Dataset Information

Development of Alcohol Use Disorder as a Function of Age, Severity, and Comorbidity with Externalizing and Internalizing Disorders in a Young Adult Cohort.

ABSTRACT: Background:As part of the ongoing Collaborative Study of the Genetics of Alcoholism, we performed a longitudinal study of a high risk cohort of adolescents/young adults from families with a proband with an alcohol use disorder, along with a comparison group of age-matched controls. The intent was to compare the development of alcohol problems in subjects at risk with and without comorbid externalizing and internalizing psychiatric disorders. Methods:Subjects (N = 3286) were assessed with a structured psychiatric interview at 2 year intervals over 10 years (2004-2017). The age range at baseline was 12-21. Results:Subjects with externalizing disorders (with or without accompanying internalizing disorders) were at increased risk for the onset of an alcohol use disorder during the observation period. Subjects with internalizing disorders were at greater risk than those without comorbid disorders for onset of a moderate or severe alcohol use disorder. The statistical effect of comorbid disorders was greater in subjects with more severe alcohol use disorders. The developmental trajectory of drinking milestones and alcohol use disorders was also accelerated in those with more severe disorders. Conclusions:These results may be useful for counseling of subjects at risk who present for clinical care, especially those subjects manifesting externalizing and internalizing disorders in the context of a positive family history of an alcohol use disorder. We confirm and extend findings that drinking problems in subjects at greatest risk will begin in early adolescence.

SUBMITTER: Nurnberger JI

PROVIDER: S-EPMC6919651 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Development of Alcohol Use Disorder as a Function of Age, Severity, and Comorbidity with Externalizing and Internalizing Disorders in a Young Adult Cohort.

Nurnberger John I JI Yang Ziyi Z Zang Yong Y Acion Laura L Bierut Laura L Bucholz Kathleen K Chan Grace G Dick Danielle M DM Edenberg Howard J HJ Kramer John J Kuperman Samuel S Rice John P JP Schuckit Marc M

Journal of psychiatry and brain science 20191025

<h4>Background</h4>As part of the ongoing Collaborative Study of the Genetics of Alcoholism, we performed a longitudinal study of a high risk cohort of adolescents/young adults from families with a proband with an alcohol use disorder, along with a comparison group of age-matched controls. The intent was to compare the development of alcohol problems in subjects at risk with and without comorbid externalizing and internalizing psychiatric disorders.<h4>Methods</h4>Subjects (<i>N</i> = 3286) were ...[more]

PMID: 31853508

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Project description:BackgroundComorbidity is the rule rather than the exception for childhood and adolescent onset mental disorders, but we cannot predict its occurrence and do not know the neural mechanisms underlying comorbidity. We investigate if the effects of comorbid internalizing and externalizing disorders on anatomical differences represent a simple aggregate of the effects on each disorder and if these comorbidity-associated cortical surface differences relate to a distinct genetic underpinning.MethodsWe studied the cortical surface area (SA) and thickness (CT) of 11,878 preadolescents (9-10 years) from the Adolescent Brain and Cognitive Development Study. Linear mixed models were implemented in comparative and association analyses among internalizing (dysthymia, major depressive disorder, disruptive mood dysregulation disorder, agoraphobia, panic disorder, specific phobia, separation anxiety disorder, social anxiety disorder, generalized anxiety disorder, post-traumatic stress disorder), externalizing (attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder) diagnostic groups, a group with comorbidity of the two and a healthy control group. Genome-wide association analysis (GWAS) and cell type specificity analysis were performed on 4468 unrelated European participants from this cohort.ResultsSmaller cortical surface area but higher thickness was noted across patient groups when compared to controls. Children with comorbid internalizing and externalizing disorders had more pronounced areal reduction than those without comorbidity, indicating an additive burden. In contrast, cortical thickness had a non-linear effect with comorbidity: the comorbid group had no significant CT differences, while those patient groups without comorbidity had significantly higher thickness compare to healthy controls. Distinct biological pathways were implicated in regional SA and CT differences. Specifically, CT differences were associated with immune-related processes implicating astrocytes and oligodendrocytes, while SA-related differences related mainly to inhibitory neurons.ConclusionThe emergence of comorbidity across distinct clusters of psychopathology is unlikely to be due to a simple additive neurobiological effect alone. Distinct developmental risk moderated by immune-related adaptation processes, with unique genetic and cell-specific factors, may contribute to underlying SA and CT differences. Children with the highest risk but lowest resilience, both captured in their developmental morphometry, may develop a comorbid illness pattern.

Project description:BackgroundExternalizing and internalizing behaviors contribute to clinical impairment in children with neurodevelopmental disorders (NDDs). Although associations between externalizing or internalizing behaviors and cortico-amygdalar connectivity have been found in clinical and non-clinical pediatric samples, no previous study has examined whether similar shared associations are present across children with different NDDs.MethodsMulti-modal neuroimaging and behavioral data from the Province of Ontario Neurodevelopmental Disorders (POND) Network were used. POND participants aged 6-18 years with a primary diagnosis of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD), as well as typically developing children (TDC) with T1-weighted, resting-state fMRI or diffusion weighted imaging (DWI) and parent-report Child Behavioral Checklist (CBCL) data available, were analyzed (total n = 346). Associations between externalizing or internalizing behavior and cortico-amygdalar structural and functional connectivity indices were examined using linear regressions, controlling for age, gender, and image-modality specific covariates. Behavior-by-diagnosis interaction effects were also examined.ResultsNo significant linear associations (or diagnosis-by-behavior interaction effects) were found between CBCL-measured externalizing or internalizing behaviors and any of the connectivity indices examined. Post-hoc bootstrapping analyses indicated stability and reliability of these null results.ConclusionsThe current study provides evidence towards an absence of a shared linear relationship between internalizing or externalizing behaviors and cortico-amygdalar connectivity properties across a transdiagnostic sample of children with different primary NDD diagnoses and TDC. Different methodological approaches, including incorporation of multi-dimensional behavioral data (e.g., task-based fMRI) or clustering approaches may be needed to clarify complex brain-behavior relationships relevant to externalizing/internalizing behaviors in heterogeneous clinical NDD populations.

Project description:Background Mental disorders are the leading cause of disability for youth worldwide. However, there is a dearth of validated, brief instruments to assess mental health in low- and middle-income countries (LMIC). We aimed to facilitate identification of mental disorders in LMIC contexts by adapting and validating measures of internalizing and externalizing disorders for adolescents in Mozambique, an LMIC in southeastern Africa. Methods We selected instruments with good support for validity in high-income and other LMIC settings: the Patient Health Questionnaire Adolescent (PHQ-A), Generalized Anxiety Disorders 7 (GAD-7), and Strengths and Difficulties Questionnaire (SDQ). Instruments were adapted by local and international mental health specialists followed by cognitive interviews (n = 48) with Mozambican adolescents. We administered the instruments along with the Miniature International Neuropsychiatric Interview for Children and Adolescents (MINI-KID)to 485 adolescents aged 12–19 years attending two secondary schools in Maputo City, Mozambique. One week later, we re-administered instruments to a randomly selected sample of 49 adolescents. Results Participants were 66.2% (n = 321) female and the average age was 15.9 (S.D = 1.7).Internal consistency (alpha = 0.80, PHQ-A; 0.84, GAD-7; 0.80, SDQ) and test–retest reliabilty (ICC = 0.74, PHQ-A; 0.70, GAD-7; 0.77, SDQ) were acceptabe for the PHQ-A, GAD-7, and the full SDQ. The SDQ internalizing subscale showed poor test–retest reliability (ICC = 0.63) and the SDQ externalizing subscale showed poor internal consistency (alpha = 0.65). All instruments demonstrated good sensitivity and specificity (> 0.70). Youden’s index identified optimal cutoff scores of 8 for the PHQ-A, 5 for the GAD-7, 10 for the SDQ internalizing and 9 for the SDQ externalizing subscales, though a range of scores provided acceptable sensitivity and specificity. Conclusions Our data supports reliability and validity of the PHQ-A, GAD-7, and SDQ instruments for rapidly assessing mental health problems in Mozambican adolescents. Use of these tools in other contexts with limited specialists may asist with expanding mental health assessment. Specific instrument and cutoff selection should be based on screening goals, treatment resources, and program objectives. Supplementary Information The online version contains supplementary material available at 10.1186/s12888-022-04189-3.

Dataset Information

Development of Alcohol Use Disorder as a Function of Age, Severity, and Comorbidity with Externalizing and Internalizing Disorders in a Young Adult Cohort.

Publications

Development of Alcohol Use Disorder as a Function of Age, Severity, and Comorbidity with Externalizing and Internalizing Disorders in a Young Adult Cohort.

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