Psychiatric phenotypes in chronic traumatic encephalopathy

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder involving cognitive, motor, and psychiatrically-relevant symptoms resulting from repetitive head impacts. Psychiatric phenotypes of CTE, including depression and suicidality, present particular challenges for CTE research, given that the diagnosis requires postmortem neuropathological examination. The pathognomonic lesion of CTE is the perivascular accumulation of hyperphosphorylated tau (ptau) protein at the depths of cortical sulci. These lesions are found in the earliest disease stages, and with advancing pathological severity, ptau deposition occurs in widespread brain regions in a four-stage scheme of severity. We review the psychiatric phenotypes of individuals neuropathologically diagnosed with CTE, and suggest that earlier CTE stages hold particular interest for psychiatric CTE research. In the early CTE stages, there is ptau pathology in frontal cortex and axonal loss in the frontal white matter, followed by progressive ptau neurofibrillary degeneration in the amygdala and hippocampus. Neuropathological changes in the frontal and medial temporal lobes may underlie psychiatric phenotypes. Additional insight into the association between CTE pathology and psychiatric sequelae may come from advancements in in vivo methods of CTE detection. Further epidemiological, clinical, and postmortem studies are needed to validate the nature of psychiatric sequelae in CTE.