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Genetic and non-genetic vulnerability factors in schizophrenia: the basis of the “Two hit hypothesis”

1999; Elsevier BV; Volume: 33; Issue: 6 Linguagem: Inglês

10.1016/s0022-3956(99)00039-4

1879-1379

Thomas A. Bayer, Peter Falkai, Wolfgang Maier,

Genetic Associations and Epidemiology

Schizophrenia is a psychiatric disorder that aCicts 0.5‐1% of the general population. It is clinically characterized by disturbed thought processes, delusions, hallucinations and/or reduced social skills (Andreasen, 1995). This severe mental disorder strikes human beings in their early adulthood, causes lifelong disability for most of the suAerers and is therefore one of the ten most expensive disorders worldwide. Its direct and indirect costs mount up to 33 billion dollars per year, while aCicting all ethic backgrounds, genders, socioeconomic classes and nationalities. The course of the illness is characterized by episodes of acute psychotic symptoms followed by phases of remission where symptoms like reduced drive and aAect as well as disturbed cognitive functions prevail. Despite the severeness of the disorder its origins are unclear until now. The neuropathological and neuroanatomical findings in patients with schizophrenia have been proposed to arise from dysfunction of structural reorganization during early brain development (Waddington, 1993; Weinberger, 1995), or postnatally from altered maturation of synaptic elimination (Feinberg, 1982). Morphometric and in vivo neuroimaging studies described enlarged ventricles, cerebral atrophy of temporal lobe and prefrontal structures, and increase in the gyrification index (Arnold and Trojanowski, 1996). One of the most consistent results is the lack of astrogliosis in schizophrenic brains, which would be a requirement for severe and chronic neurodegenerative