Chemokine levels altered in schizophrenia

By Will Boggs MD

Several chemokine levels are elevated and related to symptoms in individuals with schizophrenia, researchers report.

"Our study showed that two chemokines, macrophage-derived chemokine (MDC) and Eotaxin-1, had the strongest relationships to the diagnosis of schizophrenia, after accounting for interrelations among the chemokines," said Dr. Dilip V. Jeste from the University of California, San Diego.

"Interestingly, these two chemokines have been reported to have effects on both maintaining homeostasis in terms of immune function and affecting inflammatory response of the body," he told Reuters Health by email.

Elevated chemokine levels have been observed in several neuroinflammatory disorders and psychiatric conditions, but most studies have examined a relatively small number of chemokines.

Dr. Jeste's team assessed plasma levels of 11 chemokines in 134 individuals with schizophrenia and 112 similar healthy controls and created a Chemokine Index that they used to explore differences between the groups and their clinical correlates.

People with schizophrenia had significantly higher plasma levels of five chemokines than did healthy controls: monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, Eotaxin-1, thymus and activation-regulated chemokine (TARC), and MDC.

The final model, including MDC and Eotaxin-1, correctly identified individuals as members of the schizophrenia versus healthy control group 64% of the time, the researchers report in Schizophrenia Research, online September 17.

The Chemokine Index (CI) was slightly, but significantly, higher in persons with schizophrenia (-5.84) than in healthy controls (-5.99).

Higher CI among schizophrenia patients was associated with older age, longer duration of illness, and more negative symptoms. Among healthy controls, CI was higher in women, individuals with higher levels of subclinical depressive symptoms, worse self-rated mental well-being, and greater overall severity of generally mild medical illnesses.

"Eotaxin-1 is primarily involved in aging-associated disruptions of memory and hippocampal neurogenesis, while MDC acts mainly on peripheral cells involved in inflammatory response," Dr. Jeste explained. "The combination of MDC and Eotaxin-1 suggests possible dysregulation of inflammatory activities in the brain as well as in the periphery in schizophrenia."

"Schizophrenia is known to be associated with altered inflammation and immune function, but its pathophysiology remains elusive," he said. "While our findings do not directly address pathophysiology of schizophrenia, peripheral blood markers such as chemokines may be potentially useful as reliable and practical biomarkers of immune dysregulation in schizophrenia. It can also be speculated that physical and mental health could be improved by treatments that regulate chemokine levels in persons with schizophrenia."

"Longitudinal and functional investigations of chemokines and their receptors will advance the field in testing whether these biomarkers contribute to pathophysiological processes in schizophrenia," Dr. Jeste concluded. "Future research is needed to evaluate whether treatments that normalize chemokine dysregulation may ameliorate psychopathology and improve general health among persons with chronic schizophrenia."

SOURCE: http://bit.ly/2fiBhqV

Schizophr Res 2016.

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