Schizophrenia and Psychoses

Psychosis and the Definition of Schizophrenia

Psychosis is a syndrome characterized by severe distortions in one’s sense of reality. The most prominent symptoms of psychosis are delusions and hallucinations, which are usually defined as fixed false beliefs and perceptions without corresponding external stimuli, respectively.

In the DSMs, psychosis has been the sine qua non for schizophrenia. Ppsychosis is not specific to schizophrenia or even to psychiatric disorders. It occurs in neurological disease, and it can be caused by a range of toxic substances. Mounting evidence suggests that psychosis is the “fever” of severe mental illness-a serious but nonspecific indicator. Moreover, psychosis is an end-state condition that, in comparison with other indicators, is more distal from schizophrenia’s causes and pathophysiology.

Mapping the Pathophysiology of Schizophrenia

Psychosis almost always occurs in late adolescence or early adulthood, reaching its peak between the ages of 18 and 25, when the prefrontal cortex is still developing. Scientists reported that knocking out DISC1 for a short time in the prenatal and perinatal prefrontal cortex of the mouse brain leads to neurochemical and behavioral disorders in early adulthood. In addition, the susceptibility alleles of some candidate genes, such as NRG1 and DISC1, appear to selectively affect splicing variants mainly expressed in the developmental cortex, suggesting that isoforms exhibit great developmental changes in the expression of the prefrontal cortex.

Environmental factors identified to date are also involved in prenatal or perinatal events. Maternal malnutrition during starvation, infections in the second trimester, perinatal damage, and cytokine exposure are all associated with the subsequent increased risk of schizophrenia.

Fig.1 Neurodevelopmental model of schizophrenia. (Insel, 2010)

The Stages of Schizophrenia

At present, the diagnosis is based on the symptoms and signs of psychosis. With the advent of biomarkers and new cognitive tools as well as the identification of subtle clinical features, we are beginning to detect earlier stages of risk and prodrome. The earliest stage is a risk, before detectable deficits. Beyond the rare, highly penetrant mutations (for example, DISC1 and the 22q11 deletion), epistatic interactions between more common, fewer penetrant changes may yield higher predictions of risk than our current list. The prodrome of schizophrenia is a valid second stage of the pre-psychotic illness. Stage III of schizophrenia is psychosis manifested by hallucinations, delusions, disorganization of thought and behaviour, and psychomotor abnormalities. It is now clear that negative symptoms (loss of will, anhedonia, poverty of thought) and cognitive deficits (reduced working memory, poor cognitive control) are core features of the disorder that account for much of the long-term morbidity and poor functional outcomes. Stage IV of schizophrenia involves chronic disability. Not all individuals progress to this late stage of the illness, but for those who do the disability is not only psychiatric but medical.

Fig.2 Stages of schizophrenia. (Insel, 2010)

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Reference

1. Insel, T.R. Rethinking schizophrenia. Nature. 2010, 468(7321): 187-193.