Leo Sher, M.D.

Post-traumatic stress disorder (PTSD) is a common psychiatric disorder which is frequently comorbid with depression (1,2). A few years ago, I proposed the concept of post-traumatic mood disorder (3). I have suggested that some or all individuals diagnosed with comorbid PTSD and depression have a separate psychobiological condition that can be termed “post-traumatic mood disorder” (PTMD). The idea was based on the fact that a lot of studies suggested that patients suffering from comorbid PTSD and depression differed clinically and biologically from individuals with PTSD alone or depression alone.For example, multiple clinical studies have indicated that comorbidity of PTSD and depression is associated with more severe symptoms compared to individuals with PTSD alone or depression alone (4,5). The concept of PTMD is also supported by a significant number of neurobiological findings. Lower affinity of alpha-2 adrenoreceptors and higher plasma tyrosine availability to the brain are associated with comorbid PTSD and depression but not with PTSD alone (6). Individuals with comorbid PTSD and depression do not exhibit the classic rapid eye movement sleep architectural modifications associated with depression, despite the fact that several other psychophysiological indices of dysphoria are detectable in their sleep (7). In fenfluramine challenge studies, depressed patients with comorbid PTSD have lower plasma cortisol compared to depressed patients without comorbid PTSD (8). Cortisol levels increase with age and the number of previous major depressive episodes is a predictor of the cortisol response to fenfluramine administration in depressed patients without PTSD but not in depressed patients with comorbid PTSD (9). Depressed subjects with comorbid PTSD have higher cerebrospinal fluid homovanillic acid levels compared with depressed subjects without comorbid PTSD (10). More recently, three new studies supported the idea of PTMD (11-13). A recent study found substantial genetic overlap between PTSD and MDD and suggested that genes implicated in the etiology of MDD are strong candidates for PTSD and vice versa (11). This observation supports the idea that comorbid PTSD and MDD may be a distinct neurobiological condition, i.e., PTMD. Two recent neuroimaging studies also support the concept of PTMD (12,13). In one study, subjects with PTSD without comorbid major depression and patients with PTSD with comorbid major depression were examined using the script-driven symptom-provocation paradigm adapted to functional magnetic resonance imaging (12). This study found different patterns of brain activation in subjects with PTSD without comorbid major depression compared to patients with PTSD with comorbid major depression. Another research group reported that PTSD patients with comorbid major depression relative to both healthy controls and trauma-exposed control subject showed reduced norepinephrine transporter expression in the left thalamus (13). PTSD patients without comorbid major depression did not show differences in norepinephrine transporter expression relative to healthy controls and trauma-exposed control subject, i.e., PTSD patients showed reduced left thalamic norepinephrine transporter expression only when having comorbid major depression. In summary, individuals with post-traumatic mood disorder may represent a unique patient population.

References:

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington DC, American Psychiatric Association, 2000: 463–468.
2. Schnurr PP, Friedman MJ, Bernardy NC. Research on posttraumatic stress disorder: epidemiology, pathophysiology, and assessment. J Clin Psychol 2002; 58: 877–889.
3. Sher L. The concept of post-traumatic mood disorder. Med Hypotheses 2005;65(2):205-10.
4. Karam EG. Comorbidity of posttraumatic stress disorder and depression. In: Fullerton C, Ursano RJ (editors). Posttraumatic Stress Disorder: Acute and Long-Term Responses to Traumas and Disaster. Progress in Psychiatry Series, No. 51. American Psychiatric Press, Washington, DC, 1997; pp. 77-90.
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8. Oquendo MA, Echavarria G, Galfalvy HC, Grunebaum MF, Burke A, Barrera A, and others. Lower cortisol levels in depressed patients with comorbid post-traumatic stress disorder. Neuropsychopharmacology 2003; 28: 591– 598.
9. Sher L, Oquendo MA, Galfalvy HC, Cooper TB, Mann JJ. Age effects on cortisol levels in depressed patients with and without a history of post-traumatic stress disorder, and healthy volunteers. J Affect Disord 2004; 82: 53-59.
10. Sher L, Oquendo MA, Li S, Burke AK, Grunebaum MF, Zalsman G, Huang YY, Mann JJ. Higher cerebrospinal fluid homovanillic acid levels in depressed patients with comorbid post-traumatic stress disorder. Eur Neuropsychopharmacol 2005; 15: 203-209.
11. Koenen KC, Fu QJ, Ertel K, Lyons MJ, Eisen SA, True WR, Goldberg J, Tsuang MT. Common genetic liability to major depression and posttraumatic stress disorder in men. J Affect Disord 2008;105(1-3):109-15.
12. Lanius RA, Frewen PA, Girotti M, Neufeld RW, Stevens TK, Densmore M Neural correlates of trauma script-imagery in posttraumatic stress disorder with and without comorbid major depression: a functional MRI investigation. Psychiatry Res. 2007;155(1):45-56.
13. Czermak C, Ding Y, Henry S, B.Planeta-Wilson B, S.Kasserman S, J.Frost J, W.Williams W, J.Krystal J, R.Carson R, A.Neumeister A. Norepinephrine transporter imaging in posttraumatic stress disorder. In: 46th Annual Meeting of the American College of Neuropsychopharmacology, Boca Raton, Florida, December 9-13, 2007. Abstracts. Program No. 133.