Neurological soft signs and thyroid hormones in schizophrenia spectrum disorders

Neurological soft signs (NSS) are minor sensory and motor deviations linked to neurodevelopmental disorders and schizophrenia spectrum disorders (SSD). Thyroid hormones (TH) are essential for neurodevelopment and are suggested to be altered in SSD. Yet, the relationship between NSS and TH is unclear.

We evaluated the relationship between NSS and TH in individuals with SSD.

We examined a total of 72 individuals with SSD. We assessed NSS using the Neurological Evaluation Scale (NES) and clinical symptoms using the Positive and Negative Syndrome Scale (PANSS). We collected fasting blood samples to measure serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3). We used the t-test to compare differences between sex and the Pearson correlation to test for correlations between NSS, TH and psychopathology separately for males and females.

We observed a negative correlation between fT4 and NES total score (r = -0.374, p = .032), and NES subdomain "sensory integration" (r = -0.372, p = .033). The correlation between fT4 and "sensory integration" remained largely unchanged when controlling for age, DOI, and antipsychotic dose in OLZ equivalents by performing partial correlation analyses (r = -0.424, p = .049). Serum fT3 and TSH levels exhibited no significant correlation with NES scores but the PANSS negative symptoms score was negatively associated with fT3 (r = -0.472, p < .001).

Lower fT4 levels were associated with NSS severity and specific NSS subdomains only in male individuals. In the overall sample, we detected a significant negative correlation between fT3 and negative symptoms. Future studies should examine a larger sample of drug-naïve individuals with SSDs, followed-up longitudinally in time to infer causality.