Schizophrenia

Clinical Symptomatology of Schizophrenia

Characteristic clinical features of schizophrenia are classified into positive, negative, and disorganized symptoms. Positive symptoms include hallucinations (e.g., hearing voices that others cannot) and delusions (e.g., a persecutory delusion, involving the belief that others intend to harm the individual). Individuals with a diagnosis of schizophrenia also exhibit negative symptoms, which are defined by profound disruption of emotional expression and/or experience and motivation, often resulting in social withdrawal and a drop in day-to-day functioning. The third category, disorganization symptoms, refers to bizarre behavior, tangential and disorganized speech, and illogical thought patterns. Schizophrenia is commonly associated with a heterogeneous presentation, with individuals exhibiting different combinations of these symptoms. In addition, a wide range of outcomes is observed. For example, some individuals show improved functioning between episodes of psychosis, whereas others display a more chronic course, with the continued presence of one or more of the above symptoms.

Neurodevelopmental Model of Schizophrenia

In its earliest clinical descriptions, schizophrenia was considered a deteriorating brain disorder with a course similar to Alzheimer's disease but an onset in young adulthood. Thus, the neurodegenerative hypothesis of schizophrenia initially prevailed. However, after nearly 3 decades of research, the neurodevelopmental model of schizophrenia is now prominent. This theoretical framework holds that the disorder's neural origins arise primarily during early development, with full emergence of recognizable symptoms typically occurring during late adolescence or early adulthood. By identifying associations between prenatal and perinatal complications and elevated risk for schizophrenia, studies have implicated that adverse events during early life may contribute to the development of the disorder. Furthermore, longitudinal studies have found that subtle deficits in cognition, emotional expression, and behavior are present during early childhood among individuals who ultimately develop [Page 664]schizophrenia as adults. These findings suggest that signs of brain compromise are present long before illness onset. Finally, the majority of postmortem neuropathology studies have failed to detect evidence of a neuronal degenerative process in schizophrenia. Although debate persists regarding the details of this aberrant neurodevelopmental course, when taken together, these findings provide compelling evidence that processes comprising neuronal development are fundamental to the pathophysiology of schizophrenia.

Early Risk Factors

Schizophrenia is a highly heritable illness, with approximately 80% of an individual's likelihood of developing schizophrenia attributable to their genetic makeup. There are now numerous studies demonstrating that unaffected biological relatives of patients with schizophrenia display qualitatively similar, but quantitatively milder, neuropsychological and neuroanatomic deficits, relative to healthy controls. Such findings support the view that these deficits reflect a genetic origin rather than secondary effects of the disease process or chronic medication use. Despite this strong genetic component, however, efforts to identify the precise risk genes involved have been challenging. In fact, not only is our understanding of which genes may be involved constantly being revised, so is our set of possible routes by which any given gene may result in phenotypic variation.

...