Treatment of Mood Disorders Following Traumatic Brain Injury

Epidemiology of Depressive Disorders

The frequency with which depressive disorders manifest in patients with TBI varies, depending on the source. The current literature proposes frequencies ranging from 6 to 77% ( ). Probable explanations for the large disparity in frequencies include differences in the measures and cutoff points used to diagnose depression, as well as differences inherent to the samples studied. Our own study of depressive disorders in the first year following TBI indicated that 33% of the patients developed major depression ( ). Diagnoses were made via semi-structured interview, based on the criteria set forth by the DSM-IV-TR (an edition of the Diagnostic and Statistical Manual of Mental Disorders , published by the American Psychiatric Association). In this study, we found a significant association between the presence of anxiety disorders in individuals with TBI and the eventual development of major depression. In fact, almost 75% of our sample was diagnosed with comorbid depression and anxiety. A study using similar methods replicated this finding ( ). In general, the likelihood of developing depression appears to be the highest during the first year postinjury. Nevertheless, in individuals with TBI, the risk of developing depression is greater than that of individuals without TBI, even many years after the injury ( ).

Risk Factors of Depressive Disorders

Though the data on risk factors for depression secondary to TBI have been ambiguous, especially regarding age and gender variables ( ), it is accepted that a myriad of factors play a role in the manifestation of depression.

In particular, we still stand at the frontier of research on genetic factors that may predict neuropsychiatric disorders following TBI. Below is a selection of developments drawn from our current understanding of these factors. The apolipoprotein E-4 (APOE-4) genotype has not been associated with the rate of depressive disorders following mild ( ) and moderate-to-severe ( ) TBI, though it is otherwise linked to cognitive outcomes. Polymorphisms in genes involved in the regulation of ascending neurotransmitter systems have also been researched. A recent study did not support a link between polymorphisms of the serotonin transporter (5HTT) and the incidence or severity of depression after TBI ( ). However, it is possible that genetic variants of the 5HTT could modify a patient’s response to antidepressant treatment. For instance, in the TBI population, an individual’s genotype affects his or her response to citalopram ( ). The same study uncovered more frequent adverse treatment effects in individuals with certain 5HTT polymorphisms, including rs25531. In contrast, the C-(677)T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene and the val66met polymorphism of the brain-derived neurotrophic factor (BDNF) gene were linked to favorable treatment responses. Additional research on these topics is necessary to determine if there are true preinjury risk factors for the development and treatment of depressive disorders in patients with TBI.

Psychosocial factors, such as a history of childhood adversity, life stressors, and lack of social support, contribute to psychiatric problems in the general population. Although such factors have not yet been clarified in patients with TBI, we found associations between the development of post-TBI depression and patients’ previous history of mood and anxiety disorders and poor social functioning ( ).

Other behavioral conditions, such as alcohol misuse, also contribute to the risk of TBI and mood disorders. We followed a group of patients ( N = 158) for a year post-TBI and found that, of the 55 patients with a history of alcohol misuse, 60% developed a mood disorder, compared with 36.9% of the other patients ( N = 103), who did not have a history of alcohol problems ( ). Approximately 75% of those who abused alcohol during the first year postinjury also had a comorbid mood disorder.