Innovations In Clinical Neuroscience

ISCTM Supplement 2015

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

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Innovations in CLINICAL NEUROSCIENCE [ 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 ] 32S melancholics or controls. Patients with melancholic depression did not differ from controls on any of these three measures. For an interesting review of r ecent findings on cortisol and inflammation from other studies over the last two decades see Penninx et al. 22 Taken together, the data presented above suggest that the two different clinical entities of melancholic depression and atypical depression may result from distinct pathophysiologic processes. The pathophysiology of melancholic depression may be related to hyperactivity of the HPA-axis, smoking and even environmental stress, while that of atypical depression may be associated with increased inflammation, metabolic syndrome and obesity. These two entities may be the result of different genetic influences. This then begs the question, what might be the importance of these findings regarding treatment? Clinical trial data appear to support the importance of this biological differentiation. Raison et al 23 conducted a 12-week randomized clinical trial of three infusions of TNF antagonist infliximab versus placebo in 60 out-patients with treatment- resistant depression (TRD) There was no difference between the two treatment groups, but when analyzed as a function of baseline hs-CRP concentration, there was a trend in favor of infliximab for those patients with higher baseline concentrations of CRP. 23 In light of the above, one might well ask whether or not oral anti- inflammatory agents, such as cyclo- oxygenase (Cox) inhibitors may have a use as add-on therapy in MDD. A recent meta-analysis performed by Na et al 24 including four trials evaluating adjunctive celecoxib therapy in MDD showed that both changes from baseline in the 17-item HAM-D and remission rates after treatment favored adjunctive celecoxib. To conclude, the take-home message is that the clinical characterization of atypical and melancholic depression can be regarded as a proxy for two groups with distinct biological characteristics. Given the variability of clinical ratings, t he utilization of the characterized biological markers should even more sharply differentiate forms of depression with different response profiles. These data are in accordance with clinical data, which demonstrate that increased inflammatory markers (approximated by atypical clinical characteristics) on the one hand and increased HPA axis activity (approximated by melancholic characteristics) predict the efficacy of antidepressant compounds. Therefore, in designing any clinical trials program for MDD, it is important to take biological MDD heterogeneity into account by stratification for subgroups. PHYSIOLOGICAL SENSOR TECHNOLOGY FOR OBJECTIVE CLINICAL DATA IN PSYCHIATRY (R. Picard) In psychiatry there are few valid, reliable objective measures available to quantify disorders, but this situation is changing. Recent advances in physiological sensor technology can provide objective clinical data in a way that can now be utilized in large scale clinical trials. Autonomic nervous system activation, physical movement, temperature, and more can be measured using discreet portable sensors worn on the wrists or ankles. Both main branches of the autonomic nervous system can be measured: Sympathetic nervous system arousal elicits electrodermal activation (EDA), which can be measured as skin conductance using a comfortably wearable sensor. Parasympathetic nervous system arousal can be captured through analysis of the photoplethysmogram (PPG), also from the surface of the skin under a comfortable wearable band. Autonomic arousal, which is affected by emotional state, can be measured in subjects going about their activities of daily life as well as during sleep. Striking patterns of arousal can be found, some of which are counter- intuitive. For example, EDA peaks often happen in bursts during non- rapid eye movement (REM) sleep: Sano and Picard have found that patterns of these peaks in the first and l ast quadrant of sleep are more accurate than EEG for determining which study subjects improved the most on a learning task during sleep, which relates to memory consolidation (Figure 2). 25 A reasonable rationale exists for the use of bilateral EDA as objective measures in anxiety and depression. Stimulation of the left amygdala gives the most significant EDA response on the left palm; stimulation of the right amygdala gives the most significant EDA response on the right palm. 2 6 Direct right amygdala stimulation has been shown to contribute to significant increases in fear, anxiety, and sadness while direct left amygdala stimulation was not specific to these. 2 7 There are additional reasons to consider bilateral EDA for objective measurement in anxiety and depression. Juranek et al 28 examined a group of 42 children who met criteria for autism spectrum disorders. They found a significant association between anxious and depressed symptoms and right amygdala volume, as assessed by quantitative MRI, but not with left amygdala volume. This finding is to be expected given the hypothesized greater right amygdala activation in anxiety and sadness. Monk et al 29 examined amygdala activation in a group of 17 youth with GAD, and a control sample of 12 youth with no psychiatric diagnosis. Subjects with GAD showed larger right amygdala activation when viewing masked angry faces but not masked neutral faces. The amount of right amygdala activation correlated positively with GAD severity. As early as 1983, Ward et al 30 found that the mean resting skin conductance level (SCL) in 31 inpatients with major unipolar depression was decreased (2.63 μS/cm2 +/- SD 1.41 compared to 7.81 μS/cm2 +/- SD 3.0) in comparison in the control group. The best criterion below which an SCL could be considered abnormal was 4.3 μS/cm 2

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