Deficits in odor discrimination versus odor identification in patients with schizophrenia and negative correlations with GABAergic and DNA methyltransferase mRNAs in lymphocytes

Robert C Smith; Henry Sershen; Mary Youssef; Abel Lajtha; Hua Jin; Mumei Zhang; Anmei Chen; Alessandro Guidotti; John M Davis

doi:10.3389/fpsyt.2023.1115399

Deficits in odor discrimination versus odor identification in patients with schizophrenia and negative correlations with GABAergic and DNA methyltransferase mRNAs in lymphocytes

Front Psychiatry. 2023 Mar 28:14:1115399. doi: 10.3389/fpsyt.2023.1115399. eCollection 2023.

Authors

Robert C Smith^{1

2}, Henry Sershen^{1

2}, Mary Youssef¹, Abel Lajtha^{1

2}, Hua Jin³, Mumei Zhang⁴, Anmei Chen⁴, Alessandro Guidotti⁵, John M Davis⁵

Affiliations

¹ Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States.
² Department of Psychiatry, NYU Grossman School of Medicine, New York, NY, United States.
³ Department of Psychiatry and VA San Diego Healthcare System, University of California San Diego, San Diego, CA, United States.
⁴ Columbia University Mailman School of Public Health, New York, NY, United States.
⁵ Department of Psychiatry, Psychiatric Institute University of Illinois, Chicago, IL, United States.

Abstract

Introduction: People with schizophrenia have been reported to show deficits in tests of olfactory function. DNA methylation and GABAergic input have been implicated in biochemical processes controlling odor in animal studies, but this has not been investigated in human studies.

Methods: In a study of measures of DNA methylation and GABAergic mRNAs in lymphocytes, we also measured odor identification and discrimination with the Sniffin' Sticks battery in 58 patients with chronic schizophrenia (CSZ) and 48 controls. mRNAs in lymphocytes were assessed by qPCR using TaqManTM probes. Cognition was assessed by the MATRICS battery (Measurement and Treatment Research to Improve Cognition in Schizophrenia) in CSZ and controls, and symptoms in CSZ were assessed by PANSS scale (Positive and Negative Symptom Scale). The relationships of odor deficits with mRNA, cognition, and symptoms were explored by correlation analysis. Variables which significantly differentiated CSZ from controls were explored by logistic regression.

Results: Overall, CSZ showed significantly (P≤.001) lower scores on odor discrimination compared to controls, with a moderate effect size, but no difference in odor identification. Deficits in odor discrimination, which has not been standardly assessed in many prior studies, strongly differentiated CSZ from controls. In logistic regression analysis, odor discrimination, but not odor identification, was a significant variable predicting schizophrenia versus control class membership. This is the first study to report relationship between odor deficits and DNA methylation and GABAergic mRNAs in blood cells of human subjects. There were negative correlations of odor identification with DNA methylation enzymes mRNAs and significant negative correlations with odor discrimination and GABAergic mRNAs. Lower odor scores were significantly associated with lower cognitive scores on the MATRICS battery in CSZ but not control subjects. In CSZ, lower odor scores were significantly associated with negative symptom scores, while higher odor identification scores were associated with PANNS Excitement factor.

Discussion: Odor discrimination was a more powerful variable than odor identification in discriminating CSZ from controls and should be used more regularly as an odor measure in studies of schizophrenia. The substantive meaning of the negative correlations of odor discrimination and GABAergic mRNA variables in peripheral lymphocytes of CSZ needs more investigation and comparison with results in neural tissue.

Keywords: GABAergic mRNA; MATRICS battery; odor discrimination; olfactory deficits; schizophrenia.