Jean Reggers

Are spatial memories strengthened in the human hippocampus during slow wave sleep

In rats, the firing sequences observed in hippocampal ensembles during spatial learning are replayed during subsequent sleep, suggesting a role for posttraining sleep periods in the offline processing of spatial memories. Here, using regional cerebral blood flow measurements, we show that, in humans, hippocampal areas that are activated during route learning in a virtual town are likewise activated during subsequent slow wave sleep. Most importantly, we found that the amount of hippocampal activity expressed during slow wave sleep positively correlates with the improvement of performance in route retrieval on the next day. These findings suggest that learning-dependent modulation in hippocampal activity during human sleep reflects the offline processing of recent episodic and spatial memory traces, which eventually leads to the plastic changes underlying the subsequent improvement in performance.

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.

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.

The Short Allele of the Serotonin Transporter Promoter Polymorphism Influences Relapse in Alcohol Dependence

AIMS The short (S) allele of the serotonin transporter gene promoter polymorphism (5-HTTLPR) contributes to the risk of alcohol dependence and co-occurring clinical features. We studied the putative link between this allele and relapse. METHODS 48 alcohol-dependent male patients were recruited and genotyped for the 5-HTTLPR. Relapse to alcohol drinking was monitored during 3 months after standardized withdrawal. RESULTS The S allele was significantly associated with relapse (p = 0.008) while no other factor that was measured played a significant role. CONCLUSIONS The S allele of the 5-HTTLPR polymorphism may influence the risk of relapse in abstinent alcohol-dependent patients, possibly through intermediate phenotypes.

Further evidence on the relationship between dopamine and novelty seeking: a neuroendocrine study

In the biosocial model of Cloninger, three major personality dimensions, novelty seeking (NS), harm avoidance (HA), and reward dependence (RD) are dependent on central monoaminergic systems, respectively dopaminergic, serotonergic, and noradrenergic. This study investigated the relationships between these major personality dimensions and growth hormone (GH) responses to both apomorphine and clonidine challenge tests in healthy subjects. GH responses to apomorphine were significantly correlated with NS when peak relative values were considered (r=0.47, P=0.03). HA and RD did not show any relationships with the endocrine responses. In contrast, no significant relationship existed between GH responses to clonidine and any of the three temperament dimensions. These results gave another support of the hypothesized link between NS and dopaminergic central neurotransmission. In contrast, the results did not confirm the association between RD and noradrenergic central neurotransmission, probably because RD is poorly validated. This partial confirmation might suggest that the link between personality traits and neurotransmission systems is probably indirect.

5-HT1A dysfunction in borderline personality disorder.

Background. A number of challenge studies have reported abnormalities of serotonergic function in borderline personality disorder (BPD). There are, however, problems with the pharmacological probes used in these studies since fenfluramine and m-CPP are not only serotonergic agents but also induce release of catecholamines, particularly dopamine. Therefore, we tested whether subjects with BPD showed a blunted prolactin (PRL) response to flesinoxan, a highly potent and selective 5-HT 1A agonist. Methods. Flesinoxan challenge test was carried out in 20 BPD in-patients and 20 healthy controls matched for gender but not for age. Since 16 BPD in-patients exhibited major depressive co-morbidity, a group of 20 depressed in-patients matched for gender but not for age was also included. Results. BPD in-patients exhibited blunted PRL responses as compared to controls, whereas depressed in-patients did not differ from controls. Moreover, PRL responses were lower among BPD in-patients than among depressed in-patients. Among the BPD in-patients, PRL responses to flesinoxan were lower in patients with past history of suicide attempts (N = 8) than in those with a negative history. Conclusions. The results show major involvement of serotonergic function in BPD and are consistent with previous studies linking lower serotonergic activity with impulsivity. More particularly, our data suggest that BPD is characterized by lower 5-HT 1A receptor sensitivity. Moreover, the data support the involvement of 5-HT 1A activity in suicidal behaviour. However, this conclusion is limited because other hormonal responses such as ACTH and cortisol were not assessed, and because BPD was assessed by a self-report questionnaire and not a structured clinical interview.

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.

Harm avoidance is related to mismatch negativity (MMN) amplitude in healthy subjects

Event-related potential (ERP) studies evidenced that some personality dimensions induced different controlled cognitive attitudes towards the processing of information. However, few data are available on the possible relationships between personality and automatic attention or early sensory processing. In the present study the relationships between the mismatch negativity (MMN) and personality described by the Cloninger model of personality were investigated. Subjects were 32 healthy volunteers. The MMN was recorded with frequent stimuli tones of 1470 Hz, 70 dB and 40 ms duration, and target (20%) tones of 1470 Hz, 70 dB, 80 ms duration. The subjects completed a French version of the 226-item self-questionnaire TCI within the day following psychophysiological recording. The results showed that the HA dimension was negatively correlated with the MMN amplitude. The association was more present among women than men. No significant relationship existed between the other dimensions of personality and either the MMN amplitude or latency. These findings suggest that the MMN is related to the behavioral inhibition system (BIS), a fact which is consistent with clinical studies conducted on schizophrenia and anxiety disorders. In conclusion, this study suggests that personality dimensions induce different automatic attitudes towards the processing of information.

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 α2-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.

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.