Long-term outcome of children and adolescents with obsessive-compulsive disorder: a 7-9-year follow-up of a randomized clinical trial.

Pediatric obsessive-compulsive disorder (OCD) is an impairing disorder frequently associated with long-term persistence. Long-term follow-up studies that investigated psychopathological trajectories after initial treatment are scarce. The present study is a 7-9-year follow-up of a randomized clinical trial (RCT) that tested the efficacy of group cognitive-behavioral therapy (CBT) and sertraline for children with OCD (n = 40), and aimed to describe long-term outcomes of pediatric OCD and identify predictors of these outcomes. Thirty-five participants who were included in the original study were recruited for follow-up evaluations. Participants underwent a comprehensive assessment of demographic and clinical characteristics comprised of the Structured Clinical Interview for DSM Disorders (SCID) and/or Kiddie-Schedule of Affective Disorders and Schizophrenia Present-Lifetime (K-SADS-PL), and the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Thirty-three participants had a complete psychiatric assessment at follow-up (mean age 21 years, SD 3.2; 65% male). At follow-up, 13 (39.4%) participants had an OCD diagnosis, 10 (30.3%) had a diagnosis of any mental disorder (excluding OCD), and 10 (30.3%) did not have any diagnosis of mental disorder. In total, 23 participants (69.7%) had at least one mental disorder (including OCD). Among those without OCD (n = 20), 60.6% had a mental disorder. The following characteristics at follow-up were associated with OCD diagnosis: YBOCS total score (p < 0.001), global functioning (p = 0.008), and presence of any anxiety disorder (p = 0.027). Being treated with GCBT or sertraline during the original RCT did not predict OCD at follow-up. New treatment strategies should consider the role of psychopathological trajectories using a dynamic approach to combine or change interventions to enhance prognosis.

Amygdala and Hypothalamus: Historical Overview With Focus on Aggression.

Aggressiveness has a high prevalence in psychiatric patients and is a major health problem. Two brain areas involved in the neural network of aggressive behavior are the amygdala and the hypothalamus. While pharmacological treatments are effective in most patients, some do not properly respond to conventional therapies and are considered medically refractory. In this population, surgical procedures (ie, stereotactic lesions and deep brain stimulation) have been performed in an attempt to improve symptomatology and quality of life. Clinical results obtained after surgery are difficult to interpret, and the mechanisms responsible for postoperative reductions in aggressive behavior are unknown. We review the rationale and neurobiological characteristics that may help to explain why functional neurosurgery has been proposed to control aggressive behavior.

Reduced prefrontal activation in pediatric patients with obsessive-compulsive disorder during verbal episodic memory encoding.

OBJECTIVE: Patients with obsessive-compulsive disorder (OCD) often present with deficits in episodic memory, and there is evidence that these difficulties may be secondary to executive dysfunction, that is, impaired selection and/or application of memory-encoding strategies (mediation hypothesis). Semantic clustering is an effective strategy to enhance encoding of verbal episodic memory (VEM) when word lists are semantically related. Self-initiated mobilization of this strategy has been associated with increased activity in the prefrontal cortex, particularly the orbitofrontal cortex, a key region in the pathophysiology of OCD. We therefore studied children and adolescents with OCD during uncued semantic clustering strategy application in a VEM functional magnetic resonance imaging (fMRI)-encoding paradigm. METHOD: A total of 25 pediatric patients with OCD (aged 8.1-17.5 years) and 25 healthy controls (HC, aged 8.1-16.9) matched for age, gender, handedness, and IQ were evaluated using a block design VEM paradigm that manipulated semantically related and unrelated words. RESULTS: The semantic clustering strategy score (SCS) predicted VEM performance in HC (p < .001, R(2) = 0.635), but not in patients (p = .099). Children with OCD also presented hypoactivation in the dorsomedial prefrontal cortex (cluster-corrected p < .001). Within-group analysis revealed a negative correlation between Yale-Brown Obsessive Compulsive Scale scores and activation of orbitofrontal cortex in the group with OCD. Finally, a positive correlation between age and SCS was found in HC (p = .001, r = 0.635), but not in patients with OCD (p = .936, r = 0.017). CONCLUSION: Children with OCD presented altered brain activation during the VEM paradigm and absence of expected correlation between SCS and age, and between SCS and total words recalled. These results suggest that different neural mechanisms underlie self-initiated semantic clustering in OCD.

Comparison among clomipramine, fluoxetine, and placebo for the treatment of anxiety disorders in children and adolescents.

OBJECTIVE: The purpose of this study was to test the efficacy of clomipramine and fluoxetine, controlled by placebo, and compare their action in children and adolescents with anxiety disorders. METHOD: Thirty subjects (ages 7-17 years), who were diagnosed with generalized anxiety disorder and/or separation anxiety disorder and/or social phobia, were submitted to a 12 week double-blind, randomized, placebo-controlled trial of clomipramine and fluoxetine. The instruments included: the Schedule for Affective Disorders and Schizophrenia, the Multidimensional Anxiety Scale for Children, the Children's Depression Inventory, the Clinical Global Impressions, and the Children's Global Assessment Scale. RESULTS: All groups (clomipramine [n=9], fluoxetine [n=10], placebo [n=11]) showed a significant improvement after 12 weeks of treatment. There were significant differences between the fluoxetine and placebo groups in some ratings of anxiety severity and impairment. No significant differences were observed between clomipramine and placebo groups or between fluoxetine and clomipramine groups. CONCLUSIONS: Treatment with placebo showed an unusual high response rate. Clomipramine showed similar efficacy compared with fluoxetine, although it was not superior to placebo.