The relationship between mood and anxiety and cognitive phenotypes in adults with pharmacoresistant temporal lobe epilepsy

Objective: Patients with temporal lobe epilepsy (TLE) are often at a high risk for cognitive and psychiatric comorbidities. Several cognitive phenotypes have been identified in TLE, but it is unclear how phenotypes relate to psychiatric comorbidities, such as anxiety and depression. This observational study investigated the relationship between cognitive phenotypes and psychiatric symptomatology in TLE.Methods: A total of 826 adults (age = 40.3, 55% female) with pharmacoresistant TLE completed a neuropsychological evaluation that included at least two measures from five cognitive domains to derive International Classification of Cognitive Disorders in Epilepsy (IC-CoDE) cognitive phenotypes (i.e., intact, single-domain impairment, bi-domain impairment, generalized impairment). Participants also completed screening measures for depression and anxiety. Psychiatric history and medication data were extracted from electronic health records. Multivariable proportional odds logistic regression models examined the relationship between IC-CoDE phenotypes and psychiatric variables after controlling for relevant covariates.Results: Patients with elevated depressive symptoms had a greater odds of demonstrating increasingly worse cognitive phenotypes than patients without significant depressive symptomatology (odds ratio [OR] = 1.123-1.993, all corrected p's < .05). Number of psychotropic (OR = 1.584, p < .05) and anti-seizure medications (OR = 1.507, p < .001), use of anti-seizure medications with mood-worsening effects (OR = 1.748, p = .005), and history of a psychiatric diagnosis (OR = 1.928, p < .05) also increased the odds of a more severe cognitive phenotype, while anxiety symptoms were unrelated.Significance: This study demonstrates that psychiatric factors are not only associated with function in specific cognitive domains but also with the pattern and extent of deficits across cognitive domains. Results suggest that depressive symptoms and medications are strongly related to cognitive phenotype in adults with TLE and support the inclusion of these factors as diagnostic modifiers for cognitive phenotypes in future work. Longitudinal studies that incorporate neuroimaging findings are warranted to further our understanding of the complex relationships between cognition, mood, and seizures and to determine whether non-pharmacologic treatment of mood symptoms alters cognitive phenotype.