Immune Activation and Cognitive Impairment in Schizophrenia

ATLANTA, Georgia – The central nervous system (CNS) was once considered to be an immune-privileged site. A more recent view is that the immune system and the CNS operate in concert to exert their effects through a generally adaptive and bidirectional interaction.1 It is also becoming evident that immune system activation plays a role in various neuropsychiatric disorders, including schizophrenia.2,3 Patients diagnosed with schizophrenia often present with a combination of positive (hallucinations, delusions) and negative (apathy, low motivation, “flat affect”) symptoms. Importantly, many affected individuals also experience cognitive symptoms such as impaired learning and memory, attention, and executive function.4

A new study conducted by a team of investigators affiliated with The University of Texas Health Science Center at Houston provides further evidence for the effects of immune activation with associated inflammation on cognitive performance in patients diagnosed with schizophrenia.5

This research was presented at the 2016 Annual Meeting of the American Psychiatric Association (APA) in Atlanta, Georgia.

The immune system helps coordinate portions of the CNS, and certain physiological and behavioral responses associated with immune system activation are due to the central action of signaling molecules called cytokines. Because of their role in the communication between leukocytes, many cytokines are named interleukins. Proinflammatory cytokines such as interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and tumor-necrosis factor-alpha (TNF-alpha) may exert positive effects, but they are most notable in the neuropsychiatry literature for their negative effects. For example, proinflammatory cytokines have a potential role in neurodegenerative and inflammatory diseases, aging-related neural decline, affective disorders, and cognitive dysfunction.6-8

For the present study5, Ruchirkumar Patel, MBBS, and colleagues recruited 10 adult patients who were previously diagnosed with schizophrenia using the Mini International Neuropsychiatric Interview. They assessed cognitive flexibility, defined as the ability to adjust thoughts or actions in accordance with the situational context, by using the National Institute of Health (NIH) Toolbox Dimensional Change Card Sort Test (DCCS). They then calculated Spearman rank correlation of DCCS with fasting plasma levels of proinflammatory cytokines. The investigators reported a significant negative correlation of DCCS with IL-1beta (p=-0.78, P<.05), IL-6 (p=-0.72, P<.05), and IFN-gamma (p=-0.72, P<.05), but not with TNF-alpha.

“Our findings provide additional support and the basis for the evaluation of novel neuroimmune modulators for improving cognitive function, and specifically cognitive flexibility, in patients diagnosed with schizophrenia,” the authors concluded.


  1. Louveau A, Harris TH, Kipnis J. Revisiting the mechanisms of CNS immune privilege. Trends Immunol. 2015;36:569-577.

  2. Gibney SM, Drexhage HA. Evidence for a dysregulated immune system in the etiology of psychiatric disorders. J Neuroimmune Pharmacol. 2013;8:900-920.

  3. Khandaker GM, Dantzer R. Is there a role for immune-to-brain communication in schizophrenia? Psychopharmacology (Berl). 2016;233:1559-1573.

  4. Lin CY, Tsai GE, Lane HY. Assessing and treating cognitive impairment in schizophrenia: current and future. Curr Pharm Des. 2014;20:5127-5138.

  5. Patel RA, Goddu S, Mohite S, et al. NIH Toolbox Change Card Sort Test is negatively correlated with plasma cytokines in patients with schizophrenia. Poster presentation at: 2016 Annual Meeting of the American Psychiatric Association; May 14-18, 2016; Atlanta, GA. P7-052.

  6. Heneka MT, Kummer MP, Latz E. Innate immune activation in neurodegenerative disease. Nat Rev Immunol. 2014;14:463-477.

  7. Michaud M, Balardy L, Moulis G, et al. Proinflammatory cytokines, aging, and age-related diseases. J Am Med Dir Assoc. 2013;14:877-882.

  8. Donzis EJ, Tronson NC. Modulation of learning and memory by cytokines: signaling mechanisms and long term consequences. Neurobiol Learn Mem. 2014;115:68-77.