Research over the past decades has sought to elucidate the neurobiological causes of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). More recently, there is increasing interest into the relationship of co-morbid PTSD and MDD given their high rates of co-occurrence and the clinical challenges found in this severely ill patient population. Ligand-based imaging techniques, while more widely applied to PTSD and MDD alone, have not been utilized to examine systematically their co-occurrence. The proposed translational research study aims to expand current knowledge of the neurobiological mechanisms of the co-occurrence of PTSD and MDD using state-of-the-art brain imaging techniques with positron emission tomography (PET) on a high resolution research tomograph (HRRT) and a novel radioligand for the serotonin (5-HT) 1B receptor. A growing body of evidence suggests that the 5-HT1B receptor might play an important role in the etiology of mood and anxiety disorders, and potentially also in their co-occurrence. The 5-HT1B receptor plays a central role in the regulation of serotonin (5-HT) transmission, mesocorticolimbic circuitry functioning and in the pathophysiology of mood and anxiety disorders. As selective ligands for the 5-HT1B receptor have only recently become available, knowledge for the involvement of 5-HT1B receptors in these disorders is still limited. Thus, in vivo quantitation of the density and distribution of 5-HT1B receptors might provide important insights into mechanisms contributing to the co-morbidity of PTSD and MDD. The Yale Positron Emission Tomography (PET) Center has been a pioneer in the development of a PET radiotracer selective for 5-HT1B receptors. We propose to apply this innovative ligand to study for the first time systematically the co-occurrence of PTSD and MDD. We propose using [11C]P943, a selective, high affinity 5- HT1B receptor antagonist, to investigate 5-HT1B receptor binding potential (BPND) in PTSD subjects with co-morbid MDD and MDD subjects without history of trauma. We will also compare their data to cohorts of patients with PTSD without MDD and healthy control subjects which have been collected under a different grant mechanism. We believe that this study will generate important novel results which will inform us about the neurobiological mechanisms associated with co-morbid PTSD and MDD. In addition, the results derived from this research has the potential to inform the development of treatment procedures that are directed specifically to co-morbid symptoms, guide initial dosing of new therapeutic agents and that are central to predict symptom onset, monitor disease progression and assess the efficacy of therapeutic agents.

Public Health Relevance

The neurotransmitter serotonin plays an important role in the development of post-traumatic stress disorder (PTSD) and depression. With the use of positron emission tomography (PET) and administration of a radiotracer, we are able to measure the distribution of serotonin type 1B receptors in the brain. This method allows to determining whether people with PTSD and depression show a different number of serotonin 1b receptors in the brain as compared to healthy people without PTSD and depression and people with only depression.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BBBP-J (50))
Program Officer
Tuma, Farris K
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Icahn School of Medicine at Mount Sinai
Schools of Medicine
New York
United States
Zip Code
Neumeister, Alexander; Seidel, Jordan; Ragen, Benjamin J et al. (2015) Translational evidence for a role of endocannabinoids in the etiology and treatment of posttraumatic stress disorder. Psychoneuroendocrinology 51:577-84
Ragen, Benjamin J; Seidel, Jordan; Chollak, Christine et al. (2015) Investigational drugs under development for the treatment of PTSD. Expert Opin Investig Drugs 24:659-72
Horn, Charlotte A C; Pietrzak, Robert H; Corsi-Travali, Stefani et al. (2014) Linking plasma cortisol levels to phenotypic heterogeneity of posttraumatic stress symptomatology. Psychoneuroendocrinology 39:88-93
Pietrzak, Robert H; Naganawa, Mika; Huang, Yiyun et al. (2014) Association of in vivo ?-opioid receptor availability and the transdiagnostic dimensional expression of trauma-related psychopathology. JAMA Psychiatry 71:1262-70
Pietrzak, Robert H; Huang, Yiyun; Corsi-Travali, Stefani et al. (2014) Cannabinoid type 1 receptor availability in the amygdala mediates threat processing in trauma survivors. Neuropsychopharmacology 39:2519-28
Bailey, Christopher R; Cordell, Elisabeth; Sobin, Sean M et al. (2013) Recent progress in understanding the pathophysiology of post-traumatic stress disorder: implications for targeted pharmacological treatment. CNS Drugs 27:221-32
Potenza, Marc N; Walderhaug, Espen; Henry, Shannan et al. (2013) Serotonin 1B receptor imaging in pathological gambling. World J Biol Psychiatry 14:139-45
Neumeister, A; Normandin, M D; Pietrzak, R H et al. (2013) Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: a positron emission tomography study. Mol Psychiatry 18:1034-40
Pietrzak, Robert H; Gallezot, Jean-Dominique; Ding, Yu-Shin et al. (2013) Association of posttraumatic stress disorder with reduced in vivo norepinephrine transporter availability in the locus coeruleus. JAMA Psychiatry 70:1199-205
Matuskey, David; Pittman, Brian; Planeta-Wilson, Beata et al. (2012) Age effects on serotonin receptor 1B as assessed by PET. J Nucl Med 53:1411-4

Showing the most recent 10 out of 15 publications