Cambridge, MA, USA, Kiel, June 22, 2018. In the most comprehensive international collaboration to date on the molecular genetic basis of diseases of the central nervous system, the international research consortium, including scientists from the Kiel Pain Clinic, discovered genetic links between psychiatric and neurological disorders. The research group comprised more than 600 institutions worldwide. The discoveries far surpass previous knowledge on this topic. The team discovered that psychiatric disorders share extensive genetic similarities. In contrast, neurological disorders are genetically distinct. In a study published today in the journal Science, the authors describe the results of the most comprehensive dataset to date on the genetic links of brain disorders. The findings show that mental disorders have significant similarities at the molecular level that are not reflected in current diagnostic categories. The findings suggest that our understanding of the origin, diagnosis, and treatment of diseases of the central nervous system needs to be rethought.
If the genetic connections and the pattern of overlaps in the molecular-genetic basis of various diseases can be uncovered, the conditions that cause these diseases can also be better understood. Subsequently, specific mechanisms can be identified that offer targets for tailored treatments.
For the current study, international research consortia pooled their data to analyze the genetic patterns of 25 psychiatric and neurological disorders. These findings were made possible by the largest international analysis to date on this topic, which compiled all available data worldwide. The research group identified genetic overlaps using genome-wide association studies (GWAS) from 265,218 patients and 784,643 control subjects. The research project utilized data from several hundred researchers to deepen our understanding of how the brain works—a truly unprecedented undertaking.
The main finding was that there is a large overlap in the molecular basis of psychiatric disorders. This applies particularly to attention deficit hyperactivity disorder (ADHD), bipolar disorder, depressive episodes, and schizophrenia. The data also demonstrate a pronounced overlap in the molecular basis of anorexia nervosa, obsessive-compulsive disorder, and Tourette syndrome.
In contrast, the molecular basis of neurological diseases such as Parkinson's disease or multiple sclerosis proved to be more clearly independent. However, migraine with aura and migraine without aura were exceptions. This widespread headache disorder, which the World Health Organization (WHO) considers one of the most disabling diseases in humans, showed genetic links between attention deficit hyperactivity disorder (ADHD), depressive disorders, and Tourette syndrome.
This most comprehensive study to date on the genetic links of diseases of the central nervous system provides tangible evidence of genetic foundations for psychiatric and neurological disorders. Prof. Dr. Hartmut Göbel, co-author and head physician of the Kiel Pain Clinic, comments on the findings: “The complexity of migraine as a unique neurological disorder manifests itself in significant connections with both psychological and neurological symptoms. Migraine is therefore rightly referred to as an encyclopedia of neurology. The data also demonstrate the comprehensive symptomatology of migraine. Furthermore, they explain why the risk of mental illnesses such as depression, anxiety, and personality changes is increased eightfold in migraine patients. They also highlight the shared foundations of cerebrovascular diseases and migraine, including the increased risk of stroke and cardiovascular disease.”
A key conclusion is that current diagnostic categorization of brain disorders does not accurately reflect the underlying biological reality. The diagnostic classification of these disorders may not adequately reflect the mechanisms by which these disorders arise within the central nervous system and cause overlapping symptoms.
Further elucidation of these genetic relationships can lead to the differentiation of new clinical disease entities and enable more precise development of new treatment methods as well as the selection of patients for effective treatments. A limited association was found for comorbidity between migraine with aura and ischemic stroke. The subtypes of migraine, migraine without aura and migraine with aura, also showed substantial genetic associations. For neurological diseases, it became clear that Alzheimer's disease, intracerebral hemorrhage, ischemic stroke, and migraine exhibited significant negative genetic associations with cognitive variables.
Source: Science 22 Jun 2018:Vol. 360, Issue 6395, eaap8757, DOI: 10.1126/science.aap8757
Science 22 Jun 2018:Vol. 360, Issue 6395, eaap8757, DOI: 10.1126/science.aap8757
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