Female gender may offer protection against the development of cognitive impairment due to tardive dyskinesia in patients with schizophrenia.

Tardive dyskinesia (TD) is linked with cognitive impairment, which manifests more severely in patients with schizophrenia who have TD compared with patients without TD, noted Xiangyang Zhang, MD, PhD, and colleagues. Additionally, “several studies have found sex differences in cognitive impairment in patients with schizophrenia,” Dr. Zhang and colleagues wrote, but research is lacking on whether sex differences in cognitive performance exist among patients with schizophrenia who have TD.

For a study published in Schizophrenia Research, Dr. Zhang and colleagues sought to  determine:

  • whether patients with schizophrenia had cognitive deficits;
  • whether patients with schizophrenia with comorbid TD performed worse on tests for cognitive function activities; and
  • whether, in patients with schizophrenia with and without TD, sex differences were present in those with cognitive deficits.

Patients With Schizophrenia Performed Worse in All Cognitive Domains

The researchers recruited 496 inpatients with schizophrenia and 362 healthy controls (aged 16-76). A physical examination, medical history, and laboratory tests were conducted within the patient population; any participant with a major medical illness was excluded.

Dr. Zhang and colleagues utilized the Abnormal Involuntary Movement Scale (AIMS) to determine the severity of TD and the Positive and Negative Syndrome Scale (PANSS) to evaluate patients’ psychopathological symptoms. In 313 inpatients and 310 controls, cognitive function was assessed via the Repeatable Battery for Assessment of Neuropsychological Status (RBANS).

They observed that patients with schizophrenia performed worse in all cognitive domains compared with healthy controls (all P<0.001). Patients with TD had a higher PANSS total, PANSS negative symptom subscale, and AIMS scores (all P<0.001) compared with patients without TD. However, RBANS total, visuospatial/constructional, and attention subscale scores were significantly lower (all P<0.05).

In addition, the visuospatial/constructional and attention indices remained considerably lower in male patients with TD than those without TD (both P<0.05). However, these results were not observed in female patients. Moreover, in male patients only, visuospatial/constructional and attention indices were negatively correlated with total AIMS scores (both P<0.05).

Findings May Have Therapeutic Implications

The main findings are that patients with schizophrenia had more severe cognitive deficits and that sex differences were apparent in delayed memory compared with healthy controls, according to Dr. Zhang and colleagues. Additionally, compared with inpatients without TD, those with TD had worse cognitive performance. In patients with TD, sex differences in cognitive impairments were observed; among males, patients with TD had considerably lower visuospatial/constructional and attention index scores than those without TD. However, no differences in cognitive performance were found among female patients with and without TD (Table).

This suggests that “female gender may play a protective role in the development of TD and cognitive deficits,” Dr. Zhang and colleagues wrote. “These findings may have therapeutic implications, suggesting that female hormones, such as estrogen, may be useful in the prevention of the development of TD and impairment of cognitive function.”

The study team concluded that understanding the sex differences in cognitive function between patients with and without TD “may provide more specific directions for developing different rehabilitation programs for male and female patients with TD.”