Dopaminergic, Noradrenergic, Adrenal, and Thyroid Abnormalities in Psychotic and Affective Disorders

Abstract

Background: This study aimed to assess hypothalamic-pituitary dopaminergic (DA), noradrenergic (NA), thyroid (HPT), and adrenal (HPA) activity in schizophrenia, in schizoaffective disorder, and in bipolar disorder. Method: We investigated a combined approach of hormone responses to (1) apomorphine (APO), a short-acting DA receptor agonist which decreases prolactin secretion (PRL), and stimulates secretion of growth hormone (GH), adrenocorticotropin (ACTH), and cortisol; (2) clonidine (CLO), an alpha 2-adrenoceptor agonist which stimulates GH secretion; (3) 8 AM and 11 PM protirelin (TRH) which stimulates thyrotropin (TSH) secretion; and (4) dexamethasone which suppresses cortisol secretion, in 13 hospitalized healthy male controls and 39 untreated male inpatients: 13 with DSM-IV paranoid schizophrenia, 13 with DSM-IV schizoaffective disorder (bipolar subtype, depressed at the time of the study), and 13 with DSM-IV bipolar disorder (depressed). Results: Compared to controls, paranoid schizophrenic patients showed (1) lower APOinduced ACTH and cortisol stimulation, and (2) higher post-dexamethasone cortisol values. Compared to controls, schizoaffective and bipolar patients showed (1) lower DDTSH values (i.e., difference between 11 PM and 8 AM TRH-TSH responses), (2) lower APO-induced PRL suppression, (3) lower CLO-induced GH stimulation, and (4) higher post-dexamethasone cortisol values. Conclusions: Although results must be interpreted with caution because of the small sample, this preliminary study suggests that depressed bipolar and schizoaffective patients share common biological dysregulations, distinct from that of paranoid schizophrenic patients. From a pathophysiological viewpoint, paranoid schizophrenic patients can be characterized by hyposensitivity of the hypothalamic DA receptors (possibly resulting from an increase in presynaptic DA release) associated with increased HPA axis activity, while depressed bipolar and schizoaffective patients can be characterized by hyposensitivity of the pituitary TRH and DAD 2 receptors (possibly linked

Neuroendocrine Assessment of Dopaminergic Function during Antidepressant Treatment in Major Depressed Patients

“…Interestingly, the functionality of pituitary D 2 receptors—which inhibit the secretion of PRL and TSH, and probably also ACTH—is not impaired in depressed patients [ 27 , 28 , 35 ]. Consistent with previous reports from our group [ 27 , 37 , 50 , 51 ], ∆COR values were not significantly different between untreated patients and control subjects, suggesting that central DA D 1 - and/or D 2 -like receptors were functionally unaltered in the depressed group considered as a whole. Nevertheless, 25% of untreated patient exhibited blunted APO-induced COR stimulation, which may reflect a decrease in DA receptor responsiveness related to a reduction in tonic DA tone [ 2 , 28 ].…”

“…Confirming our previous studies [ 27 , 28 , 37 , 50 , 51 ], APO-induced COR stimulation appears to be independent of basal HPA activity, as reflected by COR BL , and of glucocorticoid receptor sensitivity, as reflected by post-DST COR max values. Given that the COR response to APO is strongly correlated with that of ACTH [ 27 , 28 , 35 , 37 , 50 , 51 ], the latter being triggered by CRH via the stimulation of D 1 -like and D 2 -like receptors [ 52 , 53 , 54 ], ∆COR may indirectly assess the functionality of hypothalamic DA D 1 - and D 2 -like receptors. Interestingly, the functionality of pituitary D 2 receptors—which inhibit the secretion of PRL and TSH, and probably also ACTH—is not impaired in depressed patients [ 27 , 28 , 35 ].…”

“…Both in depressed patients and healthy controls GH, ACTH, and COR—but not PRL—responses to APO are interrelated, suggesting common pathways at the hypothalamic level [ 27 , 28 ]. However, studies of hormonal responses to APO in depressed patients vs. controls are inconclusive: increased, decreased, or unchanged responses have been reported [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. These discrepancies could be explained by methodological differences between studies (in particular regarding the dose of APO administered; 0.5 mg or 0.75 mg SC), but also by the bio-clinical heterogeneity of depressed patients.…”

Role of Oxidative Stress and the Identification of Biomarkers Associated With Thyroid Dysfunction in Schizophrenics

“…Newly diagnosed schizophrenia patients were included and any subject with a history of smoking, alcohol intake, or on antiparkinsonian/antipsychotic medications was excluded from the study ( Duval et al, 2010 ; Bredin et al, 2013 ). All control subjects were healthy with no history of chronic diseases such as diabetes mellitus, liver diseases, and cancer ( Duval et al, 2010 ; Duval et al, 2020 ).…”

Patterns of Thyroid Hormone Prescription in Patients with Bipolar or Schizoaffective Disorder: Findings from the LiSIE Retrospective Cohort Study

“…We included both BD and SZD because disturbances in thyroid function tend to be similar in both conditions. Besides, affective and psychotic symptoms can occur on a continuum [ 32 , 33 , 34 , 35 , 36 ]. We then validated the respective diagnoses further from the medical case records according to the DSM-5 subcategories as used in a previous study [ 30 ].…”