Neuro-psychopharmacogenetics and Neurological Antecedents of Posttraumatic Stress Disorder: Unlocking the Mysteries of Resilience and Vulnerability

Abdalla      Bowirrat; Thomas      J.H. Chen; Kenneth      Blum; Margaret      Madigan; John      A. Bailey; Amanda      Lih Chuan Chen; B.      William Downs; Eric      R. Braverman; Shahien      Radi; Roger      L. Waite; Mallory      Kerner; John      Giordano; Siohban      Morse; Marlene      Oscar-Berman; Mark      Gold

Abstract

Background and Hypothesis: Although the biological underpinnings of immediate and protracted traumarelated responses are extremely complex, 40 years of research on humans and other mammals have demonstrated that trauma (particularly trauma early in the life cycle) has long-term effects on neurochemical responses to stressful events. These effects include the magnitude of the catecholamine response and the duration and extent of the cortisol response. In addition, a number of other biological systems are involved, including mesolimbic brain structures and various neurotransmitters. An understanding of the many genetic and environmental interactions contributing to stress-related responses will provide a diagnostic and treatment map, which will illuminate the vulnerability and resilience of individuals to Posttraumatic Stress Disorder (PTSD). Proposal and Conclusions: We propose that successful treatment of PTSD will involve preliminary genetic testing for specific polymorphisms. Early detection is especially important, because early treatment can improve outcome. When genetic testing reveals deficiencies, vulnerable individuals can be recommended for treatment with “body friendly” pharmacologic substances and/or nutrients. Results of our research suggest the following genes should be tested: serotoninergic, dopaminergic (DRD2, DAT, DBH), glucocorticoid, GABAergic (GABRB), apolipoprotein systems (APOE2), brain-derived neurotrophic factor, Monamine B, CNR1, Myo6, CRF-1 and CRF-2 receptors, and neuropeptide Y (NPY). Treatment in part should be developed that would up-regulate the expression of these genes to bring about a feeling of well being as well as a reduction in the frequency and intensity of the symptoms of PTSD.

Keywords: Post-traumatic Stress Disorder (PTSD), genes and environment, neurotransmitters, Reward Deficiency Syndrome (RDS), Neuro-psychopharmacogenetics, Neurological Antecedents, Posttraumatic Stress, Resilience, Vulnerability, brain-imaging, anticipatory stress, homeostasis, Hysteria, antidepressants, anxiolytic drugs, nutraceuticals, amelioration, hyper-arousability, NEUROCHEMISTRY, norepinephrine, epinephrine, transmitters, acetylcholine, endorphins, somatostatin, pressin, oxytocin, pituitary, neuropeptides, galanin, Serotonin, vasoconstrictor, tryptophan, monoamine oxidase, tyramine, veterans, Cortisol, Hippocampus, cognitive deficits, traumatic exposure, cool and cognitive, oxycodone, morphine, fentanyl, hypothalamus, Glucocorticoids, stress hormone, hypoadrenia, Cushing's disease, Addison's disease, fibromyalgia, hypothyroidism, chronic fatigue, insomnia, daytime somnolence, flashbulb memories, cortico-trophic hormone, Corticotropin Releasing Factor, pharmacotherapy, clonidine, Limbic System, amygdala, neuroendocrine, brainstem, Testosterone, Estrogen, Thalamus, reentrant thalamocortical loops, Orbitofrontal Cortex, Medial Prefrontal Cortex, drug rehabilitation