Daphne J. Korczak

Childhood Onset Major Depressive Disorder: Course of Illness and Psychiatric Comorbidity in a Community Sample

OBJECTIVEnTo examine the effect of childhood-onset major depressive disorder (MDD) on course of illness and psychiatric comorbidity, as compared with adolescent- and adult-onset MDD, in a large nonclinical sample.nnnSTUDY DESIGNnThis study included 6778 civilian noninstitutionalized participants in the National Epidemiologic Survey on Alcohol and Related Conditions with nonpsychotic, non-substance-induced MDD. Subjects were divided into 3 groups on the basis of age at first episode of MDD: childhood-onset (CHLD; onset < or =12 yrs, n = 372), adolescent-onset (ADOL; onset 13 to 17 years, n = 854), and adult-onset (ADLT; onset > or =18 years, n = 5552).nnnRESULTSnCompared with subjects with ADLT, CHLD MDD was associated with a greater number of MDD episodes, longer episode duration, increased suicidality, and increased need for hospitalization for MDD compared with adult-onset illness. Subjects with CHLD had a higher rate of psychiatric comorbidity and were more likely to have a parental history of MDD. Among subjects treated for MDD, latency from MDD onset to treatment was greater among subjects with CHLD compared with subjects with ADLT. Data for subjects with ADOL was intermediate to those of subjects with CHLD and ADLT.nnnCONCLUSIONSnThis epidemiologic study confirms and extends clinical findings of childhood-onset MDD as a more familial form of illness associated with increased comorbidity, suicidality, and treatment use.

Are children and adolescents with psychiatric illness at risk for increased future body weight? A systematic review

The aim of this paper was to review the longitudinal relationship between early‐onset depression and disruptive behaviour and adult body weight. A systematic review of prospective longitudinal studies was conducted of articles in which (1) initial assessment occurred during childhood or adolescence (<18y); and (2) the primary outcome reported as body mass index (BMI), overweight (BMI>25–<30kg/m2), obesity (BMI≥30kg/m2), or depression; and (3) validated assessment measures for assessment of depressive symptoms or disruptive behaviour problems were employed. A total number of 16 articles were identified for review. Obese adolescent females are more likely to develop depressive illness in adulthood than their non‐obese peers. Conversely, depressed adolescent females, and possibly males, are more likely to become overweight adults than non‐depressed adolescents. There are insufficient data addressing future depression risk among overweight, non‐obese, adolescents to evaluate the potentially interactive nature of this relationship. Studies to date are consistent in reporting that children with behaviour problems are at increased risk of future overweight, though whether this risk is conferred by conduct symptoms, ADHD symptoms, or both, is less clear. Care providers of children with disruptive behaviour problems and depressed adolescents should monitor weight gain. Among obese adolescent females, mood should be followed.

Child and adolescent psychopathology predicts increased adult body mass index: results from a prospective community sample.

Objective: To examine the relationship between childhood and adolescent symptoms of (1) depression, (2) attention-deficit hyperactivity disorder (ADHD), and (3) conduct disorder (CD) with adult body mass index (BMI) in a prospective longitudinal study of 3294 community participants in the Ontario Child Health Survey. Methods: One thousand nine hundred ninety-two children aged 4 to 11 years and 1302 adolescents aged 12 to 16 years at study entry in 1983 underwent follow-up in 2000. Body mass index data were available for 1886 adult participants in the year 2000, which comprised the final study sample. Data were collected from youth, parents, and teachers using a combination of parental, youth, and teacher self-report and semistructured interview. Body mass index is a derived variable determined from the self-reported height and weight in 2000. Results: Adults with depression, ADHD, or CD identified in childhood had increased body weight (BMI = 27.2 kg/m2, 27.7 kg/m2, and 27.9 kg/m2, respectively) compared with their nonaffected peers (BMI = 24.8 kg/m2; p < .001). Greater depressive symptoms in childhood were associated with increased adult BMI among boys (p = .02). Among adolescents, depression and sex interact in the association with adult BMI (p = .01). The association of childhood ADHD with adult overweight was completely accounted for by the effect of comorbid child conduct disturbance (p < .001) for both girls and boys. Greater conduct symptoms were associated with increased adult BMI (p = .04) among adolescent girls. Conclusion: This epidemiologic study suggests that psychopathology in childhood is associated with increased adult BMI. Early identification of psychiatric illness may present key opportunities for targeted prevention of obesity.

Effects of acute aerobic exercise on neural correlates of attention and inhibition in adolescents with bipolar disorder

Executive dysfunction is common during and between mood episodes in bipolar disorder (BD), causing social and functional impairment. This study investigated the effect of acute exercise on adolescents with BD and healthy control subjects (HC) to test for positive or negative consequences on neural response during an executive task. Fifty adolescents (mean age 16.54±1.47 years, 56% female, 30 with BD) completed an attention and response inhibition task before and after 20u2009min of recumbent cycling at ~70% of age-predicted maximum heart rate. 3u2009T functional magnetic resonance imaging data were analyzed in a whole brain voxel-wise analysis and as regions of interest (ROI), examining Go and NoGo response events. In the whole brain analysis of Go trials, exercise had larger effect in BD vs HC throughout ventral prefrontal cortex, amygdala and hippocampus; the profile of these effects was of greater disengagement after exercise. Pre-exercise ROI analysis confirmed this deficit in deactivation for BDs in rostral ACC and found an activation deficit on NoGo errors in accumbens. Pre-exercise accumbens NoGo error activity correlated with depression symptoms and Go activity with mania symptoms; no correlations were present after exercise. Performance was matched to controls and results survived a series of covariate analyses. This study provides evidence that acute aerobic exercise transiently changes neural response during an executive task among adolescents with BD, and that pre-exercise relationships between symptoms and neural response are absent after exercise. Acute aerobic exercise constitutes a biological probe that may provide insights regarding pathophysiology and treatment of BD.

Characterizing exercise-induced feelings after one bout of exercise among adolescents with and without bipolar disorder

BACKGROUNDnExercise may be a practical, non-pharmacological strategy for symptom and health management for adolescents with bipolar disorder (BD). The purpose of this study was to determine if adolescents with BD experience changes in exercise-induced feelings from one bout of exercise similar to their otherwise healthy peers.nnnMETHODSnThirty-two adolescents with BD (Age (SD)=16.91 (1.4)) and 31 healthy adolescents (Age (SD)=15.68 (1.76)) completed the Exercise-Induced Feeling Inventory (EFI) before and after a 20-min bout of moderate intensity exercise (heart rate goal of 60-80% of the age estimated maximum [220 - 0.7*age]) on a cycle ergometer. Repeated-Measures ANCOVA was conducted on the four EFI subscales, controlling for age and BMI.nnnRESULTSnThere were no significant between-group differences on any subscales. An increase in Physical Exhaustion was of negligible effect size in both groups (BD: d=0.05;nnnCONTROLnd=0.16). There was an improvement in Revitalization (BD: d=0.49;nnnCONTROLnd=0.61) and a reduction in Tranquility (BD: d=-0.33;nnnCONTROLnd=-0.29) post-exercise of moderate and small effect size, respectively. The control group reported an increase in Positive Engagement that was of small-to-medium effect size, (d=0.41) with negligible change in the BD group (d=0.17). Healthy adolescents reported a significantly greater tolerance for high intensity exercise than adolescents with BD.nnnLIMITATIONSnEmotions were only assessed at two time points.nnnCONCLUSIONSnAdolescents with BD experience similar exercise-induced emotional benefits as their healthy peers. Experimental research is needed to examine the role of exercise as a strategy to regulate mood-related symptoms.

Children’s Physical Activity and Depression: A Meta-analysis

Research reporting an association between early physical activity and depression is reviewed. Data from 89u2009894 participants in 50 independent samples are analyzed and discussed. CONTEXT: Research regarding the protective effects of early physical activity on depression has yielded conflicting results. OBJECTIVE: Our objective was to synthesize observational studies examining the association of physical activity in childhood and adolescence with depression. DATA SOURCES: Studies (from 2005 to 2015) were identified by using a comprehensive search strategy. STUDY SELECTION: The included studies measured physical activity in childhood or adolescence and examined its association with depression. DATA EXTRACTION: Data were extracted by 2 independent coders. Estimates were examined by using random-effects meta-analysis. RESULTS: Fifty independent samples (89u2009894 participants) were included, and the mean effect size was significant (r = –0.14; 95% confidence interval [CI] = –0.19 to –0.10). Moderator analyses revealed stronger effect sizes in studies with cross-sectional versus longitudinal designs (k = 36, r = –0.17; 95% CI = –0.23 to –0.10 vs k = 14, r = –0.07; 95% CI = –0.10 to –0.04); using depression self-report versus interview (k = 46, r = –0.15; 95% CI = –0.20 to –0.10 vs k = 4, r = –0.05; 95% CI = –0.09 to –0.01); using validated versus nonvalidated physical activity measures (k = 29, r = –0.18; 95% CI = –0.26 to –0.09 vs k = 21, r = –0.08; 95% CI = –0.11 to –0.05); and using measures of frequency and intensity of physical activity versus intensity alone (k = 27, r = –0.17; 95% CI = –0.25 to –0.09 vs k = 7, r = –0.05; 95% CI = –0.09 to –0.01). LIMITATIONS: Limitations included a lack of standardized measures of physical activity; use of self-report of depression in majority of studies; and a small number of longitudinal studies. CONCLUSIONS: Physical activity is associated with decreased concurrent depressive symptoms; the association with future depressive symptoms is weak.

The Association of Cortisol Stress Response with Early Adversity and Diabetes Control in Adolescents with Diabetes

1.1 Objectives: The hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the relationship between increased stress and poor diabetes control in children with type 1 diabetes mellitus (T1DM). The objectives of this study were two-fold: (1) To evaluate the effectiveness of the Trier Social Stress Test for Children (TSST-C) in inducing psychosocial stress in children with T1DM; (2) To investigate predictors of the cortisol stress response to the TSST-C. 1.2 Methods: Seventeen adolescents with T1DM were exposed to the TSST-C. Salivary cortisol was sampled pre-TSST-C and at six 10-minute intervals following the stress procedure. Measures of anxiety, depression, family functioning and early adversity were completed. 1.3 Results: The TSST-C induced a significant increase in cortisol response (p<.01). Early adversity predicted cortisol response to the stressor (p=.01). Early adversity was also associated with poorer diabetes control (p=.05). 1.4 Conclusion: The TSST-C was effective in producing a stress response in children with diabetes. Whereas previous research has emphasized psychological pathways which contribute to the relationship between psychosocial stressors and poor diabetes control, this study suggests that biological dysfunction may also underlie the association.

Increased cerebral blood flow among adolescents with bipolar disorder at rest is reduced following acute aerobic exercise

OBJECTIVEnCerebral blood flow (CBF) is altered in mood disorders but has not been examined among adolescents with bipolar disorder (BD). Similarly, little is known about the acute neurophysiologic effects of aerobic exercise in BD. We therefore compared CBF between adolescents with and without BD at rest and acutely following a single exercise session.nnnMETHODSnThirty-one adolescents with BD and 20 age and sex-matched controls participated in this study. CBF magnetic resonance images (MRI) were acquired using arterial spin labeling at a baseline as well as 15 and 45min after a single 20-min session of recumbent cycling. Voxel-based CBF analyses compared groups at baseline and after exercise. Clinical, body mass index (BMI) and exercise-induced feelings inventory (EFI) data were examined for their influence on CBF findings.nnnRESULTSnBaseline CBF was increased in medial frontal and middle cingulate regions in BD compared to controls. Analysis of the acute CBF changes revealed pronounced exercise-related decreases in CBF in BD. Exercise-related feelings of exhaustion were associated with CBF changes in frontal but not parietal regions.nnnDISCUSSIONnA single bout of moderate-intensity aerobic exercise reduced regional CBF to a greater extent in BD compared to controls; these time dependent CBF responses were associated with exercise-induced feelings of exhaustion.

Greater body mass index is associated with reduced frontal cortical volumes among adolescents with bipolar disorder

BACKGROUNDnHigher body mass index (BMI) and obesity is common among youth with bipolar disorder (BD) and is associated with greater psychiatric illness severity, including suicidality. Obesity has been associated with frontal, temporal and subcortical volumetric reductions in adults with BD. We examined the neurostructural correlates of BMI in adolescents early in their course of BD.nnnMETHODSnWe processed T1-weighted images of adolescents with BD and psychiatrically healthy controls using FreeSurfer to derive a priori region of interest (ROI) volumes/cortical thickness for the frontal lobe (FL), prefrontal cortex (PFC) and orbitofrontal cortex (OFC) as well as volumes for the amygdala and hippocampus. General linear models assessed the association between BMI and the ROIs, controlling for age, sex and intracranial volume. We also conducted exploratory within-BD group and whole brain vertex-wise analyses.nnnRESULTSnWe included 40 adolescents with BD and 48 controls in our analyses. In addition to a main effect of BMI on the ROIs, there were significant diagnosis × BMI interaction effects on FL volumes. In the BD group only, BMI was negatively associated with FL, OFC and PFC cortical thickness. Whole brain analysis of BMI-volume correlations revealed 2 significant interaction clusters: 1 in the medial OFC and 1 in the caudal anterior cingulate cortex, with BD showing a stronger negative correlation.nnnLIMITATIONSnReliance on BMI rather than a more nuanced measure of obesity may have influenced the findings.nnnCONCLUSIONnOur results suggest that elevated BMI among adolescents with BD is associated with frontal neurostructural differences that are not observed in controls. Prospective studies examining the direction of the observed associations and the effect of BMI optimization on brain structure in adolescents with BD are warranted.

Magnetic resonance imaging of cerebrovascular reactivity in healthy adolescents

BACKGROUNDnCerebrovascular reactivity (CVR), an important measure of cerebrovascular health in adults, has not been examined in healthy adolescents. Beyond the direct importance of understanding CVR in healthy youth, studies on this topic can yield insights regarding brain disease. We set out to evaluate 3 different CVR modelling approaches.nnnNEW METHODnThirty-nine healthy adolescents (ages 13-19 years, 20 females) completed six blocks of 15-second breath-holds separated by 30-second blocks of free-breathing. CVR was measured using blood-oxygenation-level dependent functional magnetic resonance imaging at 3-Tesla; voxel-wise analyses were complemented by regional analyses in five major subdivisions of the brain. Hemodynamic response functions were modelled using: (1) an individualized delay term (double-gamma variate convolved with a boxcar function), (2) with a standard 9-second delay term, and (3) a sine-cosine regressor.nnnRESULTSnIndividual-delay yielded superior model fit or larger cluster volumes. Regional analysis found differences in CVR and time-to-peak CVR. Males had higher brain-wide CVR in comparison to females (pu202f=u202f0.025, η2partu202f=u202f0.345). BMI and blood pressure were not significantly associated with CVR (all pu202f>u202f0.4).nnnCOMPARISON WITH EXISTING METHODSnThis was the first study to compare these methods in youth. Regional differences were similar to adult studies.nnnCONCLUSIONSnThese findings lend support to future breath-hold CVR studies in youth, and highlight the merit of applying individualized-delay estimates. Regional variability and sex-related differences in CVR suggest that these variables should be considered in future studies, particularly those that examine disease states with predilection for specific brain regions or those diseases characterized by sex differences.