Menopause Analytical Hormonal Correlate Outcome Study (MAHCOS) and the association to brain electrophysiology (P300) in a clinical setting.

Various studies have demonstrated that increased leptin levels and obesity are inversely related to cognitive decline in menopausal women. It is hypothesized that adiposity is inversely correlated with cognitive decline, as women with increased weight are less vulnerable to diminishing cognition. However, it is increasingly observed that menopausal women, even with increased adiposity, experience significant cognitive decline. Positron emission tomography (PET) has been used to analyze cognitive function and processing in menopausal women. Evoked potentials (P300) and neurophysiologic tests have validated brain metabolism in cognitively impaired patients. Post-hoc analyses of 796 female patients entering PATH Medical Clinic, between January 4, 2009 and February 24, 2013, were performed as part of the "Menopause Analytical Hormonal Correlate Outcome Study" (MAHCOS). Patient age range was 39-76 years (46.7 ± 0.2). P300 latency and amplitude correlated with a number of hormones: follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol, estrone, estriol, DHEA, pregnenolone, progesterone, free and total testosterone, thyroid stimulating hormone (TSH), Vitamins D 1.25 and D 25OH, leptin, and insulin-like growth factor-binding protein 3 (IGF-BP3). Corrected statistics did not reveal significant associations with P300 latency or amplitude for these hormones except for leptin plasma levels. However, factor analysis showed that FSH and LH clustered together with Vitamin D1.25 and Vitamin D25OH, P300 latency (not amplitude), and log leptin were found to be associated in the same cluster. Utilizing regression analysis, once age adjusted, leptin was the only significant predictor for latency or speed (p = 0.03) with an effect size of 0.23. Higher plasma leptin levels were associated with abnormal P300 speed (OR = 0.98). Our findings show a significant relationship of higher plasma leptin levels, potentially due to leptin resistance, and prolonged P300 latency. This suggests leptin resistance may delay electrophysiological processing of memory and attention, which appears to be the first of such an association.

Coupling Genetic Addiction Risk Score (GARS) with Electrotherapy: Fighting Iatrogenic Opioid Dependence.

The endemic of legal opioid iatrogenic induced prescription drug abuse is of major world-wide concern. Understanding pain pathways and the role of dopaminergic tone in the neurophysiology of pain relief provides potential therapeutic solutions. A 2011 NIDA report indicated that approximately 8.7% of the entire US population above the age of 12 years has used a psychoactive drug within the past 30 days. It has been reported that the overall genetic contribution to the variance of Substance Use Disorder (SUD) was approximately 60% but each candidate gene evaluated by GWAS was relatively small. In an attempt to combat this global endemic we are proposing a number of alternative strategies. Prevention of death due to opioid overdose and attenuation of prescription abuse should focus on strategies that target 1) high-dosage medical users; 2) persons who seek care from multiple doctors; 3) persons involved in "drug diversion"; 4) genetic testing for addiction liability and severity indices; 5) non-pharmacolgical analgesic treatments such as electrotherapy.