Quantitative autoradiography of 5-HT1D and 5-HT1E binding sites labelled by [3H]5-HT, in frontal cortex and the hippocampal region of the human brain.

In human cortex and hippocampus area, [3H]5-HT (5 nM) labels 5-HT1A, 5-HT1D and 5-HT1E sites. After masking 5-HT1A receptors by 0.1 microM 8-OH-DPAT, the binding displaced by 0.1 microM 5-CT presumably represented 5-HT1D sites and the remaining binding 5-HT1E sites. In frontal cortex, 5-HT1A receptors represented the main binding in layers II and VI and a lower fraction in other layers. 5-HT1D and 5-HT1E sites, were more homogeneously distributed in layers II to VI (21-34% of specific [3H]5-HT binding). 5-HT1E sites were of similar affinities (KD close to 6-8 nM) in the cortical layers II to VI. In CA1 field of hippocampus, (pyramidal layer, stratum radiatum, molecular layer), CA2 and dentate gyrus, 5-HT1A receptors represented the major fraction, 5-HT1D sites a significant fraction and 5-HT1E a minor fraction of the specific [3H]5-HT binding. In CA3-CA4 fields, 5-HT1A receptors were less densely present, 5-HT1D sites were predominant and 5-HT1E sites represented a significant fraction (27%). The highest densities of 5-HT1E sites have been measured in subiculum, where 5-HT1A, 5-HT1D and 5-HT1E binding sites were equally represented and in entorhinal cortex where 5-HT1E sites represented the major binding in layer III. They were also present in layers II and IV (29 and 24%) and, to a lesser extent, in layers V and VI. 5-HT1A sites were predominant in layer VI, II and V and were less abundant in other layers. 5-HT1D were homogeneously present in layers II, III, IV and were present in low amounts in other layers. No 5-HT1E were detected in choroid plexus, where [3H]5-HT was dramatically reduced by mesulergine (5-HT2C receptors). No significant displacement of [3H]5-HT by mesulergine was measured in other structures.

Bulimia nervosa and autoimmunity.

The autoantibodies that react with dopamine and serotonin are of interest in the study of bulimia nervosa. These neurotransmitters play an important role in appetite control, sexual and social behavior, and stress responses, all of which form a part of the clinical picture of bulimia nervosa. Are these autoantibodies involved in the serotoninergic hypofunctioning present in bulimia nervosa? Are they a part of an immunity regulation system essential for the cerebral system's homeostasis? To address these questions, 31 bulimic females (diagnosed according to DSM-III-R criteria) were compared with 10 control subjects (matched to the patients for sex, age, and demographic/psychosocial features). Measurement of the activity of natural autoantibodies reacting with dopamine, dopamine-beta-hydroxylase and serotonin was performed by an enzyme-linked immunosorbent assay (ELISA) for typical immunoglobulins (IgG, IgM, IgA). All of the autoantibodies of the IgG type were lower in the bulimic group than in the control group, a difference that was statistically significant for IgG anti-serotonin and IgG anti-dopamine. There was a trend for the amount of IgM anti-dopamine to be lower in patients than in controls. Dopamine and serotonin are specific components of brain cells. It can therefore be hypothesized that these antigens acting with autoantibodies could be the antigenic cerebral targets reacting with 'anti-brain' antibodies. The study of these specific autoantibodies provides information about the immunological characteristics that may be related to brain disturbances.

[Pharmacologic treatment of bulimia]. / Traitement pharmacologique de la boulimie.

The rationale for pharmacological treatment of bulimia nervosa is summarized and a review of controlled therapeutic trials shows contradictory results. A number of antidepressant agents (tricyclics: imipramine, desipramine, amitriptyline; IMAO: phenelzine, isocarboxazide; trazodone; fluoxetine) appear more effective than placebo in double-blind controlled trials of 6 to 16 weeks. In similar studies, other antidepressants (mianserine, fluvoxamine) are ineffective. Improvement reported is often incomplete and the low percentage of patients totally abstinent at the end of treatment appears of poor pronostic value for long-term outcome. Methodological limitations of existing studies are discussed, and some psychopathological factors to consider in the assessment of therapeutic response are proposed.

[Manic-depressive psychoses in adolescence. Influence of life change events. Study of family dynamics]. / Psychose maniaco-dépressive à l'adolescence. Influence des événements de vie. Etude de la dynamique familiale.

A sample of 38 adolescents hospitalized for a major depressive episode melancholic type or a manic episode during the course of a bipolar disorder (according to the DSM III-R Criteria) was examined with particular emphasis on precipating life events and family relationships. Psychosocial stressors in the year preceding onset of the affective disorder were found in a very high proportion of cases (about 80%). Stressors are most often severe. All of these stressors have to do with loss or threat of loss, particularly the most frequent one: the sentimental failure. Analyzing results of a familial dynamic questionnaire, we showed in the MDD sample the prevalence of two psychopathological index: maternal rejection, parental dysharmony.

[Bulimia and autoimmunity]. / Boulimie et auto-immunité.

In the first part of this study, we investigated the rate of natural autoantibodies, in a sample of 31 female inpatients with bulimia nervosa according to DSM III-R criteria. The control (age and sex matched) group consisted in high school students including 10 females without eating disorders, depressive disorder or immunological disease. We investigated especially natural autoantibodies reacting with compounds of the central nervous system (Dopamine, Dopamine beta Hydroxylase, Serotonin). Our first conclusion is that there is a lower level of these natural auto-antibodies among female patients with bulimia nervosa. In the second part of the study, we have especially investigated the correlation between impulsivity in bulimia nervosa and the rate of natural autoantibodies against serotonin.

[Validation study of the Depressive Experience Questionnaire]. / Etude de validation du Depressive Experience Questionnaire.

Sidney Blatt, considering as being insufficient the categorical-symptomatic approach of depression, has worked out a theory of depression and psychopathology that integrates the contributions of psychoanalysis as well as cognitive and developmental psychology. Within a broad psychoanalytic framework, Blatt's formulation focus on the quality of interpersonal relationship, the nature of object representation and early life experiences. Personality development is viewed as the consequence of the interaction of 2 basic developmental tasks: the establishment of the capacity to form stable, enduring, mutually satisfying interpersonal relationships and the achievement of a differentiated, realistic, essentially positive identity. The relationship between these 2 developmental lines involves a complex dialectical process during which progress in each line is essential for progress in the other and which contributes to the development of both a sense of identity and the capacity for interpersonal relatedness. These developmental lines permit not only to define an during individual's primary personality configuration but also enable to identify cognitive structures that are inherent in various forms of psychopathology, including depression. Disruptions at different developmental stages create vulnerability to different subsequent psychological disturbances. Blatt characterised as anaclitic or dependent the axis concerned with interpersonal relationship and as introjective or self-critical the axis concerned with development of the sense of self and identity. Depressive Experience Questionnaire was developed by Blatt et al. to determine the validity of this model of psychopathology which emphazises continuities between normal and pathological forms of depression. The instrument was developed by Blatt et al. by assembling a pool of items describing experiences frequently reported by depressed individual. Sixty-six items were selected and administered to a large nonclinical sample (500 female and 160 male undergraduates). Principal component analysis within sex performed on the answers to DEQ confirmed his assumption in identifying two principal depressive dimensions. The first factor involved items that are primarily externally directed and refer to a disturbance of interpersonal relationships (anaclitism); the second factor consists of items that are more internally directed and reflect concerns about self-identity (self-criticism). A third factor emerged, assessing the good functioning of subject and confidence in his resources and capacities (efficacy). Scales derived from these factors have high internal consistency and substantial test-retest reliability. The solutions for men and women were highly congruent. Factor structure has been replicated in several nonclinical and clinical samples, supporting considerable evidence to the construct validity of the DEQ Dependency and Self-criticism scales. An adolescent form of DEQ (DEQ-A) has successively been developed. Factor analysis revealed three factors that were highly congruent in female and male students and with the three factors of the original DEQ. The reliability, internal consistency and validity of DEQ-A indicate that the DEQ-A closely parallels the DEQ, especially in the articulation of Dependency and Self-criticism as two factors in depression. These formulations and clinical observations about the importance of differentiating a depression focused on issues of self-criticism from issues of dependency are consistent with the formulations of others theorists which, from very different theoretical perspectives, posit 2 types of depression, one in which either perceived loss or rejection in social relationships is central and the other in which perceived failure in achievement, guilt or lack of control serves as the precipitant of depression. These 2 types of experiences have been characterized as dominant other and dominant goal , as anxiously attached and compulsively self-reliant and as sociotropic and autonomous . Our work presents the results of a validation study of both forms of Blatt's questionnaire (for adults--DEQ--and for adolescents--DEQA) translated in French in a large population of normal subjects, aged 15 to 45 years. DEQ and DEQ-A were compared by inspection of items loading strongly on each factor and by correlation of the three factors of adults and adolescents. The exploratory factor analysis of DEQ and DEQA revealed three orthogonal factors, corresponding with Blatt's original dimensions. Consistency and external validity were adequate for all 3 factors of DEQ and DEQ-A. Anaclitism and self-criticism dimensions of DEQ and DEQ-A correlate positively with measures of depression (DSM-IV, Beck Depression Inventory), consistently with the results obtained by Blatt. Differently from this author, anaclitism appears to be less differentiated in males than in females, suggesting that the concept of dependence could assume different relevance for men and women.

[Manic-depressive disorders in adolescence. Mood disorders and psychoses in adolescence]. / Troubles maniaco-dépressifs à l'adolescence. Troubles de l'humeur et psychose à l'adolescence.

DISEASE ONSET: In adolescents, the different aspects of mood disorders and psychoses are closely related. The first episode of what will become schizophrenia is often suggestive of a mood disorder. The inverse is also true. Frequently, a psychotic state is the inaugural manifestation of a mood disorder. SIGNS AND SYMPTOMS: The depressive manifestations observed in adolescents are very similar to negative psychotic symptoms. More so than in adults, the thymic disorder is expressed as severe episodes of psychosis. It would appear that in this case, the psychotic elements are related to the intensity of the thymic disorder. DIAGNOSTIC ERRORS: Misdiagnosis is probably related to the fact that mood is not sufficiently taken into account in acute psychotic states. The risk inherent in "over"-diagnosis of schizophrenic disorders is related to the therapeutic implications: prescriptions of neuroleptics can hinder the psychic work involved in the structuralization process going on in the adolescent.

Treatment of adolescent patients with eating disorders: description of a psychodynamic approach in clinical practice.

Anorexia nervosa (AN) is now usually considered to be a multifactorial disorder, and there is a consensus among clinicians that its treatment should be aimed at restoring weight, altering anorexic attitudes, treating any medical complications, supporting and treating the family, enhancing autonomy, facilitating identity formation, and increasing self-esteem by means of psychotherapy. The practical aspects of such treatments not only vary from country to country, but sometimes also from one treatment team to another. International meetings dedicate considerable discussion to the subject but, as it seems to be relatively ignored in the published literature, we here describe the main elements of our own method.

Binge eating behaviours, depression and weight control strategies.

The aim of this paper was to explore the relationships between depressive symptoms and weight control strategies in DSM-IV eating disordered patients with binge eating behaviours. We hypothesised that weight control strategies characterised by a loss of control, such as vomiting and purging, may be clinically associated with increased levels of depression. The study population consisted of 402 consecutive outpatients: 27 with binge eating/purging anorexia nervosa (AN-BN), 213 with purging bulimia nervosa (BN-P), 73 with non-purging bulimia nervosa (BN-NP), and 89 with binge eating disorder (BED). The severity of depression was measured using the Beck Depression Inventory (BDI), and binge eating behaviours were investigated using the self-report scale for bulimic behaviours. In the sample as a whole, the severity of depression significantly correlated with the severity of binge eating behaviours, but no significant differences were found in the severity of depression by diagnostic sub-types. In order to avoid the confounding erasing effect of time, a smaller sample of patients with a short history of binge eating behaviours was further explored. Furthermore, because weight control strategies and the eating disorder diagnostic sub-types overlapped imperfectly, the patients were compared on the basis of presence or absence of strategies reflecting an active attempt to master the weight gain due to bingeing behaviours. The patients adopting active control strategies (N = 14) had significantly less severe depressive symptoms than those adopting non-active weight control strategies (N = 39). Finally, the Authors discuss some hypotheses concerning the defensive role of weight control strategies and the impact of illness duration on the clinical expression of depression in eating disordered patients.

Early psychopathological signs in bulimia nervosa. A retrospective comparison of the period of puberty in bulimic and control girls.

While bulimia nervosa (BN) typically begins in girls during late adolescence, puberty and associated developmental changes have been linked to negative body image and onset of a variety of psychological problems. This study aimed to identify early psychopathological signs, which could have marked the period of puberty in subjects whom later developed BN. In a case control study, we compared 49 girls with BN according to DSM-IV, aged between 18 and 20 years, to 49 girls of the same age, who were free of any past or current psychiatric diagnosis. Psychiatrists or clinical psychologists, using a semi-structured clinical interview including retrospective assessment of the emotional and behavioural changes that had occurred in puberty evaluated both groups. Before the onset of a clinical eating disorder, the subjects with BN presented significantly more often than controls weight related concerns, attitudes of withdrawal and social isolation, and negative changes in their body image and self-image, as well as in their relationships with siblings and peers. The results suggest that early psychological distress precedes the onset of an eating disorder in many cases, and that prevention efforts should be directed towards peripubertal psychopathology.