Reversal of startle gating deficits in transgenic mice overexpressing corticotropin-releasing factor by antipsychotic drugs.

Chronically elevated levels of corticotropin-releasing factor (CRF) in transgenic mice overexpressing CRF in the brain (CRF-OE) appear to be associated with alterations commonly associated with major depressive disorder, as well as with sensorimotor gating deficits commonly associated with schizophrenia. In the present study, we tested the hypothesis that antipsychotics may be effective in normalizing prepulse inhibition (PPI) of acoustic startle in CRF-OE mice, which display impaired sensorimotor gating compared to wild-type (WT) mice. The typical antipsychotic haloperidol and atypical antipsychotic risperidone improved PPI in the CRF-OE mice, but were ineffective in WT mice. The atypical antipsychotic clozapine did not influence PPI in CRF-OE mice, but reduced gating in WT mice. This effect of clozapine in the CRF-OE mice may thus be regarded as a relative improvement, consistent with the observed effect of haloperidol and risperidone. As expected, the anxiolytic, nonantipsychotic chlordiazepoxide was devoid of any effect. All four compounds dose-dependently reduced the acoustic startle response irrespective of genotype. These results indicate that antipsychotic drugs are effective in improving startle gating deficits in the CRF-OE mice. Hence, the CRF-OE mouse model may represent an animal model for certain aspects of psychotic depression, and could be a valuable tool for research addressing the impact of chronically elevated levels of CRF on information processing.     

The role of medical comorbidity in outcome of major depression in primary care: the PROSPECT study.

OBJECTIVE: The authors described the influence of specific medical conditions on clinical remission and response of major depression (MDD) in a clinical trial evaluating a care-management intervention among older primary-care patients. METHODS: Adults age 60 years and older were randomly selected and screened for depression. Participants were randomly assigned to Usual Care or to an Intervention with a depression care-manager offering algorithm-based care for MDD. In all, 324 adults meeting criteria for MDD were included in these analyses. Remission and response was defined by a score on the Hamilton Rating Scale for Depression <10 and by a decrease from baseline of > or =50%, respectively. Medical comorbidity was ascertained through self-report. Cognitive impairment was defined by a score <24 on the Mini-Mental State Exam (MMSE). RESULTS: In Usual Care, rates of remission were faster in persons who reported atrial fibrillation (AF) than in persons who did not report AF and slower in persons who reported chronic pulmonary disease than in persons who did not report chronic pulmonary disease; rates of response were less stable in persons with MMSE <24 than in those with MMSE > or =24. In the Intervention condition, none of the specific chronic medical conditions were significantly associated with outcomes for MDD. CONCLUSIONS: Because disease-specific findings were observed in persons who received Usual Care but not in persons who received more intensive treatment in the Intervention condition, our results suggest that the association of medical comorbidity and treatment outcomes for MDD may be determined by the intensity of treatment for depression.