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.

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PNECAT Group: Pilar Álvarez, Juan David Barbero, Miquel Bioque, Jesús Cobo, Núria del Cacho, Clemente García-Rizo, Javier Labad, Ana Martín-Blanco, José Antonio Monreal, Itziar Montalvo, Maria Portella, Eva Real, Elena Rubio, Virginia Soria, Judith Usall. The idea of conducting this review originated at meetings of the Psychoneuroendocrinology Workgroup from the Catalan Society of Psychiatry (PNECAT Group). We are thankful to all of the members of the PNECAT group.

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Correspondence to Javier Labad.

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JL, CGR and MB have received honoraria for lectures or advisory boards from Janssen, Otsuka and Lundbeck. VS has served as consultant or continuing medical education (CME) speaker for Servier, Rovi, Lundbeck, Exeltis, Otsuka, Pfizer, Juste. The rest of the authors have no conflicts of interest to declare.


This review was supported in part by a grant from the Carlos III Health Institute through the Ministry of Economy and Competitiveness (PI15/01386), the European Regional Development Fund (ERDF) “A way to build Europe”. Javier Labad received an Intensification of the Research Activity Grant (SLT006/17/00012) by the Health Department of the Generalitat de Catalunya.

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The members of PNECAT Group are listed in “Acknowledgements”.

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Tost, M., Monreal, J.A., Armario, A. et al. Targeting Hormones for Improving Cognition in Major Mood Disorders and Schizophrenia: Thyroid Hormones and Prolactin. Clin Drug Investig 40, 1–14 (2020) doi:10.1007/s40261-019-00854-w

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