Chronic traumatic encephalopathy—a blueprint for the bridge between neurological and psychiatric disorders

Abstract

Chronic traumatic encephalopathy (CTE) is a perplexing condition characterized by a broad and diverse range of neuropathology and psychopathology. While there are no agreed upon or validated clinical criteria for CTE, case series of CTE have described a wide range of neuropsychiatric symptoms that have been attributed to repetitive traumatic brain injuries (rTBI). However, the direct links between the psychopathology of psychiatric and neurological conditions from rTBI to CTE remains poorly understood. Prior studies suggest that repetitive cerebral injuries are associated with damage to neural circuitry involved in emotional and memory processes, but these studies do not offer longitudinal assessments that prove causation. More recent studies on novel targets, such as transmission of misfolded proteins, as well as newly advanced non-invasive imaging techniques may offer more direct evidence of the pathogenesis of CTE by tracing the progression of pathology and display of related behavioral impairments. Understanding this interface in the context of rTBI can play an important role in future approaches to the definition, assessment, prevention, and treatment of CTE and mental illnesses.

Suicide Following Traumatic Brain Injury: Pathogenesis and Neurocognitive Mechanisms

“…Prominent suicide theories explain this counterintuitive prospective association as reflecting either (a) a contributory (causal) effect of NSSI on future SBs or (b) shared vulnerability that produces multi-final psychopathological outcomes (possibly depending on the presence of moderating factors; see [32] for a review). The latter position is consistent with the notion of a latent transdiagnostic risk factor implicated across neuropsychiatric syndromes, including aforementioned behavioral and/or emotional symptoms arising from affective control deficits, which commonly characterize nonsuicidal/suicidal self-injury [9-11, 14, 33] and repetitive TBI/CTE [5][6][7][8].…”

“…However, even acute mild TBI (mTBI; c.f., "concussion") can produce lasting neuropsychological deficits and increase risk for progressive neuropsychiatric sequalae, including chronic traumatic encephalopathy (CTE), cognitive decline, neurological diseases (i.e., Parkinson's disease and other dementias), prolonged post-concussive syndrome (diagnosed as "neurocognitive disorder due to traumatic brain injury"), and adverse mental health outcomes [1][2][3][4][5]. CTE -most often a consequence of repetitive mTBI -is especially tied to psychiatric illness [6], and is itself characterized by dysregulated behavior and mood, beyond non-specific cognitive deficits associated with other forms of TBI, e.g., attentional difficulties, executive dysfunction, and memory impairment [7,8]. Behavioral and mood symptoms of CTE, which frequently include suicidal ideation [6], implicate impaired affective control, or insufficient "top-down" cognitive (inhibitory) control from frontal cortical regions over "bottom-up" stimulus-driven impulses generated by subcortical areas, e.g., limbic circuitry [9][10][11][12][13].…”

“…CTE -most often a consequence of repetitive mTBI -is especially tied to psychiatric illness [6], and is itself characterized by dysregulated behavior and mood, beyond non-specific cognitive deficits associated with other forms of TBI, e.g., attentional difficulties, executive dysfunction, and memory impairment [7,8]. Behavioral and mood symptoms of CTE, which frequently include suicidal ideation [6], implicate impaired affective control, or insufficient "top-down" cognitive (inhibitory) control from frontal cortical regions over "bottom-up" stimulus-driven impulses generated by subcortical areas, e.g., limbic circuitry [9][10][11][12][13]. Affective control impairment (and consequent behavioral/emotional dysregulation) is a hypothesized central feature of psychiatric conditions trans-diagnostically and proposed latent vulnerability factor for suicide [9,[11][12][13][14][15].…”

“…My colleagues and I recently advanced a novel conceptual framework for understanding relations among NSSI, suicide, and affective control: the g-a-p model [9], referring to the overlapping roles of (a) the theorized latent "g factor" representing general intellectual capacities (c.f. "cognitive reserve"; see [6] and Section 2.2.3 below) and (b) the correspondingly proposed "p factor" of underlying vulnerability to diverse manifestations of psychopathology. The g-a-p model is supported by multiple converging lines of empirical evidence.…”

Chronic Traumatic Encephalopathy: Update on Current Clinical Diagnosis and Management

“…While several well-characterized animal models, like the non-impact head acceleration, blast wave, weight drop, fluid percussion, and controlled cortical impact (CCI) models exist for traumatic brain injury, animal model development for CTE is still in the early stages as none fully reflect the known progressive pathological, neurocognitive, and psychiatric findings. Still, many models inflicting repetitive mild TBI reflect some findings like neurofibrillary tangles, Aβ, phosphorylated tau, and TDP-43 deposition, microgliosis, astrogliosis, ER stress, glutamate excitotoxicity, and white matter changes, as well as the sequelae involving progressive cognitive impairment and mood changes [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53].…”