Psychiatrie im Wandel: neuronale Netzwerkstörungen lassen sich mit moderner Kernspintomographie sichtbar machen

Abstract

Over the last 20 years major advances in mathematics and computing opened up remarkable opportunities for studying the function, biochemistry and microstructure of the human brain. Magnetic resonance imaging (MRI) in neuroscience describes the functional organisation of the brain at the level of large neuronal groupings, networks and systems. By relating these to normal and disturbed information processing and behaviour in humans, means for the systematic analysis of the spatio-temporal functional architecture of the human brain along with the plasticity of that architecture are provided. At the same time, the focus of psychiatric research is increasingly moving from the differential description of phenomenology and disease course to an understanding of the biological basis of mental disorders. This also becomes evident when considering the spectrum of schizophrenia where investigators have consistently tried to identify the neurobiological substrate of information-processing deficits that seem characteristic for schizophrenic patients. Widespread abnormalities in different stages of information processing seem to lead to a cascade of downstream effects on higher cortical functions such as working memory or concept formation. In recent studies, the phenotypic characterisation of basic information processes as well as cognitive abnormalities in schizophrenic patients have been elaborated with new MRI methods. In both neuroleptic naive first episode and chronically ill schizophrenic patients in remission functional MRI demonstrated a dysfunction of the first relay station of the thalamus and in the prefrontal cortex as compared to normal controls. Furthermore, this technique revealed significant differences in prefrontal function between patients with typical and atypical antipsychotics. Using MR-spectroscopy in accordance with these functional data patients receiving typical neuroleptic medication showed a significantly lower mean NAA (marker for neuronal viability) in the anterior cingulate gyrus in comparison to the group of patients receiving atypical antipsychotic drugs, and had significantly more perseveration errors in the WCST. No significant group differences were found in either the creatine and phosphocreatine signal or the signal from choline-containing compounds. However, there was a clear association between the age-corrected NAA signal in the cingulate gyrus and the perseveration errors as well as the length of atypical treatment. In addition to differences between patients and healthy subjects these findings also showed differences within the patient group depending on treatment. These results support the hypothesis of a dysfunction in prefronto-temporo-limbic and early visual information-processing networks in schizophrenia. Furthermore, there was a specific relationship between neuronal and neuropsychological functioning. In keeping with animal data these results also indicate that chronic treatment with antipsychotics has regionally specific effects on the prefrontal cortex. Based on functional and metabolic MRI, circuit dysfunctions have been demonstrated within prefrontal and thalamic areas. In future, the non-invasive monitoring of therapeutic interventions with modern imaging methods in a multimodal approach may help to improve treatment by allowing approaches to be tailored for the individual patient.