Diseases of white matter and schizophrenia-like psychosis

Abstract

Production of psychotic symptoms may result from functional asynchrony of interdependent regions, due to alterations in critical circuits as a result of pathology. The nature, location and timing of white matter pathology seem to be the key factors in the development of psychosis, especially during the critical adolescent period of association area myelination. Diseases that disrupt the normal formation of myelin appear to cause psychosis at higher rates than those that disrupt mature myelinated structures. Diffuse rather than discrete lesions, in particular those affecting frontotemporal zones, are also more strongly associated with schizophrenia-like psychosis. These illnesses point to the central role that white matter plays in maintaining CNS connectivity and to how pathology of the white matter may contribute to the neurobiology of psychosis.

Glia‐related genes and their contribution to schizophrenia

“…lesions (i.e., leukodystrophies, leukoencephalopathies, and multiple sclerosis) frequently present with psychotic symptoms that are sometimes indistinguishable from those of schizophrenia. [8][9][10] In summary, increasing evidence suggests that oligodendrocytes and demyelination are involved in schizophrenia. Moreover, an association between oligodendrocytes and schizophrenia has been replicated by a wide range of genetic analyses and post-mortem gene expression studies.…”

Linking white and grey matter in schizophrenia: Oligodendrocyte and neuron pathology in the prefrontal cortex

“…The importance of myelination for cognitive functioning becomes apparent in diseases that are known to be caused or affected by deficiencies in myelin, where patients show deficits in intellectual, social and emotional functioning (Dwork et al, 2007; Schmahmann et al, 2008). Leukodystrophies and leukoencephalopathies, diseases characterized by progressive degeneration of the white matter, if diagnosed in late adolescence or early adulthood can present with psychotic symptoms sometimes indistinguishable from those of schizophrenia (Davis et al, 2003; Denier et al, 2007; Walterfang et al, 2005). Likewise, patients with multiple sclerosis who display cognitive and psychiatric symptoms frequently have white matter lesions in the frontal and temporal lobes, which are the brain regions most implicated in schizophrenia (Davis et al, 2003).…”

“…In dysmyelinating and hypomyelinating diseases such as the leukoencephalopathies, the effects of a myelin deficiency may be striking and fatal (see reviews by Lyon et al, 2006; Schmahmann and Pandya, 2007; Schmahmann et al, 2007, 2008; Walterfang et al, 2005). If the myelin hypothesis holds true, and myelin deficiencies prove to be one of the central causes of the development of schizophrenia, one might argue and question why classic schizophrenia patients show so few neurologic symptoms.…”

Zebrafish as a model to investigate CNS myelination

“…It is a defining pathological feature of multiple sclerosis (MS) and also commonly occurs following traumatic brain injury (Richardson et al, 2010), spinal cord injury (Waxman, 1989), stroke (Zhang et al, 2013), and during normal aging (Bartzokis, 2004). A growing number of disorders have also been linked to dysmyelination including cerebral palsy (Azzarelli et al, 1980), schizophrenia (Walterfang et al, 2005), depression (Fields, 2008) and several devastating developmental disorders known collectively as the leukodystrophies (for extensive reviews, see Faust et al, 2010;Perlman and Mar, 2012). Thus, therapies aimed at replacing damaged myelin could minimize axonal loss and prevent the neurological decline associated with chronically demyelinated or dysmyelinated pathologies in a wide variety of developmental or adult disorders.…”