network profiling of genes bound by ΔFosB in APP mice, Pilo mice, and respective control mice revealed that functional domains modulated by ΔFosB in the hippocampus are expanded and diversified in APP and Pilo mice (vs. respective controls). Domains of interest in both disease contexts involved neuronal excitability and neurotransmission, neurogenesis, chromatin remodeling, and cellular stress and neuroinflammation. To assess the gene targets bound by ΔFosB regardless of seizure etiology, we focused on 442 genes with significant ΔFosB binding in both APP and Pilo mice (vs. respective controls). Functional analyses identified pathways that regulate membrane potential, glutamatergic signaling, calcium homeostasis, complement activation, neuron-glia population maintenance, and chromatin dynamics. RNA-sequencing and qPCR measurements in independent mice detected altered expression of several ΔFosB targets shared in APP and Pilo mice. Our findings indicate that seizure-induced ΔFosB can bind genes in patterns that depend on seizure etiology, but can bind other genes regardless of seizure etiology. Understanding the factors that underlie these differences, such as chromatin accessibility and/or abundance of co-factors, could reveal novel insights into the control of gene expression in disorders with recurrent seizures.
PMCID:7268090
PMID: 32536852
ISSN: 1662-4548
CID: 4484462
Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups
OBJECTIVE:Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data. METHODS:-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures). RESULTS:No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood. CONCLUSIONS:The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.
PMID: 32539527
ISSN: 1535-7228
CID: 4484542
What Is the Health and Well-Being Burden for Parents Living With a Child With ADHD in the United Kingdom?
Objective: To explore the burden associated with childhood ADHD in a large observational study. Methods: We recruited familes with at least one child (6-18 years) with ADHD via 15 NHS trusts in the UK, and collected data from all family members. We made careful adjustments to ensure a like-for-like comparison with two different control groups, and explored the impact of controlling for a positive parental/carer ADHD screen, employment, and relationship status. Results: We found significant negative impacts of childhood ADHD on parents'/carers' hours and quality of sleep, satisfaction with leisure time, and health-related quality of life (measured by the EuroQol-5D [EQ-5D]). We found a decrement in life satisfaction, mental well-being (as measured by the Short-Warwick Edinburgh Mental Well-Being Scale [S-WEMWBS]), and satisfaction with intimate relationships, but this was not always robust across the different control groups. We did not find any decrement in satisfaction with health, self-reported health status, or satisfaction with income. Conclusion: The study quantifies the impact on the health and well-being of parents living with a child with ADHD using a survey of families attending ADHD clinics in the United Kingdom.
PMID: 32552265
ISSN: 1557-1246
CID: 4484952
Investigating inhibition deficit in schizophrenia using task-modulated brain networks
Schizophrenia subjects have shown deficits of inhibition in conditions such as a stop signal task. The stop signal response time (SSRT) is consistently longer compared with healthy controls, and is accompanied by decreased brain activations in the right inferior frontal gyrus. However, as to how the response inhibition function is supported by distributed brain networks, and whether such networks are altered in schizophrenia are largely unknown. We analyzed functional MRI data of a stop signal task from 44 schizophrenia patients and 44 matched controls, and performed whole-brain psychophysiological interaction analysis to obtain task-modulated connectivity (TMC). Support vector classification was used to classify schizophrenia, and support vector regression was applied to explore the relationships between TMC and behavior indexes, such as SSRT. Schizophrenia group showed a decreased TMC pattern which mainly involved the fronto-parietal network, and increased TMC related to the sensorimotor network. Moreover, TMC could only successfully predict SSRT in the control group, further suggesting an abnormal task modulation in schizophrenia. Lastly, we compared the classification and prediction results from different types of measures, i.e., TMC, task-independent connectivity (TIC), task-functional connectivity (TFC), and resting-state functional connectivity (RSFC). TMC performed better in the behavior predictions, while TIC performed better in the classification. TFC and RSFC had similar classification and prediction performance as TIC. The current results provide new insights into the altered brain functional integration underlying response inhibition in schizophrenia, and suggest that different types of connectivity measures are complementary for a better understanding of brain networks and their alterations.
PMID: 32356019
ISSN: 1863-2661
CID: 4481812
Transdiagnostic subtyping of males with developmental disorders using cortical characteristics
BACKGROUND:Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are biologically heterogeneous and often co-occur. As within-diagnosis heterogeneity and overlapping diagnoses are challenging for researchers and clinicians, identifying biologically homogenous subgroups, independent of diagnosis, is an urgent need. METHODS:MRI data from 148 adult males with developmental disorders (99 primary ASD, mean age = 31.7 ± 8.0, 49 primary ADHD; mean age = 31.7 ± 9.6) and 105 neurotypical controls (NTC; mean age = 30.6 ± 6.8) were analyzed. We extracted mean cortical thickness (CT) and surface area (SA) values using a functional atlas. Then, we conducted HeterogeneitY through DiscRiminant Analysis (HYDRA) to transdiagnostically cluster and classify individuals. Differences in diagnostic likelihood and clinical symptoms between subtypes were tested. Sensitivity analyses tested the stability of the number of subtypes and their membership by excluding 13 participants diagnosed with both ASD and ADHD and by using a different atlas. RESULTS:In relation to both CT and SA, HYDRA identified two subtypes. The likelihood of ASD or ADHD was not significantly different from the chance of belonging to any of these two subtypes. Clinical characteristics did not differ between subtypes in either CT or SA based analyses. The high consistency in membership was replicated when utilizing a different atlas or excluding people with dual diagnoses in CT (dice coefficients > 0.94) and in SA (>0.88). CONCLUSION/CONCLUSIONS:Although the brain-derived subtypes do not match diagnostic groups, individuals with developmental disorders were successfully and stably subtyped using either CT or SA.
PMID: 32526684
ISSN: 2213-1582
CID: 4478572
The Differential Effect of Anxiety and ADHD Symptoms on Inhibitory Control and Sustained Attention for Threat Stimuli: A Go/No-Go Eye-Movement Study
Objective: This study examined the synergistic effects of ADHD and anxiety symptoms on attention and inhibitory control depending on the emotional content of the stimuli. Method: Fifty-four typically developing individuals (27 children/adolescents and 27 adults) completed an eye-movement based emotional Go/No-Go task, using centrally presented (happy, angry) faces and neutral/symbolic stimuli. Sustained attention was measured through saccade latencies and saccadic omission errors (Go trials), and inhibitory control through saccadic commission errors (No-Go trials). ADHD and anxiety were assessed dimensionally. Results: Elevated ADHD symptoms were associated with more commission errors and slower saccade latencies for angry (vs. happy) faces. In contrast, angry faces were linked to faster saccade onsets when anxiety symptoms were high, and this effect prevailed when both anxiety and ADHD symptoms were high. Conclusion: Social threat impacted performance in individuals with sub-clinical anxiety and ADHD differently. The effects of anxiety on threat processing prevailed when both symptoms were high.
PMID: 32513052
ISSN: 1557-1246
CID: 4478032
Intimate partner violence and psychological interventions in low-income and middle-income countries [Comment]
PMID: 31981528
ISSN: 2215-0374
CID: 4474612
