Initial Validation of the Mid-Atlantic Mental Illness Research, Education, and Clinical Center Assessment of Traumatic Brain Injury.

With the increasing prevalence of traumatic brain injury (TBI), the need for reliable and valid methods to evaluate TBI has also increased. The purpose of this study was to establish the validity and reliability of a new comprehensive assessment of TBI, the Mid-Atlantic Mental Illness Research, Education, and Clinical Center (MIRECC) Assessment of TBI (MMA-TBI). The participants in this study were post-deployment, combat exposed veterans. First, MMA-TBI outcomes were compared with those of independently conducted clinical TBI assessments. Next, MMA-TBI outcomes were compared with those of a different validated TBI measure (the Ohio State University TBI Identification method [OSU-TBI-ID]). Next, four TBI subject matter experts independently evaluated 64 potential TBI events based on both clinical judgment and Veterans Administration/Department of Defense (VA/DoD) Clinical Practice Guidelines. Results of the MMA-TBI algorithm (based on VA/DoD clinical guideline) were compared with those of the subject matter experts. Diagnostic correspondence with independently conducted expert clinical evaluation was 96% for lifetime TBI and 92% for deployment-acquired TBI. Consistency between the MMA-TBI and the OSU-TBI-ID was high (κ = 0.90; Kendall Tau = 0.94). Comparison of MMA-TBI algorithm results with those of subject matter experts was high (κ = 0.97-1.00). The MMA-TBI is the first TBI interview to be validated against an independently conducted clinical TBI assessment. Overall, results demonstrate the MMA-TBI is a highly valid and reliable instrument for determining TBI based on VA/DoD clinical guidelines. These results support the need for application of standardized TBI criteria across all diagnostic contexts.

Monoamine oxidase (MAO) intron 13 polymorphism and platelet MAO-B activity in combat-related posttraumatic stress disorder.

BACKGROUND: The neurobiology of posttraumatic stress disorder (PTSD) involves alterations in multiple neuroendocrine and neurotransmitter systems. Platelet monoamine oxidase (MAO-B) has been associated with susceptibility to various psychiatric disorders, personality traits and behaviors. METHODS: Platelet MAO-B activity and MAO-B intron 13 polymorphism (a G/A substitution) were determined in male war veterans (n=106) with DSM-IV diagnosed current and chronic PTSD, divided into subgroups of PTSD patients with (n=28) or without (n=78) psychotic features, combat exposed veterans (n=41) who did not develop PTSD, and healthy control men (n=242). RESULTS: Two-way ANOVAs revealed a significant effect of diagnosis and smoking, a significant effect of smoking, no significant effect of genotype, and no significant interaction between genotype, smoking or diagnosis, on platelet MAO-B activity. One-way ANOVAs showed significantly lower platelet MAO-B activity in smokers than in nonsmokers. After controlling for smoking, veterans with psychotic PTSD had significantly higher platelet MAO-B activity than veterans with or without PTSD, or healthy subjects. LIMITATIONS: The results were obtained on peripheral biochemical marker, i.e. platelet MAO activity. CONCLUSIONS: The MAO-B intron 13 polymorphism was not functional, and did not affect platelet MAO-B activity. The allele frequencies of the MAO-B genotype were similarly distributed among healthy controls and veterans with or without PTSD and/or psychotic symptoms. The results suggest that platelet MAO-B activity, controlled for smoking status, might be used as a peripheral marker of the psychotic symptoms in PTSD.

Dopamine beta-hydroxylase (DBH) activity and -1021C/T polymorphism of DBH gene in combat-related post-traumatic stress disorder.

The roles of dopamine (DA) and norepinephrine (NE) in posttraumatic stress disorder (PTSD) are unclear. The aim of the study was to determine plasma dopamine beta-hydroxylase (DBH) activity and DBH-1021C/T gene polymorphism in combat veterans with (N = 133) or without (N = 34) chronic PTSD. Similar frequencies in genotype or allele distribution were found between veterans with or without PTSD. War veterans with PTSD had lower DBH activity, associated with the DBH-1021C/T variant in DBH genes, than veterans without PTSD. A significantly lower plasma DBH activity was found in combat veterans with PTSD carrying the CC genotype as compared to veterans without PTSD carrying the corresponding genotype. Since both groups were exposed to the same trauma, it is possible that a pre-existing trait difference in regulation of NE function contributed to a differential vulnerability to develop PTSD, or that the regulation of DBH expression was different in response to trauma. The results suggest that that genotype-controlled measurement of plasma DBH activity might be used as a potential biological marker of the response to trauma, and that further studies of DBH and other loci related to DA and NA in PTSD are warranted.

Platelet adenylate cyclase and phospholipase C activity in posttraumatic stress disorder.

Adenylate cyclase and phospholipase C activity were examined in platelet membranes obtained from 19 male subjects with combat-related posttraumatic stress disorder (PTSD) and 35 age- and gender-matched healthy controls. Basal and forskolin-stimulated adenylate cyclase activity were significantly lower in the PTSD group whereas aluminum chloride plus sodium fluoride (AlCl3/NaF)- and prostaglandin E1 (PGE1)-stimulated responses were normal. There was no difference in phospholipase C activity between the two groups. The lower basal and forskolin-stimulated adenylate cyclase responses replicate a previous report and suggest that PTSD may be associated with an abnormality of the catalytic subunit of the receptor-adenylate cyclase complex.

Posttraumatic stress disorder and platelet serotonin measures.

The role of serotonin (5HT) in the pathophysiology of posttraumatic stress disorder (PTSD) has been suggested by the overlap in clinical symptoms between PTSD and psychiatric conditions in which a serotonin dysfunction is implicated, as well as by the therapeutic efficiency of 5HT-related drugs (antidepressants, selective serotonin reuptake inhibitors and monoamine oxidase inhibitors) in alleviating symptoms in PTSD. In the present study, the blood platelet, which has been proposed as a peripheral model for the central serotonergic neurons, has been used to search for alterations in 5HT mechanisms in PTSD. Platelet serotonin level and kinetics of serotonin transporter and monoamine oxidase (MAO-B) were assessed in 63 combat-related PTSD patients and 43 sex and age-matched control subjects. A significant reduction in maximal velocity of platelet MAO-B (approx. 30%), with no changes in the enzyme affinity was observed in our patient sample. Conversely, no alterations in kinetic parameters (V(max), K(m)) of platelet serotonin transporter, as well as in platelet 5HT level, were found in the PTSD group.

Plasma dopamine beta-hydroxylase activity in psychotic and non-psychotic post-traumatic stress disorder.

Recognition and treatment of comorbid chronic psychotic symptoms in post-traumatic stress disorder (PTSD) has become of increasing clinical interest. Altered dopamine beta-hydroxylase (DBH) activity has been reported in mood disorders. Plasma DBH is reduced in major depression with psychosis and elevated in bipolar disorder with psychosis compared with their respective non-psychotic diagnostic groups. DBH is likely a trait marker with interindividual variations secondary to genetic polymorphism. We therefore evaluated DBH activity in PTSD patients with and without psychotic features and compared these groups with age- and gender-matched control subjects. Vietnam combat veterans with PTSD (n = 19) (including patients with and without psychotic features) and normal control subjects (n = 22) had plasma DBH enzyme activity assayed photometrically. DBH was significantly higher in patients with PTSD with psychotic features than in patients without psychotic features (80.6 +/- 13.4 vs. 42.1 +/- 7.3 mM/min, P < 0.01) and was also higher than normal control subjects (46.12 +/- 4.93, P < 0.01). Plasma DBH activity may differentiate psychotic and non-psychotic subtypes of PTSD. The observed changes are, interestingly, opposite to those seen in psychotic depression but comparable to psychotic bipolar disorder. Since DBH is a genetic marker, this may reflect individual vulnerabilities to develop psychosis in the context of trauma.