ABSTRACT
Considerable progress has been achieved over the past 15 years in uncovering the biological basis of major psychiatric disorders. To determine patterns of brain dysfunction and to uncover the mechanism of action of centrally active compounds we used single photon emission computerized tomography (SPECT) as well as positron emission tomography (PET) in patients diagnosed with schizophrenia, depression, bulimia and Tourette's disorder. Striatal D2 and 5-HT1A receptors were studied in schizophrenia and 5-HT transporters (5-HTT) in depression and bulimia. Patients were either drug-naïve or drug free, or we studied the influence of specifically acting compounds on receptor/transporter occupancy. We could demonstrate that atypical antipsychotics have a dose-dependent (with the exception of clozapine and quetiapine) lower striatal D2 receptor occupancy rate compared with typical neuroleptics, paralleling the more favourable extrapyramidal side effects of atypical antipsychotics. However, no association between striatal D2 receptor occupancy rates and antipsychotic efficacy has been found. The measurement of 5-HT1A receptors in drug-naïve schizophrenic patients using the in vivo PET methodology revealed an increase of cortical 5-HT1A receptor binding potential in schizophrenia. beta-CIT as a ligand for measurement of 5-HT transporter densities (5-HTT) revealed lower rates in depression compared to age- and sex-matching healthy controls, a measurement that has also been obtained for bulimia. We also documented seasonal variations in brain serotonergic function by our finding of reduced brain 5-HTT availability in winter (compared to summer) in healthy controls. Furthermore, displaceable [123I] beta-CIT binding in the area corresponding to the left striatum (representing predominantly the density of dopamine transporters) was significantly reduced in SAD patients compared to healthy controls. In depression as well as in bulimia, selective serotonin reuptake inhibitors significantly decreased the beta-CIT binding potential, however, no significant dose relationship has been obtained in depression. Genotyping depressed patients for the serotonin transporter promoter gene region (5-HTTLPR) did not provide evidence for in vivo functional regulation of 5-HTT availability by 5-HTTLPR in the thalamus-hypothalamus and mesencephalon-pons of healthy subjects. In patients suffering from Tourette's disorder (TD) we were unable to detect differences of dopamine transporter densities between psychotropic drug-naïve TD patients and controls. Furthermore, no difference could be found between currently treated (with antipsychotics) and psychotropic drug-naïve TD patients. Our data provide insight into the pathophysiology of neuropsychiatric disorders and may guide future psychopharmacological drug developments.
Subject(s)
Antidepressive Agents/therapeutic use , Antipsychotic Agents/therapeutic use , Brain/metabolism , Bulimia , Bulimia/metabolism , Carrier Proteins/metabolism , Depressive Disorder, Major , Membrane Glycoproteins/metabolism , Membrane Transport Proteins/metabolism , Nerve Tissue Proteins , Receptors, Dopamine/metabolism , Receptors, Serotonin/metabolism , Schizophrenia , Tourette Syndrome , Bulimia/drug therapy , Bulimia/genetics , Corpus Striatum/metabolism , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/genetics , Depressive Disorder, Major/metabolism , Dopamine Plasma Membrane Transport Proteins , Humans , Promoter Regions, Genetic/genetics , Schizophrenia/diagnostic imaging , Schizophrenia/drug therapy , Schizophrenia/genetics , Seasons , Serotonin Plasma Membrane Transport Proteins , Tomography, Emission-Computed , Tomography, Emission-Computed, Single-Photon , Tourette Syndrome/drug therapy , Tourette Syndrome/genetics , Tourette Syndrome/metabolismABSTRACT
Transcranial magnetic stimulation (TMS) has been a well-established diagnostic tool in neurological practice for many years. It has been shown to be a safe and well tolerated method. Lately this technique has also found its way to psychiatry for the treatment of mood disorders. Several studies which investigated TMS of deeper brain regions found antidepressive effects in analogy to electro convulsive therapy (ECT). This could present a significant advantage, because TMS provides non-invasive and painless stimulation of the cerebral cortex. The method is based on the principle that a time-varying magnetic field induces an electric field which leads to activation of inhibitory and excitatory neurons in neural tissue. The magnetic field pervades the intact scalp and skull without loss of energy. Both case reports as well as clinical studies have shown that TMS could present a promising option in the treatment of depression. A review of the literature demonstrates that further studies are needed to clarify many questions regarding technical and clinical aspects, such as dosage, duration of application, localization of the coils, as well as the impact of rapid-rate TMS and stronger magnetic field generators, before TMS will become an established tool in the treatment of psychiatric disorders.
