New insights into the link between cardiovascular disease and depression.

INTRODUCTION: Although the association between depression and cardiovascular disease (CVD) is well documented, the underlying mechanisms for this relationship remain unclear. In this paper, we present three possible models which account for the comorbidity between depression and cardiovascular disease. MODELS: The first model outlines depression as a risk factor for CVD and the second model presents CVD as a risk factor for depression. The third model proposes a common underlying pathway related to the effects of chronic stress on the body in manifesting as depression or cardiovascular disease. CONCLUSIONS: If the proposed model holds true, it may be possible that an intervention initiated before overt manifestations of CVD or depression become apparent, may delay or prevent the onset of these serious clinical entities.

Effect of fluoxetine on regional cerebral metabolism in autistic spectrum disorders: a pilot study.

The regional metabolic effects of fluoxetine were examined in patients with autism spectrum disorders. Six adult patients with DSM-IV and Autism Diagnostic Interview (ADI) diagnoses of autism (n = 5) and Asperger's syndrome (n = 1), entered a 16-wk placebo-controlled cross-over trial of fluoxetine. The patients received (18)F-deoxyglucose positron emission tomography with co-registered magnetic resonance imaging at baseline and at the end of the period of fluoxetine administration. After treatment, the patients showed significant improvement on the scores of the Yale--Brown Obsessive--Compulsive Scale -- Obsessions subscale and the Hamilton Anxiety Scale; Clinical Global Impressions -- Autism scores showed 3 of the patients much improved and 3 unchanged. Relative metabolic rates were significantly higher in the right frontal lobe following fluoxetine, especially in the anterior cingulate gyrus and the orbitofrontal cortex. Patients with higher metabolic rates in the medial frontal region and anterior cingulate when unmedicated were more likely to respond favourably to fluoxetine. These results are consistent with those in depression indicating that higher cingulate gyrus metabolic rates at baseline predict SRI response.

Increased growth hormone response to sumatriptan challenge in adult autistic disorders.

Serotonergic (5-HT) abnormalities have been documented in autism. To assess sensitivity of the 5-HT1d receptor, growth hormone response to the 5-HT1d receptor agonist sumatriptan was studied in adult autistic patients and matched normal controls. In this study, 11 adult patients with autism or Asperger's disorder were compared with nine matched controls. All subjects were randomized to single dose sumatriptan (6 mg SQ) and placebo challenges, separated by a 1-week interval, and growth hormone was measured before and during the challenges. The results showed a highly significant diagnosisxdrugxtime interaction on repeated measure analysis covaried for baseline. This suggests that autistic patients had significantly greater growth hormone response to sumatriptan than normal controls, independent of placebo effects. Therefore, abnormalities in 5-HT regulation in autism may be related to increased sensitivity of the 5-HT1d inhibitory receptor in autism.

Short-term single-blind fluvoxamine treatment of pathological gambling.

OBJECTIVE: The authors' goal was to assess the efficacy and tolerability of the selective serotonin reuptake inhibitor fluvoxamine in the treatment of pathological gambling. METHOD: Sixteen patients with pathological gambling entered an 8-week placebo lead-in phase, and 10 of these patients completed an 8-week single-blind fluvoxamine trial. RESULTS: Seven of the 10 patients who completed the fluvoxamine trial were judged treatment responders at the end of the study: 1) they had greater than 25% decreases in their gambling behavior scores on the pathological gambling modification of the Yale-Brown Obsessive Compulsive Scale, and 2) their clinician-rated Clinical Global Impression scores for gambling severity were very much improved or much improved. Fluvoxamine treatment resulted in gambling abstinence in seven of the 10 patients. CONCLUSIONS: Findings from this preliminary study suggest that fluvoxamine may be effective in reducing the urge to gamble. Randomized placebo-controlled and maintenance trials are required to confirm these findings and to determine whether improvement persists.

Diagnosis, neurobiology, and treatment of pathological gambling.

Pathological gambling is a disabling disorder that affects at least 2 1/2 million Americans and their families. Although pathological gambling has been characterized as an impulse control disorder, it has also been associated with compulsivity. Essential features of pathological gambling include constantly recurring gambling behavior that is maladaptive, in that personal, familial, and/or vocational endeavors are disrupted. Affective disorders and substance abuse often co-occur. Incidence of suicidality is extremely high. Despite the fact that this disorder is a widespread public health problem, few controlled studies of causes or treatment have been conducted. Preliminary neurobiological studies implicate serotonergic dysfunction in pathological gamblers. Treatment with serotonin reuptake inhibitors, such as clomipramine and fluvoxamine, may be effective in treating this disorder. Well-defined and controlled clinical trials in large samples of pathological gamblers are needed.

Neuropsychiatric and neuropsychological findings in conduct disorder and attention-deficit hyperactivity disorder.

Neuropsychiatric and neuropsychological evaluations were performed in a pilot study of adolescents with DSM-III-R disruptive behavior disorders, including conduct disorder (CD) and attention-deficit hyperactivity disorder (ADHD). The following comparisons were made: 1) CD comorbid with ADHD vs. CD only; 2) all subjects with ADHD vs. all non-ADHD; and 3) all subjects with CD vs. all non-CD. The CD + ADHD group had increased left-sided soft signs compared with the CD group. CD + ADHD subjects significantly underperformed CD subjects on several executive functioning measures, with no differences on Verbal IQ subtests. Results are discrepant with previous findings of deficient verbal functioning in delinquent populations. However, findings may not be generalizable because of sampling limitations.