Transcranial magnetic stimulation (TMS) is an effective treatment for individuals with pharmacoresistant major depressive disorder (MDD), yet identifying which patients best respond remains an important area of inquiry. The Brief Symptom Inventory (BSI-18) serves as a screen for psychological distress, providing measures across three separate domains (e.g., somatization, depression, and anxiety) and one composite score (i.e., global severity index). The psychometric properties of the BSI-18 have been validated across multiple studies; however, it has sparsely been used to track changes in patient symptoms in response to intervention. Assessing patient symptom severity across these domains is imperative since these symptoms can negatively influence cognitive functioning. Accordingly, the current study utilized the BSI-18 to measure psychological distress across these different domains in patients receiving TMS treatment. We hypothesized that all domains of the BSI-18 would see a significant decrease after treatment, that elevated scores in specific domains would predict a less favorable response to treatment, and that measurement of depressive symptoms will be consistent across measures of similar scope.

Veterans (n=94) with MDD and met standard clinical TMS criteria were administered the BSI-18 before and after receiving an adequate dose of treatment (e.g., 30 sessions). Paired Samples T-test were used to compare the pre-treatment and post-treatment scores across domains.

The results of paired sample t-tests indicated a statistically significant reduction in measures of global psychological distress (t(93) = 7.99, p < .001, Cohen's d =.82), as well as depressive (t(93) = 8.34, p < .001, d = .86), anxious (t(93) = 7.64, p < .001, d = .79), and somatic symptoms (t(92) = 5.29, p < .001, d = .55) after receiving treatment. Individuals with elevated levels of anxiety (e.g., BSI-A>63) saw a significant reduction in depressive (t(62) = 8.15, p < .001, d = 1.03), anxious (t(62) = 8.34, p < .001, d = 1.05) and somatic (t(61) = 4.94, p < .001, d = .63) symptoms. Lastly, two measures of depressive symptoms, the BSI-D and PHQ-9, had a statistically significant strong, positive relationship before (r=.66) and after (r=.88) treatment (all n=65 and p<.001).

The BSI-18 can detect changes in different domains of psychological distress as a function of TMS treatment. Unexpectedly, TMS patients with elevated levels of anxiety responded well to treatment despite comorbid anxiety often being associated with less favorable outcomes in treatment trials. The positive relationship of the BSI-D and PHQ-9 before and after treatment suggests the use of the BSI as a valid, additional measure of depressive symptoms.

Blast-related traumatic brain injury (bTBI) is one of the most common injuries among Veterans who have served in recent wars in Iraq and Afghanistan. Despite representing a distinct mechanism of injury, long-term clinical and functional outcomes of bTBI are generally comparable with non-blast-related traumatic brain injury (TBI). However, controversy remains over whether bTBI etiology differentially impacts emotional regulation and neurocognition - particularly with respect to post-traumatic stress disorder (PTSD) and verbal and visual memory. Through diffusion tensor imaging (DTI), the present study investigates the microstructural pathophysiology of bTBI, compared to non-blast TBI, in neural pathways involved in emotional regulation and cognitive control.

Participants included 36 Veterans (25% female; age M = 36.33, SD = 10.11; years of education M = 15.67, SD = 2.34). Axial diffusivity (AD) in networks of emotional and cognitive control was acquired using magnetic resonance imaging (MRI) with a DTI protocol. Analyses of variance (ANOVA) were used to compare Veterans with self-reported bTBI (n = 23) to those with non-blast-related TBI (n = 13).

In the left hemisphere, Veterans with bTBI exhibited significantly smaller AD in axonal projections from the caudate nucleus (CN) to the orbitofrontal cortex (OFC), as well as in projections from the putamen to the OFC (p < 0.05). In the right hemisphere, Veterans with bTBI also exhibited significantly smaller AD in networks connecting the hippocampus to the amygdala (p < 0.05).

Compared to Veterans with non-blast-related TBI, Veterans with bTBI exhibited decreased AD in neural pathways from the CN to the OFC, the putamen to the OFC, and the hippocampus to the amygdala - indicative of increased axonal injury in these areas. Our results suggest that, on a microstructural level, emotional and cognitive networks are susceptible to longitudinal blast-related white matter damage. This is consistent with the literature in post-concussion syndrome (PCS) and provides a potential mechanism underlying results previously reported from this sample, describing subjective cognitive complaints in the absence of objective clinical deficits. As such, therapies that target networks of emotional and cognitive control may be particularly beneficial for Veterans with bTBI.

Repetitive transcranial magnetic stimulation (TMS) is an evidenced based treatment for adults with treatment resistant depression (TRD). The standard clinical protocol for TMS is to stimulate the left dorsolateral prefrontal cortex (DLPFC). Although the DLPFC is a defining region in the cognitive control network of the brain and implicated in executive functions such as attention and working memory, we lack knowledge about whether TMS improves cognitive function independent of depression symptoms. This exploratory analysis sought to address this gap in knowledge by assessing changes in attention before and after completion of a standard treatment with TMS in Veterans with TRD.

Participants consisted of 7 Veterans (14.3% female; age M = 46.14, SD = 7.15; years education M = 16.86, SD = 3.02) who completed a full 30-session course of TMS treatment and had significant depressive symptoms at baseline (Patient Health Questionnaire-9; PHQ-9 score >5). Participants were given neurocognitive assessments measuring aspects of attention [Wechsler Adult Intelligence Scale 4th Edition (WAIS-IV) subtests: Digits Forward, Digits Backward, and Number Sequencing) at baseline and again after completion of TMS treatment. The relationship between pre and post scores were examined using paired-samples t-test for continuous variables and a linear regression to covary for depression and posttraumatic stress disorder (PTSD), which is often comorbid with depression in Veteran populations.

There was a significant improvement in Digit Span Forward (p=.01, d=-.53), but not Digit Span Backward (p=.06) and Number Sequencing (p=.54) post-TMS treatment. Depression severity was not a significant predictor of performance on Digit Span Forward (f(1,5)=.29, p=.61) after TMS treatment. PTSD severity was also not a significant predictor of performance on Digit Span Forward (f(1,5)=1.31, p=.32).

Findings suggested that a standard course of TMS improves less demanding measures of working memory after a full course of TMS, but possibly not the more demanding aspects of working memory. This improvement in cognitive function was independent of improvements in depression and PTSD symptoms. Further investigation in a larger sample and with direct neuroimaging measures of cognitive function is warranted.