Increasing Attention Has Provided Information

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26/01/2005 - Increasing attention has provided information about social phobia - Neuroscience

2005 JAN 28 - -- The neurobiology and pharmacotherapy of social phobia were the focus of a recent report.

NewsRxGenomicsGenetics via NewsEdge Corporation : 2005 JAN 28 - (NewsRx.com & NewsRx.net) -- The neurobiology and pharmacotherapy of social phobia were the focus of a recent report.

According to the report from France, "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."

B. Aouizerate and colleagues of the University Victor-Segalen, Bordeaux continued, "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 (e.g., 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," the scientists observed.

"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," they added.

"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 5HT(1A) and 5HT(2) serotonin receptor subtypes, as reflected by increased anxiety and hormonal responses to serotoninergic probes," the researchers reported.

"Platelet 5HT(2) 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 alpha2-adrenergic agonist, was reported. This suggests reduced post-synaptic alpha2-adrenergic receptor functioning related to norepinephrine overactivity in social phobia," they noted.

The authors continued, "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 D-2 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," noted Aouizerate and colleagues.

"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," they observed.

"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," the authors reported.

"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," the scientists said.

They continued, "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," noted the authors.

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 2 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," they cautioned.

The researchers added, "Beta-blockers such as atenolol and propanolol have commonly been employed in performance anxiety, decreasing autonomic symptoms (e.g., 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."

They concluded, "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."

Aouizerate and colleagues published their report in Encephale - Revue de Psychiatrie Clinique Biologique Et Therapeutique (Neurobiology and pharmacotherapy of social phobia. Encephale, 2004;30(Suppl. S):301-313).

For additional information, contact B. Aouizerate, University Bordeaux 2, Center Hospital Charles Perrens, Center Carreire, Service Psychiatry Adultes, 121, Rue Bechade, F-33076 Bordeaux, France.

The publisher of the journal Encephale - Revue de Psychiatrie Clinique Biologique Et Therapeutique can be contacted at: Masson Editeur, 21 Street Camille Desmoulins, Issy, 92789 Moulineaux Cedex 9, France.

The information in this article comes under the major subject areas of Cortico-limbic Pathways, Monoaminergic Neurotransmitter Systems, Selective Serotonin Reuptake Inhibitors, Social Phobia, Mental Health, Neurology, Neuroscience, Pharmaceutical & Drug Development, Genetic Disorders and Therapy.

This article was prepared by Genomics & Genetics Weekly editors from staff and other reports. Copyright 2005, Genomics & Genetics Weekly via NewsRx.com & NewsRx.net.