Stress is a major risk factor for numerous neuropsychiatric diseases. However, susceptibility to stress and the qualitative nature of stress effects on behavior differ markedly among individuals. This is partly because of the moderating influence of genetic factors. Inbred mouse strains provide a relatively stable and restricted range of genetic and environmental variability that is valuable for disentangling gene-stress interactions. Here, we screened a panel of inbred strains for anxiety-and depression-related phenotypes at baseline (trait) and after exposure to repeated restraint. Two strains, DBA/2J and C57BL/6J, differed in trait and restraint-induced anxiety-related behavior (dark/light exploration, elevated plus maze). Gene expression analysis of amygdala, medial prefrontal cortex, and hippocampus revealed divergent expression in DBA/2J and C57BL/6J both at baseline and after repeated restraint. Restraint produced strain-dependent expression alterations in various genes including glutamate receptors (e.g., Grin1, Grik1). To elucidate neuronal correlates of these strain differences, we performed ex vivo analysis of glutamate excitatory neurotransmission in amygdala principal neurons. Repeated restraint augmented amygdala excitatory postsynaptic signaling and altered metaplasticity (temporal summation of NMDA receptor currents) in DBA/2J but not C57BL/6J. Furthermore, we found that the C57BL/6J-like changes in anxiety-related behavior after restraint were absent in null mutants lacking the modulatory NMDA receptor subunit Grin2a, but not the AMPA receptor subunit Gria1. Grin2a null mutants exhibited significant (ϳ30%) loss of dendritic spines on amygdala principal neurons under nonrestraint conditions. Collectively, our data support a model in which genetic variation in glutamatergic neuroplasticity in corticolimbic circuitry underlies phenotypic variation in responsivity to stress.

This article describes a second treatment-outcome study of cognitive trauma therapy for battered women with posttraumatic stress disorder (PTSD; CTT-BW). CTT-BW includes trauma history exploration: PTSD education; stress management; exposure to abuse and abuser reminders; self-monitoring of negative self-talk; cognitive therapy for guilt; and modules on self-advocacy, assertiveness, and how to identify perpetrators. One hundred twenty-five ethnically diverse women were randomly assigned to immediate or delayed CTT-BW. PTSD remitted in 87% of women who completed CTT-BW, with large reductions in depression and guilt and substantial increases in self-esteem. White and ethnic minority women benefited equally from CTT-BW. Similar treatment outcomes were obtained by male and female therapists and by therapists with different levels of education and training. Gains were maintained at 3- and 6-month follow-ups.

This paper describes a treatment-outcome study of Cognitive Trauma Therapy for Battered Women (CTT-BW) with PTSD. Derived from psychological learning principles, CTT-BW emphasizes the role of irrational beliefs and evaluative language in chronic PTSD. CTT-BW includes trauma history exploration, PTSD psychoeducation, stress management, psychoeducation about dysfunctional self-talk and self-monitoring of self-talk, exposure to abuse reminders, Cognitive Therapy for Trauma-Related Guilt (E. S. Kubany & F. P. Manke, 1995), and modules on assertiveness, managing contacts with former partners, self-advocacy strategies, and avoiding revictimization. Thirty-seven ethnically diverse women were assigned to Immediate or Delayed CTT-BW. PTSD remitted in 30 of 32 women who completed CTT-BW. Gains were maintained at 3-month follow-up. CTT-BW was efficacious across ethnic backgrounds. Issues related to disseminability of CTT-BW are discussed.

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