Serge Mosovich

Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger's disorders.

Autism is a neurodevelopmental disorder characterized by dysfunction in three core behavioral domains: repetitive behaviors, social deficits, and language abnormalities. There is evidence that abnormalities exist in peptide systems, particularly the oxytocin system, in autism spectrum patients. Furthermore, oxytocin and the closely related peptide vasopressin are known to play a role in social and repetitive behaviors. This study examined the impact of oxytocin on repetitive behaviors in 15 adults with autism or Aspergers disorder via randomized double-blind oxytocin and placebo challenges. The primary outcome measure was an instrument rating six repetitive behaviors: need to know, repeating, ordering, need to tell/ask, self-injury, and touching. Patients with autism spectrum disorders showed a significant reduction in repetitive behaviors following oxytocin infusion in comparison to placebo infusion. Repetitive behavior in autism spectrum disorders may be related to abnormalities in the oxytocin system, and may be partially ameliorated by synthetic oxytocin infusion.

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 Aspergers 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.

NSAIDs Are Associated with Lower Depression Scores in Patients with Osteoarthritis

BACKGROUND Studies have demonstrated the success of augmentation of antidepressant therapy with nonsteroidal anti-inflammatory drugs (NSAID) in decreasing depressive symptoms; however, little is known about the benefit of NSAID therapy on depressive symptoms. METHODS This study pooled data from 5 postapproval trials, each trial a 6-week, multicenter, randomized, double-blinded, placebo-controlled, active-comparator, parallel-group study in subjects with active osteoarthritis. Subjects were randomized to placebo group, ibuprofen 800 mg 3 times daily or naproxen 500 mg twice daily group, or Celebrex 200 mg daily group. Apart from different ethnicities enrolled, these trials had identical study designs. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Outcomes measured were change in PHQ-9 score after 6 weeks of NSAID therapy and change in classification of depression with a PHQ-9 score ≥10 as a marker of depression. RESULTS There were 1497 patients included. Median PHQ-9 score was similar in all 3 groups at baseline and after 6 weeks of treatment. Multivariable regression analysis demonstrated a detectable effect in lowering PHQ-9 score in the ibuprofen or naproxen group (-0.31) and Celebrex group (-0.61) (P = .0390). With respect to the change in classification of depression, logistic regression analysis demonstrated a trend towards significant treatment effect of all NSAIDs compared with placebo. CONCLUSION Our analysis of pooled data from 5 postapproval trials shows that NSAID usage demonstrates a trend towards reduction of depression symptoms in patients with osteoarthritis based upon PHQ-9 scores. Future clinical trials should investigate this association with maximum dosage of drugs, increased treatment duration, and monitoring of social and environmental changes.

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 Aspergers 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.

Chagas disease as a mechanistic model for testing a novel hypothesis

The association between depression and cardiovascular disease is well documented. Nevertheless, the process through which they are linked remains unknown, as does the direction of this relationship. Studies have suggested both that depression is a risk factor for heart disease and that heart disease is a risk factor for depression. A number of studies have established that a relationship exists between depression and inflammation, with alterations in the levels of inflammatory markers (IL-1, IL-6, TNF-alpha and others). Depressive symptoms have also been identified in many diseases characterized by inflammatory processes e.g. rheumatoid arthritis, bronchial asthma, diabetes, tuberculosis and cardiovascular diseases. In this brief viewpoint, we explain and propose how to use Chagas disease, a disorder characterized by inflammatory processes and leading to cardiovascular and autonomic problems, as a model for studying the directionality of the relationship between heart disease and depression.

The Neuropsychiatry of Autism and Asperger's Disorder: Review of the Literature and Case Reports

The literature on neuropsychiatric, neuropsychological, and neuroimaging findings in autism and Aspergers disorder is briefly reviewed. Neurological soft sign, neuropsychological, and positron-emission tomography findings in one patient with Aspergers disorder and one patient with autism are highlighted, discussed as examples of heterogeneity, and integrated with the relevant literature.