Two patients walk into a clinic...a genomics perspective on the future of schizophrenia
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OPINION
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Two patients walk into a clinic...a genomics perspective on the future of schizophrenia Aiden P Corvin*
Abstract Progress is being made in schizophrenia genomics, suggesting that this complex brain disorder involves rare, moderate to high-risk mutations and the cumulative impact of small genetic effects, coupled with environmental factors. The genetic heterogeneity underlying schizophrenia and the overlap with other neurodevelopmental disorders suggest that it will not continue to be viewed as a single disease. This has radical implications for clinical practice, as diagnosis and treatment will be guided by molecular etiology rather than clinical diagnostic criteria.
In 2011, two people meet in a psychiatrist’s waiting room. To the untrained eye they have little in common. Patient A has a history of brief psychotic episodes characterized by persecutory delusions and auditory hallucinations. She is married, with a good job and has been asymptomatic since starting medication three years before. Patient B is slow and unreactive in his responses, communicates poorly, has poor hygiene and is suspicious of other people. He believes that aliens have implanted a device in his head that controls his thoughts, feelings and actions. He hears them talking about him and commenting on his behavior. He has spent much of the last three years in hospital and has few remaining social contacts. Despite the obvious differences in symptomatology and illness course, their treating psychiatrist has diagnosed them both with schizophrenia, prescribes them the same medication and enrolls them as participants in a research study of schizophrenia. Schizophrenia affects approximately 1% of the adult population and reduces life expectancy by an average of 20 to 25 years through the impact of the disorder on selfcare and physical health, as well as through suicide [1]. At *Correspondence: [email protected] Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine and Department of Psychiatry, Trinity College Dublin, Dublin 2, Ireland
the present time the etiological mechanisms underlying schizophrenia are poorly understood. Schizophrenia is diagnosed clinically, based on characteristic symptoms of psychosis, disorganization and so called ‘negative’ symptoms (representing a reduced range of emotional expression, reduced production of speech and a lack of volition/motivation); duration of illness; impaired functioning; and the exclusion of other disorders such as autism and bipolar disorder. For clinicians, identifying which psychotic patients have schizophrenia requires clinical acumen and familiarity with the DSM-IV or ICD-10 diagnostic manuals [2,3]. Psychiatrists generally agree on cases where these criteria are met and this has helped standardize approaches to research and treatment, but as the vignette highlights, the symptoms are heterogeneous and outcome is variable even with treatment. Although the diagnostic criteria are stringent, at the level of individual symptoms schizophrenia overlaps with other p
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