Targeting Hormones for Improving Cognition in Major Mood Disorders and Schizophrenia: Thyroid Hormones and Prolactin

Cognitive deficits are a core feature of serious mental illnesses such as major depression, bipolar disorder and schizophrenia and are a common cause of functional disability. However, the efficacy of pharmacological interventions for improving the cognitive deficits in these disorders is limited. As pro-cognitive pharmacological treatments are lacking, we aimed to review whether thyroid hormones or drugs that target prolactin may become potential candidates for 'repurposing' trials aiming to improve cognition. We conducted a narrative review focused on thyroid hormones and prolactin as potential targets for improving cognition in major mood disorders or schizophrenia. The role of thyroid hormones and prolactin on cognitive processes in non-psychiatric populations was also reviewed. Although clinical trials regarding these hormones are lacking, particularly in patients with schizophrenia, bipolar disorder or major depression, there is evidence from observational studies for the contribution of these hormones to cognitive processes. Patients with bipolar disorder and subclinical hypothyroidism show poorer cognitive function than euthyroid patients. In patients with early psychosis, lower free thyroxine concentrations have been associated with poorer attention whereas increased prolactin levels have been associated with poorer speed of processing. Only two small clinical trials tested the potential pro-cognitive effects of thyroid hormones, with positive findings for triiodothyronine (T3) treatment in patients receiving lithium or electroconvulsive therapy. In sum, thyroid hormones and prolactin might contribute to the cognitive performance of patients with major mood disorders and psychotic disorders. Thyroid hormones and prolactin-lowering drugs (e.g. cabergoline, aripiprazole) are candidate drugs to be tested in repurposing clinical trials aiming to improve the cognitive abilities of patients with major mood disorder and schizophrenia.