Amygdala and hippocampus volumes in pediatric major depression.

BACKGROUND: The purpose of this study was to measure amygdala and hippocampus volumes in pediatric major depressive disorder (MDD) and to address the question of neuroanatomical continuity with adult-onset depression. METHODS: We studied 20 children and adolescents with MDD (17 female subjects) and 24 healthy comparison subjects (16 female subjects) using 1.5 Tesla magnetic resonance imaging. Group differences in left and right amygdala and hippocampus volumes were examined using repeated measures analyses of covariance, adjusting for age, gender, and whole brain volume. RESULTS: Depressed children had significant reductions of left and right amygdala volumes compared with healthy subjects. Hippocampus volumes did not differ between the groups. No significant correlations were found between amygdala volumes and depressive symptom severity, age at onset, or illness duration. CONCLUSIONS: Smaller amygdalas are present early in the course of pediatric depression and may predispose to the development of this disorder or perhaps more generally of childhood mood disorders. Future research should examine the longitudinal course and functional correlates of amygdala volume abnormalities in childhood-onset depression, including their possible moderation by gender.

New formulations of stimulants for attention-deficit hyperactivity disorder: therapeutic potential.

New formulations of stimulant medications for the treatment of attention-deficit hyperactivity disorder (ADHD) have been an important focus for pharmaceutical industry research and development over the past decade. In this article, we review and assess the therapeutic potential of five new stimulant formulations (one immediate release and four longer-acting preparations) that have recently become available for the treatment of ADHD. While the therapeutic potential of immediate-release enantiomers of methylphenidate has not yet been clinically realised, new long-acting formulations of stimulants have changed the standard of care for children, adolescents and adults with ADHD. The longer duration of action of these once-daily compounds, and the consequent expansion of the duration of daily ADHD coverage afforded by them, has introduced the realistic possibility of reducing the overall daily burden of ADHD on affected individuals. Although more expensive, these new stimulant formulations are easier for patients to use than older stimulants, more resistant to abuse and misuse, and allow for increased privacy of ADHD treatment at school or work.

Proactive and reactive aggression in referred children and adolescents.

Investigating different types of aggression is important to facilitate a better understanding of excessive maladaptive aggression in referred youth. Using regression analysis, the authors investigated demographic, historical, diagnostic, and treatment correlates of proactive aggression and reactive aggression in a heterogeneous population (N = 323) of psychiatrically referred youths. Ratings of proactive and reactive aggression significantly correlated with more established measures of aggression. Results suggest the importance of hyperactive/impulsive behavior, disruptive behavior disorders, and self-reported hostility in youths with both reactive and proactive aggression. Substance use disorders, a family history of substance abuse, and family violence were specifically associated with proactive aggression. Younger age and a history of abuse were correlated with reactive aggression. Implications for clinical interventions and future research are discussed.

Gender differences in reactive and proactive aggression.

The purpose of our investigation was to study gender differences in proactive and reactive aggression in a sample of 323 clinically referred children and adolescents (68 females and 255 males). Proactive aggression and reactive aggression were assessed using the Proactive/Reactive Aggression Scale. Demographic, historical, family, diagnostic, and treatment variables were entered into stepwise regression analyses to determine correlates of proactive and reactive aggression in males and females. Results reveal high rates of aggression in both males and females in the sample. Self reported drug use, expressed hostility, and experiences of maladaptive parenting were correlated with proactive aggression for both genders. Hyperactive/impulsive behaviors were correlated with male reactive aggression. An early age of traumatic stress and a low verbal IQ were correlated with female proactive aggression. Gender differences in correlates of proactive and reactive aggression may provide possible targets for research, prevention, and treatment efforts focused on reducing maladaptive aggression in clinically referred youth.

Correlates of comorbid psychopathology in children with ADHD.

OBJECTIVE: To investigate correlates of internalizing and externalizing psychopathology in a clinical sample of children with attention-deficit/hyperactivity disorder (ADHD). METHOD: Parent and teacher Child Behavior Checklists were administered to 300 children with ADHD to ascertain comorbid symptoms. Based on previous research, a seven-step hierarchical regression analysis was developed. Six hierarchical regression analyses were conducted with either parent or teacher Child Behavior Checklist aggression, delinquency, or anxious/depressive comorbid symptoms as dependent measures. RESULTS: Controlling for (1) variables known to increase risk for ADHD child psychopathology and (2) estimated duration of ADHD, our results suggest that the presence of comorbid symptoms is influenced by age of onset. An early age of onset of ADHD was correlated with a greater rate of parent-reported child aggressive symptoms, and a later age of onset was correlated with a greater rate of parent-reported child anxious/depressive symptoms. Elevated levels of comorbid externalizing and internalizing symptoms are associated with greater ADHD symptom severity. CONCLUSIONS: Comorbid externalizing and internalizing symptoms are correlated with age of ADHD onset and are related to the severity of clinical presentation in a referred sample of children with ADHD.

Aggressive behavior in abused children.

Our objective was to investigate the relationship between a lifetime history of traumatic stress, defined as physical and/or sexual abuse and aggression and psychosocial functioning in a sample of clinically referred and nonclinically referred children and adolescents. This is a retrospective case comparison study. Three groups of children were identified, assessed, matched for age, and partially matched for gender. Children clinically referred to residential treatment with a history of abuse (N = 29) were compared with children clinically referred to residential treatment without a history of abuse (N = 29), and a nonclinical group of children residing in the community (N = 29). Variables investigating specific types of aggression, IQ, and psychopathology were assessed across the three groups. Clinically referred children scored worse on all measures compared with nonclinical community children. Clinically referred abused children scored higher on measures of aggression and significantly higher on measures of reactive aggression and verbal aggression than clinically referred nonabused children. Clinically referred abused children had significantly lower verbal IQ scores than clinically referred nonabused children, but no difference in psychopathology. Results support the importance of assessing specific types of aggression in samples of traumatized youths. Verbal information processing may be especially vulnerable in abused children and adolescents and enhance vulnerability to aggressive responding.

Smaller frontal lobe white matter volumes in depressed adolescents.

BACKGROUND: Prior studies have demonstrated reduced frontal lobe volumes in depressed adolescents. In this study, frontal lobe gray and white matter volumes in adolescents with major depressive disorder were evaluated. METHODS: Nineteen depressed and thirty-eight healthy comparison adolescents were recruited for a magnetic resonance imaging study. Images were segmented into gray matter, white matter, and cerebrospinal fluid. Morphometric measurements of the whole brain and frontal lobe region were completed. RESULTS: Whole brain volumes were significantly smaller in depressed subjects compared with the healthy comparison subjects. Significantly smaller frontal white matter volumes and significantly larger frontal gray matter volumes were found in the depressed subjects, after controlling for age and whole brain volume. CONCLUSIONS: These results are consistent with the hypothesis that a deficit in frontal volume exists during cortical development in adolescents with depression. Further studies are needed to assess whether volume differences resolve over time and the extent to which these differences influence response to treatment.

Brain-to-serum lithium ratio and age: an in vivo magnetic resonance spectroscopy study.

OBJECTIVE: The authors' goal was to determine if there is an association between brain-to-serum lithium ratios and age. METHOD: Lithium-7 magnetic resonance spectroscopy was used to measure in vivo brain lithium levels in nine children and adolescents (mean age=13.4 years, SD=3.6) and 18 adults (mean age=37.3, SD=9.1) with bipolar disorder. RESULTS: Serum and brain lithium concentrations were positively correlated. Younger subjects had lower brain-to-serum concentration ratios than adults: 0.58 (SD=0.24) versus 0.92 (SD=0.36). The brain-to-serum concentration ratio correlated positively with age. CONCLUSIONS: These observations suggest that children and adolescents may need higher maintenance serum lithium concentrations than adults to ensure that brain lithium concentrations reach therapeutic levels.