Brain Regions Associated With Internalizing and Externalizing Psychiatric Symptoms in Patients With Penetrating Traumatic Brain Injury

Abstract

A factor structure underlying DSM-IV diagnoses has been previously reported in neurologically intact patients. The authors determined the brain regions associated with factors underlying DSM-IV diagnoses and compared the ability of DSM-IV diagnoses, factor scores, and self-report measures to account for the neuroanatomical findings in patients with penetrating brain injuries. This prospective cohort study included 254 Vietnam War veterans: 199 with penetrating brain injuries and 55 matched control participants. Measures include DSM-IV diagnoses (from a Structured Clinical Interview for DSM), self-report measures of depression and anxiety, and CT scans. Factors underlying DSM-IV diagnoses were determined using an exploratory factor analysis and correlated with percent of brain regions affected. The ability of the factor scores, DSM-IV diagnoses, and the self-report psychiatric measures to account for the anatomical variance was compared with multiple regressions. Internalizing and externalizing factors were identified in these brain-injured patients. Damage to the left amygdala and bilateral basal ganglia was associated with lower internalizing factor scores, and damage to the left medial orbitofrontal cortex (OFC) with higher, and bilateral hippocampi with lower, externalizing factor scores. Factor scores best predicted left amygdala and bilateral hippocampal involvement, whereas DSM-IV diagnoses best predicted bilateral basal ganglia and left OFC involvement. Damage to the limbic areas involved in the processing of emotional and reward information, including structures involved in the National Institute of Mental Health's Research Domain Criteria Negative Valence Domain, influences the development of internalizing and externalizing psychiatric symptoms. Self-report measures underperformed DSM-IV and factor scores in predicting neuroanatomical findings. DSM is a classification system of psychiatric disorders based on the clustering of psychiatric symptoms in patients as observed by clinicians.1 There is a growing body of evidence, however, that a factor structure underlies, and can cut across, DSM diagnoses. 2-4 It has been hypothesized, but not yet tested, that these factors underlying DSM diagnoses will be more closely associated with the neuroanatomical bases of psychiatric symptoms than DSM diagnosis. In the current study, we determined the factor structure of psychopathology underlying the DSM diagnoses of 199 Vietnam War veterans who suffered penetrating brain injuries and 55 matched control participants. We then determined which neuroanatomical structures, when damaged, were associated with higher or lower factor scores compared with participants without damage to that structure. We also compared the ability of DSM-IV categorical diagnoses, factors derived from DSM-IV diagnoses, and continuous self-report measures of depressive and anxiety symptoms to predict the neuroanatomical findings. This study had two goals: 1) to determine which specific brain regions are associated with core components of psychopa...

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