Increased Pituitary Volume in Antipsychotic-Free and Antipsychotic-Treated Patients of the Æsop First-Onset Psychosis Study

Abstract

Subjects at their first psychotic episode show an enlarged volume of the pituitary gland, but whether this is due to hypothalamicpituitary-adrenal (HPA) axis hyperactivity, or to stimulation of the prolactin-secreting cells by antipsychotic treatment, is unclear. We measured pituitary volume, using 1.5-mm, coronal, 1.5 T, high-resolution MRI images, in 78 patients at the first psychotic episode and 78 age-and gender-matched healthy controls. In all, 18 patients were antipsychotic-free (12 of these were antipsychotic-naïve), 26 were receiving atypical antipsychotics, and 33 were receiving typical antipsychotics. As hypothesized, patients had a larger pituitary volume than controls ( þ 22%, po0.001). When divided by antipsychotic treatment, and compared to controls, the pituitary volume was 15% larger in antipsychotic-free patients (p ¼ 0.028), 17% larger in patients receiving atypicals (p ¼ 0.01), and 30% larger in patients receiving typicals (po0.001). Patients receiving typicals not only had the largest pituitary volume compared to controls but also showed a trend for a larger pituitary volume compared to the other patients grouped together ( þ 11%, p ¼ 0.08). When divided by diagnosis, and compared to controls, the pituitary volume was 24% larger in patients with schizophrenia/schizophreniform disorder (n ¼ 40, po0.001), 19% larger in depressed patients (n ¼ 13, p ¼ 0.022), 16% larger in bipolar patients (n ¼ 16, p ¼ 0.037), and 12% larger in those with other psychoses (n ¼ 9, p ¼ 0.2). In conclusion, the first-episode of a psychotic disorder is associated with a larger pituitary independently of the presence of antipsychotic treatment, and this could be due to activation of the HPA axis. Typical antipsychotics exert an additional enlarging effect on pituitary volume, likely to be related to activation of prolactin-secreting cells. This activation of the hormonal stress response could participate to the important metabolic abnormalities observed in patients with psychosis.

Tardive Dyskinesia in Schizophrenia is Associated with Prolactin-Related Sexual Disturbances

“…In contrast, their simultaneous clustering over time in those exposed to prolactin-sparing medications suggests an underlying common and central vulnerability, involving more than one central dopamine tract, that may be intrinsic to schizophrenia itself, and only detectable in the absence of external agents causing substantial increases in plasma prolactin that overshadow this internal, illness-related, association. Indeed, a recent investigation reported pituitary enlargement in nevermedicated patients with schizophrenia, compatible with the hypothesis of a central, illness-related, mechanism (Pariante et al, 2005). Similarly, a recent report found high prolactin levels in a paranoid subgroup of never-medicated psychotic patients, suggestive of the existence of subtypes of psychotic illness associated with differences in dopaminergic tone (Segal et al, 2004).…”

Toward earlier identification and preventative intervention in schizophrenia: evidence from the London Child Health and Development Study

“…higher diurnal cortisol levels and greater blunting of the CAR) were associated with poorer memory and executive function, possibly reflecting underlying dysfunction in the brain regions which mediate both HPA axis function and these cognitive functions [43]. Neither ASz nor FHx children were characterised by pituitary volume enlargements [35], which contrasts with those identified among individuals with firstepisode psychosis [66][67][68][69] and in some (but not all) studies of older individuals at-risk for psychosis [69,70]. Among FHx children only, pituitary volume was negatively associated with current distress relating to negative life events and exposure to physical punishment [35], implying that psychosocial stressors may contribute to pituitary volume changes among those with family history.…”

Brain morphological changes associated with exposure to HSV1 in first-episode schizophrenia

“…Animal studies have shown that circulating glucocorticoids play a permissive role in inducing the host immune response and behavioral changes such as increased locomotion and aggression. 24 Interestingly, several studies have reported elevated cortisol levels, increased production of interleukin-2 (IL-2) and IL-6 45,46 and increased volume of the pituitary gland 47,48 in schizophrenia patients compared to healthy controls. IL6 has been shown to stimulate the hypothalamicpituitary axis 46 thus possibly setting up a vicious circle that may confer vulnerability to brain structural alterations in schizophrenia patients but not in healthy subjects.…”