Antonio Gonzalez Moreno

Dopaminergic function in panic disorder: Comparison with major and minor depression

Several lines of evidence suggest that dopamine might be involved in anxiety states. In this study, we assessed the growth hormone (GH) response to apomorphine (a dopaminergic agonist) 0.5 mg SC in nine drug-free inpatients meeting Research Diagnostic Criteria (RDC) for panic disorder who were age-matched and gender-matched with nine major depressive, and nine minor depressive inpatients. The three groups differed significantly in their mean GH peak response: 5.29 +/- 2.75 ng/ml in major depressives, 26.27 +/- 12.71 ng/ml in minor depressives, and 37.28 +/- 10.58 ng/ml in panics, with a significantly higher response in panic than in either minor or major depressive patients. These results support dopaminergic overactivity in panic disorder as compared with major and minor depression.

Suicidal behavior and growth hormone response to apomorphine test

Abstract Several cerebrospinal fluid (CSF) studies have provided support for a possible role for the dopaminergic system as a biological correlate of suicidal behavior. Indeed, low CSF levels of the dopamine metabolite homovanillic acid (HVA) have been described in depressed patients with a history of suicide attempts. In this study, we assessed the dopamine receptor sensitivity in relationship to suicidal behavior by measuring growth hormone (GH) response to apomorphine 0.5 mg subcutaneously (sc) in 15 DSM-III-R (APA 1987) major depressive inpatients with a history of suicide attempts, compared to age-matched and gender-matched major depressive inpatients without a history of suicide. Patients with a history of suicidal behavior exhibited a significantly lower GH response to apomorphine than patients who never attempted suicide ( t = 3.60, df=1.28, p = 0.0012). Therefore, these results suggests that a blunted GH response to apomorphine could represent a biological marker of suicidal behavior.

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.

Relationship between alpha2-adrenergic function and suicidal behavior in depressed patients

The current main neurochemical theories of the biological correlates of suicidal behavior involve serotonergic and, to a lesser extent, dopaminergic systems. Few data are available about the possible implication of the noradrenergic function. In the present study, we assessed the growth hormone response to clonidine, a selective alpha 2-adrenergic agonist, in 15 DSM-III-R major depressive inpatients with a history of suicide attempts, compared with 15 age- and gender-matched major depressive inpatients without a history of suicidal behavior. Mean (+/- SD) growth hormone peak responses to clonidine were significantly lower in the group of suicide attempters than in the control group: 2.93 +/- 3.01 ng/ml vs. 8.28 +/- 8.15 ng/ml. Therefore, these results suggest that a blunted growth hormone response to clonidine could be a biological correlate of suicidal behavior.

Reduced dopamine function in depressed patients is related to suicidal behavior but not its lethality

Several lines of evidence suggest a role for dopamine in the control of suicidal behaviour. Previously, we suggested an involvement of D2-dopaminergic function in the biology of suicide by demonstrating a smaller growth hormone (GH) response to apomorphine, a dopaminergic agonist, in depressed patients who later died by suicide. The purpose of the present study was to assess GH response to apomorphine in major depressed in-patients with a history of highly lethal suicide attempt compared to depressed patients with a low lethal lifetime suicide attempt history and non-attempters. The study was performed in a sample of 26 male depressed in-patients with a history of suicide attempt compared to 26 male depressed non-attempters. We observed a significant difference between suicide attempters and non-attempters (for GH peak, 6.3+/-5.1 ng/ml vs 15.8+/-14.2 ng/ml, F=10.3, df=1, 50, P=0.002). Moreover, GH peak responses to apomorphine did not differ between depressed patients with a high lethal lifetime suicide attempt history and patients who made low lethal lifetime suicide attempt. In conclusion, the results of the present study support a role for dopamine in the biology of suicidal behaviour. More specifically, an impaired GH response to apomorphine could be a marker of suicide risk.

Psychopathological correlates of dopaminergic disturbances in major depression.

In a recent report, we confirmed the role of dopamine in the pathophysiology of depression by demonstrating a blunted response of growth hormone (GH) to apomorphine, a selective dopaminergic agonist, in endogenous depressive patients. Few data are available on the possible psychopathological correlates of disturbances in the apomorphine test. In this study, we assessed the relationship between GH response to apomorphine and the Minnesota multiphasic personality inventory (MMPI) scales in a sample of 20 major depressive inpatients. The GH response (area under the curve) after apomorphine injection was positively correlated with the social introversion scale scores (r = 0.56, df = 19, p less than 0.01) and the anxiety scale scores (r = 0.45, df = 19, p = 0.04). These results suggest dopaminergic overactivity in anxious psychopathology rather than in depressive psychopathology. The relationship between the social introversion scale score and the apomorphine test is in agreement with the dopaminergic hypothesis of schizophrenic disorders.

Growth hormone response to apomorphine in panic disorder: comparison with major depression and normal controls.

Several lines of evidence suggest that dopamine might be involved in anxiety states. In the present study we assessed the growth hormone (GH) response to 0.5 mg apomorphine (a dopaminergic agonist) in 10 male drug-free inpatients meeting Research Diagnostic Criteria for panic disorder who were compared with 10 male major depressive inpatients and 10 male normal controls. The three groups differed significantly in the GH peak response (mean ± SD): 27.8±12.5 ng/ml in panics, 5.4±4.0 ng/ml in major depressives, and 25.8±11.3 ng/ml in normal controls (F(2,27)=15.3;P=0.00003). Although there were significant differences between panics and major depressives (P=0.00004), and between major depressives and controls (P=0.00004), panics did not significantly differ from controls. These results do not support the hypothesis of an overlap between panic and affective disorders, and suggest that the hypothalamo-GH-somatomedin axis could be intact in panic disorder.