Roland Jouvent

Early and late onset bipolar disorders: two different forms of manic-depressive illness?

BACKGROUND Conflicting results in genetic studies of bipolar disorders may be due to the clinical and genetic heterogeneity of the disease. Age at onset of bipolar disorders may be a key indicator for identifying more homogeneous clinical subtypes. We tested whether early onset and late onset bipolar illness represent two different forms of bipolar illness in terms of clinical features, comorbidity and familial risk. METHODS Among a consecutively recruited sample of 210 bipolar patients, we compared early onset (n=58) and late onset (n=39) bipolar patients; the cut-off points were age at onset before 18 years and after 40 years for the two subgroups. The subgroups were compared by independent t tests and a contingency table by raw chi-square test. Morbid risk among first-degree relatives was measured by the survival analysis method. RESULTS The early onset group had the most severe form of bipolar disorder with more psychotic features (P=0.03), more mixed episodes (P=0.01), greater comorbidity with panic disorder (P=0.01) and poorer prophylactic lithium response (P=0.04). First degree relatives of early onset patients also had a higher risk of affective disorders (P=0.0002), and exhibit the more severe phenotype, i.e bipolar disorder. CONCLUSION Our data suggest that early and late onset bipolar disorders differ in clinical expression and familial risk and may therefore be considered to be different subforms of manic-depressive illness.

Alexithymia and anxiety: compounded relationships? A psychometric study.

This study is a careful examination of the relationships between different components of the alexithymia construct and state versus trait anxiety. In order to study the relations between anxiety and alexithymia in a subclinical population, we administered to 125 female college students a test battery including measures of alexithymia (TAS26), state and trait anxiety (STAI) and depression (QD2A). Results indicated positive correlations between depression, anxiety (state and trait) and alexithymia scores. Partial correlations revealed a tight link between trait anxiety and alexithymia. Furthermore, in agreement with the view that alexithymia is a multidimensional construct, the various alexithymia dimensions were found to be diversely correlated with anxiety. On the basis of partial correlation analyses, a descriptive model of the relationships between depression, state anxiety, trait anxiety and alexithymia was postulated. This model was confirmed by pathways analyses.

The Temperament and Character Inventory-Revised (TCI-R): psychometric characteristics of the French version

Objective:  To explore the psychometric characteristics of a modified version of the Cloningers personality questionnaire, the Temperament and Character Inventory‐Revised (TCI‐R).

Gaze avoidance in social phobia: Objective measure and correlates

Gaze aversion could be a central component of the physiopathology of social phobia. The emotions of the people interacting with a person with social phobia seem to model this gaze aversion. Our research consists of testing gaze aversion in subjects with social phobia compared to control subjects in different emotional faces of men and women using an eye tracker. Twenty-six subjects with DSM-IV social phobia were recruited. Twenty-four healthy subjects aged and sex-matched constituted the control group. We looked at the number of fixations and the dwell time in the eyes area on the pictures. The main findings of this research are: confirming a significantly lower amount of fixations and dwell time in patients with social phobia as a general mean and for the 6 basic emotions independently from gender; observing a significant correlation between the severity of the phobia and the degree of gaze avoidance. However, no difference in gaze avoidance according to subject/picture gender matching was observed. These findings confirm and extend some previous results, and suggest that eye avoidance is a robust marker of persons with social phobia, which could be used as a behavioral phenotype for brain imagery studies on this disorder.

Sensation seeking, nicotine dependence, and smoking motivation in female and male smokers

Sensation-seeking scores in female (n = 36) and male (n = 60) French smokers were compared with those for a control group of female (n = 23) and male (n = 45) nonsmokers. The findings clearly show that smokers of both sexes are higher in sensation seeking than their nonsmoking counterparts: they score higher on the Disinhibition, Experience Seeking, and Boredom Susceptibility components of sensation seeking. Smoking women were particularly high on Experience Seeking. The relationships among the sensation-seeking components, nicotine dependence, and motives for smoking were assessed in the smokers. Disinhibition and Experience Seeking moderately correlated with nicotine dependence in females, as assessed by the Fagerström questionnaire and the Addictive factor of the Russell Classification of Smoking by Motives. Women high in Experience Seeking may be at particular risk for smoking and possibly for dependence. Further research is needed to state that the high sensation seeker is a person who might be expected to be particularly sensitive to the stimulating reward of smoking, and thus particularly vulnerable to becoming a dependent smoker.

Information processing deficits in relatives of manic depressive patients.

BACKGROUND The importance of genetic factors in the aetiology of manic-depressive illness (MDI) has been repeatedly confirmed and indicators of vulnerability to the illness in families with affective disorders are needed. Abnormal event-related potentials (ERP) may be markers of genetic vulnerability to mental illness. Long latency and low amplitude of P300 have consistently been reported in schizophrenic patients and their relatives. A few studies have also shown P300 deficits in MDI patients, but no ERP study has been performed on their relatives. METHODS ERPs were recorded during an auditory oddball task in 19 relatives belonging to families with two or more bipolar patients and in controls with no familial or personal history of affective disorders. The relatives were selected as having no affective disorders on a lifetime basis, but eight had an anxiety disorder. RESULTS In all relatives, a lower P300 amplitude and a longer P300 latency was found, with much longer reaction time and post-N200 duration till button-press than controls. A lack of P300 amplitude dominance in the right hemisphere was also found in relatives in comparison with controls. There also appeared to be a frontal predominance of ERP abnormalities in relatives. CONCLUSION We report the first evidence of deficits in reaction time and in P300 amplitude and latency, and a lack of P300 right-sided dominance, in relatives of manic-depressive patients. This pattern may constitute an endophenotypic marker of manic-depressive disorder.

Sensation-seeking and emotional disturbances in depression: relationships and evolution

The French abbreviated form of the sensation-seeking scale was given to 183 hospitalized depressed subjects meeting the DSM-III-R criteria for major depression. Depressed subjects, men and women, scored significantly lower than controls from the general population, paired as to age and sex, on all of the subscales. There was no relationship to the intensity of depression and anxiety. Relationships between emotional disturbances and sensation-seeking were differentiated according to the specificity of each subscale and to age and sex. There was no significant difference between baseline and after-treatment sensation-seeking scores and subjects at discharge still scored significantly lower than controls. Hypotheses on evolution at a later date after the hospitalization are made. The finding of positive relationships for some subjects between sensation-seeking and anhedonia is interpreted in regard to a compensatory process.

Affective disturbances in Alzheimer's disease.

To evaluate the emotional disturbances in patients with Alzheimers disease (AD) using both a categorical and a dimensional approach.

Clinical and neurochemical effect of acute tryptophan depletion in unaffected relatives of patients with bipolar affective disorder

BACKGROUND The lowering of mood induced by an acute tryptophan depletion (ATD) has been proposed as a candidate endophenotype for the vulnerability to manic-depressive illness. This study tests this hypothesis in relatives of probands from well-characterized multiplex families affected with bipolar affective disorder (BAD). METHODS In a double-blind, crossover design, 20 unaffected relatives (URs) and 19 control subjects received either a 100-g amino acid (AA) drink devoid of tryptophan or a placebo, respectively. Clinical and biochemical effects of ATD were compared between unaffected relatives of BAD probands and age- and sex-matched control subjects. RESULTS At 5 hours after AA drink ingestion, relative to the placebo, ATD resulted in 74% and 84% decreases in total plasma tryptophan concentrations in control subjects and relatives of patients with BAD, respectively. Unlike control subjects unaffected relatives experienced a lowering of mood during ATD but not with the placebo. Furthermore, URs tended to show increased impulsivity in the ATD condition. Measurements obtained before ingestion of the AA drink indicated that, relative to control subjects URs exhibited lower serotonin platelet concentrations, lower affinity, and fewer binding sites of the serotonin transporter for imipramine; these differences were unaffected by ATD. CONCLUSION These results replicate and extend previous findings suggesting that URs of patients with BAD are more susceptible to low tryptophan availability. This finding may bear significance in the purported role of serotonergic mechanisms in the vulnerability to depressive syndrome and/or illness.

Transfer of learning across durations and ears in auditory frequency discrimination.

Frequency-discrimination thresholds (FDTs) for 1-kHz tone pips with durations of 40, 100, and 200 msec were measured in the left and right ears of 10 normal-hearing listeners, before and after six 2-h frequency-discrimination training sessions involving, exclusively, the 200-msec duration and the right ear. In the trained ear, highly significant improvements in FDTs were observed at all durations. Further inspection of the data suggested complete generalization between 200 and 100msec, but not at 40 msec. Post-training FDTs were not found to differ between the two ears for the two untrained durations, but proved significantly smaller in the right (trained) than in the left (untrained) ear at the trained (200-msec) duration only. A control experiment involving 10 additional subjects allowed us to establish the absence of intrinsic differences in pretraining FDTs between the right and left ears. Overall, these findings indicate that frequency-discrimination learning generalizes widely across stimulus durations and across ears, but that part of the improvement is specific to the range of durations and to the ear used in training.