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Biomedical subjects

William Pitchot

Publications and source records attributed to William Pitchot.

5 recordsLinked to original sources

5-Hydroxytryptamine 1A receptors, major depression, and suicidal behavior.

BACKGROUND: Several lines of evidence suggest a clear relationship between serotonin (5-hydroxytryptamine, 5-HT) hypoactivity and suicidal behavior across several psychiatric diagnoses. Few data are available, however, regarding the possible specific role of 5-HT1A receptors in the biology of suicidality. Therefore, the aim of our study was to use a neuroendocrine strategy to test the hypothesis of a role for 5-HT1A receptors in the biology of suicidal behavior. METHODS: Hormonal (adrenocorticotropic hormone [ACTH], cortisol, prolactin [PRL]) and temperature responses after administration of flesinoxan, a highly potent and selective 5-HT1A receptor full agonist, were assessed in 40 inpatients with major depression, divided into two subgroups (20 suicide attempters and 20 nonattempters), compared with 20 normal control subjects matched for gender and age. RESULTS: Compared with nonattempters, suicide attempters exhibited significantly lower PRL (p = .01), cortisol (p = .014), and temperature (p = .0002) responses. Prolactin (p = .007), cortisol (p = .04), and temperature (p = .00003) responses were also decreased in suicide attempters compared with normal control subjects. In contrast, we did not observe any significant differences in hormonal or temperature responses to flesinoxan between depressed patients without a history of suicide attempt and normal control subjects. CONCLUSIONS: The present study tends to confirm the role of 5-HT and more specifically 5-HT1A receptors in the biology of suicidal behavior in major depression.

Adrenocorticotropic Hormone↗

Hormonal and temperature responses to flesinoxan in normal volunteers: an antagonist study.

RATIONALE: Flesinoxan is a highly potent and selective 5-HT1A agonist. In a recent study, in normal volunteers, flesinoxan induced a significant and dose-dependent increase in adrenocorticotropic hormone (ACTH), cortisol, prolactin (PRL), growth hormone (GH) and a decrease in body temperature. OBJECTIVES: In order to better define the role of 5-HT receptor subtypes in response to flesinoxan, we assessed the influence of 5-HT1A and 5-HT2 antagonists on hormonal and temperature responses to flesinoxan. METHODS: Hormonal and temperature responses were studied in 6 volunteers with or without pretreatment with pindolol (30 mg p.o.), a 5-HT1A antagonist, or ritanserin (10 mg p.o.), a selective 5-HT2 antagonist, using a double-blind crossover design. RESULTS: Pindolol significantly antagonized ACTH, PRL, GH and temperature responses to flesinoxan and ritanserin exhibited similar activity on PRL and ACTH responses. CONCLUSIONS: These results show the role of 5-HT1A mechanisms in the PRL, ACTH, GH, and temperature responses to flesinoxan, and the role of 5-HT2 mechanisms in PRL and ACTH responses. Therefore, they confirm the interest of flesinoxan as a 5-HT neuroendocrine probe.

Adrenocorticotropic Hormone↗

Catecholamine and HPA axis dysfunction in depression: relationship with suicidal behavior.

A large body of evidence suggests a potential role for catecholaminergic function as a possible biological factor in the control of suicidal behavior. Recently, we have used a neuroendocrine strategy to study dopaminergic and noradrenergic activities in depressed suicide attempters. However, some problems are associated with the use of growth hormone (GH) response to catecholaminergic challenge, because GH release could be decreased by a direct effect of corticosteroids at the pituitary level. Therefore, the purpose of the present study was to assess GH response to both apomorphine, a dopaminergic agonist, and clonidine, an alpha2-adrenergic agonist, according to the dexamethasone suppression test (DST) status in a sample of 20 major depressed inpatients with a history of suicide attempt compared with nonattempters. Our results tended to show that hypercortisolemia as assessed by post-DST cortisol values did not inhibit GH response to apomorphine or clonidine, suggesting that hypothalamo-pituitary-adrenal axis overactivity does not explain the impaired GH response to apomorphine in major depressed patients with a history of suicide attempt.

Adrenergic alpha-Agonists↗

Event-related potentials to emotional and neutral stimuli in alcoholism.

Several studies have demonstrated that the emotional value of stimuli affects P300 amplitude. In the present study, the influence of alcohol-related stimuli in alcoholic patients was investigated. Subjects were 10 alcoholic inpatients (3 female) and 10 age- and sex-matched controls. Eight alcohol-related and 8 neutral words served as stimuli in a visual oddball paradigm. Acohol-related words were targets (48 stimuli, 33%) and neutral words were standard stimuli (96 stimuli, 66%). Results showed that P300 amplitude for targets did not differ significantly between the two groups. However, P300 latency for targets as well as reaction time were significantly shorter in male alcoholic patients. In contrast, P300 latency was increased in female alcoholic patients but reaction time did not differ. These results suggest that male alcoholics process information linked to alcohol cues more rapidly than neutral cues, probably because a specific semantic network is activated in these patients. The decreased reaction time confirms the impulsive behavior frequently found in male alcoholism, as it has been described in type II alcoholism. Besides, the results imply that information processing was delayed in female alcoholic patients. Therefore this study demonstrates a gender-dependent impact of alcohol-related stimuli on information processing.

Adult↗

Hormonal and temperature responses to the 5-HT1A receptor agonist flesinoxan in normal volunteers.

RATIONALE: Flesinoxan is a highly potent and selective 5-HT(1A) agonist and appears to be a potentially interesting neuroendocrine serotonergic probe. OBJECTIVES: We assessed hormonal (ACTH, cortisol, prolactin and growth hormone) and temperature responses to flesinoxan in normal volunteers. METHODS: In a double-blind placebo-controlled study, single doses of 0.5 mg and 1 mg were injected over 10 min into 12 healthy male volunteers at 1-week intervals. Temperature and hormonal responses were measured at times -30, 0, 15, 30, 60, 90, and 120 min. RESULTS: Flesinoxan induced a significant and dose-dependent increase in adrenocorticotropic hormone (ACTH), cortisol, prolactin (PRL), growth hormone (GH) and a decrease in body temperature. Tolerance to flesinoxan was excellent. CONCLUSIONS: These results showed the role of 5-HT(1A) mechanisms in the PRL, ACTH, cortisol, GH, and temperature responses to flesinoxan. In the present study, flesinoxan appears a very promising serotonergic neuroendocrine probe.

Adult↗