Distinct and shared contributions of diagnosis and symptom domains to cognitive performance in a case-control study of severe mental illness in the Paisa population

Susan K. Service; Cristian Vargas Upeguí; Mauricio Castaño Ramírez; Allison M. Port; Tyler M. Moore; Marfred Munoz Umanes; Luis Guillermo Agudelo Arango; Ana M. Díaz‐Zuluaga; Juanita Melo Espejo; María Cecilia López; Juan David Palacio; Sergio Ruiz Sánchez; Johanna Valencia Echeverry; Terri M. Teshiba; Alesandra Espinoza; Loes M. Olde Loohuis; Juan De La Hoz; Benjamin B. Brodey; Chiara Sabatti; Javier I. Escobar; Victor I. Reus; Carlos López‐Jaramillo; Ruben C. Gur; Carrie E. Bearden; Nelson B. Freimer

doi:10.1016/s2215-0366(20)30098-5

NeuroscienceThe Lancet PsychiatryApr 27, 2020

Peer-reviewed journal article

Distinct and shared contributions of diagnosis and symptom domains to cognitive performance in a case-control study of severe mental illness in the Paisa population

Susan K. Service iD, Cristian Vargas Upeguí iD, Mauricio Castaño Ramírez, Allison M. Port iD, Tyler M. Moore iD, Marfred Munoz Umanes iD, Luis Guillermo Agudelo Arango, Ana M. Díaz‐Zuluaga iD, Juanita Melo Espejo, María Cecilia López, Juan David Palacio iD, Sergio Ruiz Sánchez, Johanna Valencia Echeverry iD, Terri M. Teshiba, Alesandra Espinoza, Loes M. Olde Loohuis iD, Juan De La Hoz iD, Benjamin B. Brodey iD, Chiara Sabatti iD, Javier I. Escobar iD, Victor I. Reus iD, Carlos López‐Jaramillo iD, Ruben C. Gur iD, Carrie E. Bearden iD, Nelson B. Freimer iD

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Abstract

BackgroundSevere mental illness (SMI) diagnoses display overlapping symptomatology and shared genetic risk, motivating trans-diagnostic investigations of disease-relevant quantitative measures. We analyzed relationships between neurocognitive performance, symptom domains, and diagnoses, in a large sample of SMI cases (ascertained agnostic to diagnosis) and healthy controls from a single, homogeneous population. Methods2,406 participants (1,689 cases, 717 controls; mean age 39 years, 64% female) were assessed for speed and accuracy using the Penn Computerized Neurocognitive Battery (CNB). Cases carried structured-interview based diagnoses of schizophrenia (SCZ, n=160), bipolar-I (BP-I, n=519), bipolar-II (BP-II, n=204) and major depressive disorder (MDD, n=806). Linear mixed models, using CNB tests as repeated measures, modeled neurocognition as a function of diagnosis, sex, and all interactions. Follow-up analyses, in cases, included symptom factor scores obtained from exploratory factor analysis of symptom data, as main effects. FindingsBP-I and SCZ displayed nearly identical impairments in accuracy and speed, across cognitive domains. BP-II and MDD performed similarly to controls, with subtle deficits in executive and social cognition. A three-factor model (psychosis, mania, and depression) best represented symptom data. Controlling for diagnosis, premorbid IQ, and disease severity, high lifetime psychosis scores were associated with reduced accuracy and speed across cognitive domains, while high depression scores were associated with increased social cognition accuracy. InterpretationTrans-diagnostic investigations demonstrated that neurocognitive function in SMI is characterized by two distinct profiles (BP-I/SCZ and BP-II/MDD), and is associated with specific symptom domains. These results suggest the utility of this design for elucidating SMI causes and trajectories.