Neurobiology of schizophrenia spectrum disorders.

The schizophrenia spectrum disorders are a group of psychiatric diagnoses that share several clinical features, typically involving reality distortion. Each is considered a disorder, diagnosed with a distinct set of diagnostic criteria. Spectrum conveys the idea that they are somehow similar to each other. Such similarity could be defined on purely clinical grounds or at the level of disease mechanism and aetiology. It is this tension of distinctiveness and similarity that makes the scientific study of the schizophrenia spectrum disorders challenging. The concept of the schizophrenia spectrum can be traced back to Bleuler and his book Dementia Praecox or the Group of Schizophrenias. 1 The schizophrenias are characterised by significant heterogeneity of signs and symptoms, disease course and outcome. This gives rise to various clinical subtypes and to variants defined by a shorter duration of illness. Most importantly, the outcome of the schizophrenias ranges from long-term disability to full remission. As a result, the current version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) 2 recognises 5 subtypes of schizophrenia undifferentiated and residual), 2 forms of schizophrenia with shorter duration (i.e., schizophreniform disorder and brief psychotic disorder), 2 delusional disorders (i.e., delusional disorder and shared psychotic disorder), and 3 personality disorders with features that resemble schizophrenia (i.e., schizotypal, paranoid, and schizoid personality disorder). In addition, 3 diagnoses capture psychotic patients with significant mood symptoms – one with an emphasis on psychosis (schizoaffective disorder) and two with an emphasis on mood symptoms (psychotic bipolar disorder and psychotic depression). How can we test the hypothesis that these 15 diagnoses identify distinct disorders? Most importantly for clinicians, a prediction of illness course and outcome would support the validity of the diagnoses. While there is evidence for a gradient of dysfunction (with schizophrenia having the greatest and personality disorder the smallest burden of disability), 3 there remains substantial variability within each diagnostic group. For example, some patients with schizophrenia respond poorly to all available treatments and have a poor outcome, while others respond well to treatment, some with full remission of all symptoms and full recovery to the premorbid level of functioning. 4 This significantly limits the usefulness of our diagnostic labels and raises concern about the stigmatisation of a person who will recover from a bout of psychosis. This has led some to argue for the removal of the diagnosis of schizophrenia altogether. 5 The neurobiological exploration of schizophrenia spectrum disorders …