The effect of naltrexone on body fat mass in olanzapine-treated schizophrenic or schizoaffective patients: a randomized double-blind placebo-controlled pilot study.

Olanzapine (OLZ), a commonly prescribed second generation antipsychotic drug, is associated with obesity and metabolic syndrome and may contribute to increased cardiovascular morbidity and mortality. Opioidergic neurotransmission may be implicated in the development of these metabolic disturbances. The objective of this study was to assess the effects of opioid blockade on OLZ-treated patients' metabolic status. Patients with schizophrenia or schizoaffective disorder (n=30) on a stable dose of OLZ were randomized in a double-blind fashion to receive an opioid receptor antagonist, naltrexone (NTX), (n=14) or placebo (n=16). The primary outcome measure was the change in body mass index (BMI) at 12 weeks. Secondary measures included body fat and fat-free mass, along with homeostasis model assessment-estimated insulin resistance (HOMA-IR), plasma lipids and liver function tests (LFTs). There was no significant change in BMI between the treatment arms. However, in comparison to the OLZ + placebo combination, the OLZ + NTX group displayed a significant decrease in the fat and increase in fat-free mass along with a trend towards improvement in HOMA-IR values. There were no significant differences in plasma lipids and LFTs. These findings suggest that addition of NTX to OLZ may attenuate OLZ-induced body fat mass gain. A larger study of longer duration will be needed to confirm these results.

Neurological soft signs in individuals with pathological gambling.

Increased neurological soft signs (NSSs) have been found in a number of neuropsychiatric syndromes, including chemical addiction. The present study examined NSSs related to perceptual-motor and visuospatial processing in a behavioral addiction viz., pathological gambling (PG). As compared to mentally healthy individuals, pathological gamblers displayed significantly poorer ability to copy two- and three-dimensional figures, to recognize objects against a background noise, and to orient in space on a road-map test. Results indicated that PG is associated with subtle cerebral cortical abnormalities. Further prospective clinical research is needed to address the NSSs' origin and chronology (e.g., predate or follow the development of PG) as well as their response to therapeutic interventions and/or their ability to predict such a response.

Yohimbine-induced amygdala activation in pathological gamblers: a pilot study.

RATIONALE AND OBJECTIVES: There is evidence that drug addiction is associated with increased physiological and psychological responses to stress. In this pilot functional magnetic resonance imaging (fMRI) study we assessed whether a prototype behavioral addiction, pathological gambling (PG), is likewise associated with an enhanced response to stress. METHODS: We induced stress by injecting yohimbine (0.2-0.3 mg/kg, IV), an alpha-2 adrenoceptor antagonist that elicits stress-like physiological and psychological effects in humans and in laboratory animals, to four subjects with PG and to five non-gamblers mentally healthy control subjects. Their fMRI brain responses were assessed along with subjective stress and gambling urges ratings. RESULTS: Voxelwise analyses of data sets from individual subjects, utilizing generalized linear model approach, revealed significant left amygdala activation in response to yohimbine across all PG subjects. This amygdala effect was not observed in the five control individuals. Yohimbine elicited subjective stress ratings in both groups with greater (albeit not statically significantly) average response in the PG subjects. On the other hand, yohimbine did not induce urges to gamble. CONCLUSIONS: The present data support the hypothesis of brain sensitization to pharmacologically-induced stress in PG.

Gender differences in psychosocial stress and in its relationship to gambling urges in individuals with pathological gambling.

Gender differences in the impact of psychosocial stress and in negative affective states were assessed in a group of pathological gamblers matched by demographic characteristics and by severity of gambling. Women displayed higher impact scores on the Daily Stress Inventory. Other stress measures, obtained with the Profile of Mood States (POMS), were also significantly elevated in the women group. Furthermore, women's gambling urges correlated with both stress and the POMS measure, whereas men's gambling urges correlated with the stress ratings only. These data suggest distinctive determinants of gambling urges in women with pathological gambling vis-a-vis those of men.

Psychosocial stress and its relationship to gambling urges in individuals with pathological gambling.

We sought to explore a potential link between psychosocial stress exposure and pathological gambling (PG). Patients with PG displayed significantly higher scores on the daily stress inventory (DSI) than did healthy subjects. PG patients also displayed other heightened measures of stress, including the profile of mood states, the Spielberger state-trait anxiety inventory, the Hamilton rating scale for depression and the Beck depression inventory. Multiple regression analysis revealed that only the DSI impact score was an independent predictor of gambling urges. These findings support the role of psychosocial stress in the course of PG and suggest that the former association with the urge to gamble is relatively specific to stressful events assessed with the DSI.