مطالعه مقدماتی مهار دوپامین واسطه پرولاکتین در هراس اجتماعی عمومی
|کد مقاله||سال انتشار||مقاله انگلیسی||ترجمه فارسی||تعداد کلمات|
|30679||2002||صفحه PDF||سفارش دهید||محاسبه نشده|
Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)
Journal : Psychiatry Research, Volume 111, Issue 1, 5 August 2002, Pages 87–92
The biology of social phobia has been little studied, but a possible role for dopamine has been implicated in this disorder. The aim of this study was to examine central dopaminergic function in patients with generalised social phobia using the prolactin response to quinagolide, a dopamine D2 receptor agonist, and to compare responses with those of normal controls. The study included 14 patients with moderate or severe generalised social phobia and 14 healthy age- and gender-matched comparison subjects. Quinagolide (0.5 mg) was administered orally and prolactin responses were measured over 4 h. There was no significant difference between prolactin responses in patients and healthy controls, nor was there a correlation between prolactin response and age, sex, or severity of illness. This would suggest that tuberoinfundibular dopamine D2 receptor sensitivity is normal in this disorder.
Social phobia, also known as social anxiety disorder, is a common psychiatric disorder, which results in significant distress and social disability (Stein, 1998). It is characterized by a persistent fear of situations in which the individual may be exposed to the scrutiny of others, and in which he or she may act in a way that is humiliating or embarrassing (American Psychiatric Association, 1994). Social phobia has been subdivided into two types, generalised social phobia characterised by fear and/or avoidance of most social situations (American Psychiatric Association, 1994) and ‘specific’ or ‘discrete’ social phobia, the former subtype being associated with the most severe disability (Brunello et al., 2000). Despite 2–10% of the population being affected by this disorder (Myers et al., 1984, Davidson et al., 1994, Kessler et al., 1994 and Stein et al., 1994), its biology has been little studied. Investigators have implicated a possible role for dysfunction of the serotonin, noradrenaline or GABA neurotransmitter systems (for reviews, see Stein, 1998 and Bell et al., 1999). However, findings from such studies are by no means conclusive. Dopamine has also been implicated. Evidence for an association of social phobia with subnormal transmission in the dopamine system includes the clinical effectiveness of monoamine oxidase inhibitors but not tricyclic antidepressants (Liebowitz et al., 1987a), a report of the dopamine and noradrenaline reuptake inhibitor buproprion being used successfully in this disorder (Emmanuel et al., 1991), low cerebrospinal fluid levels of homovanillic acid among panic disorder patients with comorbid social phobia (Johnson et al., 1994), a high rate of social phobia among patients with comorbid Parkinson's disease (Stein et al., 1990) and increased symptoms of social phobia in patients suffering with Tourette's syndrome when treated with haloperidol (Mikkelsen et al., 1981). In addition, recent studies using single photon emission computed tomography (SPECT) have also implicated a possible role for this monoaminergic system in patients with social phobia. Tiihonen et al. (1997) noted markedly reduced striatal dopamine reuptake site densities in patients with social phobia in comparison to controls and speculated that this may be due to a smaller number of dopamine synapses (and neurons) or fewer dopamine reuptake sites per neuron. Schneier et al. (2000) subsequently found decreased striatal D2 receptor binding potential in these patients. However, Mathew et al. (2001) have concluded that SPECT studies of the dopamine transporter and D2 receptor in the striatum thus far are inconclusive in confirming a hypothesis of low dopamine innervation in this disorder. To complement these studies, we attempted to examine the functional activity of dopamine D2 receptors using a neuroendocrine challenge. Plasma levels of prolactin reflect a balance between stimulation via serotonin and inhibition via dopamine. The dopamine inhibition is at the level of the pituitary (Lamberts and Macleod, 1990). The facts that dopamine receptors on the lactotrophic cells of the anterior pituitary are activated humorally via dopamine circulating in the portal vessels, and not at limited synaptic contact areas with comparatively high local dopamine concentrations, apparently results in a particularly high receptor sensitivity (Wachtel, 1991). Quinagolide is an octahydrobenzo[g]quinoline with highly specific dopamine D2 agonist properties (Closse et al., 1988) which inhibits prolactin release (Gaillard and Brownell, 1988). This drug is used in the treatment of hyperprolactinemia and prolactinoma (Nobels et al., 2000, Rohmer et al., 2000 and Schultz et al., 2000). To the authors’ knowledge, it has not previously been used as a neuroendocrine probe in any psychiatric disorder. The dopamine agonist-induced decline of serum prolactin levels represents a sensitive functional test in vivo, which in humans responds to extremely low doses of dopamine agonists (Wachtel, 1991). An augmented decline in prolactin levels would therefore suggest hypersensitivity of D2 receptors; a diminished decline would reflect subsensitivity. The aim of this study was to examine central dopaminergic function in patients with generalised social phobia using prolactin responses to quinagolide and to compare them with those of normal controls.