Traumatic brain injury (TBI) is associated with various neuropsychiatric sequelae, including an increased risk for later suicidal behaviors (CPs). There is overlap between neuropsychological deficits after TBI and suggested biobehavioral indicators of suicide risk. This article provides information on the overlapping neurobiology of traumatic brain injury (TBI) and suicide.
Pathophysiology of Traumatic Brain Injury (TBI)
The pathogenesis of TBI is dynamic and progressive, both at the impact site and at the site of the impact. In its polar opposite position on the skull, that is, impact-contrecoup injury index includes primary focal lesions due to head trauma. In turn, it promotes secondary brain damage from localized and systemic dysfunction and manifests as a reduction in functional brain connectivity that may worsen over time. In summary, head injury initiates a metabolic cascade, via allostatic and epigenetic mechanisms, that produces permanent, microscopic, brain damage. Trauma-related changes occur in the permeability of lipid membranes that disrupt the flow of sodium ions.
In addition, the biomechanical force from the impact directly damages the delicate cytoskeletal structure of glial cells and neurons, especially the unmyelinated axonal protrusions. This facilitates disconnection, a chronic imbalance between excitatory (glutamate) and inhibitory (GABA) neurotransmission. Prolonged glutamatergic hyperexcitability resulting from ionic specifically calcium dysregulation enhances microglial immune responses that promote localized and systemic encephalitis, such as increased proinflammatory cytokine signaling.
Thus, immuno- accelerates apoptotic and necrotic neuronal cell death through a process called In conclusion, persistent inflammation and other cytotoxic processes, such as oxidative stress due to mitochondrial metabolic dysfunction, blood-brain barrier disruption or genetic damage resulting from dysregulated immune signaling, and other cytotoxic processes contribute to the progressive neurodegeneration characteristic of TBI.Ultimately, it produces the distinctive cognitive, behavioral, and emotional sequelae of head trauma.
TBI is also associated with numerous structural and functional changes in neural circuits at the network or system level, beyond morphological and molecular changes in neurons, glial support cells, and the extracellular matrix. Patterns of neurocognitive dysfunction secondary to TBI are influenced by a number of factors, including the location and strength of the primary impact, as well as the patient’s pre-existing vulnerabilities as well as those related to the event, such as the physical characteristics of TBI from blast injury and motor vehicle accident trauma. There are patient factors associated with this and some of these factors are as follows:
• Cognitive reserve or basic intellectual abilities,
• Substance use and neuropsychiatric history, especially previous TBI,
• Comorbid conditions from trauma, eg concomitant post-traumatic stress disorder or spinal cord injury,
The neurocognitive deficits associated with TBI are usually nonspecific, but most frequently associated with attention, memory, socio-emotional abilities such as emotional control, mentalization and self-referential processing, and cold executive functions. (EF) includes impairments in both low-level cognitive control and EF.For example, monitoring sensory information, behavioral responses, integrating and inhibiting in addition to coordinating and inhibiting. The main components of these functional circuits include cortical and subcortical nodes, hubs and cerebral tracts in the frontal lobes, and multimodal association cortices in the temporoparietal regions. may be difficult or impossible to achieve. In fact, neuropsychological assessment may not be sensitive enough to fully capture the long-term uncertainty of neurocognitive consequences, especially in mild TBI. Diffuse axonal injury (DI) is the primary source of TBI-related neural circuit dysfunction, such that leading researchers have referred to post-concussion syndrome as a brain connectivity disorder involving disruption of multiple functional networks connecting brain structure to cognition.
DAH refers to the acute biomechanically induced disruption of bundles of myelinated axonal fibers, the integrity of which is necessary for proper neurotransmission.Axonal white matter tracts are the basis of all neural circuits and networks. Thus, FAI interferes with communication in the brain, which helps explain the myriad cognitive, behavioral, and emotional symptoms following TBI. A 2018 meta-analytical review of neuroimaging data collected using diffusion tensor imaging, a method sensitive enough to detect microstructural changes in white matter, shows that axonal shift occurs frequently. In up to 95% and in more severe cases up to 100%, structural changes occur most commonly in the subcortical regions of the hindbrain, the corpus callosum (commissural inter-hemispheric fibers), the inner and outer capsules, as well as the anterior lobe. These structural changes can persist for years or even decades after injury, with profound long-term effects on cognition and behavior regardless of TBI severity. Indeed, radiological evidence of DI is a prognostic predictor of adverse clinical outcomes, which, according to a recent meta-analytic review, is three times more likely than TBI without DAY.
EF deficits, including impaired cognitive control, e.g. It predisposes frontal areas and associated brain circuits affected by recurrent TBI/chronic traumatic encephalopathy (CTE) to propagate axonal insult along relevant neural circuits.Specifically, lesions in the cingulum bundle (connecting the ventromedial prefrontal cortex to the posterior cingulate) and other components of the putative mode network are associated with post-TBI deficits in sustained attention and post-concussion symptom severity. Whereas, lateral temporoparietal, mesial temporal lesions or posterior cingulate/precuneus tracts cause learning and memory problems associated with CTE.
It is also reflected by the hippocampal abnormalities observed after TBI. Basal ganglia and limbic structures, such as the hippocampus and amygdala, are particularly susceptible to TBI-related white matter damage. For example, the fornix containing axonal projections originating from hippocampal neuronal cell bodies. In summary, the available empirical literature suggests that TBI disrupts the functional connectivity of core circuits between the anterior hemispheres via the genu of the corpus callosum, which is essential for cognitive and emotional inhibitory control, particularly the neural pathways that connect prefrontal cortical regions to subcortical areas via the thalamus. Damage to prefrontal white matter tracts thus helps to explain the heterogeneous deficits in self-regulatory capacities secondary to TBI/CTE, which overlap significantly with psychiatric disorders and related phenomena, including suicide, which is one of the leading causes of TBI-related death.
Neurobiological Links to Suicide
Suicidal thoughts and behaviors share pathophysiological mechanisms with TBI, particularly impaired functional connectivity in the corticolimbic, frontoparietal, and frontostriatal circuits responsible for affective control and goal-directed behavior.
Those associated with negative suicidal ideation, indirect self-harming thoughts and behaviors, eg substance abuse, eating disorder, etc. are also included in SPs. This is the latent P factor that reflects the shared variance in different clinical outcomes.
In general, CPs are characterized by structural and functional abnormalities in many regions of the frontal lobe, for example, in the dorsolateral, orbitofrontal, and ventromedial prefrontal cortices, as well as in the dorsal anterior cingulate. CPs are particularly associated with altered serotonin signaling in these areas, which may be reflected by cold EF deficits, particularly in cognitive inhibitory control and value-based decision making. However, converging evidence suggests that CPs may be more strongly or specifically associated with disability when compared with suicidal attempts and consequent self-harming behaviors, i.e. suicidal thoughts.
Hot EF and corresponding dysfunction affect emotional negative valence systems. It has blocker control over it. This concept is consistent with evidence for morphological changes in the subcortical limbic, particularly the elongated amygdala, and SP-related abnormalities in the striatal regions.Heritability estimates for CP vary widely, from 4% to 55%, and evidence suggests a genetic link between the P factor, such as emotion differentiation, susceptibility to suicidal thoughts, and various areas of cognitive function related to suicidal thoughts. Not surprisingly, similar genetic overlap has been observed between TBI outcomes and neurocognitive functioning (particularly EF), explained in part by the latent factor of general intelligence. It is well known in CPs among individuals characterized by negative emotionality/emotional instability (those who give high scores on personality traits) or poor self-regulation. The proposed functional manifestations of factor P are the various contributing factors to distress, accordingly known risk factors for CPs. The researchers suggest that these different sources of vulnerability ultimately operate through a common co-multiple pathway involving epigenetically mediated dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and consequent stress reactivity.
HPA axis dysregulation due to allostasis. is self-sustaining through a positive feedback loop.Disruptions in these major neurotransmitter pathways are mirror patterns of white matter damage often associated with TBI.