JOURNAL ARTICLE
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Duration of untreated illness as a key to early intervention in schizophrenia: A review.

Neuroscience Letters 2018 March 17
The first psychotic episode is classically viewed as a critical period which management is important in determining the long-term outcome of the schizophrenia (SCZ). For this reason, the duration of untreated illness (DUI), defined as the interval between the onset of the psychiatric disorder and the administration of the first pharmacological treatment, is a clinical variable that has been increasingly investigated due to its potentially modifiable nature and its value as a predictor of outcome. DUI is poorly applicable and highly unreliable in psychosis. The present critical review examines the impact of DUI and its more operative definition of "duration of untreated psychosis" (DUP) in the course and outcome of SCZ, focusing on its epidemiologic, clinical, prognostic factors. Length of DUP has been identified as positively related to a worst treatment response, symptom control and overall functional outcome in SCZ. Negative symptoms appear to be prominently related to longer DUP. Neuroimaging correlates of DUP have not been clearly outlined: few of the studies considering first-episode patients and DUP showed structural abnormalities. A low proportion of significant associations were found mostly in cerebellum and occipital lobe of patients with longer DUP. Also, evidence of an inverse correlation between cognitive alterations and DUP is not conclusive. DUI and DUP are multidimensional constructs that imply both intrinsic, illness related (e.g. subtle symptoms at onset) and extrinsic factors (e.g. access to mental health services), so that from its study sprouted in the last decades First-Episode Units, aimed at providing secondary prevention in SCZ such as providing a timely diagnosis and treatment to patients experiencing their first psychotic episode. Early intervention seems to ensure a shortened DUP, especially for people presenting with brief limited intermittent psychotic symptoms, and, ultimately, ensure a more favorable prognosis for patients affected by SCZ.

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