White Matter Integrity and Symptom Profile in First Episode Schizophrenia

Abstract

The last 20 years have brought about a virtual explosion of studies on brain connectivity in schizophrenia. These studies have shown that white matter organization is disrupted in schizophrenia, and that these disruptions have important implications for psychiatric symptomatology and sensory and cognitive deficits seen in the disorder. Recent studies showing that variations in white matter integrity are associated with genetic variants (e.g., in neuregulin) that have been implicated in schizophrenia offer an exciting and important avenue to better understand the mechanism of these abnormalities, as do converging neuro-pathological studies of white matter (Dwork et al., 2012).

While gray matter deficits in schizophrenia have been widely reported (Kim et al., 2003; Lui et al., 2009a,b; Whitford et al., 2005), only a few studies have focused on cerebral white matter, and they have produced inconsistent results. However, studying the white matter is crucial to understanding the neurobiological substrate of schizophrenia, because the abnormalities in white matter may play a fundamental role in the neurobehavioral manifestations of schizophrenia (Guo et al., 2012).

Furthermore, one of the debated hypotheses of the etiopathogenesis of schizophrenia is the dysfunction in the neural connectivity (misconnection) of different cerebral areas or the neural circuitry (Andreasen et al., 1999; McGuire and Frith, 1996).

In recent decades, diffusion tensor imaging (DTI), a magnetic resonance imaging technique sensitive to the orientation of water diffusion restricted within the neuron sheath and myelination, has been widely used in psychiatric research. One of the commonly used DTI measures is fractional anisotropy (FA), which is thought to reflect the anatomical features of neural fibers, such as the axon caliber, fiber density and myelination (Scholz et al., 2009).

At present there is substantial DTI data available on the early phase of schizophrenia from the current study and other research groups. Taking the current study results and the results of other studies together, DTI abnormalities in first-episode patients appear less robust than in chronic patients, suggesting that progression to more extensive abnormalities occurs after illness onset. There are also indications for accelerated aging effects in schizophrenia. These findings suggest the possibility that early intervention may help to preserve white matter integrity (Peters et al., 2010)