Leo Sher, M.D.

The research team led by Alexander Neumeister, MD, Associate Professor of Psychiatry at Mount Sinai School of Medicine and a Distinguished Guest of our website www.internetandpsychiatry.com (please, see the “Distinguished Guests” section of our website), found that a history of severe trauma exposure in patients with posttraumatic stress disorder (PTSD) and trauma exposed individuals without PTSD was associated with marked reductions in regional [¹¹C]P943 binding potential in the caudate, the amygdala, and the anterior cingulate cortex. Participant age at first trauma exposure was strongly associated with low [¹¹C]P943 binding potential.

R-1-[4-(2-methoxy-isopropyl)-phenyl]-3-[2-(4-methyl-piperazin-1-yl)benzyl]-pyrrolidin-2-one (P943) is a potent 5‑HT_1B antagonist in vitro, which binds with high affinity to the human 5‑HT_1B receptor expressed in HeLa cells (K_I = 0.77 nM). The affinity of P943 for other 5‑HT and non-5‑HT receptors is at least 100-fold lower, making this a highly 5‑HT_1B-selective ligand (e.g. K_I = 85 nM for 5‑HT_1A receptors). This means that [¹¹C]P943 binding potential reflects the function of the 5‑HT_1B receptors.

This observation by Prof. Neumeister and his associates is consistent with a notion that trauma at a young age causes long-lasting neurobiological and psychological effects. The patients in the study included victims of childhood abuse, domestic violence, and military veterans.

The results of the study have been published in the Archives of General Psychiatry. The authors of the article in the Archives are: James W. Murrough, MD; Christoph Czermak, MD; Shannan Henry, BS; Nabeel Nabulsi, PhD; Jean-Dominique Gallezot, PhD; Ralitza Gueorguieva, PhD; Beata Planeta-Wilson, MS; John H. Krystal, MD; John F. Neumaier, MD, PhD; Yiyun Huang, PhD; Yu-Shin Ding, PhD; Richard E. Carson, PhD; and Alexander Neumeister, MD. For more information, please click here.