We will separate two notions generally confounded in the literature: anatomical and functional connectivity. The rationale for this is that we suppose the latter to be related to the common pathophysiological pathway leading to the clinical expression of the disease. The anatomical aspect is assumed to be one of the possible causes for the dysfunction. We will also discuss two levels of connectivity:

a local level, mainly concerning the direct surroundings of the neurons in the gray matter, and a longrange level, mainly concerning the white fiber tracts Inhibitors,research,lifescience,medical connecting distant parts of the brain. A third anomaly of connectivity could be related to neurons connecting with erroneous targets. Gray matter connectivity Gray matter hypotrophy and atrophy have both been described in schizophrenic patients. Hypotrophy buy Imatinib refers Inhibitors,research,lifescience,medical to a congenital reduction in the quantity of gray matter. It has been shown that such a reduction exists in patients as early as the first episode, with

the most robust evidence in the external temporal lobe, but with Inhibitors,research,lifescience,medical reductions also in the hippocampus and frontal and parietal lobes/’ However, it might be that part of the reduction is already related to an earlier origin of the disorder. Indeed, the average duration of untreated psychosis is 2.4 years, and some markers can even be traced back to the disease process long before that.7 However, the presence of similar, although lesser, gray matter reduction in relatives of patients also speaks for a congenital problem. Atrophy refers

to an acquired reduction in gray matter. The acceleration of gray matter decrease seems to occur mainly during the first year(s) of the disease process. Inhibitors,research,lifescience,medical Later on, the slope of the decrement is less striking. This gray matter reduction does not seem to be related to neuronal loss occurring after the second trimester. Indeed, Inhibitors,research,lifescience,medical only a few studies have found evidence for gliosis, a reputedly robust marker of neuronal necrosis, in the brains of patients with schizophrenia.8,9 It might be possible that some neurons are lost by apoptosis not necessarily accompanied by gliosis, but the general consensus is that most gray matter atrophy represents a reduction in only neuronal volume.10 As a matter of fact, cortical neurons are generally described as being smaller with higher density in pathological studies. Many authors have pointed out that the compartment showing the larger reduction could be the volume of axons and dendrites. In other words, there should be a reduction in the connecting parts of the neurons. In line with these arguments, synaptic spines and synaptic markers are reduced,11 as well as synaptic gene expression.12 In short, there is evidence of a reduction in local connectivity in some cortical areas in schizophrenia.