Olivier Halfon

Anxiety disorders in subjects seeking treatment for eating disorders: a DSM-IV controlled study

Women who were referred with an eating disorder (ED) were compared with a matched normal control group to answer the following questions: What are the frequencies of anxiety disorders in cases of anorexia and bulimia nervosa diagnosed according to DSM-IV criteria? Are anxiety disorders significantly more frequent among women with an eating disorder than among women from the community? We assessed the frequencies of six specific anxiety disorders among 271 women with a current diagnosis of anorexia or bulimia nervosa and 271 controls, using the Mini-International Neuropsychiatric Interview, French DSM-IV version. A lifetime comorbidity with at least one anxiety disorder was found in 71% of both the anorexic and the bulimic subjects, significantly higher than the percentage of controls with an anxiety disorder. The prevalence was significantly higher in the eating disorder groups than in controls for most types of anxiety disorder, and between 41.8 and 53.3% of comorbid cases had an anxiety disorder preceding the onset of the eating disorder. Anxiety disorders are significantly more frequent in subjects with eating disorders than in volunteers from the community, a finding that has important etiological and therapeutic implications.

TORC1 is a calcium- and cAMP-sensitive coincidence detector involved in hippocampal long-term synaptic plasticity

A key feature of memory processes is to link different input signals by association and to preserve this coupling at the level of synaptic connections. Late-phase long-term potentiation (L-LTP), a form of synaptic plasticity thought to encode long-term memory, requires gene transcription and protein synthesis. In this study, we report that a recently cloned coactivator of cAMP-response element-binding protein (CREB), called transducer of regulated CREB activity 1 (TORC1), contributes to this process by sensing the coincidence of calcium and cAMP signals in neurons and by converting it into a transcriptional response that leads to the synthesis of factors required for enhanced synaptic transmission. We provide evidence that TORC1 is involved in L-LTP maintenance at the Schaffer collateral–CA1 synapses in the hippocampus.

Depressive personality dimensions and alexithymia in eating disorders

An association has been reported between high levels of alexithymia and depression in patients with eating disorders. This study has examined alexithymic features and depressive experiences in patients with DSM-IV eating disorder (restricting anorexia, n=105; purging anorexia, n=49; bulimia, n=98) and matched controls (n=279). The subjects were assessed with the Toronto Alexithymia Scale (TAS-20); the Beck Depression Inventory; and the Depressive Experiences Questionnaire, which defines two types of depressive personality style (dependent and self-critical). The patients had high levels of alexithymic features and depressive symptoms. Comparisons of alexithymic features between patients and controls after adjustment for depression showed a significant difference between bulimic patients and controls for the TAS Difficulty Identifying Feelings factor, and between restricting anorexic patients and controls for the TAS Difficulty Describing Feelings factor. With regard to depressive personality styles, only scores on the self-critical dimension were significantly higher in bulimic patients than in restricting anorexic patients and controls. In the entire group of eating disorders, dependency was associated with the TAS Difficulty Identifying Feelings factor only in anorexic patients. Self-criticism, on the other hand, was associated with the TAS Difficulty Identifying Feelings factor in all subtypes of eating disorders, although the relationship was significantly stronger in restricting anorexic than in bulimic patients. The results of this study suggest that people with restricting anorexia and bulimia show specific clinical profiles associating alexithymic features and depressive dimensions.

Parent-child agreement and prevalence estimates of diagnoses in childhood: direct interview versus family history method.

Diagnostic information on children is typically elicited from both children and their parents. The aims of the present paper were to: (1) compare prevalence estimates according to maternal reports, paternal reports and direct interviews of children [major depressive disorder (MDD), anxiety and attention‐deficit and disruptive behavioural disorders]; (2) assess mother–child, father–child and inter‐parental agreement for these disorders; (3) determine the association between several child, parent and familial characteristics and the degree of diagnostic agreement or the likelihood of parental reporting; (4) determine the predictive validity of diagnostic information provided by parents and children. Analyses were based on 235 mother–offspring, 189 father–offspring and 128 mother–father pairs. Diagnostic assessment included the Kiddie‐schedule for Affective Disorders and Schizophrenia (K‐SADS) (offspring) and the Diagnostic Interview for Genetic Studies (DIGS) (parents and offspring at follow‐up) interviews. Parental reports were collected using the Family History – Research Diagnostic Criteria (FH‐RDC). Analyses revealed: (1) prevalence estimates for internalizing disorders were generally lower according to parental information than according to the K‐SADS; (2) mother–child and father–child agreement was poor and within similar ranges; (3) parents with a history of MDD or attention deficit hyperactivity disorder (ADHD) reported these disorders in their children more frequently; (4) in a sub‐sample followed‐up into adulthood, diagnoses of MDD, separation anxiety and conduct disorder at baseline concurred with the corresponding lifetime diagnosis at age 19 according to the child rather than according to the parents. In conclusion, our findings support large discrepancies of diagnostic information provided by parents and children with generally lower reporting of internalizing disorders by parents, and differential reporting of depression and ADHD by parental disease status. Follow‐up data also supports the validity of information provided by adolescent offspring. Copyright

Deletion of CREB-regulated transcription coactivator 1 induces pathological aggression, depression-related behaviors, and neuroplasticity genes dysregulation in mice.

BACKGROUND Mood disorders are polygenic disorders in which the alteration of several susceptibility genes results in dysfunctional mood regulation. However, the molecular mechanisms underlying their transcriptional dysregulation are still unclear. The transcription factor cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and the neurotrophin brain-derived neurotrophic factor (BDNF) have been implicated in rodent models of depression. We previously provided evidence that Bdnf expression critically rely on a potent CREB coactivator called CREB-regulated transcription coactivator 1 (CRTC1). METHODS To further evaluate the role of CRTC1 in the brain, we generated a knockout mouse line and analyzed its behavioral and molecular phenotype. RESULTS We found that mice lacking CRTC1 associate neurobehavioral endophenotypes related to mood disorders. Crtc1(-/-) mice exhibit impulsive aggressiveness, social withdrawal, and decreased sexual motivation, together with increased behavioral despair, anhedonia, and anxiety-related behavior in the novelty-induced hypophagia test. They also present psychomotor retardation as well as increased emotional response to stressful events. Crtc1(-/-) mice have a blunted response to the antidepressant fluoxetine in behavioral despair paradigms, whereas fluoxetine normalizes their aggressiveness and their behavioral response in the novelty-induced hypophagia test. Crtc1(-/-) mice strikingly show, in addition to a reduced dopamine and serotonin turnover in the prefrontal cortex, a concomitant decreased expression of several susceptibility genes involved in neuroplasticity, including Bdnf, its receptor TrkB, the nuclear receptors Nr4a1-3, and several other CREB-regulated genes. CONCLUSIONS Collectively, these findings support a role for the CRTC1-CREB pathway in mood disorders etiology and behavioral response to antidepressants and identify CRTC1 as an essential coactivator of genes involved in mood regulation.

Child care in the preschool years: Attachment, behaviour problems and cognitive development

The possible implications of the experience of non parental care on cognitive development and on behaviour problems are considered in interaction with individual and contextual variables. A sample of 47 Swiss children who experienced varying kinds of care arrangements were studied longitudinally between 1 and 5 years of age. The effects of the experience of care were related to mothers’ reports of behavioral problems (CBCL, with subscales of internalizing and of externalizing problems) at age 5, and to cognitive developmental quotients (at 1, 2 and 5 years). Several variables were considered for their potential interaction with the experience of care, such as the pattern of attachment to the mother (observed at 21 months of age in the “Strange Situation”), characteristics of the experience of care (duration and type of care), its quality (relationship with non parental caregivers), the socio-economic status of the family, etc. The effect of non parental care on behaviour problems (5 years) happened to be mediated by the the pattern of attachment to the mother: insecurely attached children had some risk to be reported as having externalizing problems, but this didn’t occur when they had an extended experience of non parental care, and when non parental care was mainly family-based. The effect of non parental care on cognitive development was mediated by the quality of care: children with a positive contact with the caregivers had greater cognitive gains between 2 and 5 years; the relationship with the care-givers itself was influenced by the quality of the relationship with the mother. The limited size and origin of the sample restricts generalization, however these data might contribute to the notion that non parental care can have varying effects depending of the type of care, the quality of the relation with the caregivers, the age and personal traits of the child.RésuméUn échantillon de 47 enfants suisses ayant connu différents types de garde non-parentale a fait l’objet d’une étude longitudinale entre les âges de un et cinq ans. Les effets des modes de garde ont été appréhendés à cinq ans à partir des problèmes de comportement rapportér par les mères (échelle CBCL) et des quotients de développement cognitifs établis à un, deux et cinq ans. Plusieurs variables ont été prises en compte du fait de leur liaison éventuelle avec l’expérience de garde: pattern d’attachement à la mère (observé à 21 mois), durée, type et qualité (relations avec les gardiennes) de la prise en charge, statut socio-économique de la famille, etc. L’effet de la garde sur le problèmes comportementaux varient en fonction du pattern d’attachement à la mère. L’ effet sur le développement cognitif dépend la qualité de la relation avec les gardiennes, cette dernière dépendant elle-même de la qualtté de la relation à la mère.

Adult attachment representations predict cortisol and oxytocin responses to stress

There are many factors contributing to individual variations in the response to stressful experiences. The present study evaluated the patterns of stress responses according to attachment representations in 28 adults from a community sample, plus 46 subjects expected to be particularly sensitive to stress, having been exposed during childhood and/or adolescence to traumatizing events such as abuse or potentially lethal illnesses. Subjects were given the Adult Attachment Interview, which provides attachment classifications, and the Trier Social Stress Test (TSST), involving an experimental psychosocial challenge. Subjective responses to the TSST, as well as saliva samples (assayed for cortisol) and blood plasma samples (assayed for ACTH and oxytocin) were collected before, during and after the stress procedure. The stress responses presented specific patterns according to attachment classifications. Subjects with an autonomous attachment classification reported relatively low subjective stress, they presented a moderate response of the hypothalamic-pituitary-adrenal (HPA) axis (ACTH and cortisol), and a high level of oxytocin. Subjects with a dismissing classification reported a moderate subjective stress, they presented an elevated response of the HPA axis, and moderate levels of oxytocin. Subjects with a preoccupied classification presented moderate levels of subjective stress, and of HPA response, and a relatively low level of oxytocin. Finally, subjects with an unresolved classification reported elevated subjective stress; they presented a suppressed HPA response, and moderate levels of oxytocin. These data support the notion that attachment representations may affect stress responses, and suggest a specific role of oxytocin in both the attachment system and the stress system.

Alexithymia, Depressive Experiences, and Dependency in Addictive Disorders

Alexithymia, depressive feelings, and dependency are interrelated dimensions that are considered potential “risk factors” for addictive disorders. The aim of this study was to investigate the relationships between these dimensions and to define a comprehensive model of addiction in a large sample of addicted subjects, whether affected by an eating disorder or presenting an alcohol- or a drug use-related disorder. The participants in this study were gathered from a multicenter collaborative study on addictive behaviors conducted in several psychiatric departments in France, Switzerland, and Belgium between January 1995 and March 1999. The clinical sample was composed of 564 patients (149 anorexics, 84 bulimics, 208 alcoholics, 123 drug addicts) of both genders with a mean age of 27.3 ± 8 years. A path analysis was conducted on the 564 dependent patients and 518 matched controls using the scores of the Toronto Alexithymia Scale, the Depressive Experiences Questionnaire, and the Interpersonal Dependency Inventory. Statistical analyses showed good adjustment (Goodness of Fit Index = 0.977) between the observable data and the assumed model, thus supporting the hypothesis that a depressive dimension, whether anaclitic or self-critical, can facilitate the development of dependency in vulnerable alexithymic subjects. This result has interesting clinical implications because identifying specific patterns of relationships leading from alexithymia to dependency can provide clues to the development of targeted strategies for at-risk subjects.

Party drug use in techno nights: A field survey among French-speaking Swiss attendees

This study was designed to investigate the lifestyle and substance use habits of dance music event attendees together with their attitudes toward prevention of substance misuse, harm reduction measures and health-care resources. A total of 302 attendees aged 16-46 years (mean=22.70, S.D.=4.65) were randomly recruited as they entered dance music events. Rates for lifetime and current use (last 30 days) were particularly high for alcohol (95.3% and 86.6%, respectively), cannabis (68.8% and 53.8%, respectively), ecstasy (40.4% and 22.7%, respectively) and cocaine (35.9% and 20.7%, respectively). Several patterns of substance use could be identified: 52% were alcohol and/or cannabis only users, 42% were occasional poly-drug users and 6% were daily poly-drug users. No significant difference was observed between substance use patterns according to gender. Pure techno and open-air events attracted heavier drug users. Psychological problems (such as depressed mood, sleeping problems and anxiety attacks), social problems, dental disorders, accidents and emergency treatment episodes were strongly related to party drug use. Party drug users appeared to be particularly receptive to harm reduction measures, such as on-site emergency staff, pill testing and the availability of cool water, and to prevention of drug use provided via counseling. The greater the involvement in party drug use, the greater the need for prevention personnel to be available for counseling. General practitioners appeared to be key professionals for accessing health-care resources.

Mental disorders in offspring of parents with bipolar and major depressive disorders

Vandeleur C, Rothen S, Gholam‐Rezaee M, Castelao E, Vidal S, Favre S, Ferrero F, Halfon O, Fumeaux P, Merikangas KR, Aubry J‐M, Burstein M, Preisig M. Mental disorders in offspring of parents with bipolar and major depressive disorders. Bipolar Disord 2012: 14: 641–653.