Marc Ansseau

Harm avoidance and serotonin.

The relationships between the Tridimensional Personality Questionnaire (TPQ) and serotonergic activity has been described in some studies with controversial results. These studies have focused on specific patient populations rather than normal controls. Therefore, the aim of the present study is to examine the relationships between the TPQ and serotonergic activity in a group of non-patient subjects. Twenty-three normal subjects answered the TPQ, and the serotonergic activity was assessed by the prolactin response to a highly potent and selective 5-HT1a agonist (flesinoxan). A positive relationship between harm avoidance and PRL response to flesinoxan was found. This study is consistent with the hypothesized link between serotonergic activity and the harm avoidance dimension of the biosocial model of Cloninger.

Depressive vulnerability is not an independent risk factor for osteoporosis in postmenopausal women

Major depression has been repeatedly but not consistently reported to be associated with low bone mineral density (BMD) and to an increased risk for fracture in women. We have investigated, in healthy postmenopausal women, whether depressive symptomatology, assessed by the General Health Questionnaire (GHQ), was associated to a significant decrease in BMD, hence supporting the hypothesis of an independent pathogenetic link between the two disorders. We investigated 121 postmenopausal women, aged 48-77 years, spontaneously attending a screening visit for osteoporosis in an outpatient facility. BMD of the spine and the non-dominant hip (total and neck areas) were measured by Dual Energy X-Ray absorptiometry. All subjects completed to the General Health Questionnaire translated and validated in French. No significant correlations were observed between the GHQ score and BMD of the spine (P = 0.54), the total hip area (P = 0.65), or the femoral neck area (P = 0.65). No differences in terms of spinal or femoral BMD were observed between women with GHQ score < 5 or > or = 5. When comparing values of BMD between women within the upper and the lower quartiles for GHQ score, no difference was observed for spine (P = 0.69), total hip (P = 0.80), or femoral neck (P = 0.93). Similarly, GHQ scores were not significantly different when comparing women in the upper and lower quartiles of BMD distribution at the spine or the hip. In conclusion, notwithstanding the clinical pattern of postmenopausal osteoporosis can lead to depression and, on the other hand, hormonal and behavioral disturbances reported in depression might be enhancing factors for accelerated bone loss, our present results do not support the hypothesis that otherwise healthy postmenopausal women with increased depressive complaints are also more prone to exhibit osteoporotic fractures.

Reduced dopaminergic activity in depressed suicides

Several data are available about the implication of the dopaminergic system in the control of inward-directed aggression. Previously, we suggested an involvement of D2-dopaminergic function in the expression of suicidal behavior by demonstrating a smaller growth hormone (GH) response to apomorphine, a dopaminergic agonist, in depressed patients with a history of suicide attempts in comparison to nonattempters. In the present study, the purpose was to analyze GH responses to apomorphine in depressive patients who later died by suicide. Our sample comprised eight male depressive inpatients who died by suicide within one year after hospitalisation. These patients were compared to 18 male major depressed inpatients who never attempted suicide. Mean GH peak responses to apomorphine differed significantly between suicide completers and controls (mean +/- SD): for GH peak, 7.6 +/- 4.1 ng/ml vs 18.9 +/- 14.2 ng/ml, U = 30, Z = -2.33, P = 0.02. Our results tend to confirm the role of dopamine in the biology of suicide in depression.

Relationship between clinical effects, serum drug concentration, and concurrent drug interactions in depressed patients treated with citalopram, fluoxetine, clomipramine, paroxetine or venlafaxine.

The relationship between clinical effects and plasma concentrations of citalopram, fluoxetine, clomipramine, paroxetine and venlafaxine was studied in 119 cases of major depression. Clinical effects were evaluated using the Clinical Global Impression (CGI) improvement scale. Antidepressants were quantified by a separative chromatographic methodology. Plasma concentrations in responder patients were compared with the plasma concentrations proposed in literature as effective values. We found that the usual therapeutic window is convenient for citalopram and clomipramine, but could be reduced for fluoxetine and increased for venlafaxine and paroxetine. Concurrent drug interactions were also evaluated and clomipramine or citalopram plasma levels were found to be influenced by the presence of associated drugs. A larger study is needed, taking into account not only plasma concentrations and clinical effects, but also some pharmacokinetic data, especially the metabolic activity characterising the patient, and the presence or not of associated drugs. Copyright

Hpa Axis Dysfunction in Major Depression: Relationship to 5-Ht(1a) Receptor Activity

Major depression is associated with a dysfunction of the serotonergic activity and the hypothalamic-pituitary- adrenal (HPA) axis. Moreover, a reciprocal relationship between the serotonergic and HPA axis systems has been hypothesized. The purpose of the present study was to assess the relationship between sensitivity of 5-HT1A receptors as measured by hormonal (ACTH, cortisol and PRL) and temperature responses to flesinoxan and HPA axis activity as measured by the dexamethasone suppression test. The sample included 21 inpatients with major depression. Dexamethasone nonsuppressors exhibited lower ACTH responses to flesinoxan as compared with dexamethasone suppressors. The results showed that a dysfunction in 5-HT1A receptor activity could be due to a hypersecretion of cortisol.

P300 event-related brain potential and personality in depression

P300 is an event-related brain potential (ERP) particularly interesting to the study of cognitive processes in normal subjects and in psychopathology. P300 has been applied in depression with controversial results. A major source for these controversial results could result from the diversity of depressed patients included in the different studies. Supporting this assumption, impulsivity, blunted affect, suicidal behavior and psychotic features significantly influence P300 amplitude. However, no data are available on the possible influences of the personality of depressed patients on P300. Since personality is related to P300 in normal subjects, the aim of the present study is to investigate the relationship between ERPs (P200, N200, and P300) and the Temperament and Character Inventory (TCI) in 54 depressed patients. The main results of the study concern the absence of major correlations between personality dimensions as assessed by the TCI and ERP parameters among depressed patients. Only weak partial positive correlations relate N200 latency with harm avoidance, and P300 amplitude (Pz) with the self-directedness dimension. N200 amplitude is also negatively correlated to persistence. However, the preliminary nature of the presented results with respect to the weak statistical significance should be underlined.

P300 event-related potential and serotonin-1A activity in depression.

The identification of the brain structures and neurotransmitters responsible for the generation and/or modulation of P300 could lead to important clinical implications. Since serotonin disturbances seem to play a critical role in depression, the aim of the study was to assess the possible relationships between the P300 event-related brain potential and serotonergic activity in depression. The study was conducted among 45 major depressive inpatients, and serotonergic activity was assessed by prolactin (PRL) response to flesinoxan (a 5-HT1A agonist). Results showed a significant negative correlation between P300 amplitude and PRL response to flesinoxan (r = -0.40, P = 0.007 at Cz; r = -0.47, P = 0.001 at Pz). In contrast, both P300 latency and reaction time were not related to endocrine response. This study supports a role for serotonin-1A in the neurobiological modulation of P300 amplitude.

Serotonergic-1a activity and contingent negative variation.

While cholinergic, dopaminergic, noradrenergic, and gabaergic effects on contingent negative variation (CNV) have been largely described, little is known about serotonergic influence. Therefore, the relationship between CNV and serotonergic activity as reflected by prolactin (PRL) response to flesinoxan, a 5-HT(1A) full agonist, has been investigated in 28 healthy volunteers. To investigate the clinical implications of the relationship between CNV and serotonergic-1a activity, a group of 43 depressed patients was included in the study. Results among healthy volunteers showed a significant negative relationship between PRL response to flesinoxan and CNV amplitude at Fz, but no relationship for the other electrodes (Cz and Pz). In depressed patients, the relationships were not significant. Overall, this study does not support serotonergic effects on CNV. However, this information is indirect (correlations) and is limited to 5-HT(1A) activity.

Alpha-2-adrenoreceptors in depressed suicide attempters : relationship with medical lethality of the attempt

Several lines of evidence tend to suggest a role for noradrenaline, and more specifically alpha-2-adrenoreceptors, in the biology of suicidal behavior. The purpose of this study was to assess the growth hormone (GH) response to clonidine, an alpha-2-adrenergic agonist, in majorly depressed inpatients with a history of highly lethal suicide attempt compared to depressed patients with a history of low lethal suicide attempt and nonattempters. Our sample included 20 male depressed inpatients with a history of suicide attempt compared to 20 male depressed nonattempters. We did not observe any significant difference between suicide attempters and nonattempters for GH peak values (2.4 ± 2.9 vs. 4.1 ± 3.7 ng/ml; F = 2.52, d.f. = 1, 38, p = 0.12). Moreover, GH peak responses to clonidine were not related to the degree of lethality of the attempt. The results of the present study do not support a major role for noradrenaline in the biology of suicidal behavior.