August 17, 2016

Neuroprogression in Patients With Bipolar Disorder and PTSD

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Ives Cavancate Passos, MD, PhD, and Flávio Kapczinski, MD, PhD

The University of Texas Health Science Center at Houston and Federal University of Rio Grande do Sul, Porto Alegre, Brazil


A subset of patients with bipolar disorder has a pernicious course characterized by episode acceleration, functional impairment, drug use, and/or worse quality of life. Indeed, Kraepelin and others described a potentially progressive course of bipolar disorder, with its functional and clinical aftermaths. More recently, the concept of neuroprogression has been used to describe progressive clinical changes that may take place in the course of bipolar illness. But what are the clinical risk factors associated with neuroprogression? Recently, it has been proposed that traumatic stress and number of mood episodes may show sensitization to themselves and cross-sensitization to one another, leading to residual vulnerabilities to further occurrences of mood episodes, functional impairment, and early drug misuse. Therefore, one could hypothesize that the stress-induced behavioral sensitization related to posttraumatic stress disorder (PTSD) may be associated with a neuroprogressive course of bipolar disorder.

To test this hypothesis, we conducted a study in which we compared patients with bipolar disorder who did and did not have PTSD. We reported that subjects with bipolar disorder and PTSD had an accelerated course of illness, with a younger age at onset of manic episodes and earlier initiation of illicit drug use. Such patients were more likely to be younger when they received the diagnosis of bipolar disorder and had a higher number of manic/hypomanic episodes, even when we adjusted for age at onset of the first manic/hypomanic episode. In addition, quality of life was worse in all domains among subjects with the comorbidity, and functional impairment was greater. It is worth mentioning that the lifetime prevalence of PTSD among subjects with bipolar disorder was 19.7% in our clinical sample. This rate is similar to that found in the Systematic Treatment Enhancement Program for Bipolar Disorder (17.2%) and more than twice the prevalence of PTSD in the general adult population (8.0%).

These findings are in line with the notion that the stress sensitization related to PTSD leaves residual vulnerability to further occurrences of mood episodes and accelerated illness progression. We know that PTSD and bipolar disorder share some biological underpinnings, such as inflammatory abnormalities and decreased levels of neurotrophins, which may potentially explain neuroprogression in this subset of patients.

Financial disclosure:Dr Kapczinski has received grant/research support from Stanley Medical Research Institute and NARSAD and is a member of the speakers/advisory boards for Eli Lilly, Janssen-Cilag, and Servier. Dr Passos had no relevant financial relationships to report.​

Category: Bipolar Disorder , PTSD
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2 thoughts on “Neuroprogression in Patients With Bipolar Disorder and PTSD

  1. I 100% believe that this is true and it’s a very important observation. I have developed a theory positing that the presence of CYP21A2 mutations (congenital adrenal hyperplasia in homozygous form, most mutations currently uncharacterized, probably 20% of the population) predispose to PTSD by wiring the brain for danger, predispose to PTSD and predispose to chronic stress induced illnesses due to elevated catecholamines and threat wiring. I base this on the fact that CYP21A2 is often co-inherited with TNXB which codes for tenascin and C4 implicated in schizophrenia (this is the only part of the genome this can happen). Hypermobiles often have features of tenascin mutations, C4 related diseases and bipolar disorder (an easily develop PTSD, anecdotal) In my experience, PTSD, bipolar disorder, autoimmune diseases (C4) and adrenal/sex hormone disorders and chronic stress illnesses (CYP21A2) are found to run in the same families. I have called this the RCCX Theory and have created a website discussing the theory, the research backing it and my experience of viewing patients through this lens. I won’t post the link to the website, but it can easily be found.
  2. I wonder what types of trauma were identified. Were they single events or persistent and what age were they experienced? All these factors have a bearing on what brain changes could have occurred and whether they would be equally likely to coexist with Bipolar Disorder.

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