Attention-deficit/hyperactivity disorder is a prevalent and disabling disorder that is characterized by inattention and/or hyperactivity-impulsivity, impairment in executive functions, structural and functional abnormalities in frontal-striatal circuitry, associations with particular catecholamine gene variants, and responsiveness to dopaminergic and noradrenergic agents. There is a growing integration of findings from basic and clinical studies, of data from different methods (eg, genetics and imaging), and of empirical data with hypotheses drawn from evolutionary thinking. Here we briefly summarize work on the cognitive-affective neuroscience of attention-deficit/hyperactivity disorder.

Anxiety disorders are commonly treated with exposure-based therapies that rely on extinction of conditioned fear. Persistent fear and anxiety following exposure therapy could reflect a deficit in the recall of extinction learning. Animal models of fear learning have elucidated a neural circuit for extinction learning and recall that includes the amygdala, ventromedial prefrontal cortex (vmPFC), and hippocampus. Whereas the amygdala is important for extinction learning, the vmPFC is a site of neural plasticity that allows for the inhibition of fear during extinction recall. We suggest that the vmPFC receives convergent information from other brain regions, such as contextual information from the hippocampus, to determine the circumstances under which extinction or fear will be recalled. Imaging studies of human fear conditioning and extinction lend credence to this extinction network. Understanding the neural circuitry underlying extinction recall will lead to more effective therapies for disorders of fear and anxiety.

Introduction: The diagnosis of borderline personality disorder is complex as is its pharmacologic treatment. Lamotrigine may offer promise in the treatment of this condition.

Objective: To assess the use of lamotrigine to treat symptoms of affective instability in patients with borderline personality disorder.

Methods: Charts of patients treated with lamotrigine in a private practice during the period of 2003–2004 were reviewed. Patients were included in the analysis if they had been given a clinical diagnosis of borderline personality disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision, had continued to display affective instability while taking their previous medications before being treated with lamotrigine; had received a Clinical Global Impression-Severity score before and after lamotrigine therapy; had been treated with lamotrigine, as monotherapy or adjunctive therapy, at a dose ranging from 50–200 mg/day; and continued to take lamotrigine for at least 3 months.

Results: The charts of 13 patients were reviewed and included in the analysis. All patients were female, 19–43 years of age, and had reported continuing symptoms of affective instability despite treatment with two to seven psychotropic drugs, including, but not limited to, fluoxetine, paroxetine, escitalopram, buproprion, and clonazepan. The duration of lamotrigine treatment, before the end of the period covered by the chart review was 3–15 months. The patients had initial Clinical Global Impression-Severity scores of 5 or 6 and a final scores of 1 or 2, except for one patient with an initial score of 3 and a final score of 1 and one patient with an initial score of 6 and a final score of 7.

Conclusion: Lamotrigine seems to be a safe and effective option for the treatment of patients with symptoms of affective instability associated with borderline personality disorder.

The last decade has witnessed remarkable progress in the understanding of the mammalian cannabinoid system, from the cloning of the endogenous cannabinoid receptor to the discovery of new pharmacologic compounds acting on this receptor. Current and planned studies in humans include compounds with effects ranging from direct antagonists to inhibitors of reuptake and breakdown. This progress has been accompanied by a much greater understanding of the role of the cannabinoid system in modulating the neural circuitry that mediates anxiety and fear responses. This review focuses on the neural circuitry and pharmacology of the cannabinoid system as it relates to the acquisition, expression, and extinction of conditioned fear as a model of human anxiety. Preclinical studies suggest that these may provide important emerging targets for new treatments of anxiety disorders.

Introduction: Because major depressive disorder (MDD) is often chronic and recurrent, even pediatric patients who are treated successfully during an acute episode may need longer-term treatment. Yet, data on long-term treatment with antidepressants in pediatric MDD are limited.

Objective: To evaluate long-term effectiveness and safety of treatment with venlafaxine extended-release (ER) in children and adolescents with MDD.

Methods: Subjects (n=86) 7–17 years of age with MDD entered a multicenter, open-label study of flexible-dose venlafaxine ER for 6 weeks of acute treatment, followed by continuation treatment for up to 6 months total treatment. The primary efficacy variable was the Children's Depression Rating Scale-Revised (CDRS-R) total score (intent-to-treat population).

Results: Mean CDRS-R total score decreased from 60.1±10.0 at baseline to 36.3±13.1 at week 6, and to 33.8±15.0 at 6 months (last observation carried forward). Among completers (n=36), the mean CDRS-R total score was 24.3±7.6 at the end of 6 months of treatment. The most frequent treatment-emergent adverse events were headache (53%), nausea (26%), infection (24%), abdominal pain (22%), vomiting (21%), and pharyngitis (19%). Fifteen (17%) participants discontinued due to adverse events, 9 of whom did so within the first 6 weeks. Serious adverse events (suicide attempt [two], hostility [two], hallucinations, depression, and pharyngitis) occurred in seven patients. There were no suicides.

Conclusion: Most improvement with venlafaxine ER occurs during the first 6 weeks of treatment. Prescribers should be alert to signs of suicidal ideation and hostility in pediatric patients.