"According to the World Health Organization, major depression will be the second leading cause of disability by the year 2020 (Blazer, 2000). Diagnosis of depression is mainly based on symptomatic criteria, such as depressed mood, fatigue, low self-esteem and recurrent thoughts of death and suicide, and the heterogeneity of the disease suggests that multiple different biological mechanisms may underlie its aetiology (Nestler et al., 2002; Duman, 2002). "
[Show abstract][Hide abstract] ABSTRACT: Hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis and increased levels of glucocorticoid hormones in patients with depression have mostly been ascribed to impaired feedback regulation of the HPA axis, possibly caused by altered function of the receptor for glucocorticoid hormones, the glucocorticoid receptor (GR). Antidepressants, in turn, ameliorate many of the neurobiological disturbances in depression, including HPA axis hyperactivity, and thereby alleviate depressive symptoms. There is strong evidence for the notion that antidepressants exert these effects by modulating the GR. Such modulations, however, can be manifold and range from regulation of receptor expression to post-translational modifications, which may result in differences in GR nuclear translocation and GR-dependent gene transcription. The idea that the therapeutic action of antidepressants is mediated, at least in part, by restoring GR function, is consistent with studies showing that decreased GR function contributes to HPA axis hyperactivity and to the development of depressive symptoms. Conversely, excessive glucocorticoid signalling, which requires an active GR, is associated with functional impairments in the depressed brain, especially in the hippocampus, where it results in reduced neurogenesis and impaired neuroplasticity. In this review, we will focus on the GR as a key player in the precipitation, development and resolution of depression. We will discuss potential explanations for the apparent controversy between glucocorticoid resistance and the detrimental effects of excessive glucocorticoid signalling. We will review some of the evidence for modulation of the GR by antidepressants and we will provide further insight into how antidepressants may regulate the GR to overcome depressive symptoms.
"With the other drugs examined here, the number of cases of drug dependence was too small to warrant detailed probing into the background associations. There has been considerable discussion of the meaning, utility and importance of the concept of " clinical significance " within the current DSM-IV classification system (Beals et al., 2004; Blazer and Kaplan, 2000; Frances, 1998; Narrow et al., 2002 "
[Show abstract][Hide abstract] ABSTRACT: There is a need for large-scale epidemiological surveys to be (a) faithful to diagnostic specifications and (b) constrain time and participant burden associated with each section of a possibly lengthy interview.
To examine whether one "gating" approach devised for recent large-scale international psychiatric surveys results in a reduced number of identified cases of drug dependence and/or biases in estimated associations with background characteristics.
Data from a recently released cross-sectional, nationally representative household survey, the United States National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were analysed.
Forty-three thousand ninety-three English speaking adults aged 18 years and over.
Dependence upon cocaine and other illegal drug dependence, defined in two ways: "ungated" and "gated". "Ungated" dependence included all persons meeting criteria for DSM-IV dependence, without regard for DSM-IV drug abuse clinical features. "Gated" dependence required at least one feature of DSM-IV drug abuse.
There was no statistically robust decrement in the estimated prevalence of cocaine or other drug dependence using a "gated" assessment. Patterns of association of cocaine dependence with background characteristics were not appreciably different when the gated and ungated approaches were applied.
In panoramic mental health surveys, the inefficiency of an ungated approach must be balanced against the anticipated number of cases of dependence without associated social role impairments or harm. In this study, the reduction in the number of identified cocaine dependence cases appeared to be so small that even in a sample of over 40,000 participants, attenuation in population prevalence would prove difficult to detect.
Drug and Alcohol Dependence 04/2008; 93(3):227-32. DOI:10.1016/j.drugalcdep.2007.09.024 · 3.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study of a representative community survivor sample of 695 respondents from the 1954 Midtown Manhattan Study found that parental socioeconomic status unequivocally predicted help-seeking. Age, gender, adult SES, and impaired mental health in 1954 predicted help-seeking interactively. The mental health of help-seekers continued to be unfavorable, or was worsening, from 1954 to 1974.
American Journal of Orthopsychiatry 11/2001; 71(4):450-6. DOI:10.1037/0002-94188.8.131.520 · 1.36 Impact Factor
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