In vivo imaging of synaptic function in the central nervous system: II. Mental and affective disorders

This review gives an overview of those in vivo imaging studies on synaptic neurotransmission, which so far have been performed on patients with mental and affective disorders. Thereby, the focus is on disease-related deficiencies within the functional entities of the dopaminergic, serotonergic, cholinergic, histaminergic, glutamatergic, or GABAergic synapse. So far, in vivo investigations have yielded rather inconsistent results on the dysfunctions of specific synaptic constituents in the pathophysiology of the diseases covered by this overview. Among the more congruent results are the findings of increased synthesis (8 out of a total of 12 reports) and release of dopamine (4 out of 4 reports) in the striatum of schizophrenic patients, which supports the dopamine hypothesis of schizophrenia. Results on both dopaminergic and serotonergic neurotransmission are inconsistent in both major depressive disorder and bipolar illness, and fail to clearly agree with the dopamine and/or serotonin hypothesis of depression. The majority of in vivo findings suggest no alterations (25 out of a total of 50 reports on serotonin synthesis, transporter as well as receptor binding) rather than a deficiency (merely 13 out of these 50 reports) of cortical serotonergic neurotransmission in major depression, whereas a decrease of cortical serotonergic neurotransmission (3 out of a total on 5 reports) can be assumed in bipolar illness. In borderline personality disorder, an increased binding of serotonin transporter binding was observed (merely 1 report). Due to the limited evidence, this result only with due caution may be interpreted as an indication for increased availability of serotonin in the synaptic cleft. Patients with Tourette syndrome exhibited increases of DAT binding in the neostriatum (5 out of 10 reports) increases of dopamine storage and dopamine release in the ventral striatum (1 report, each). Moreover, striatal D2 receptor binding was found to be decreased in advanced stages of the disease. Results, tentatively, may be interpreted in terms of an increased dopaminergic neurotransmission in the mesolimbic system. There is limited evidence of decreased dopamine synthesis in both children and adults with attention-deficit/hyperactivity disorder (4 out of a total of 10 reports). These findings as well as the reduction of striatal dopamine release observed in adults (merely 1 report) are in line with the notion of mesocortical dopaminergic hypofunction in attention-deficit/hyperactivity disorder. Thereby, however, in children, results on dopamine synthesis indicate a deficiency in the ventral tegmentum rather than in the prefrontal cortex, whereas, with increasing age, the prefrontal cortex rather than the sites of origin of DAergic innervation become predominantly affected (merely 1 report, each). In anxiety disorders, varying results have been obtained for both pre- and/or postsynaptic dopaminergic, serotonergic and GABAergic binding sites. Thereby, results on posttraumatic stress disorder are homogenous reporting a decrease of GABA A receptor binding in all investigated brain regions including striatum, thalamus, neocortex and limbic system (2 out of 2 reports, each). Moreover, patients with obsessive-compulsive disorder displayed increases of dopamine transporter binding (2 out of 4 reports) and decreases of both D1 (merely 1 report) and D2 receptor binding (4 out of 5 reports), respectively. These findings, tentatively, may be interpreted in terms of an increased availability of synaptic dopamine in the neostriatum, which is compensated for both pre- and postsynaptically by increasing dopamine reuptake into the presynaptic terminal, and decreasing (inhibitory) signal transduction of efferent fibers. The observed reduction of GABA A receptor binding in frontocortical neurons (in 11 out of a total of 21 reports on anxiety disorders) is in line with this assumption. The inconsistency (and, partially, also incompleteness) of in vivo findings on mental and affective disorders constitutes a major result of this overview. Discrepancies indicate that the regulation state of synaptic constituents may not only vary between the subtypes of disorders but also between subject cohorts and, even, individual patients depending on variables such as the predominance of symptoms, medication status or onset and duration of disease. This, for the time being, limits the application of in vivo imaging methods for differential diagnosis of mental and affective disorders. In vivo imaging results on anxiety disorders, however, are of possible interest with regard to psychoanalysis, as they offer a neurochemical correlate for Freud's theories on the pathogenesis of anxiety- and compulsion-related disorders.