28-30 In general, most articulations of this model have emphasized

the importance of very early developmental processes, which occurred either prior to birth or shortly afterward. The model assumes that a genetic vulnerability may be present, and that this vulnerability is expressed if a sufficient number of releasing factors converge in the vulnerable individual early in life. Some of these may occur prior to birth, such as viral infections, maternal malnutrition, or exposure to toxins in utero; some may occur shortly after, such as obstetrical complications and birth injuries, Inhibitors,research,lifescience,medical or viral infections. These factors are presumed to injure the developing brain, to express themselves in the type of neuropathology that was described in the 1986 Inhibitors,research,lifescience,medical Benes study and later ones, and to create impairments

in structural or functional connectivity that will be the substrate upon which schizophrenia will develop at a later age. Clinical findings in support of an early developmental abnormality include a variety of premorbid indicators or markers, such as decreased cranial size, motor impairments and neurological Inhibitors,research,lifescience,medical soft signs, and cognitive and social impairments. These findings have been repeatedly replicated in highrisk samples or studies of children who later developed schizophrenia using a variety of ingenious designs.10-18 During the ensuing years, MR studies also continued to add to the evidence in support of the neurodevelopmental hypothesis. Many of the early MR studies examined samples of convenience, such as institutionalized Inhibitors,research,lifescience,medical patients or patients with established chronicity. Determining if brain abnormalities are present in individuals with schizophrenia at the time of onset (“first-episode patients,” FEP) provides a crucial test of Inhibitors,research,lifescience,medical the hypothesis, since any abnormalities noted would have presumably antedated the clinical presentation. Investigators conducting studies of FEP began to study patients at

the time of onset of illness and to find that many types Calpain of brain abnormalities are present early in the illness. These include decreased cerebral size, decreased frontal and temporal lobe size, decreased thalamic size, decreases in GM and WM volume, and increased CSF on the brain surface and in the ventricles.22,31 Does tissue loss continue after onset? Another critical question about the lifetime Autophagy inhibitor supplier trajectory of schizophrenia and the related concept of neurodevelopment is whether the brain abnormalities that are present at onset continue to worsen over time. If patients with schizophrenia lose tissue at a greater rate than healthy normals, this could suggest that the disorder also has a neuroprogressive or neurodegenerative component.