Potential role of prolactin in antipsychotic‐mediated association of schizophrenia and type 2 diabetes

Abstract

It remains unclear why atypical antipsychotics confer a risk for hyperglycemia compared to typical antipsychotics. Atypical antipsychotics antagonize dopamine receptors-2 (D(2)) and serotonin (5-HT) receptors-2, while typical antipsychotics antagonize only D(2) receptors. We aimed at elucidating the mechanistic differences between the role of typical and atypical antipsychotics on prolactin levels and glucose regulation. A Medline search was conducted during 2010 using the search terms type 2 diabetes (T2D), typical/atypical antipsychotics, schizophrenia, prolactin, and serotonin. We discuss the effect of typical and atypical antipsychotics on prolactin levels and glucose regulation. Given that prolactin is under negative control by dopamine and positive control by serotonin, typical antipsychotics induce elevations in prolactin, while atypical antipsychotics do not. Research studies show protective effects of prolactin on T2D. We hypothesize that the difference in induction of T2D between typical and atypical antipsychotics is due to the antipsychotic receptor binding mediated effect in changes in prolactin levels.

Serum prolactin concentrations as risk factor of metabolic syndrome or type 2 diabetes?

“…Thus, one may speculate if common anti-psychotics could probably protect from T2DM onset and progression by increasing PRL concentrations through the inhibition of the D2 receptor [31]. However, since previous studies [28-30] were exclusively cross-sectional, cause and effect in the association of PRL with T2DM are difficult to determine.…”

Co‐shared genetics and possible risk gene pathway partially explain the comorbidity of schizophrenia, major depressive disorder, type 2 diabetes, and metabolic syndrome

“…As we previously highlighted (Gragnoli, Reeves, Reazer, & Postolache, ), the PRL‐pathway genes ( PRL , PRLHR , PRLR , OXT , OXTR , and NPY ) may thus contribute to SCZ, T2D, and/or MetS. Several studies suggest that the PRL‐pathway may contribute to SCZ‐mental traits: (a) male‐PRL levels are reduced compared to female‐PRL levels, and SCZ has earlier onset in males (Hafner, Maurer, Loffler, & Riecher‐Rossler, ); (b) PRL levels have been reported decreased (Meaney & O'Keane, ; Rao et al, ) as well as increased in SCZ drug‐naive patients (Gonzalez‐Blanco et al, ), and decreased in depression (Depue et al, ); (c) PRL increases with anti‐depressant (Faron‐Gorecka et al, ) and typical anti‐psychotic action (Oberweis & Gragnoli, ); (d) a more severe SCZ first‐episode is associated with decreased PRL (Gorobets & Matrosova, ); (e) PRL is an anxiolytic secreted during stress response (Insana & Wilson, ; Torner et al, ) and enhances bonding, social interaction, and attachment (Gordon et al, ; Neumann, ); and (f) PRL‐levels changes are associated with dissociative symptoms of depression (Bob et al, ). Thus, PRL‐levels changes are associated with SCZ; however, association does not imply causality.…”

Crosstalk between Schizophrenia and Metabolic Syndrome: The Role of Oxytocinergic Dysfunction

“…Evidence for increased prolactin levels in persons with schizophrenia treated with antipsychotics has been found for decades [103]. Given the role of prolactin in metabolic homeostasis and lipid metabolism, the risk of metabolic syndrome in persons with schizophrenia depends on the prolactin levels that resulted from different antipsychotics [102,104]. Despite advances in pathophysiology and the delineation of risk factors that predispose people to metabolic syndrome by antipsychotics, there are many key aspects that remain unclear.…”