Neuroendocrine Responses to a Cold Pressor Stimulus in Polydipsic Hyponatremic and in Matched Schizophrenic Patients

Abstract

Schizophrenia, many believe, reflects an enhanced vulnerability to psychological stress. Controlled exposure to stressors, however, has produced inconclusive results, particularly with regards to neurohormones. Some of the variability may be attributable to the nature and psychological significance of the stimulus and failure to control physiologic confounds. In addition, it is possible that the heterogeneity of schizophrenia is an important factor. In a carefully designed study and in a controlled setting, we measured the neuroendocrine response of eight polydipsic hyponatremic (PHS), seven polydipsic normonatremic (PNS), and nine nonpolydipsic normonatremic (NNS) (ie normal water balance) schizophrenic in-patients as well as 12 healthy controls (HC) to two different stressors: one of which appears to influence neuroendocrine secretion through its psychological (cold pressor) and the other (upright posture) through its systemic actions. Subjects in the three psychiatric groups were stabilized and acclimated to the research setting, and all received saline to normalize plasma osmolality. Following the cold pressor, plasma adrenocorticotropin and cortisol levels showed a more prolonged rise in PHS patients relative to PNS patients. NNS patients, in contrast, exhibited blunted responses relative to both of the polydipsic groups and the HC. Peak vasopressin responses were also greater in PHS and blunted in NNS patients. Responses to the postural stimulus were similar across patient groups. These findings provide a mechanism for life threatening water intoxication in schizophrenia; help to reconcile conflicting findings of stress responsiveness in schizophrenia; and potentially identify a discrete patient subset with enhanced vulnerability to psychological stress.

Decreased pain sensitivity among people with schizophrenia

“…However, the funnel plot identified one striking outlier [22] for pain tolerance . After removal of this study, schizophrenia patients had significantly greater pain tolerance than controls (ES=0.566, 95% CI=0.235-0.897, p=0.0001, I 2 =49%, studies=6, Egger=2.26, p=-0.58, Begg=0.13, p=0.70, studies=6, n=330).…”

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

“…The other two contrasts compared PNS to NNS and HC; and the NNS to HC. We hypothesized that oxytocin activity would be PNS < NNS + HC, and NNS> HC based on the corresponding pAVP and HPA responses in these groups (Goldman et al, 2007c(Goldman et al, , 2007b.…”

“…The cold pressor was chosen because it is a reliable stressor in schizophrenia and likely increases neuroendocrine secretion as a consequence of its emotional impact (see Goldman et al, 2007c). The test was performed in the evening when the hypothalamic pituitary adrenal (HPA) axis is comparatively quiescent and hippocampal influences predominate (van Eekelen et al, 2003).…”

“…Specifically, these patients do not exhibit the normal hippocampal-mediated constraint of pAVP and the HPA axis following stress (Goldman et al, 2007c) and exhibit blunted hippocampal-mediated glucocorticoid negative feedback (Goldman et al, 2007b;Tessner et al, 2007). Indeed, they also have smaller volumes of the hippocampal segment (i.e.…”

“…2.21 Cold Pressor-All subjects completed a standard cold pressor test during the fifth week of admission in which they immersed their nondominant hand in ice water for one minute (see Goldman et al, 2007c for details). The cold pressor was chosen because it is a reliable stressor in schizophrenia and likely increases neuroendocrine secretion as a consequence of its emotional impact (see Goldman et al, 2007c).…”