40 Thompson and colleagues41 have also reported an accelerated decrease in gray matter volume in early-onset schizophrenia. Of particular note, in a recent review of the literature, DeLisi et al42 reviewed evidence for progressive changes in both chronic and first-episode patients. They concluded that progressive changes over time in chronic

patients are far less than what is observed in first-episode patients, again underscoring the Inhibitors,research,lifescience,medical fact that progressive changes in the early stages of illness may be more dramatic than changes observed later in the course of the illness. Another recent review43 sheds further light on the issue of progressive changes following first episode. Inhibitors,research,lifescience,medical This review found that progressive changes following first episode were more pronounced in the first 20 years and less pronounced after this time period compared with healthy controls. Of further note, the changes observed included gray matter volume reductions in the frontal and temporal lobes,

as well as increased lateral ventricles. In addition, these changes were associated with more progressive changes associated with poor outcome, more negative symptoms, and poor performance on neurocognitive measures. A review by Pantelis and coworkers17 of longitudinal MRI studies of first-episode patients, prodromal patients, and high-risk individuals also suggests an acceleration of gray matter Inhibitors,research,lifescience,medical reduction early in the course of illness. Specifically, there is gray matter reduction in prefrontal regions, which these investigators believe leads to further progressive changes in medial temporal and Inhibitors,research,lifescience,medical orbitofrontal brain regions. These investigators also interpret findings, to date, as

indicative of an early neurodevelopmental insult or lesion that likely “renders the brain vulnerable to later brain maturation processes” and which takes place during adolescence or early adulthood. These interpretations are reminiscent of Mednick and McNeil’s 1968 two-hit theory of schizophrenia,33 and order inhibitor Feinberg’s Inhibitors,research,lifescience,medical 198232 theory that schizophrenia results from abnormal synaptic pruning. The number of first-episode studies is, however, relatively small compared with Dacomitinib the number of chronic studies. Additionally, the selection of patients differs in that some studies make it clear include patients that have been ill for several years, and, while they may not be chronic per se, they might be better classified as reflecting “early schizophrenia” rather than as first-episode schizophrenia. Having said this, however, there are a number of highresolution longitudinal studies that have investigated brain abnormalities at first episode of illness. Some, including Gur and coworkers,37 and Kasai and coworkers,39 are noted above. Another study by Lieberman et al44 reported larger lateral ventricles and reduced volume of the hippocampus at baseline, but only increased lateral ventricles at follow-up 1 year later.