The Effects of Inattentiveness and Hyperactivity on Posttraumatic Stress Symptoms: Does a Diagnosis of Posttraumatic Stress Disorder Matter?

Objective: To address the nature of associations between ADHD symptoms and posttraumatic stress disorder (PTSD) psychopathology in adult military veterans. Method: Ninety-five combat veterans, with PTSD (n = 63) and without PTSD (n = 32), were recruited for this study. PTSD was assessed with the Clinician-Administered PTSD Scale (CAPS) and ADHD was assessed with Connors' Adult ADHD Rating Scale-Self-Report: Short Version (CAARS-S:S). Results: PTSD participants endorsed greater hyperactivity or restlessness, inattention or memory problems, and impulsivity or emotional lability scores than participants without PTSD. Among PTSD participants, inattention or memory problems and impulsivity or emotional lability were significant predictors of total PTSD symptoms, but only inattention or memory problems significantly predicted PTSD symptoms when other ADHD symptom clusters were considered simultaneously. Conclusion: Our data suggest that inattention may serve as a risk factor for posttraumatic stress symptoms following combat exposure.

Cue-dependent inhibition in posttraumatic stress disorder and attention-deficit/hyperactivity disorder.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) are common among military veterans, but the comorbidity of these two psychiatric disorders remains largely unstudied. Evaluating response inhibition and cue-dependent learning as behavioral and neurocognitive mechanisms underlying ADHD/PTSD can inform etiological models and development of tailored interventions. METHOD: A cued go/no-go task evaluated response inhibition in 160 adult males. Participants were recruited from the community and a Veterans Administration medical center. Four diagnostic groups were identified: ADHD-only, PTSD-only, ADHD+PTSD, controls. RESULTS: Group differences were observed across most indices of inhibitory functioning, reaction time, and reaction time variability, whereby PTSD-only and ADHD+PTSD participants demonstrated deficits relative to controls. No cue dependency effects were observed. CONCLUSION: Finding complement prior work on neurocognitive mechanisms underlying ADHD, PTSD, and ADHD+PTSD. Lack of expected group differences for the ADHD-only group may be due to limited power. Additional work is needed to better characterize distinctions among clinical groups, as well as to test effects among women and youth.

Relationships between GAT1 and PTSD, Depression, and Substance Use Disorder.

Post-traumatic stress disorder (PTSD), Major Depressive Disorder (MDD), and Substance Use Disorder (SUD) have large public health impacts. Therefore, researchers have attempted to identify those at greatest risk for these phenotypes. PTSD, MDD, and SUD are in part genetically influenced. Additionally, genes in the glutamate and gamma-aminobutyric acid (GABA) system are implicated in the encoding of emotional and fear memories, and thus may impact these phenotypes. The current study examined the associations of single nucleotide polymorphisms in GAT1 individually, and at the gene level, using a principal components (PC) approach, with PTSD, PTSD comorbid with MDD, and PTSD comorbid with SUD in 486 combat-exposed veterans.  Findings indicate that several GAT1 SNPs, as well as one of the GAT1 PCs, was associated with PTSD, with and without MDD and SUD comorbidity. The present study findings provide initial insights into one pathway by which shared genetic risk influences PTSD-MDD and PTSD-SUD comorbidities, and thus identify a high-risk group (based on genotype) on whom prevention and intervention efforts should be focused.

An exploratory approach demonstrating immune skewing and a loss of coordination among cytokines in plasma and saliva of Veterans with combat-related PTSD.

Studies have suggested PTSD to be associated with an inflammatory state, although few studies have examined the balances between stimulatory and inhibitory immune mediators in PTSD. An exploratory approach was taken to assess the immune imbalances between Th1 stimulatory, inflammatory and inhibitory mediators associated with PTSD. This approach focused on a tightly-controlled and relatively homogeneous population of Veterans, all with similar levels of combat exposure in the Afghanistan and Iraq wars, but some testing negative and others testing positive for PTSD. Although the sample size was small (6 controls and 7 with PTSD) and a limitation of this study, the results showed significant imbalances in immune cytokines favoring a Th1 and inflammatory state, with reduced levels of inhibitory cytokines in Veterans with PTSD. This was particularly prominent in the saliva of PTSD subjects compared to in their plasma.

Exploring the association between a cholecystokinin promoter polymorphism (rs1799923) and posttraumatic stress disorder in combat veterans.

BACKGROUND: Cholecystokinin (CCK) is a neuropeptide that has been implicated in understanding the acquisition and extinction of fear. Research on CCK in anxiety has primarily focused on understanding panic attacks and panic disorder. Emerging data suggests that CCK may also hold promise in understanding the development and maintenance of posttraumatic stress disorder (PTSD). METHOD: The present study examined whether a single nucleotide polymorphism in the promoter region of the CCK gene (C>T; rs1799923) was associated with an increased prevalence of PTSD as well as with severity of PTSD symptoms among a sample of 457 combat veterans. RESULTS: Results demonstrated that participants with either the heterozygous or homozygous T allele had an increased prevalence of PTSD relative to participants with the CC genotype (OR=2.17; 95% CI [1.37-3.43]). LIMITATIONS: The relatively small sample size precluded examination of racial/ethnic differences. Findings were also limited by the absence of a systematic assessment of comorbid anxiety psychopathology. CONCLUSIONS: These data offer preliminary evidence supporting an association between the rs1799923 polymorphism in the CCK gene and PTSD. Additional research is needed to better understand the nature of this relationship.

Variation in SLC1A1 is related to combat-related posttraumatic stress disorder.

Candidate gene studies have yet to investigate the glutamate system, the primary excitatory neurotransmitter of the HPA-axis related to PTSD risk. We investigated 13 SNPs in the glutamate transporter gene (SLC1A1) in relation to PTSD among combat-exposed veterans. Participants (n=418) completed a diagnostic interview and provided a blood sample for DNA isolation and genotyping. A subset of participants (n=391) had severity and combat exposure data available. In the primary logistic regression gender and rs10739062 were significant predictors of PTSD diagnosis (OR=0.50; OR=1.43). In the linear regression analysis, combat exposure was the only significant predictor (ß=0.16) of severity. A computed genetic risk sum score was significant in relation to PTSD diagnosis (OR=1.15) and severity scores (ß=0.14) above and beyond the effects of combat exposure. This study provides preliminary support for the relationship of glutamate transporter polymorphisms to PTSD risk and the need for further genetic studies within this system.