Abstract
Winter depressions in seasonal affective disorder (SAD) are associated with central serotonergic (5-HT) dysfunction. SAD patients demonstrate rather specific, state-dependent, abnormal increases in 'activation-euphoria' ratings following intravenous infusion of the 5-HT receptor agonist meta- chlorophenylpiperazine (m-CPP). Several studies are also consistent with abnormal serotonergic regulation of the hypothalamic-pituitary-adrenal (HPA) axis in SAD. Here, we investigated the effects of the 5-HT(1A) receptor partial agonist ipsapirone, which produces behavioral effects and HPA-axis activation, to further characterize the 5-HT receptor subtype-specificity of these disturbances in SAD. Eighteen SAD patients and 18 control subjects completed two drug challenges (ipsapirone 0.3 mg/kg and placebo) separated by 3-5 days in randomized order. We measured behavioral responses with the NIMH self-rating scale, and plasma ACTH, cortisol, and prolactin concentrations. Compared with placebo, ipsapirone was associated with significant increases in self-rated 'functional deficit' and 'altered self-reality', and in each of the hormones. There were no differences between groups on any measures. The level of depression in SAD patients was inversely correlated with their ipsapirone-induced cortisol responses. There were significant drug x order effects on baseline 'anxiety' scores, ACTH and cortisol concentrations, such that subjects were significantly more stressed (higher 'anxiety', ACTH and cortisol) prior to their first challenge compared with their second. In conclusion, post-synaptic 5-HT(1A) receptors appear to function normally in SAD. The previously observed m-CPP-induced behavioral abnormality may be mediated by either 5-HT(2C) or 5-HT7 receptors.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 9-28 |
| Number of pages | 20 |
| Journal | Psychiatry Research |
| Volume | 86 |
| Issue number | 1 |
| DOIs | |
| State | Published - Apr 19 1999 |
| Externally published | Yes |
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Keywords
- 5-HT(1A) receptors
- ACTH
- Adrenocorticotropic hormone
- Cortisol
- Ipsapirone
- Prolactin
- Seasonal affective disorder
ASJC Scopus subject areas
- Psychiatry and Mental health
- Biological Psychiatry
- Psychology(all)
Cite this
Serotonin hypothesis of winter depression : Behavioral and neuroendocrine effects of the 5-HT(1A) receptor partial agonist ipsapirone in patients with seasonal affective disorder and healthy control subjects. / Schwartz, Paul J.; Turner, Erick; Garcia-Borreguero, Diego; Sedway, Jan; Vetticad, Rina G.; Wehr, Thomas A.; Murphy, Dennis L.; Rosenthal, Norman E.
In: Psychiatry Research, Vol. 86, No. 1, 19.04.1999, p. 9-28.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Serotonin hypothesis of winter depression
T2 - Behavioral and neuroendocrine effects of the 5-HT(1A) receptor partial agonist ipsapirone in patients with seasonal affective disorder and healthy control subjects
AU - Schwartz, Paul J.
AU - Turner, Erick
AU - Garcia-Borreguero, Diego
AU - Sedway, Jan
AU - Vetticad, Rina G.
AU - Wehr, Thomas A.
AU - Murphy, Dennis L.
AU - Rosenthal, Norman E.
PY - 1999/4/19
Y1 - 1999/4/19
N2 - Winter depressions in seasonal affective disorder (SAD) are associated with central serotonergic (5-HT) dysfunction. SAD patients demonstrate rather specific, state-dependent, abnormal increases in 'activation-euphoria' ratings following intravenous infusion of the 5-HT receptor agonist meta- chlorophenylpiperazine (m-CPP). Several studies are also consistent with abnormal serotonergic regulation of the hypothalamic-pituitary-adrenal (HPA) axis in SAD. Here, we investigated the effects of the 5-HT(1A) receptor partial agonist ipsapirone, which produces behavioral effects and HPA-axis activation, to further characterize the 5-HT receptor subtype-specificity of these disturbances in SAD. Eighteen SAD patients and 18 control subjects completed two drug challenges (ipsapirone 0.3 mg/kg and placebo) separated by 3-5 days in randomized order. We measured behavioral responses with the NIMH self-rating scale, and plasma ACTH, cortisol, and prolactin concentrations. Compared with placebo, ipsapirone was associated with significant increases in self-rated 'functional deficit' and 'altered self-reality', and in each of the hormones. There were no differences between groups on any measures. The level of depression in SAD patients was inversely correlated with their ipsapirone-induced cortisol responses. There were significant drug x order effects on baseline 'anxiety' scores, ACTH and cortisol concentrations, such that subjects were significantly more stressed (higher 'anxiety', ACTH and cortisol) prior to their first challenge compared with their second. In conclusion, post-synaptic 5-HT(1A) receptors appear to function normally in SAD. The previously observed m-CPP-induced behavioral abnormality may be mediated by either 5-HT(2C) or 5-HT7 receptors.
AB - Winter depressions in seasonal affective disorder (SAD) are associated with central serotonergic (5-HT) dysfunction. SAD patients demonstrate rather specific, state-dependent, abnormal increases in 'activation-euphoria' ratings following intravenous infusion of the 5-HT receptor agonist meta- chlorophenylpiperazine (m-CPP). Several studies are also consistent with abnormal serotonergic regulation of the hypothalamic-pituitary-adrenal (HPA) axis in SAD. Here, we investigated the effects of the 5-HT(1A) receptor partial agonist ipsapirone, which produces behavioral effects and HPA-axis activation, to further characterize the 5-HT receptor subtype-specificity of these disturbances in SAD. Eighteen SAD patients and 18 control subjects completed two drug challenges (ipsapirone 0.3 mg/kg and placebo) separated by 3-5 days in randomized order. We measured behavioral responses with the NIMH self-rating scale, and plasma ACTH, cortisol, and prolactin concentrations. Compared with placebo, ipsapirone was associated with significant increases in self-rated 'functional deficit' and 'altered self-reality', and in each of the hormones. There were no differences between groups on any measures. The level of depression in SAD patients was inversely correlated with their ipsapirone-induced cortisol responses. There were significant drug x order effects on baseline 'anxiety' scores, ACTH and cortisol concentrations, such that subjects were significantly more stressed (higher 'anxiety', ACTH and cortisol) prior to their first challenge compared with their second. In conclusion, post-synaptic 5-HT(1A) receptors appear to function normally in SAD. The previously observed m-CPP-induced behavioral abnormality may be mediated by either 5-HT(2C) or 5-HT7 receptors.
KW - 5-HT(1A) receptors
KW - ACTH
KW - Adrenocorticotropic hormone
KW - Cortisol
KW - Ipsapirone
KW - Prolactin
KW - Seasonal affective disorder
UR - http://www.scopus.com/inward/record.url?scp=0033583452&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033583452&partnerID=8YFLogxK
U2 - 10.1016/S0165-1781(99)00017-7
DO - 10.1016/S0165-1781(99)00017-7
M3 - Article
C2 - 10359479
AN - SCOPUS:0033583452
VL - 86
SP - 9
EP - 28
JO - Psychiatry Research
JF - Psychiatry Research
SN - 0165-1781
IS - 1
ER -