Neuropsychological Functioning in Patients with Posttraumatic Stress Disorder Following Short-Term Paroxetine Treatment

According to the National Comorbidity Survey (1995), posttraumatic stress disorder (PTSD) affects 7.8% of the US population at some time in their lives (10.4% of women, 5% of men).1 In contrast, a recent study of an urban primary care population found that 34% of participants met diagnostic criteria for lifetime PTSD and 23% met criteria for current PTSD.2 Clearly, these prevalence estimates indicate that PTSD constitutes a major public health concern. Studies have shown that PTSD is associated with lasting changes in neurobiological systems and brain areas that mediate both the stress response and cognition. Extreme psychological stress has been associated with alterations in neurons of the hippocampus, a brain area involved in learning and memory. A number of neuroimaging studies have found smaller hippocampal volume in traumatized individuals with PTSD.3–7 Functional imaging studies have also shown alterations in brain activity in other regions associated with memory, including the amygdala and medial prefrontal cortex, in patients with PTSD.40 It has been hypothesized that these changes may, in part, be related to stress-induced alterations in serotonergic function.8 Learning and memory impairments are frequently reported in patients with PTSD.9–12 Verbal memory deficits in particular have been found to be present more often than visual memory deficits,6,13,14 but some studies show mixed findings. Vasterling and colleagues15 found that Persian Gulf veterans with PTSD demonstrated more intrusive responses and had deficits in initial and delayed recall as well as retention on a verbal learning task, and worse learning on a visual memory task. In a sample of Vietnam veterans, Bremner and colleagues (1993) found that the PTSD group demonstrated deficits in immediate and delayed recall on verbal, but not figural, subtests of the Wechsler Memory Scale (WMS).16,17 However, deficits were found in both verbal and visual indices measuring total recall, long-term storage, and long-term retrieval on the Selective Reminding Test (SRT).18 Related deficits in attention and executive functioning have been observed in individuals with PTSD. Attentional resources, such as sustained attention, are necessary for proper memory encoding, and some studies have found these abilities to be impaired in participants with PTSD using continuous performance and digit repetition tasks.15,19 However, these authors did not find that posttraumatic psychopathology was significantly related to poor performance on tasks that required category shifting, such as the Wisconsin Card Sorting Test (WCST),20 which is consistent with the findings of other investigators.21 The authors15,19 did, however, find errors of commission on this task, reflecting decreased ability to respond to irrelevant information, and related this to high symptoms of arousal found in their samples. Some authors22 have suggested that the neuropsychological impairments found in PTSD are more likely related to premorbidly low intellectual functioning than stress-related neurobiological insult. While Vasterling and colleagues19 found premorbid estimates of IQ to be significantly lower in veterans with PTSD, scores on intellectual functioning alone did not account for deficits found in sustained attention and learning of verbal material in their sample. Medications that modulate serotonergic function, including the selective serotonin reuptake inhibitors (SSRIs), have been shown to be efficacious in the treatment of PTSD (for a review, see 23, 41). Paroxetine and sertraline are the two SSRIs approved by the Food and Drug Administration (FDA) as first-line psychopharmacological treatments for PTSD.24 Paroxetine, specifically, has been shown in two controlled trials to be efficacious in treating clinical symptoms of PTSD,25,26 and may likewise be useful in improving cognitive function via modulation of serotonergic function in limbic structures, particularly the hippocampus. Animal studies have demonstrated that treatment with SSRIs promotes neurogenesis in the hippocampus.27 Bartfai et al. (1991) administered clomipramine, which inhibits norepinephrine and serotonin reuptake, for three weeks to subjects with depression28 and found strong correlations between levels of serotonin metabolites (5-HIAA) found in cerebrospinal fluid and performance on neuropsychological measures. The authors observed a decrease in depressive symptoms and improvements in verbal fluency scores, however, verbal learning and retention was more impaired after treatment. Although paroxetine has demonstrated effectiveness in the treatment of clinical symptoms of PTSD and depression, only one study to date has examined the effects of paroxetine on cognitive functioning in participants with PTSD.5 This study found a decrease in PTSD symptomatology in participants following 12 months of open-label treatment with paroxetine, significant improvements in delayed recall and percent retention on logical memory and improved immediate recall for figural memory subtests of the WMS-R. Additionally, participants’ performances on verbal and visual memory indices of the SRT were significantly improved with treatment. The purpose of the current study was to replicate the previous open label study and extend it by the addition of a paroxetine-placebo comparison. We hypothesized that paroxetine treatment would be associated with improved performance on measures of verbal declarative memory.