[Neurobiology and pharmacotherapy of social phobia]. / Neurobiologie et pharmacothérapie de la phobie sociale.

Social phobia (also known as social anxiety disorder) is still not clearly understood. It was not established as an authentic psychiatric entity until the diagnostic nomenclature of the American Psychiatric Association DSM III in 1980. In recent years, increasing attention among researchers has contributed to provide important information about the genetic, familial and temperamental bases of social phobia and its neurochemical, neuroendocrinological and neuroanatomical substrates, which remain to be further investigated. Up to date, there have been several findings about the possible influence of variables, including particularly genetic, socio-familial and early temperamental (eg behavioral inhibition) factors that represent risk for the later development of social phobia. Clinical neurobiological studies, based on the use of exogenous compounds such as lactate, CO2, caffeine, epinephrine, flumazenil or cholecystokinin/pentagastrin to reproduce naturally occurring phobic anxiety, have shown that patients with social phobia appear to exhibit an intermediate sensitivity between patients with panic disorder and control subjects. No difference in the rate of panic attacks in response to lactate, low concentrations of CO2 (5%), epinephrine or flumazenil was observed between patients with social phobia and normal healthy subjects, both being less reactive compared to patients with panic disorder. However, patients with social phobia had similar anxiety reactions to high concentrations of CO2 (35%), caffeine or cholecystokinin/pentagastrin than those seen in patients with panic disorder, both being more intensive than in controls. Several lines of evidence suggest specific neurotransmitter system alterations in social phobia, especially with regard to the serotoninergic, noradrenergic and dopaminergic systems. Although no abnormality in platelet serotonin transporter density has been found, patients with social phobia appear to show an enhanced sensitivity of both post-synaptic 5HT1A and 5HT2 serotonin receptor subtypes, as reflected by increased anxiety and hormonal responses to serotoninergic probes. Platelet 5HT2 receptor density has also been reported to be positively correlated to symptom severity in patients with social phobia. During anticipation of public speaking, heart rate was elevated in patients with social phobia compared to controls. Norepinephrine response to the orthostatic challenge test or to the Valsalva maneuver was also greater in patients with social phobia. While normal beta-adrenergic receptor number was observed in lymphocytes, a blunted response of growth hormone to clonidine, an a2-adrenergic agonist, was reported. This suggests reduced post-synaptic a2-adrenergic receptor functioning related to norepinephrine overactivity in social phobia. Decreased cerebrospinal fluid levels of the dopamine metabolite homovanillic acid have also been observed. There are relatively few reports of involvement of the adrenal and thyroid functions in social phobia, and all that has been noted is that patients with social phobia show an exaggerated adrenocortical response to a psychological stressor. Recent advances in neuro-imaging have contributed to find low striatal dopamine D2 receptor binding or low dopamine transporter site density in patients with social phobia. They have also demonstrated the involvement of the cortico-limbic pathways, including the prefrontal cortex, hippocampus and amygdala, which show an increased activity in different experimental conditions. These brain regions have extensively been reported to play an important role in the cognitive appraisal in determining the significance of environmental stimuli, in the emotional and mnemonic integration of information, and in the expression of contextual fear-conditioned behaviors, which might be disrupted in the light of the phenomelogical aspects of social phobia. A substantial body of literature based on case reports, open and placebo-controlled trials, has now clearly examined the efficacy of major classes of psychotropic agents including monoamine oxidase inhibitors, beta-blockers, selective serotonin reuptake inhibitors and benzodiazepines in social phobia. Until recently, irreversible non-selective monoamine oxidase inhibitors, of which phenelzine was the most extensively evaluated, were considered as the most efficacious treatment in reducing the symptomatology associated with social phobia in 50-70% of cases after 4 to 6 weeks. However, side effects and dietary restrictions limit their use. This led to the development of reversible inhibitors of monoamine oxidase A, for which careful dietary monitoring is not required. Moclobemide has been the most widely studied but produced unconvincingly therapeutic effects on social phobic symptoms. To date, selective serotonin reuptake inhibitors may be considered as a reasonable first-line pharmacotherapy for social phobia. There is growing evidence for the efficacy of the selective serotonin reuptake inhibitors fluvoxamine, fluoxetine, citalopram, paroxetine and sertraline. They have beneficial effects with response rates ranging from 50 to 80% in social phobia. It has been recommended that the treatment period should be extended at least 6 months beyond the early improvement achieved within the first 4 to 6 weeks. The overall advantages include tolerability with a low risk of adverse events. The benzodiazepines clonazepam and alprazolam have also been proposed for the treatment of social phobia. Symptomatic relief occurred in 40 to 80% of the cases with a relatively rapid onset of action within the first two weeks. Untoward effects, discontinuation-related withdrawal symptoms and abuse or dependence liability constitute major concerns about the use of benzodiazepines, so they should be reserved for cases unresponsive to the safer medications cited above. Beta-blockers such as atenolol and propanolol have commonly been employed in performance anxiety, decreasing autonomic symptoms (eg, tachycardia, sweating and dry mouth). However, they are not effective in the generalized form of social phobia. Other pharmacologic alternatives seem helpful for the management of social phobia, including venlafaxine, gabapentin, bupropion, nefazodone or augmentation with buspirone. Preliminary studies point to promising effects of these agents. Larger controlled clinical trials are now needed to confirm their potential role in the treatment of social phobia.

[Prevalence of depressive disorders in children and adolescents attending primary care. A survey with the Aquitaine Sentinelle Network]. / Prévalence des troubles dépressifs chez l'enfant et l'adolescent consultant en médecine générale.

UNLABELLED: Since depressive disorders in children and adolescents have not been widely studied in the context of gene-ral medicine, we conducted an epidemiological survey among general practitioners (GP's) consulted by young subjects aged 7 to 17 years for various reasons. OBJECTIVE: The aims were the following: to estimate the prevalence of depressive disorders in general practice, to detect the eventual existence of particular clinical forms, to assess the frequency of comorbid disorders and to determine to what degree these disorders were diagnosed by GP's. METHOD: The study was conducted over 6 months in concert with 45 practitioners of the Aquitaine Sentinelle Network because of their strong experience in the field of epidemiological surveys, especially regarding psychiatric disorders. The population included all consecutive attenders aged 7 to 17 years. Consent to participate was obtained from children and adolescents and their parents. Finally 155 patients took part. A two-stage epidemiologic strategy was used, including screening tests in the first stage and semi structured interview by clinician in the second stage for diagnostic confirmation. During the first stage, information was obtained from children and adolescents and general practitioners using three questionnaires. The self-report questionnaire Center for Epidemiological Studies Depression (CES-D) was used for screening depression in 13 to 17 years old adolescents and the 20 items of the scale were modified to make it more comprehensible and relevant for children aged 7 to 12. The cut-off of 21 used in France appeared to be the more appropriate in both males and females and was taken to indicate high likelihood of depressive disorder. Therefore people with score 21 or more were approached for the second stage. The Child Behavior Checklist (CBCL), an instrument of well-established validity and reliability, provided information from parents about the child's behavior and competencies. Demographic and environmental data, as well as the reason for the visit and the presence of associated psychological factors were collected from a questionnaire devised for the study and completed by the practitioner. The 21 patients initially detected were invited to take part in the second stage. A total of 18 agreed to meet the psychiatrist. Sex-ratio female/male of this sample was 1,25 and mean age was 12,5 years. All of them underwent the Schedule for Affective Disorders and Schizophrenia for School Aged Children (Kiddie-SADS), a semi structured research interview of established validity. Diagnoses were made according to the DSM IV criteria (American Psychiatric Association). RESULTS: Results showed that more than one child out of 10 aged less than 13 years had a depressive disorder, and that the prevalence in the adolescent sub-group was 5%. Major depressive episode was present in 6% of the children sample, dysthymia in 4% and maladjustment disorder with depressive mood in about 1%. All depressive disorders were moderate. Atypical depression (in the Anglosaxon sense of the term) was present in half of the depressed adolescents. Other disorders included anxiety disorders with a rate of about 4% overanxious in the adolescent sample, obsessive compulsive disorder, panic disorder. Disruptive disorders were considerably less common. Psychiatric comorbidity, usually involving different types of emotional disorders, was present in about 50% of psychiatric cases, with a prevalence of anxiety disorders. The reasons why depressed subjects consulted were not specific. The most common reasons for visiting the GP were the somatic complaints with a rate of 50% in both populations, whatever the CES-D's score was. A few per cent of patients attending primary care presented with mental health complaints, and the rate was similar in the two populations. Frequency of consultation was not a discriminant factor of depression. Familial cohesion and school performance were not associated with the CES-D's score, nor familial psychiatric history. Personal psychiatric history was related to depression, whereas the occurrence of bereavement made the CES-D score positive but was not significantly associated with fully- blown depression. Finally, we estimated that 70% of diagnoses of depression were not made during the consultation with GP's. CONCLUSION: No particular characteristic of depressed children consulting GP's could be established. These findings underline the importance of training GP's in the screening of depressive disorders in children and adolescents. A better knowledge that young general practice attenders have high rates of depressive disorders may facilitate more rapid referral for psychiatric assessment and treatment.