Diminished plasma oxytocin in schizophrenic patients with neuroendocrine dysfunction and emotional deficits

Abstract

Polydipsic hyponatremic schizophrenic patients (PHS) exhibit enhanced plasma arginine vasopressin (pAVP) and hypothalamic pituitary adrenal (HPA) axis responses to stress that appear attributable to anterior hippocampal dysfunction. Neuroanatomic and electrophysiologic studies indicate oxytocin activity in PHS patients should also be affected. Furthermore, oxytocin normally diminishes HPA responses to stress and facilitates cognitive and behavioral functions impaired in schizophrenia, suggesting that diminished oxytocin activity could contribute to this subsets' neuropsychiatric disorder. In the present study, we measured plasma oxytocin levels at intervals before and after stress induction in six polydipsic hyponatremic (PHS), four polydipsic normonatremic (PNS), five nonpolydipsic normonatremic schizophrenic (NNS) patients and seven healthy controls. Most of these subjects also completed studies measuring their medial temporal lobe volumes, their hippocampal-mediated HPA feedback and their ability to discriminate different facial emotions (an oxytocin-sensitive measure which is markedly impaired in schizophrenia). Results demonstrated that 1) plasma oxytocin levels were lower (p = .006) in hyponatremic patients relative to the other three groups, whose levels were similar and did not change. Oxytocin levels across all subjects were 2) inversely correlated with anterior hippocampal (p = .004) (but not posterior hippocampal or amygdala volumes), and 3) directly correlated with the integrity of hippocampal-mediated HPA feedback (p = .039). Finally, 4) oxytocin levels predicted schizophrenic patients' ability to correctly identify facial emotions (p = .004). These preliminary data provide further evidence that neuroendocrine dysfunction in PHS reflects anterior hippocampal pathology and contributes to a characteristic neuropsychiatric syndrome.

Functional organization of the hippocampal longitudinal axis

“…In addition, the locus of pathology on the long axis is associated with specific cognitive impairments (for example, schizophrenia is associated with anterior hippocampal pathology and with impaired transitive inference [159][160] ) as well as with clinical manifestations of particular diseases. For example, in view of the greater connectivity between ventral (anterior) hippocampus and endocrine hypothalamic nuclei 26 , impaired hormonal regulation by the hypothalamus (such as hyponataraemic polydypsia reported in schizophrenia patients with decreased AH volume [161][162][163] ) may be a common finding in patients with AH damage -this is something that has been relatively under-investigated in medial temporal lobe epilepsy [164][165][166] . Furthermore, given the role of VH 111 -and ventral DG in particular 167 -in models of innate anxiety, this region could prove an important future target for a range of neurotic disorders.…”

Oxytocin, vasopressin, and human social behavior

“…Initial studies suggested enhanced concentrations of OT [15] and neurophysin II, the hypothalamic-pituitary carrier of OT [98,105], in patients with schizophrenia compared to healthy controls, whereas a follow-up study did not confirm these results [52]. In contrast, Goldman and colleagues showed that blunted OT levels in schizophrenia were associated with low performance in a facial affect rating task [53]. Another study investigating the effect of a trust-related interaction on peripheral OT levels revealed that schizophrenic patients lacked the interaction-induced increase in peripheral OT observed in healthy controls [88].…”

Regulation of neuronal chloride homeostasis by neuromodulators

“…2007; Goldman et al . 2008). Moreover, exogenous OXT can restore various aspects of social behaviour and cognitive dysfunction associated with neuropsychiatric disorders including autism spectrum disorders (ASDs) (Gordon et al .…”