Psychiatric Manifestations of Traumatic Brain Disorder

Overview

The human brain can be injured in a variety of ways. Head trauma, vascular disorders, degenerative disorders, toxic exposure, infectious processes, neoplasms, anoxia, metabolic or endocrine disorders, and nutritional deficiencies can each damage neuroanatomical structures and alter neurological function. Closed head injury (or traumatic brain injury [TBI]) is the most common source of acquired brain injury.

TBI, referred to as a “silent epidemic,” is one of the leading causes of death and disability in the US ; nearly 1.7 million head injuries occur each year and of these, approximately 52,000 people die from their injuries, 275,000 require hospitalization, and 1.365 million are treated and released from the Emergency Department (ED). An unknown number of additional patients with TBI are never seen at the hospital. Injury to the brain disrupts cognitive, physical, emotional, and behavioral functioning. Long-term outcome can range from complete recovery to severe impairments and disability. While the majority of individuals who sustain a TBI recover, a sizable number of individuals sustain permanent neuropsychiatric disabilities each year ; physical, cognitive, behavioral, and emotional impairments result in substantial disability and cause significant stress within families. Complications (e.g., suicide, divorce, chronic unemployment, economic strain, substance abuse) develop after TBI. The consulting psychiatrist plays an important role in the evaluation and treatment of patients with TBI at all stages of recovery.

Epidemiology and Risk Factors

Among the most common causes of TBI are falls (35.2%) and motor vehicle accidents (17.3%). Having the head struck by, or against, an object (16.5%), being assaulted (10%), and other or unknown causes (21%) make up the remaining cases. Men sustain a TBI at a rate 1.4 times higher than women and are hospitalized almost twice as frequently. TBI occurs most often in children < 4 years of age, followed by older adolescents (15–19 years of age). The highest rates of hospitalization and death following TBI are found in adults over the age of 75. Falls produce the most injuries for children younger than 15 years and for adults over the age of 55. Motor vehicle accidents account for the most injuries among adolescents (aged 15–19) and adults, aged 20–55. Earlier research has found that 56% of adults identified as having brain injuries had an elevated blood alcohol level (BAL) at the time of injury; 49% of them had a BAL at or above the legal level. Recurrent brain injury is common; the risk of a second injury is three times higher than it is for those in the general (non-injured) population. Following a second injury, the risk for a third injury becomes nearly 10 times higher than the risk for an initial injury. Finally, review of data from the U.S. National Health Interview, a national database used to estimate the incidence and features of persons with brain injury, found that the highest rates of injury occurred in families with the lowest income levels ( Box 82-1 ).

Pathophysiology

TBI is a spectrum disorder. Damage can occur as a result of forces exerted on the brain at the time of injury, known as the primary injury, and from subsequent physiological processes (such as swelling or hypoxia) triggered by the initial insult; the latter are classified as secondary injuries. Damage can be focal, diffuse, or both. Focal damage is typically the result of a contusion or mass lesion. Most often it arises from contact injuries (such as falls or blows to the head) and results in skull fractures and hematomas (extradural, subarachnoid, subdural, or intracerebral hematomas). Hematomas may develop at the point of contact and at a point contralateral to the point of contact (known as coup–contrecoup contusion) . Contusions are seen more frequently in the poles of the frontal lobes, the inferior aspects of the frontal lobes, the cortex above and below the operculum of the Sylvian fissures, the temporal poles, and the lateral and inferior aspects of the temporal lobes. They may develop within minutes of the injury or evolve slowly over several hours or days. The presence of these contusions contributes to neuronal necrosis and to elevated intracranial pressure (ICP). In addition to contusions, contact forces can result in small or complete tears at the pontomedullary junction, damage to any of the cranial nerves, damage to the hypothalamus or pituitary gland, and damage to blood vessels. Moreover, there can be multiple areas of focal damage.

Diffuse damage involves multiple neurological structures. It is seen more frequently in injuries that involve rapid acceleration/deceleration or rotational forces. Diffuse damage can also result from disruption of vascular function and from hypoxia. Diffuse axonal injury (DAI), as an example, consists of microscopic traumatic axonal damage involving the whole brain, but it is found most commonly in white matter areas (subcortical frontal and temporal white matter, the corpus callosum, and brainstem). It disrupts cellular function and structures. While DAI is triggered by the mechanical forces of the original injury, it evolves over several hours to days. Because this damage occurs at a microscopic level and evolves over time, DAI is often missed on computed tomography (CT) scans, particularly if it is performed in the ED. It is more easily identified with magnetic resonance imaging (MRI), where the signature axonal swelling and axonal bulbs can be seen more readily, particularly if the brain is imaged several days after the injury. Even with MRI, however, the absence of significant findings on radiological imaging does not mean that damage has not taken place. Newer techniques, such as diffusion tensor imaging (DTI), susceptibility-weighted imagining (SWI), positron emission tomography (PET) scans, functional magnetic resonance imaging (fMRI), and high angular resolution diffusion imaging (HARDI), many of which are available only through academic research facilities, are helping to identify structural and functional changes following TBI more accurately. Continued research involving the identification of characteristic biomarkers, such as elevations in cytokines, adipokines, chemokines associated with inflammation, markers of astrocyte activation, neuronal injury, or oxidative stress following injury, holds the promise of more accurate diagnosis of brain injury, particularly in the case of mild TBI.

In addition to the primary injuries, further damage can occur as a result of complications associated with TBI (known as secondary injury). Hematomas develop as a result of the hemorrhaging from torn blood vessels. Edema develops when there is an increase in inter- and/or intracellular water concentration due to direct mechanical forces or changes in cell permeability. Since the skull of adults is fixed and unable to expand, hematomas and edema raise the intracranial pressure (ICP), which leads to further neurological damage as the surrounding (softer) structures become deformed. The pressure can push the brain through the base of the skull, with resulting damage to the brainstem. When the brain's vascular system is compressed, the blood flow is restricted, resulting in ischemic damage. Compromised cardio-pulmonary function, as either a direct result of brain damage or the structural damage sustained in the initial multi-organ trauma, can lead to hypoxic injury. Hyper-release of catecholamines following TBI can produce transient hypertension, as well as changes in glucose, cortisol, and thyroid hormones, which further disrupts neurological function. Massive releases of excitatory amino acids (such as glutamate or aspartate) from injured brain cells act as cytotoxins, damaging neighboring cells, and unleashing a cascade of autodestructive events that can continue for hours or days after the original injury. Inflammatory mechanisms, such as activated macrophages and microglia, may also contribute to the enlargement of the initial injury over days to weeks. Focal contusions can produce seizures (that convey the severity of the injury in that they are seen more frequently following a severe injury than with a moderate or mild injury).

TBI resulting from exposure to explosions has come to be known as the signature injury for soldiers returning from Iraq and Afghanistan due to the frequent use of improvised explosive devices (IEDs) affecting 10%–20% of returning veterans. The explosion generates a blast wave that causes direct and indirect injury. Direct injury results from the pressure wave (with fluid-filled structures being the most sensitive), from objects or shrapnel propelled by the blast, from the body being thrown against solid objects, and from exposure to burns and noxious gases. The above physical forces can produce skull fractures, cerebral edema, increased ICP, contusions, hemorrhages and shearing injuries to the brain. Brain injury also results indirectly from injury-generated air emboli that reach the brain and from increased cerebral vasoconstriction and activation of platelets/leukocytes, which may exacerbate the primary effects of the brain injury. Due to the nature of the combat theater and deployment rotations, there is a high risk of repeated exposure to subsequent blasts, particularly when the brain is still recovering from the prior exposure. Exposure to blasts during this period of increased vulnerability can result in more severe injuries.

The brain's plasticity, or neuroplasticity, produces structural and organizational changes that result in recovery of function. The hippocampus retains the ability to generate new neurons from progenitor cells in the dentate gyrus. Surviving cortical structures take over the function of damaged areas. Other adaptive and restorative processes include changes in the amount of neurotransmitters released, the number and distribution of post-synaptic receptors, the size and complexity of the dendritic trees of spared neurons, and the collateral sprouting of spared axons to innervate de-afferented neurons. These processes depend on purposeful and active interactions with the environment. Unfortunately, they are not well regulated, and can lead to maladaptive, as well as to beneficial, changes. While they are responsible for restoring function, they can result in dysfunctional behaviors and psychiatric disorders. In the case of mild TBI, symptoms will usually resolve within 6 months of their injury. In the case of moderate-to-severe TBI, the greatest amount of recovery typically takes place in the first 1–2 years following injury. Recovery can continue, however, at an increasingly slower pace for many years following the injury.

TBI is typically classified as mild, moderate, or severe ( Table 82-1 ) based primarily on the duration of altered mental status (including the degree of responsiveness, as measured by the Glasgow Coma Scale [GCS], and the duration of disrupted memory). These terms can be misleading as they reflect the degree of damage the brain has sustained; they do not necessarily reflect the severity of the disruption in the patient's daily functioning. Individuals with a severe injury can make essentially full recovery while others with mild-to-moderate injuries can remain significantly disabled for many years. The GCS, developed by Teasdale and Jennett, assigns points for increasingly complex levels of response to three dimensions (verbal and motor response and eye opening); the ratings in each domain are totaled to produce an overall score that can range from 3 to 15 ( Table 82-2 ). Ratings can also be done serially to provide a measure of recovery. GCS scores have been predictive of ultimate outcome, with lower initial scores being associated with more severe injury and worse recovery.

Mild TBI, also described as a concussion, may not show up on a CT scan, on a conventional MRI and/or an electroencephalogram (EEG). Where there are positive radiological findings, the injury is classified as a complicated mild TBI. Performance on a routine neurological examination, which tends to focus on sensorimotor function, may be essentially normal, although performance may represent a decline relative to pre-injury performance. Acute symptoms may persist for varying lengths of time. Physical symptoms often include nausea, vomiting, dizziness, headaches, blurred vision, an increased sensitivity to noise and light, diminished libido, disturbed sleep, quickness to fatigue, lethargy, or sensory loss ( Table 82-3 ). Cognitive deficits typically involve attention, concentration, perception, memory, speech/language, or executive functions. These cognitive deficits are best identified through an in-depth neuropsychological evaluation. Behavior changes, such as irritability, quickness to anger, disinhibition, or emotional lability, may follow. Symptoms generally resolve within 6 months of the injury. Physical, cognitive, emotional, and behavioral symptoms that cannot be accounted for by other peripheral injuries, or one's emotional state or psychological reaction to physical or emotional stressors, can persist. Repeated exposure to mild TBI, such as seen in athletes with repeated concussions or soldiers with repeated blast exposures, can have a cumulative effect and it has been associated with the development of chronic traumatic encephalopathy (CTE). CTE typically occurs after many years with varying symptoms, ranging from mild cognitive complaints to dementia, parkinsonian symptoms, and behavioral changes.

While neurological damage can occur without loss of consciousness (LOC), LOC is considered a hallmark of most TBI. The duration of lost consciousness generally reflects the severity of injury. The longer the duration, the more severe the injury and more guarded the prognosis for recovery. No single pattern of recovery follows a brain injury, as there are many variables involved (e.g., the location and extent of injury, the patient's age and overall health, the presence of alcohol, the medical and psychological history, concurrent processes [such as infections or seizures], availability of appropriate rehabilitation services and supports).

Clinical Features

No single profile characterizes the presentation of TBI. A patient's profile is the result of the location, depth, and volume of focal lesions and the extent of diffuse axonal injury. Age, previous injury, use of alcohol, co-morbid conditions (such as hypoxia or hypertension) further contribute to the specific collection of deficits observed. Generally speaking, cognitive deficits, personality and behavioral changes, and psychiatric disorders follow TBI. The domains of attention, memory, language, and executive function are typically affected. Since they are somewhat hierarchical, deficits in more fundamental areas (such as attention) can limit performance in higher-level tasks of executive function. Day-to-day and within-day performance can vary considerably.

Cognitive Impairment ( Table 82-4 )

Impaired attention is one of the most common deficits associated with TBI involving the reticular activating system and the prefrontal or connecting white matter. Individuals with attentional difficulties report decreased concentration, being unable to follow conversations in a group setting (where they need to focus on the conversation in which they are interested and screen out other simultaneously occurring conversations), losing track of what they are reading, being distractible, being unable to do more than one thing at a time, and being unable to sustain attention. Reduced speed of information processing, while not strictly an attention deficit, is the most notable consequence after mild TBI ; it limits the amount of information that can be processed, the ability to respond quickly, and the ability to complete tasks within traditional time frames.

Impaired memory is also common following TBI. The duration of post-traumatic amnesia (PTA), the inability to recall information presented after the accident, correlates with the severity of one's injury. While some patients have a period of retrograde amnesia (i.e., the inability to recall information acquired before the trauma), problems with acquiring, storing, and retrieving new information are more common. Memory is not a unitary construct; there are different forms of memory that may be affected to differing degrees depending on the nature and the location of injury. Because different neuroanatomical structures are involved with these various forms, there is typically sparing of some forms of memory. Procedural memory (i.e., memory for motor sequences that occurs outside of conscious awareness) is typically less affected than is memory for more language-based or visual information. This also means that there is not a specific profile of memory deficit associated with TBI. Declarative memory (i.e., the ability to recall events [episodic memory] and specific facts [semantic memory]) is more vulnerable to damage because of the active processes involved. Encoding, consolidating, and retrieving new information involve a degree of effortful, controlled, and generally conscious processing. Much of this activity appears to involve the hippocampus, as well as the prefrontal, temporal, and frontal structures. The hippocampus is particularly vulnerable to damage from TBI. The prefrontal and frontal areas, such as the dorsolateral prefrontal and orbitofrontal cortices, due to their anatomic location and their proximity to orbital cranial structures, are especially vulnerable to contusions and hematoma formation. The ability to retrieve old or previously-learned information typically returns before the ability to acquire new information. For a period of time amnestic individuals may confabulate, or generate false memories, which can be problematic as they can be indistinguishable from “real memories.” False memories typically have elements of truth embedded within them, as people involved in the memories may actually exist or events recalled may really have happened. The memories, however, contain significant distortions. The affected individual may recall a visit the day before from a friend who has been dead for many years, or may report returning from a trip the day before that had taken place a number of years ago. Confabulation is distinguished from delusional thought in that the confabulation is often more isolated, less organized, and often more transient than delusions. It typically resolves as the patient's overall memory improves. The ability to recall new information typically takes more time to resolve and may be a persistent or permanent deficit. Acquisition, storage, and retrieval of new information are procedures that involve attention, sensory function, language, and executive function. Deficits in any of these areas limit the acquisition of new learning. Even in individuals with mild TBI, new learning is less efficient, requiring more effort and time than was required before the injury. This inefficiency and increased effort makes it harder for an individual to sustain performance relative to pre-injury levels.

Impaired language results from damage to frontal and temporal areas. The nature of the deficits will depend on the location and extent of the injury. Disruption of language (both receptive and expressive) occurs more frequently after moderate-to-severe injuries than after mild TBI, where disturbances tend to be limited to difficulties with word-finding and with decreased fluidity when speaking. Global aphasia (total loss of both receptive and expressive language) is relatively rare. More common are specific aphasic syndromes, such as anomic aphasia (in which an individual presents with difficulty naming specific objects and proper names), paraphasic errors (in which incorrect words are substituted for the intended word), and circumlocution (in which the individual talks around the missing word describing or demonstrating the missing word). In addition to these primary language impairments, patients with TBI tend to generate less speech, are less efficient in their discourse, and have more trouble managing the interpersonal pragmatics of speech (such as taking turns, maintaining a topic of conversation, taking a listener's perspective, and interpreting the non-verbal elements of communication).

Finally, impaired executive functions can be seen at all levels of TBI. These skills are the functions of the frontal lobes and their projections, which are particularly prone to injury. Executive function encompasses those skills needed to operate independently in the world (i.e., to identify goals, to plan, and to organize behavior to meet those goals). They involve initiating and monitoring behavior, inhibiting competing impulses or behaviors, and correcting behavior in response to feedback. They are essential for self-determination, self-direction, and self-regulation. Problems with regulation of attention, working memory, insight and empathy, verbal fluency, decision-making, perseveration, and flexibility frequently follow damage to the frontal lobes.

Personality and Behavioral Changes

In many respects the changes in behavior and personality that follow TBI, particularly when there is frontal lobe involvement, are more disabling than are the cognitive changes ( Table 82-5 ). They limit an individual's ability to participate in therapy. They are a source of significant stress on families and caretakers. They can prevent the individual from returning home and returning to work. The individual may appear to move about aimlessly, become preoccupied with seemingly trivial matters, or perseverate on topics or concerns in an obsessional manner. They may fail to be aware of, or take in, information from the environment or to alter their behavior in response to feedback. As a result they may have difficulty learning from their mistakes. Because of deficits in executive function, several tasks become difficult. Looking ahead and anticipating the implications or consequences of one's actions becomes difficult following frontal lobe damage; this can interfere with participation in therapy as the individual fails to grasp the long-term benefits of treatment in the absence of more immediate gratification. Deficits in the modulation of affect, self-awareness, and self-monitoring result in socially-inappropriate behaviors. Temper outbursts and mood swings, often dysphoric in nature, are common after temporal lobe damage. Flat affect and indifference, belligerence and aggression, childishness, euphoria and abnormal jocularity, irritability and reduced tolerance for frustration, disinhibition, and lack of empathy may arise, interfering with normal social relationships. Individuals have difficulty identifying and initiating activities that foster social interaction. Previously active people will be content to sit and watch television for hours on end. Individuals may begin to avoid social gatherings because the demands of selectively attending, shifting attention, self-monitoring, comprehending language, and emotive expression are overwhelming. They may become irritable and aggressive when feeling overwhelmed by these cognitive demands. All of these deficits are subject to the effects of fatigue and environmental variables (such as supportive structure, level of sensory stimulation, and degree of familiarity). Others see the individual's behavior as erratic and difficult to predict. Social isolation becomes common as friends and even family withdraw as a result of behaviors that are disruptive, embarrassing, or dangerous. The burden these behaviors place on families who are already stressed by changes in financial resources and the demands of physical care and increased dependence can be enormous.

Aggressive behavior is perhaps the most disruptive of the behavioral changes observed after TBI. Agitated, combative, disinhibited behavior is common during the initial stages of post-traumatic delirium. Agitated behavior at this stage tends to be reactive in nature, and often arises in response to seemingly minor or trivial stimuli. It is neither planned nor serves a purpose other than to eliminate the source of irritation. The behavior is often explosive and occurs with little build-up or warning. Brief outbursts alternate with long periods of calm. When the individual is aware of his or her behavior, he or she is often upset or embarrassed by their behavior. Early agitation tends to resolve as cognition improves.

Agitated and aggressive behavior can persist beyond the acute phase of recovery; it has been observed following severe TBI in 31%–71% of cases studied and in 5%–71% of cases involving mild TBI. Aggressive behavior has been associated with damage to the inferior orbital surface of the frontal lobes, the anterior temporal lobes, the hypothalamus, and limbic structures. Changes in neurotransmitter levels (particularly serotonin, norepinephrine [noradrenaline], dopamine, acetylcholine, and GABA) have been associated with impulsive and aggressive behavior. A pre-injury history of psychiatric illness, attention deficit disorder (ADD), aggressive behavior, poor social function, and alcohol and drug abuse have been identified as risk factors for aggressive behavior following TBI.

Aggressive behavior may also occur as a result of a mood disorder, psychosis, or seizure disorder, although aggressive behavior occurring in the context of seizure disorders can take different forms. Ictal or post-ictal behavior tends to be less focused or directed and is accompanied by an altered level of consciousness. Following the outburst the individual is likely to express regret and remorse when informed about the behavior. Inter-ictal aggression tends to be more directed and less ego-dystonic. Delirium resulting from hypoxia, electrolyte imbalance, metabolic disorders, dehydration, or infection can trigger aggressive behavior. Drugs and medications can produce aggressive behavior. Alcohol, barbiturates, benzodiazepines, analgesics, steroids, antidepressants, amphetamines, antipsychotics, and anticholinergic drugs can contribute to sedation and to disinhibition as well as irritability and aggression. Aggressive behavior may be unwittingly reinforced by the response of others to the behavior. For instance, increased attention or the withdrawal of unpleasant demands following aggressive behaviors may increase, or maintain, aggressive behavior.

Psychiatric Disorders

Psychiatric disorders, particularly mood disorders, are found more frequently in individuals with TBI than they are in the general population; they are associated with longer recovery time, worse outcomes, and higher mortality rates as compared to those who have suffered a TBI, but without psychiatric disturbances. Koponen and colleagues found that 48% of patients developed an Axis I disorder (most commonly major depression, alcohol abuse or dependence, panic disorder, specific phobias, and psychotic disorder) after TBI ( Box 82-2 ). Roughly one-fourth of the patients developed an Axis II personality disorder (avoidant, paranoid, or schizoid) after the injury.

Depression is the most common psychiatric disorder observed after TBI, with a frequency rate ranging from 26% to 77%. Presence of depression is associated with poor psychosocial outcome, increased psychological distress, and a greater number and intensity of perceived post-injury symptoms. Depression may develop acutely within the first month of the injury, or have a delayed onset. It may develop as a result of neurotransmitter changes linked with structural damage or in response to improved insight and awareness of the multiple changes and losses from the injury. Symptoms may resolve within the first 6 months or may persist for many years. Depression after TBI is associated with anxiety (77%), aggressive behavior (57%) fatigue (29%), distractibility (28%), anger or irritability (28%) and rumination (25%). Depression has not been associated with the severity of injury or with cognitive impairment. A pre-injury history of substance abuse, worse pre-morbid social function, less than a high school education, and an unstable work history predict depression post-TBI. Individuals with TBI should be considered at greater risk for depression as a reaction to the loss of capabilities and competencies, changes in social supports, capacity for work, increased financial and medical concerns, loss of role and income, and decreased quality of life. In addition to these psychosocial factors, depression is associated with the neurophysiological changes and changes in neurotransmitter levels that follow TBI. While no single structure is responsible for the development of depression, depression during the acute stage of recovery has been closely associated with damage to left frontal and basal ganglia regions.

Individuals with TBI are at higher risk for thoughts of suicide, suicide attempts, and suicide. TBI and suicide share risk factors: age (mid-adolescence to mid-twenties); gender (males more than females); lower socioeconomic level; presence of drug or alcohol use; and psychological disturbance ( Table 82-6 ). Key features of TBI (such as cognitive and motor disturbances, emotional lability and impulsivity, rigidity and hyperactivity, poor problem-solving, inability to identify alternatives, heightened aggression, and hostility) increase the risk for suicide. Individuals with TBI who have attempted suicide have not differed significantly from suicide attempters without TBI in terms of age of first suicide attempt, suicidal ideation, suicidal intent, number of attempts, or maximum lethality. When comparing attempters with non-attempters, Oquendo and co-workers found that those who attempted suicide had higher levels of aggression and hostility, were more likely to have a substance abuse history, and were more likely to have a Cluster B personality disorder than non-attempters. Presence of profound feelings (of hopelessness, despair, worthlessness, loss of sense of integrity), relationship breakdown, and problems with isolation, contribute to the risk for suicide.

Evaluating patients with a history of TBI for depression is complicated by the fact that the neurovegetative signs of depression (e.g., sleep disturbance, changes in appetite, anhedonia, loss of libido) occur frequently as a result of TBI. At the same time, deficits in self-awareness can interfere with an individual's ability to identify symptoms of depression. Depression must be distinguished from an adjustment disorder, post-traumatic stress disorder (PTSD), organic apathy, and emotional lability. Pathological laughing or crying, which can occur with focal prefrontal lesions, occurs suddenly, uncontrollably, and may or may not be mood congruent, but is recognized by the individual as disproportionate to the mood or precipitating stimuli. Such an individual tends to have more anxiety, aggression, and worse social functioning than an individual without this syndrome. Apathy (marked by lack of motivation, absence of emotional reaction, and difficulty with initiation of actions) frequently follows frontal lobe damage. Apathy can co-occur with depression.

The diagnosis of depression is more convincing when the psychological symptoms of depression (e.g., presence of depressed affect, irritability, ruminations, feelings of hopelessness and worthlessness, and having difficulty enjoying activities) are manifest. These factors may distinguish depressed from non-depressed patients following TBI. Depression should be diagnosed via a semi-structured or structured psychiatric interview. Since cognitive deficits (involving awareness, memory, self-monitoring, expression, and language comprehension) are frequently present, information from family and caretakers is invaluable.

Anxiety disorders are found at all stages of recovery: immediately following the injury, during the post-acute phase, and in those who have persistent problems. Generalized anxiety disorder (GAD), panic attacks, obsessive-compulsive disorder (OCD), simple phobias, acute stress disorder, and Post Traumatic Stress Disorder (PTSD) have all been observed following TBI. For most of the disorders, the presence or severity of the anxiety disorder has not been associated with the severity of injury. The exception to this is PTSD, in which an inverse relationship has been observed (i.e., PTSD is more likely in individuals with a mild TBI than it is in individuals with severe TBI). Anxiety is frequently accompanied by depression and by alcohol dependence. Anxious patients experience higher levels of functional disability and report higher levels of injury and cognitive impairment.

Anxiety may develop in the early stages of recovery when the individual has trouble with simple, previously automatic tasks (such as dressing and bathing) or sees significant decline in areas that were particular strengths (due to the cognitive and functional changes that have taken place). The immediate environment becomes unfamiliar and unpredictable as a consequence of problems with memory and information processing. The individual loses a sense of competence and confidence in their ability to control their immediate environment. Given the sudden and traumatic nature of the injury an increased sense of vulnerability, as well as fears about further injury or increased fears about loved ones getting injured, are not uncommon. Fears arise regarding the permanence of their deficits and their ability to return to previous roles and activities. Avoidance behaviors may develop. Somatic conditions (e.g., vertigo, headaches, complex partial seizures) that frequently accompany TBI may be interpreted by the individual as symptoms of anxiety. Alcohol withdrawal may be mistaken for primary anxiety. At the same time, anxiety may develop as a result of damage to the temporal lobes, the frontal lobe pathways connecting to the caudate nucleus, the hippocampus, and the amygdala. Increases or dysregulation of circulating cortisol or catecholamines may produce primary anxiety. Damage to the orbitofrontal cortex, anterior cingulate, and the caudate nucleus has been associated with the development of OCD. Orbitofrontal, cingulate, and medial temporal cortical areas, which are frequently damaged in TBI, have been associated with panic attacks.

OCD occurs after TBI at rates (0.5%–7.8%) similar to those for the general population. Unfortunately, research has focused on single cases or small group studies, which limits what is known about the impact of demographic variables, the severity of TBI, or co-morbidity. Fully developed OCD following TBI in the absence of pre-injury OCD is rare. In diagnosing OCD following TBI, it is important to appreciate the role that cognitive dysfunction may play in the development of obsessions and compulsive or ritualistic behaviors. The rituals may be an effort to compensate for poor memory and problem-solving ability. The slowness, indecisiveness, and avoidance may reflect a realistic appraisal, based on their post-injury experiences, of the individual's ability to carry out tasks accurately and independently and to make good decisions.

PTSD following TBI often occurs in the context of a traumatic, life-threatening event (such as combat, a motor vehicle accident, or assault). While there is debate as to whether patients with amnesia for the traumatic event go on to develop PTSD (with its hallmark of re-experiencing of the original trauma), PTSD following severe TBI is well documented even in cases where the individual has no explicit or episodic memory of the event. In cases where there is amnesia for the trauma, the individual may be less likely to have intrusive re-experiencing of the event in the form of flashbacks or nightmares. They can, however, experience heightened emotional reactivity in response to trauma-related stimuli. Memories may have been formed at a more emotional level and stored through mechanisms mediated by the amygdala, independent from explicit memories mediated by more vulnerable hippocampal pathways. Individuals may also react to stimuli from events prior to the LOC or upon regaining consciousness. PTSD is often accompanied by depression and anxiety. Diagnosing PTSD following TBI can be complicated by the overlap in symptoms between the two disorders. The PTSD symptoms of dissociative amnesia, disassociation, depersonalization, derealization, reduced drive, altered consciousness, and confusion resemble post-traumatic amnesia and delirium that follow TBI.

Psychosis is not a typical feature of TBI, though it does occur at a higher rate in this population than in the general population (0.7%–9.8% vs 0.8% life-time incidence). The presence of a first-degree relative with schizophrenia, pre-morbid pathology, temporal lobe epilepsy, depression, or mania is associated with post-TBI psychosis. That psychosis can occur as a result of TBI is not surprising given that the areas of the brain associated with schizophrenia (the prefrontal cortex, temporal lobes, and hippocampus) are all vulnerable to injury. Post-traumatic psychosis can develop at any time following the injury. Visual hallucinations and delusions are a common feature of post-traumatic delirium. Following the period of post-traumatic delirium, psychosis is more likely to be seen months to years after the injury. It is associated with more moderate-to-severe injury and is seen more frequently following damage to the left hemisphere and to the temporal lobes. Content-specific delusions and misidentification syndromes (such as Capgras syndrome [a loved one has been replaced by an identical-appearing imposter] or reduplicative paramnesia [a familiar place exists in another location simultaneously]) are associated with right hemisphere damage. There may be a prodromal period of bizarre or antisocial behavior, social withdrawal, affective instability, and deterioration in overall function. Delusions are more common than hallucinations. Where they occur, auditory hallucinations are more common than visual hallucinations. Positive symptoms of schizophrenia are more common than negative symptoms. Delusions tend to involve themes of persecution, ideas of reference, grandiosity, and religiosity. Concerns that their thoughts are not their own, and that thoughts are being inserted or withdrawn or being broadcast are also common. Agitated or assaultive behaviors can occur with psychosis.

Alcohol may be a contributing factor in a majority of cases of TBI. An elevated BAL at the time of injury is associated with a longer hospitalization, a longer period of agitation, greater cognitive impairment at the time of discharge, and worse overall outcome. Alcohol and drug use contribute to the development of psychiatric symptoms and worsen existing symptoms, especially those associated with TBI. Within the TBI population, alcohol abuse and/or dependence has been found to occur more frequently among patients who developed a mood disorder. At the same time, patients with a history of alcohol abuse who relapsed were at higher risk for developing a subsequent mood disorder. Alcohol and TBI appear to interact to produce a greater degree of disruption in neural circuitry involved in reward systems, and mood and executive function. Individuals with alcohol abuse/dependence and mood disorders tend to have a more difficult time resuming a productive life following a TBI. Post-injury patterns of alcohol use vary. Not all individuals with previous alcohol problems resume drinking post injury. Sometimes where no problem existed, alcohol dependence may develop after an injury. Prior alcohol use and drinking problems are predictive of post-injury patterns of use. Those with significant pre-injury histories of alcohol-related problems are 10 times more likely to have significant problems post-injury compared to normal drinkers. Most importantly, drinking patterns tend to remain stable over time and are reasonably well established by the end of the first year; thus evaluation and treatment for alcohol problems during the first year following the TBI is critical.