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Posttraumatic Stress Disorder 183

cortex of the brain (Bland et al., 2003). Such eff ects have been associated with
changes in anxiety (Hashimoto, Inoue & Koyama, 1999) and coping (Berridge,
Mitton, Clark & Roth, 1999; Horger & Roth, 1996). Thus, it is reasonable to con-

sider that genes involved in brain dopaminergic activity might also play a role
in PTSD, although at present there is only modest clinical evidence to support a
direct association between dopamine neurotransmission and PTSD (Geracioti,
Jr. et al., 1999; Spivak et al., 1999; Strawn et al., 2002). Three studies have con-

sidered the possible involvement of dopamine-2 (D2) receptor polymorphisms
and PTSD risk, with mixed results (Comings, Muhleman & Gysin, 1996;
Gelernter et al., 1999; Young et al., 2002). However, these studies were limited in
several respects, including small sample size, failure to assess trauma exposure
in control subjects, and failure to exclude substance-abusing probands. Segman

et al. (2002) reported a statistically significant relationship between the SLCA3
9-repeat allele and PTSD in a large, well-characterized, population-stratifi ed
sample (N = 206). However, the authors of this study did not fi nd evidence
that the genetic variation was associated with comorbid depression in the PTSD
subjects.
Based upon reports of an association between glucocorticoid (GC)
receptor sensitivity and PTSD (Yehuda, Boisoneau, Lowy & Giller, 1995),
Bachmann et al. (2005) recently investigated GC receptor polymorphisms
(N363S and Bcll) in a small cohort of Australian Vietnam veterans with
PTSD. This study revealed no evidence for association between variations in

either the N363S gene or the Bcll gene and PTSD diagnosis. Nor was there
evidence for an association between variations in N363S or Bcll and a specifi c
measure of GC receptor sensitivity known as the “low-dose dexamethasone
suppression test” (Bachmann et al., 2005).

Gene Expression Profi ling

Gene expression studies attempt to identify genes that are diff erentially
expressed in disparate individuals, for example, in those with or without a
particular disease, and which might therefore serve as putative molecular
markers for the disease in question. In the case of PTSD, Segman et al. (2005)
have attempted to identify a peripheral blood mononuclear cell (PBMC) gene

expression profile that might predict individual risk for developing PTSD

after exposure to life-threatening events. The investigators used oligonucle-

otide microarrays, which have been designed to interrogate the expression
levels of thousands of genes simultaneously, and PBMCs that were obtained

immediately after exposure and again 4 months later. For the gene expres-
sion data collected both immediately after exposure and 4 months later,

the expression levels of specific genes could be used to distinguish between
individuals who met DSM-IV diagnostic criteria for PTSD and individuals
who did not. Specifi cally, Segman et al. (2005) found a general reduction in

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