Questionable utility of the Montreal Cognitive Assessment (MoCA) in detecting cognitive impairment in individuals with comorbid PTSD and SUD.

Posttraumatic stress disorder (PTSD) is frequently comorbid with substance use disorder (SUD) in individuals seeking treatment for substance use. Further, SUD and PTSD are individually associated with cognitive impairment (CI) and poor treatment outcomes. Despite the frequent use of the Montreal Cognitive Assessment (MoCA) as a screening tool for CI, the validity of the MoCA has not been established in individuals with comorbid SUD-PTSD. We assessed the criterion validity of the MoCA in 128 participants seeking inpatient medically-assisted detoxification using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) as a reference for CI. The correlation between the RBANS and MoCA was weaker in those with SUD-PTSD (r = .32) relative to SUD alone (r = .56). Receiver operating characteristic (ROC) curves demonstrated that the MoCA had moderate-to-high ability to discriminate CI in individuals with SUD alone, with an area under the ROC curve of .82 (95% CI .69-.92) and optimal cutoff score of ≤23. However, in individuals with comorbid SUD-PTSD, the ROC analysis was not significant. Results suggest that PTSD, when comorbid with SUD, reduces the criterion-related validity of the MoCA. We recommend exercising caution when classifying CI in individuals with SUD-PTSD using the MoCA and suggest reducing the cutoff score to ≤23 in order to limit the rate of false-positive CI diagnoses in SUD-PTSD populations.

Sustained attention performance deficits in the three-choice serial reaction time task in male and female rats after experimental brain trauma.

Impaired attention is central to the cognitive deficits associated with long-term sequelae for many traumatic brain injury (TBI) survivors. Assessing complex sustained attention post-TBI is clinically-relevant and may provide reliable avenues towards developing therapeutic and rehabilitation targets in both males and females. We hypothesized that rats subjected to a moderate TBI will exhibit attentional deficits seen as reduced accuracy and increased distractibility in an operant 3-choice serial reaction time task (3-CSRT), designed as an analogue of the clinical continuous performance test. Upon reaching baseline of 70% accuracy at the 300 ms cue, adult male and female Sprague-Dawley rats were subjected to a controlled cortical impact (2.8 mm deformation at 4 m/s) or sham injury over the right parietal cortex. After two weeks of recovery, they were retested on the 3-CSRT for ten days. Dependent measures include percent accuracy (overall and for each of the three cue ports), percent omissions, as well as latency to instrumental poke and retrieve reward. Results demonstrate that both males and females displayed reduced percent accuracy and increased omissions when re-tested post-TBI on 3-CSRT compared to Sham rats and to their own pre-insult baseline (p's < 0.05). Performance accuracy was impaired consistently throughout the ten days of post-surgery re-testing, suggesting pronounced and long-lasting dysfunction in sustained attention processes. Deficits were specifically more pronounced when the cue was pseudorandomly presented in the left-side cue port (p < 0.05), mirroring clinical hemispatial neglect. These data demonstrate significant and persistent complex attention impairments in both sexes after TBI, rendering identifying efficient therapies for cognitive recovery as pivotal.

Depression, anxiety, and stress in pregnancy and postpartum: A longitudinal study during the COVID-19 pandemic.

INTRODUCTION: Symptoms of depression, anxiety, and stress in pregnant women are generally highest in the first trimester and then decrease throughout pregnancy, reaching their lowest point in the postpartum period. Pregnant women are a high-risk population for mortality and mental health symptoms due to COVID-19. However, the extent to which the chronic stress of the COVID-19 pandemic alters the trajectory of depression, anxiety and stress symptoms in pregnant/postpartum women is unknown. METHODS: Women (N=127) who were pregnant or who had given birth less than one month prior were recruited via online advertising during the COVID-19 pandemic. Participants were assessed up to three times during the pregnancy and at 1-month postpartum for depression (Edinburgh Postnatal Depression Scale), anxiety, and stress (Depression, Anxiety, and Stress Scale-21). Random intercepts models examined symptom change over time as well as predictors of elevated postpartum psychopathology. RESULTS: On average, women completed their surveys at 8.5 weeks (first trimester), 21 weeks (second trimester), 32 weeks (third trimester) and 7-weeks postpartum. Women reported mild-moderate levels of depression, anxiety, and stress throughout pregnancy. There was a significant change in symptoms of depression and anxiety over time which was best represented by a quadratic rather than linear trajectory: symptoms increased until week 23-25 and then decreased. Stress levels remained consistently elevated over time. Higher symptom levels at 1-month postpartum were predicted by younger age, lower social support, and worry about going to a healthcare facility. Change in routine due to COVID-19 was not predictive of symptom trajectory from pregnancy to postpartum. CONCLUSIONS: During COVID-19, symptoms of depression and anxiety increased from early to mid-pregnancy but then declined slightly while stress levels remained elevated. Observed reductions in symptoms were small. Given the substantial persistent impact of perinatal distress and poor mental health on maternal and fetal health, providers should be aware of heightened levels of these symptoms in pregnant women during large-scale external health stressors such as COVID-19, and should implement screening procedures to identify and appropriately intervene with at-risk women.

50 Years After Political Protest Violence, Posttraumatic Growth is Associated with PTSD and Anxiety but not Depression or Sleep Difficulties.

Rates of, and relationships between, posttraumatic stress disorder (PTSD), depression, anxiety, and posttraumatic growth (PTG) decades after a single-incident trauma remain unclear. During a two-month period surrounding the 50th anniversary of the political protest violence at Kent State University on May 4, 1970, 132 individuals completed measures of PTG, PTSD, depression, anxiety, and sleep difficulties. Participants were, on average, 19 years old (SD = 3.01) on May 4, 1970, and 44% were present at the protests. 17% met cutoff scores consistent with PTG, 6% for PTSD, 8% for anxiety, 11% for depression and 20% for sleep difficulties. PTG was significantly and positively correlated with PTSD (r = .32, 95% CI: 0.17-0.44) and anxiety (r = .23, 95% CI: 0.08-0.38) but not depression or sleep difficulties after controlling for additional trauma exposure since May 4, 1970. All relationships were best explained by linear rather than curvilinear relationships and were not moderated by proximity to the events of May 4, 1970. Results indicate that clinicians working with survivors of trauma decades later may be able to capitalize on the adaptive functions of PTG to foster positive treatment outcomes.

Milnacipran Ameliorates Executive Function Impairments following Frontal Lobe Traumatic Brain Injury in Male Rats: A Multimodal Behavioral Assessment.

Traumatic brain injuries (TBIs) affect more than 10 million patients annually worldwide, causing long-term cognitive and psychosocial impairments. Frontal lobe TBIs commonly impair executive function, but laboratory models typically focus primarily on spatial learning and declarative memory. We implemented a multi-modal approach for clinically relevant cognitive-behavioral assessments of frontal lobe function in rats with TBI and assessed treatment benefits of the serotonin-norepinephrine reuptake inhibitor, milnacipran (MLN). Two attentional set-shifting tasks (AST) evaluated cognitive flexibility via the rats' ability to locate food-based rewards by learning, unlearning, and relearning sequential rule sets with shifting salient cues. Adult male rats reached stable pre-injury operant AST (oAST) performance in 3-4 weeks, then were isoflurane-anesthetized, subjected to a unilateral frontal lobe controlled cortical impact (2.4 mm depth, 4 m/sec velocity) or Sham injury, and randomized to treatment conditions. Milnacipran (30 mg/kg/day) or vehicle (VEH; 10% ethanol in saline) was administered intraperitoneally via implanted osmotic minipumps (continuous infusions post-surgery, 60 µL/h). Rats had a 10-day recovery post-TBI/Sham before performing light/location-based oAST for 10 days and, subsequently, odor/media-based digging AST (dAST) on the last test day (26-27 days post-injury) before sacrifice. Both AST tests revealed significant deficits in TBI+VEH rats, seen as elevated total trials and errors (p < 0.05), which generally normalized in MLN-treated rats (p < 0.05). This first simultaneous dual AST assessment demonstrates oAST and dAST are sufficiently sensitive and robust to detect subtle attentional and cognitive flexibility executive impairments after frontal lobe TBI in rats. Chronic MLN administration shows promise for attenuation of post-TBI executive function deficits, thus meriting further investigation.

The 50th anniversary of May 4, 1970 is associated with elevations of distress but no increase in mental health symptoms.

Anniversaries of traumatic events are associated with increased symptoms of posttraumatic stress disorder (PTSD), depression, and anxiety, especially in individuals with prior mental health symptoms. However, research has largely focussed on 1-year anniversaries, and it is unclear whether symptom exacerbation persists for more distal, or milestone, anniversaries. Symptoms typically decrease over time after traumatic events, but major anniversaries may be associated with increases in mental health symptoms. During and 3 months after the 50th anniversary of the political protest violence at Kent State University on May 4, 1970, 115 individuals completed measures of PTSD, depression, anxiety, and anniversary-related stress. Participants reported greater stress (t(97) = 4.04 p ≤ .001) during the 50th anniversary compared to 3 months later, but there were no differences in total PTSD (t(114) = .65, p = .52) or depression/anxiety symptoms (all p's > .05). Even in higher-risk individuals (those who previously received mental health services), symptoms did not differ during versus after the anniversary. In general, long-term anniversaries may contribute to transient increases in distress but do not induce major changes in mental health symptoms.

Chronic treatment with galantamine rescues reversal learning in an attentional set-shifting test after experimental brain trauma.

Approximately 10 million new cases of traumatic brain injury (TBI) are reported each year worldwide with many of these injuries resulting in higher order cognitive impairments. Galantamine (GAL), an acetylcholine esterase inhibitor (AChEI) and positive allosteric modulator of nicotinic acetylcholine receptors (nAChRs), has been reported to ameliorate cognitive deficits after clinical TBI. Previously, we demonstrated that controlled cortical impact (CCI) injury to rats resulted in significant executive function impairments as measured by the attentional set-shifting test (AST), a complex cognitive task analogous to the Wisconsin Card Sorting Test (WCST). We hypothesized that chronic administration of GAL would normalize performance on the AST post-TBI. Isoflurane-anesthetized adult male rats were subjected to moderate CCI (2.8 mm tissue deformation at 4 m/s) or sham injury. Rats were then randomized into one of three treatment groups (i.e., 1 mg/kg GAL, 2 mg/kg GAL, or 1 mL/kg saline vehicle; VEH) or their respective sham controls. GAL or VEH was administered intraperitoneally daily commencing 24 hours post-surgery and until AST testing at 4 weeks post-injury. The AST data revealed significant impairments in the first reversal stage after TBI, seen as increased trials to reach criterion and elevated total errors (p < 0.05). These behavioral flexibility deficits were equally normalized by the administration of both doses of GAL (p < 0.05). Additionally, the higher dose of GAL (2 mg/kg) also significantly reduced cortical lesion volume compared to TBI + VEH controls (p < 0.05). In summary, daily GAL administration provides an efficacious treatment for cognitive deficits and histological recovery after experimental brain trauma. Clinically, these findings are promising considering robust results were attained using a pharmacotherapy already used in the clinic to treat mild dementia.