Personality modulation of P300 wave recorded within an emotional oddball protocol.

OBJECTIVES: Several studies reported that personality modulates responses to emotional stimuli, including cognitive and attentional aspects of the emotional response. The aim of this study was to refine these results while using visual event-related potentials (ERPs) and referring to Cloninger's personality model. METHODS: ERPs were recorded in 46 normal subjects within a visual oddball protocol with checkerboards as the standard stimuli and pictures selected as neutral, pleasant or unpleasant from the International Affective Picture System as the target stimuli. RESULTS: N200 amplitude was smaller and P300 amplitude was larger following the presentation of pleasant pictures in low-harm avoidance but not high-harm avoidance subjects. CONCLUSIONS: These results support the idea that both automatic and selective cognitive processing of emotional pictures is modulated by personality.

Plasma oxytocin levels and anxiety in patients with major depression.

Cerebrospinal fluid and plasmatic levels of oxytocin (OT) have been found to change in mood disorders. In post-mortem studies, the numbers of OT-expressing neurons in the paraventricular nucleus have been reported to be increased. Moreover, OT is considered as an endogenous antistress hormone. It has also revealed antidepressive effects. OT may contribute to the dysregulation of the HPA system in major depression. The aim of the study was to assess a possible relationship between anxiety and plasma oxytocin (OT) levels in depressive patients. Severity of depression was estimated with the Hamilton Depression Rating Scale and anxiety by using the Spielberger State-Anxiety Inventory. Results showed a significant negative correlation between oxytocin and the scored symptoms depression (r=-0.58, p=0.003) and anxiety (r=-0.61, p=0.005).

[Impact of personality on the alcohol withdrawal syndrome intensity: a preliminary study with the Cloninger's model]. / Impact de la personnalité sur l'intensité du syndrome de sevrage alcoolique: une étude préliminaire avec le modèle de Cloninger.

INTRODUCTION: The personality of alcohol dependant patients as a factor influencing the intensity of the alcohol withdrawal syndrome has been seldom examined. Cloninger's biosocial model of personality describes four temperaments (novelty seeking, harm avoidance, reward dependence, persistence) which, except for persistence, are admittedly linked to specific central neurotransmitters, and three characters. Novelty seeking is linked with low levels of mesencephalic dopamine, harm avoidance with high levels of serotonin in the septo-hippocampic system and reward dependence with low levels of noradrenaline in the ascending pathways from the locus coeruleus to the limbic system. The same neurotransmitters pathways are known to be involved in alcohol withdrawal, with a decrease of dopaminergic activity in the mesolimbic system, a decrease of serotonergic activity in the nucleus accumbens and an increase of the noradrenergic system. In view of the similarities between the neurobiological systems involved in Cloninger's model and in the neurobiological changes occurring during the withdrawal period, one would expect to observe severe withdrawal symptoms more frequently for patients with high novelty seeking, low harm avoidance and low reward dependence. METHODS: To test this hypothesis, alcohol dependent patients according to DSM IV classification criteria who have drunk in the last twenty four hours were included in the study and received a standardized withdrawal treatment. The withdrawal syndrome intensity was examined with repeated measures of CIWA-Ar, the scores of which were correlated with TCI-R. RESULTS: Twenty eight patients, between 30 et 65 years old and drinking 22,2 +/- 12 standard drinks per day were included. Antidepressant drugs, benzodiazepines and neuroleptics treatment introduced before hospitalisation were stopped or decreased as much as possible. A correlation matrix was carried out between all the variables which could influence withdrawal intensity (age at the hospitalisation, age at the begining of the dependance, ratio between the time of the dependance and the patients' age, the number of alcohol withdrawals carried out and the number of standard drinks per day), and showed a positive correlation between the number of standard drinks per day and withdrawal intensity at day 3 (r=0.7, p<0.000), at day 4 (r=0.52, p<0.005), at day 7 (r=0.41, p<0.036) and at day 8 (r=0.44, p<0.02); as between the ratio between the time of the dependance and the patients' age and withdrawal intensity at day 2 (r=0.43, p<0.03) and at day 5 (r=0.5, p<0.01). Therefore, partial correlations were calculated between the dimensions of personality and withdrawal intensity. The study showed a positive correlation between withdrawal intensity and harm avoidance from day 5 onwards (r=0.6 and P<0.003 at day 5, r=0.59 and P<0.004 at day 6, r=0.56 and P<0.006 at day 7, r=0.66 and P<0.001 at day 8), a negative correlation between withdrawal intensity and reward dependence at day 7 and 8 (r=- 0.45 and P<0.037 at day 7, r=- 0.49 and P<0.02 at day 8) and a negative correlation between withdrawal intensity and persistence from day 6 onwards (r=- 0.5 and P<0.017 at day 6, r=- 0.5 and P<0.019 at day 7, r=- 0.51 and P<0.014 at day 8). No correlation was found between withdrawal intensity and novelty seeking. The same relevant results were found again with the 22 patients without anti-depressant drugs' population. DISCUSSION: Personality dimensions seem to influence alcohol withdrawal intensity once the severe symptomatology is over, while high doses of anti withdrawal treatment in the first days of abstinence may decrease the influence of personality on withdrawal symptoms. The positive correlation between harm avoidance and withdrawal intensity seems to invalidate our neurobiological hypotheses, but can be explained by clinical observations and corroborate studies assessing the influence of personality in benzodiazepine withdrawal intensity and in pain perception. This result encourages the introduction of support therapy during withdrawal and a cognitive-behavioural therapy before withdrawal in order to decrease patients' sensitivity to anxiety. The negative correlation between reward dependence and withdrawal intensity confirms the neurobiological hypotheses, but the weak correlation demands to be cautious in the interpretation of the results. The negative correlation between persistence and withdrawal intensity was expected. CONCLUSION: The characteristics associated with persistence seem to act as protective factors during alcohol withdrawal, whereas those associated with harm avoidance appear to increase the symptoms of alcohol withdrawal. In contrast, the neurobiological hypotheses are only partially confirmed.

AVP- and OT-neurophysins response to apomorphine and clonidine in major depression.

A number of studies have reported abnormalities of neurohypophyseal secretions in major depressive disorder. The purpose of the present study was to test the influence of apomorphine and clonidine injections on plasma vasopressin (AVP)-neurophysins and oxytocin(OT)-neurophysins levels, as direct index of posterior pituitary activation in major depression. Apomorphine and clonidine tests were carried out in 25 medication-free depressive patients and 25 age and gender-matched healthy controls. Blood for neurophysins analysis was drawn by venipuncture at t0, t + 20, t + 40, t + 60 and t + 120. Baseline AVP-neurophysins concentrations were significantly lower in depressives (0.12 +/- 0.14 ng/ml) than in healthy subjects (0.24 +/- 2.15 ng/ml) (p < 0.04). The response to apomorphine test revealed a significant reduced response at 20 (p = 0.01), 40 (p = 0.007) and 60 (p = 0.02) and 120 (p = 0.02)min. Following clonidine test, post hoc tests also revealed a significant decrease at 0 (p = 0.04), 20 (p = 0.01), 40 (p = 0.007) and 60 (p = 0.02) and 120 (p = 0.006)min. Concerning OT-neurophysins, no significant differences were found between depressed and controls in response to clonidine or apomorphine injections. Following clonidine and apomorphine, major depressives exhibited a significantly lower peak GH response than controls. The study supports partially the hypothesis of a reduced vasopressinergic activity in depression. Moreover, we did not find any influence of acute apomorphine or clonidine injections on vasopressin-neurophysin or oxytocin-neurophysin in depressive patients.

Additional intranasal oxytocin to escitalopram improves depressive symptoms in resistant depression: an open trial.

The aim of this open trial was to assess the antidepressant/anxiolytic effects of oxytocin used as an adjunct to antidepressant in treatment-resistant depression. Fourteen patients, who have not responded to 40mg of escitalopram, received intranasal synthetic oxytocin during 4 weeks, in association with antidepressant. This is the first open trial study suggesting OT in association with escitalopram significantly reduced scores on Hamilton Depression Rating Scale.

Suicidal behavior and growth hormone response to apomorphine test.

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 suggest 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.

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.

Catecholaminergic function and temperament in major depressive disorder: a negative report.

In the biosocial model of Cloninger, the three personality dimensions are related to different central neurotransmission systems. In agreement with this model, a recent study (Wiesbeck et al., 1995) showed an association between growth hormone response to apomorphine, an indirect assessment of the dopaminergic system, and novelty seeking score in alcohol-dependent men. In the present study we investigated the same methodology in a sample of major depressive patients. In addition, we assessed the relationship between noradrenergic function and Cloninger's dimensions using the clonidine test, an indirect assessment of the noradrenergic system. Growth hormone responses to apomorphine and clonidine were not associated with novelty seeking, reward dependence or harm avoidance dimension scores. This study therefore does not confirm the results of Wiesbeck et al. (1995), and does not support an association between noradrenergic activity and reward dependence dimension. However, given the complexity of central neurotransmission systems and the limitations of neuroendocrine challenges for the assessment of those processes, this study could not be considered as definitive evidence against the association between personality dimensions and their hypothesized central substrates.

Neuroendocrine evaluation of 5-HT1A function in male alcoholic patients.

BACKGROUND: Preclinical evidences support the hypothesis of a serotonergic dysfunction in alcohol preference. In human, studies have demonstrated a serotonergic hypoactivity in alcoholism. However, little is known about the role of 5-HT1A receptors. METHODS: We assessed the hormonal (prolactin and cortisol) responses to flesinoxan (a highly potent and selective 5-HT1A agonist) in 12 male inpatients meeting DSM-IV criteria for alcohol dependence, 3 weeks after the last reported use of alcohol and antidepressants. These patients were compared to 10 male controls. RESULTS: There was a highly significant difference between alcoholic patients and controls for the area under the curve relative (AUCr) values of prolactin responses. AUCr values of cortisol responses to flesinoxan showed a trend towards lower values in alcoholics compared to controls. CONCLUSION: These results support the implication of the serotonergic system, and particularly a decreased sensitivity of post-synaptic 5-HT1A receptors, in alcoholism.

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.

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.

Temperament and character inventory (TCI) and depression.

Although several studies have assessed the relationships between the temperament dimensions of the Cloninger model of personality and depression, little is known about the role played by the character dimensions proposed by the seven-factor model of Cloninger in depression. In this study, the relationships between the Temperament and Character Inventory (TCI) and depression were examined in a sample of 40 major depressive patients and 40 healthy controls. Depressed patients exhibit higher harm avoidance and self-transcendence scores as well as lower self-directedness and cooperativeness scores as compared to healthy controls. However, the three other dimensions do not differ between depressive patients and controls. Among the depressive group, harm avoidance, self-directedness and cooperativeness dimensions are related to the severity of depression as assessed by the Hamilton scale. This study confirms the state dependence of the harm avoidance dimension and suggests a relationship between the character dimensions of the Cloninger model and depression.

Personality profile and drug of choice; a multivariate analysis using Cloninger's TCI on heroin addicts, alcoholics, and a random population group.

As personality may predispose, precipitate or perpetuate substance abuse and/or dependence, and as it is considered to remain stable across the years in a given subject, potential links with the drug of choice may help screen future patients before drug consumption. The present study compared three groups: 42 patients with heroin dependence (mean age: 31.2; standard deviation (SD): 5.5; 10 females), 37 patients with alcohol dependence (mean age 44.2; SD: 9.1; 9 females) and 83 subjects from a random population sample (mean age: 38.8; SD: 6.9; 20 females). Personality was measured by Cloninger's Temperament and Character Inventory (TCI). Pillai's MANCOVA with age as a covariate and gender as a cofactor was highly significant. Univariate ANOVA analyses using TCI dimensions as dependent variable showed most variables to vary in parallel for the two patient groups in comparison with controls. Post-hoc tests showed heroin patients to score higher in Novelty-Seeking and Self-Directedness than alcohol patients. Sub-dimensions Exploratory Excitability, Fear of the Uncertain, Responsibility, Congruent Second Nature and Transpersonal Identification were also significantly different in the two patient samples. Logistic regression showed Exploratory Excitability to segregate up to 76% of heroin patients from alcohol patients. In conclusion, personality profiles were linked to some preferential choice of drug and personality screening might be tested in preventive strategies.

P300 and personality: an investigation with the Cloninger's model.

The relationships between P300 and personality have been explored mainly in reference to the model of personality described by Eysenck because of its biological bases. Recently, Cloninger and his colleagues have proposed a model of personality based on four temperaments and three characters. The Temperament and Character Inventory (TCI) is a 226-item self-questionnaire developed to assess these seven dimensions of personality. In the present study, the relationships between these dimensions of personality and P300 have been investigated in 43 normal subjects. The results show that P300 amplitude is positively correlated with the novelty seeking dimension and negatively correlated with the harm avoidance dimension. In contrast, the other dimensions of the TCI were not related to P300 amplitude. Moreover, P300 latency and reaction time were not associated with the TCI dimensions of personality. This study confirms that personality is related to P300.

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.

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.

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.

Relationship between alpha 2-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.

[The p300 cognitive event-related potential. I. Theoretical and psychobiologic perspectives]. / Le potentiel évoqué cognitif P300 (I): aspects théorique et psychobiologique.

The P300 is a positive wave which arises when an attended stimulus is detected. Its parameters depend on a number of variables, in particular the subject's mental state, the task that has to be accomplished, the significance of the stimulus, and the degree of attention. It can be recorded with accuracy, and the different stages of information processing can therefore be analyzed. The P300 wave shows the modifications in neuronal activity which take place during the cognitive process: P300 latency provides an indirect indication of the duration of the processes involved in stimulus discrimination while its amplitude, which is influenced by a number of variables, provides an index of the intensity of the energetic activation or arousal involved. The P300 wave consists of several components which reflect distinct information-processing events (P3a, P3b, P3e, P-SR, P-CR). According to the theoretical models, it is hypothesized that P300 could either represent the adaptation of the working memory to further environmental input ('context updating'), or indicate a closing process ('context closure') in information processing. As regards the physiological aspect of P300 and its association with cortical networks, various studies have suggested that several cortical generators of P300 may co-exist: the medial temporal lobe, the temporo-parietal junction, and the medial and lateral frontal lobe. Psychopharmacological studies have shown that different neurotransmitter systems are involved in the generation and modulation of P300, namely the cholinergic, noradrenergic, dopaminergic, serotoninergic and gabaergic systems. It appears that the noradrenergic agonists increase the amplitude of P300, dopaminergic agonists may have a biphasic effect (increase/reduction), while cholinergic antagonists and gabaergic agonists reduce P300 amplitude and prolong its latency.