Neurocognitive performance in drug dependent males and females with PTSD symptoms

Sex differences in neurobiological mechanisms of substance dependence are well documented but studies of sex differences in associated neurocognitive deficits have produced inconsistent results. PTSD is comorbid with substance dependence and frequently affects neurocognition. Thus, we investigated the effects of sex and PTSD symptoms on sustained attention and inhibition abilities among 126 female and 297 male substance dependent individuals (SDIs) using the Immediate Memory Test (IMT). Females with significant PTSD (PTSD+) symptoms demonstrated significantly impaired IMT performance relative to other participants. These results represent progress in efforts to delineate sex-specific risk factors for neurocognitive deficits among SDIs. Recent literature has reported evidence of sex differences in neurobiological, behavioral, and environmental aspects of addiction (Fattore, Altea, & Fratta, 2008; Lynch, Roth, & Carroll, 2002; Tuchman, 2010; Wetherington, 2007). Although substance use disorders (SUDs) are more prevalent among males, females accelerate their drug use and transition to substance dependence more rapidly (Greenfield, Back, Lawson, & Brady, 2010). Recent investigators (Cahill, 2006; Wetherington, 2007) have emphasized the critical importance of detailed study of sex differences in addiction neuroscience. They note, for example, that neuroimaging studies have shown qualitatively different, and in some instances, opposing patterns of frontal and limbic activity in male and female substance dependent individuals (SDIs) (Kilts, Gross, Ely, & Drexler, 2004; Ray Li, Kosten, & Sinha, 2005; Volkow et al., 2011). Several factors contribute to neurobiological mechanisms of sex differences in drug addiction, including cortisol and estrogen systems and their interactions with dopaminergic and serotonergic transmission (Fattore et al., 2008; Sava, McCaffrey, & Yurgelun-Todd, 2009; White, Justice, & de Wit, 2002). Given the profound effects these systems exert on brain-behavior relationships, it is reasonable to expect some sex differences in integrity of neurocognitive functions commonly affected by substance use disorders (Chambers, Garavan, & Bellgrove, 2009; Fernández-Serrano, Pérez-Garcia, Verdejo-García, 2011; Gruber, Silveri, & Yurgelun-Todd, 2007). Indeed, recent studies have shown significantly poorer performance among female compared with male SDIs on tests of complex decisionmaking (Van der Plas, Crone, van den Wildenberg, Tranel, & Bechara, 2009) and spatial working memory (Wang et al., 2007). Conversely, other studies demonstrated that male drug users showed poorer attention and recognition memory abilities than females (Rahman & Clarke, 2005) and that, compared with female SDIs, male SDIs demonstrated poorer Correspondence concerning this article should be addressed to Jessica Paxton, Department of Psychiatry, University of Illinois, Chicago, IL 60612. jpaxton@psych.uic. edu. Jessica L. Paxton, Department of Psychiatry, University of Illinois, Chicago; Jasmin Vassileva, Department of Psychiatry, University of Illinois, Chicago; Raul Gonzalez, Departments of Psychiatry and Psychology, University of Illinois, Chicago; Pauline M. Maki, Departments of Psychiatry and Psychology, University of Illinois, Chicago; Eileen M. Martin, Psychiatry, Psychology, and Neurology, University of Illinois, Chicago. NIH Public Access Author Manuscript J Clin Exp Neuropsychol. Author manuscript; available in PMC 2013 June 01. Published in final edited form as: J Clin Exp Neuropsychol. 2012 June ; 34(5): 521–530. doi:10.1080/13803395.2012. 665436. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript visual-spatial paired associate learning (Ersche, Clark, London, Robbins, & Sahakian, 2006). As a whole, the current literature indicates a need for detailed investigation of substance use characteristics and premorbid disorders as potential influences on the type and presence of sex differences in neurocognition among SDIs (see Sava et al., 2009, for a review). Female SDIs are more commonly affected by comorbid psychiatric disorders (Tuchman, 2010), and therefore, when comparing male and female SDIs, it is important to consider specific neurocognitive risk factors that may interact with sex and have an effect on neurocognition in female SDIs. Thus, in the current study, we were interested in assessing neurocognition in SDIs with comorbid posttraumatic stress disorder (PTSD) because it is one of the most common comorbid disorders in SDIs (Brady, Back, & Coffey, 2004) and PTSD has shown the strongest association with substance dependence in individuals who did not also have a comorbid externalizing disorder such as ADHD (Hofmann, Richey, Kashdan, & McKnight, 2009). Also, compared with males, females are twice as likely to develop PTSD (Kessler, Sonnega, Bromet, Hughes, & Nelson, 1995). Furthermore, PTSD has been associated with dysfunction of neural circuitry that includes the hippocampus (Woodard et al., 2009), amygdala (Brohawn, Offringa, Pfaff, Hughes, & Shin, 2010), and prefrontal cortex (Liberzon & Sripada, 2008). Numerous studies have demonstrated impairment in sustained attention, working memory, verbal learning and inhibitory control (Vasterling et al., 2002) among different PTSD populations, including combat veterans, abuse survivors, and refugees/war victims (e.g., Qureshi et al., 2009). Still, the only study showing evidence of sex differences in neurocognitive features of PTSD suggested that PTSD symptoms were associated with executive functioning deficits in women but not men (Leskin & White, 2007). We found no previous studies evaluating sex differences in the neurocognitive effects of comorbid substance dependence and PTSD. Consistent with our goal to investigate sex differences in SUD and PTSD, we targeted executive control functions involving attention and inhibitory control as neurocognitive outcomes of interest as these are consistently impaired among patients with SUD (Fernández-Serrano, Pérez-Garcia, Verdejo-García, 2011; Perry & Carroll, 2008) and PTSD (Aupperle, Melrose, Stein, & Paulus, 2011; Falconer et al., 2007; Wu et al., 2010). Thus, in the current study, we compared neurocognitive performance of male and female SDIs with and without significant PTSD symptoms using a modified Continuous Performance Task assessing both sustained attention and inhibitory control, the Immediate Memory Test (IMT; Dougherty, Marsh, & Mathias, 2002). Our primary goals were to examine the extent to which sustained attention and/or response inhibition are impaired among SDIs with significant symptoms of PTSD; and to determine if sex and PTSD exert distinct or additive effects on these outcomes. We compared four groups of SDIs: males without significant PTSD symptoms, males with significant PTSD symptoms, females without significant PTSD symptoms, and females with significant PTSD symptoms. We hypothesized that SDIs with significant PTSD symptoms would perform more poorly than SDIs without PTSD given that both PTSD patients and SDIs show difficulties with attention and inhibition abilities.