SYNOPSISVarious factors are discussed in the pathophysiology of anxiety disorders, including dysfunctions of the (DA)ergic, serotonin(5-HT)ergic and GABAergic system. We assessed the contribution of the individual synaptic constituents by subjecting all available in vivo imaging studies on patients with anxiety disorders to a retrospective analysis. On a total of 504 patients with obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD), panic disorder (PD), phobia, or posttraumatic stress-disorder (PTSD) and 593 controls, investigations of VMAT2, DAT, SERT, D,, D 2 , 5-HT,A, 5-HT 2A , GABA A , and NK1 receptor binding in neostriatum, ventral striatum, thalamus, neocortex, limbic system, cingulate, midbrain/ pons or cerebellum were performed using either PET or SPECT.
Separate analyses of the individual disorders showed significant decreases of striatal D 2 receptors in OCD (-18%), mesencephaiic SERT in OCD (-13%), frontocortical GABA A receptors in PD (-13%) and temporocortical GABA A receptors in GAD (-16%). Pooling of all disorders yielded a significant reduction of mesencephaiic SERT (-13%), mesencephaiic (-27%) as well as cingulate 5-HTi A receptors (-18%), striatal D 2 receptors (-21%) and frontal (-14%), temporal (-14%), occipital (-13%) andcingulate GABAA receptors (-15%). The results show that DA, 5-HT, and GABA play a major role in all subtypes of anxiety disorders. In particular, the findings imply that the regulation state of DA as modulated by GABA and 5-HT may be crucial for the development of anxietyand compulsion-related disorders. As GABA and 5-HT inhibit DAergic neurotransmission, the reductions of GABAA, 5-HT 1A and SERT can be assumed to result in an enhanced activity of the mesolimbic DAergic system. This notion is also reflected by the decrease of striatal D2 receptor binding, which is indicative of an increased availability of synaptic DA.
