An fMRI study examining effects of acute D-cycloserine during symptom provocation in spider phobia.

BACKGROUND: Exposure-based therapy for anxiety disorders is believed to operate on the basis of fear extinction. Studies have shown acute administration of D-cycloserine (DCS) enhances fear extinction in animals and facilitates exposure therapy in humans, but the neural mechanisms are not completely understood. To date, no study has examined neural effects of acute DCS in anxiety-disordered populations. METHODS: Two hours prior to functional magnetic resonance imaging scanning, 23 spider-phobic and 23 non-phobic participants were randomized to receive DCS 100 mg or placebo. During scanning, participants viewed spider, butterfly, and Gaussian-blurred baseline images in a block-design paradigm. Diagnostic and treatment groups were compared regarding differential activations to spider versus butterfly stimuli. RESULTS: In the phobic group, DCS enhanced prefrontal (PFC), dorsal anterior cingulate (ACC), and insula activations. For controls, DCS enhanced ventral ACC and caudate activations. There was a positive correlation between lateral PFC and amygdala activation for the placebo-phobic group. Reported distress during symptom provocation was correlated with amygdala activation in the placebo-phobic group and orbitofrontal cortex activation in the DCS-phobic group. CONCLUSIONS: Results suggest that during initial phobic symptom provocation DCS enhances activation in regions involved in cognitive control and interoceptive integration, including the PFC, ACC, and insular cortices for phobic participants.

Efficacy and safety of selective serotonin reuptake inhibitors in the treatment of depression in children and adolescents: practitioner review.

BACKGROUND: Given the widespread reports involving the use of selective serotonin reuptake inhibitors (SSRIs) in children, the present paper reviews and discusses published double-blind, placebo-controlled studies assessing the safety and efficacy of SSRIs in children and adolescents with major depressive disorder. METHODS: Published and unpublished double-blind, placebo-controlled studies of SSRIs in children and adolescents with depression during the years 1990-2004 were reviewed. A MEDLINE search was performed using the words 'depression', 'randomised controlled trial', 'SSRIs', 'children' and 'adolescents'. The GlaxoSmithKline website was also searched for relevant studies on paroxetine. Outcome measures were the Clinical Global Impressions scale, the Children's Depression Rating Scale-Revised, the Hamilton Rating Scale for Depression, the depression subscales of the Kiddie Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version, and the Montgomery and Asberg Depression Rating Scale. Adverse effects and withdrawal rates are reported. RESULTS: There were seven randomised, placebo-controlled trials involving 1619 children and adolescents aged 6-18 years in total. The SSRIs fluoxetine, paroxetine, sertraline and citalopram were reported to exhibit safety and efficacy for treatment of depression in children and adolescents. Reanalysis of published and unpublished studies by the US FDA and the UK's Medicines and Healthcare products Regulatory Agency (MHRA) raised alerts regarding higher suicidal ideation rates from SSRIs in this population. Present guidelines are discussed. CONCLUSIONS: SSRIs remain a first-line pharmacological treatment for depression in children and adolescents for whom psychotherapy has failed or is unavailable. Suicidal ideation and behaviours merit close monitoring. More studies are needed.