Regulation of 5-HT Receptors and the Hypothalamic-Pituitary-Adrenal Axis

Disturbances in the serotonin (5-HT) system is the neurobiological abnormality most consistently associated with suicide. Hyperactivity of the hypothalmic-pituitary-adrenal (HPA) axis is also described in suicide victims. The HPA axis is the classical neuroendocrine system that responds to stress and whose final product, corticosteroids, targets components of the limbic system, particularly the hippocampus. We will review resulsts from animal studies that point to the possibility that many of the 5-HT receptor changes observed in suicide brains may be a result of, or may be worsened by, the HPA overactivity that may be present in some suicide victims. The results of these studies can be summarized as follows: (1) chronic unpredictable stress produces high corticosteroid levels in rats; (2) chronic stress also results in changes in specific 5-HT receptors (increases in cortical 5-HT2A and decreases in hipocampal 5-HT1A and 5-HT1B); (3) chronic antidepressant administration prevents many of the 5-HT receptor changes observed after stress; and (4) chronic antidepressant administration reverses the overactivity of the HPA axis. If indeed 5-HT receptors have a partial role in controlling affective states, then their modulation by corticosteroids provides a potential mechanism by which these hormones may regulate mood. These data may also provide a biological understanding of how stressful events may increase the risk for suicide in vulnerable individuals and may help us elucidate the neurobiological underpinnings of treatment resistance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73437/1/j.1749-6632.1997.tb52357.x.pd

Randomised controlled trials in the evaluation of non-biomedical therapeutic interventions for pain: The gold standard?

This paper offers a critical review of important issues in the implementation and interpretation of randomised controlled trials (RCTs) used to evaluate non-biomedical therapeutic interventions for pain. The analysis of methodological issues focuses on the validity, relevance and clinical importance of outcome measures; sampling and randomization bias; blinding procedures used to control for the placebo response and therapist influences, and treatment standardisation. A key issue is that pain management is inextricably linked to the establishment of a therapeutic relationship. In such circumstances, it is argued that the 'gold standard' double-blind RCT is impracticable. Those relying on RCTs as sources of evidence need to be aware that an 'unblinded' RCT can enhance placebo responses to the intervention and introduce important sources of bias. The challenge faced by healthcare researchers is to identify alternative research designs able to provide valid and reliable evidence that the proposed therapeutic intervention is capable of achieving cost-effective, clinically important and personally relevant outcomes in naturalistic settings