William Pitchot

P300 in posttraumatic stress disorder

In the present study, P300 has been recorded in 26 subjects (15 women) 1 month after an aggression without organic complications. Among our sample, 16 subjects fulfilled DSM-III-R criteria for posttraumatic stress disorder (PTSD) and 10 did not. P300 amplitude was significantly lower in the 16 PTSD subjects as compared to the 10 subjects without PTSD. This study supports information processing disturbances in PTSD.

Suicidal behavior in depressive disorder: an event-related potential study.

P300 and contingent negative variation (CNV) were recorded in depressive inpatients with and without history of suicide attempt. The results showed a significant reduction of P200, P300, and CNV and a significant increase of postimperative negative variation (PINV) in patients who had attempted suicide compared to patients with a negative history. Moreover, P300 amplitude was negatively related with the Suicidal Risk and the Hopelessness but not with the Hamilton scales. These results stress the need to differentiate clinical subgroups of patients to assess the psychophysiology of depression, and indicate that patients who attempted suicide exhibit lower cortical resources and poorer cortical performance than patients without history of suicide attempt.

Catecholaminergic function and P300 amplitude in major depressive disorder (P300 and catecholamines).

The neurobiology of P300 is still a subject of controversy. P300 amplitude appears to be modulated by multiple neurotransmitter systems, especially dopaminergic, noradrenergic as well as cholinergic and GABAergic. In this study, we investigated the relationship between P300 amplitude and catecholaminergic neurotransmission as assessed by the growth hormone (GH) response to clonidine and apomorphine challenges in 20 major depressive patients. Results showed a correlation of P300 amplitude with the apomorphine test (r = 0.54; P = 0.01), but not with the clonidine test (r = 0.22; NS). This study supports a role for dopamine in the neurobiological modulation of P300 amplitude.

Psychophysiological correlates of suicidal behavior in depression. A preliminary study

P300 and contingent negative variation (CNV) were recorded in depressive inpatients with and without history of suicide attempt. The results show a significant reduction of both P300 and CNV in patients who had attempted suicide as compared with patients who had not. Moreover, a significant correlation was found between the suicidal risk scale and CNV amplitude. Psychophysiological and biochemical implications are discussed.

Effect of Previous Antidepressant Therapy on the Growth Hormone Response to Apomorphine

Several lines of evidence suggest a role for dopamine in the pathophysiology of depression. In 1988, we reported a blunted response of growth hormone (GH) to apomorphine, a dopaminergic agonist, in endogenous depression. However, an antidepressant washout period is a major confounding factor in studies assessing the GH response to apomorphine. Indeed, whereas the influence of tricyclic antidepressants on the GH response to apomorphine is presently unknown, several reports have suggested that tricyclics may impair the GH response to clonidine for periods longer than 3 weeks following their discontinuation. In the present study, we hypothesized that a blunted GH response to apomorphine in depressed patients could be related to the recent administration of antidepressants. Therefore, the GH response to apomorphine (0.5 mg) was studied in 11 male DSM-III-R major depressive inpatients who had never received antidepressant therapy (group 1) compared to 11 normal controls and 11 major depressive inpatients drug free for at least 2 weeks (group 2). The three groups differed significantly in the GH peak response to apomorphine: mean (SD) 5.4 (4.0) ng/ml in group 1, 25.5 (10.7) in normal controls, and 5.5 (5.1) in group 2 (F = 15.5, df = 3, 30, p = 0.00001). While group 1 and normal controls (F = 21.8, p = 0.0002) as well as group 2 and controls (F = 5.6, p = 0.03) differed significantly, group 1 and group 2 did not (F = 0.18, p = 0.68). These results suggest that a washout period of 2 weeks could be sufficient in studies assessing the GH response to apomorphine.

The flesinoxan/5-HT1A receptor challenge in major depression

The prevailing neurochemical theory about biological correlates of suicidal behavior focuses on the serotonergic system. In this study, we assessed the cortisol, ACTH, GH, prolactin and temperature responses to flesinoxan, a5-HT1A agonist, in 30 DSM-III-R major depressed inpatients subgrouped into suicide attempters (n = 15) and nonattempters (n = 15). The patients were assessed after a drug-free period of at least 3 weeks. A subsample of 16 patients completed the Buss-Durkee Hostility Inventory as a measure of impulsive aggressive behavior. Mean delta cortisol responses to flesinoxan were significantly lower in the group of depressed patients with a history of suicide attempts than in the group without history of suicidal behavior: for the delta cortisol values 14.5 +/- 16.3 micrograms/l vs 101 +/- 94 micrograms/l (F = 8.9, df = 5.25, p = 0.006). There was also a very significant difference between suicide attempters and nonattempters for the temperature (delta T degrees) responses to flesinoxan: 0.20 +/- 0.24 degrees C vs. 0.60 +/- 0.24 degrees C (F = 18.1, df = 5.25, p = 0.0003). Hormonal and temperature responses to flesinoxan were not correlated with BDHI irritability or assault subscale scores. The results of the present study support the implication of the serotonergic system, particularly 5-HT1A receptors, in the control of self-directed aggressive behavior. Moreover, in depressed patients, serotonergic abnormalities do not appear to be related to aggressive behavior.