Elsevier

The Lancet

Volume 374, Issue 9690, 22–28 August 2009, Pages 635-645
The Lancet

Seminar
Schizophrenia

https://doi.org/10.1016/S0140-6736(09)60995-8Get rights and content

Summary

Schizophrenia is still one of the most mysterious and costliest mental disorders in terms of human suffering and societal expenditure. Here, we focus on the key developments in biology, epidemiology, and pharmacology of schizophrenia and provide a syndromal framework in which these aspects can be understood together. Symptoms typically emerge in adolescence and early adulthood. The incidence of the disorder varies greatly across places and migrant groups, as do symptoms, course, and treatment response across individuals. Genetic vulnerability is shared in part with bipolar disorder and recent molecular genetic findings also indicate an overlap with developmental disorders such as autism. The diagnosis of schizophrenia is associated with demonstrable alterations in brain structure and changes in dopamine neurotransmission, the latter being directly related to hallucinations and delusions. Pharmacological treatments, which block the dopamine system, are effective for delusions and hallucinations but less so for disabling cognitive and motivational impairments. Specific vocational and psychological interventions, in combination with antipsychotic medication in a context of community-case management, can improve functional outcome but are not widely available. 100 years after being so named, research is beginning to understand the biological mechanisms underlying the symptoms of schizophrenia and the psychosocial factors that moderate their expression. Although current treatments provide control rather than cure, long-term hospitalisation is not required and prognosis is better than traditionally assumed.

Introduction

Although the precise societal burden of schizophrenia is difficult to estimate, because of the wide diversity of accumulated data and methods employed, cost-of-illness indications uniformly point to disquieting human and financial costs.1 Schizophrenia does not just affect mental health; patients with a diagnosis of schizophrenia die 12–15 years before the average population, with this mortality difference increasing in recent decades.2 Thus, schizophrenia causes more loss of lives than do most cancers and physical illnesses. Although some deaths are suicides, the main reason for increased mortality is related to physical causes, resulting from decreased access to medical care and increased frequency of routine risk factors (poor diet, little exercise, obesity, and smoking).2

Section snippets

Diagnosis

Identification of delusions and hallucinations in psychosis is not difficult, but their classification has not been simple. Psychosis is not exclusive to schizophrenia and occurs in various diagnostic categories of psychotic disorder (panel). The criteria used to distinguish between these different categories of psychotic disorder are based on duration, dysfunction, associated substance use, bizarreness of delusions, and presence of depression or mania. However, the resulting diagnostic

Epidemiology

A systematic review of epidemiological data indicates that, if the diagnostic category of schizophrenia is considered in isolation, the lifetime prevalence and incidence are 0·30–0·66% and 10·2–22·0 per 100 000 person-years, respectively.17 Rates vary three-fold depending on the diagnostic definition of schizophrenia that is used: a narrow definition, including patients with illness duration of at least 6 months, age below 45 years, and negative symptoms has lower rates than a broad definition

Gene and environment interplay

Vulnerability for schizophrenia is partly genetic. Twin studies suggest that the syndrome has heritability estimates of around 80% (compared with ∼60% for osteoarthritis of the hip and 30–50% for hypertension). Despite this genetic association, the identification of specific molecular genetic variation has not been easy. Modification of diagnostic criteria and uncertainty about the natural phenotype of psychosis are likely to have hampered progress in this regard.

Recent findings have suggested

Prognosis

The traditional clinical and societal view of schizophrenia is of a debilitating and deteriorating disorder with poor outcome. However, most patients now live independently outside the hospital and the typical duration of admission is short (a few weeks). Although most patients need some degree of formal or informal financial and daily-living support, the perspective now is one of recovery, where the patient takes an active role in the development of new meaning and purpose while growing beyond

Pathophysiology

Since the advent of modern neuroimaging techniques, the number of studies of the pathophysiological changes of schizophrenia has dramatically increased, with more than 1000 reports published in the past 10 years. Structural brain imaging studies have shown a subtle, almost universal, decrease in grey matter, enlargement of ventricles, and focal alteration of white matter tracts.96, 97, 98

Neurochemical imaging studies to test the dopamine hypothesis of schizophrenia with 18F-dopa and 11

Clinical management

Diagnosis of schizophrenia is made by reference to the criteria in DSM-IV and ICD-10. Even though these are clinical criteria, diagnosis can be achieved with acceptably high inter-rater reliability and compares well with diagnostic reliability in the rest of medicine. Unfortunately, no objective test exists for this diagnosis. Although several biological abnormalities have been reproduced (eg, abnormally large ventricles, abnormal dopamine concentration, and altered P300), they are not

Prevention

Because psychotic disorders occur in young people and disrupt educational and social development, early intervention is crucial and could favourably affect long-term prognosis. A few studies have assessed the use of specialised early interventions for first-episode psychotic disorder patients with encouraging results in the first year;136 follow-up, however, suggests that the benefits of early intervention might be lost after 5 years.137

Whether early intervention can be extended to at-risk

Cognition

Almost 100 years ago when schizophrenia was first defined in its current form, it was called dementia praecox, the focus being on the intellectual deterioration that accompanied the syndrome. In the following years, the focus shifted to the psychosis, the delusions, and the hallucinations as the cardinal features of the illness, perhaps because they are easy to identify and greatly affect functioning and society. However, during the past 10 years, there has been a resurgence of interest in the

Conclusions

In the 100 years that we have known the diagnosis of schizophrenia, its definition has swung between a biological illness, a psychological dysfunction, and a social construct. The advances of genetics, epidemiology, imaging, and pharmacology now allow us to put these perspectives together (figure 4). A clear genetic susceptibility exists in schizophrenia; however, what one inherits is not the illness, but altered brain development, shared partly with developmental disorders, such as autism, and

Search strategy and selection criteria

We searched publications in PubMed using the search terms ”schizophr*[ti]” or ”psychosis[ti]” or ”psychotic[ti]”. We used 1558 English language reviews and meta-analyses published in the past 5 years. These reports were downloaded into an Endnote library file and scanned for relevance with regard to the topics selected for this review. Further focused searches on PubMed were then done on the selected topics.

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