Innovations In Clinical Neuroscience

ISCTM Supplement 2015

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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[ V O L U M E 1 2 , N U M B E R 3 – 4 , S U P P L E M E N T A , M A R C H – A P R I L 2 0 1 5 ] Innovations in CLINICAL NEUROSCIENCE 33S with a resulting sensitivity of 87 percent and specificity of 89 percent. There was a significant difference in SCL between male and female subjects but none between drug-free and medicated patients. SCL was abnormal in all depression subtypes. Thus, the SCL may represent a biological final common pathway in depression and may prove to be a very effective diagnostic test for depression. Today these data can easily be collected in real-life activities, where extreme stressors occur, in contrast with traditional measures in labs, where patient behavior may not have fully reflected their behavioral range. Among the reasons to examine EDA as an objective treatment measure in schizophrenia are that electrodermal response recovery rate has been shown to be an especially valid predictor in some risk studies of schizophrenia. 31,32 Other evidence shows disturbances in the hippocampus and amygdala in schizophrenics, structures that elicit EDA. 33 The recommendation, if there is believed to be involvement of the amygdala, hippocampus, or anterior cingulate, is to measure the EDA on both wrists, allowing significant asymmetries in activation to be detected. In general, studies that at one time were done in the lab, measuring only one side of EDA (usually the non-dominant side) can now be easily conducted over full days and weeks, on both sides of the body if desired. The results give a more complete and objective picture of autonomic activation and its variation in conditions of depression and schizophrenia. These measures have the potential to create objective and significant personalized characterizations of patient subgroups and their responses to treatment. Therefore, a specific activity pattern can be used to define subgroups which may respond preferably to a given compound. Moreover, changes in the activity pattern may be used as markers of target engagement and therefore necessary early response markers. TARGET-BASED BIOMARKER SELECTION: MINERALOCORTICOID RECEPTOR-BASED BIOMARKERS AND TREATMENT OUTCOME IN DEPRESSION (H. Murck) It is generally considered that the era of modern psychopharmacology began in the 1950s with the introduction of antipsychotic and antidepressive medication. Imipramine, the parent compound of current antidepressants, was introduced in 1957. Following the observation of its clinical effect, hypothesis about the pathophysiology of depression were constructed around the known pharmacology of imipramine at the time. This led to the catecholamine hypothesis of depression, 34 which was most influential. However, besides the focus on monoamines two alternative biochemical hypotheses of depressive were clearly identified in the early years of modern biological psychiatry: the stress-hormone-hypothesis and the electrolyte-hypothesis. 35 Nevertheless, the monoamine hypothesis became the basis for most drug developments in the area of depression despite the fact, that the parent compound imipramine, whose pharmacology provided the basis for this hypothesis, has a much more complex pharmacology than being just a monoamine reuptake inhibitor. 3 6 The stress-hormone hypothesis focused on hypercortisolism, which can be identified in the most severe patients with depression, 37 whereas other stress hormones did not find much interest. The electrolyte hypothesis was mainly neglected for the last 50 years. This is despite the fact that a connection between the neuroendocrine changes of stress and electrolyte regulation was recognized earlier: In 1969 Coppen noted that "in view of the considerable disturbances in electrolyte distribution found in depression studies on aldosterone secretion would be most valuable." 38 A newer area of research, which is in good alignment with the potential importance of aldosterone in depression, is based on the observation of inflammatory changes in depression. 39 This link between inflammation and mineralocorticoids was recognized as early as in the 1950s by the founder of stress research. 40 Selye classified "prophlogistic" corticoids (PC), and identified those with the mineralocorticoids, such as aldosterone and "antiphlogistic" corticoids (AC), which he identified with glucocorticoids such as cortisol. Despite the neglect of aldosterone as the principal ligand of the mineralocorticoid receptor (MR), this receptor itself was studied in the context of major depression: The expression of the mineralocorticoid (MR) receptors, but not the glucocorticoid receptors (GR) are FIGURE 2. Skin conductance analysis of sleep peaks. The green arrows indicate regions with high-frequency peaks abutting transitions to REM. The yellow arrows indicate regions with high frequency peaks interrupted by wake.

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