The relationship of the metachromatic leukodystrophies to neuropsychiatric disorders

Abstract

The possible relationship between the metachromatic leukodystrophies and neuropsychiatric disorders is reviewed. Four kinds of evidence are considered: psychiatric symptoms as preemergent markers of the neurodegenerative process; increased behavioral problems in leukodystrophy families; screening for low enzyme levels among psychiatric populations; and studies in model systems. Whereas the basic postulate of an increased risk for psychiatric problems among individuals with lower levels of the enzymes deficient in the leukodystrophies remains attractive, there is no strong evidence in its support. Low enzyme levels can be found in psychiatric populations, but they may not be any more frequent than in the general population.

Metachromatic Leukodystrophy: A Model for the Study of Psychosis

“…21 Although abundant evidence suggests that schizophrenia is predominantly a disease of gray matter and MLD is a disease of white matter, there is evidence of neuronal dysfunction in MLD and white matter abnormalities in schizophrenia. 8 This supports the suggestion that accumulation of cerebroside sulfate is toxic to the brain. 25 Furthermore, the anatomical distinction between cortical and subcortical disease is not corroborated by either clinical observation or functional imaging.…”

“…3,7,8 Baumann et al 7 described two distinct clinical patterns of adult MLD. 3,7,8 Baumann et al 7 described two distinct clinical patterns of adult MLD.…”

“…8 Subtle deficits in visuospatial perception, construction, stereognosis, and visual search tasks have been found in MLD heterozygotes. In favor of the low-ARS-A-activityneuropsychiatric-phenotype model is the observation of increased psychopathology in some first-degree relatives of MLD patients.…”

“…[22][23][24] Decreased fractional anisotropy in the inferior frontal white matter is inversely correlated with negative symptoms in schizophrenia. 5,8,26,27 One interpretation of these discrepant results, based on in vitro studies, is that low-enzyme activity individuals may be at greater risk of neuropsychiatric disability if they are exposed to environmental or endogenous stressors such as ethanol consumption. A functional disturbance of neuronal metabolism and activity at a remote site after injury to an anatomically connected area of brain (diaschisis) is frequently found, and it may be the explanation for the SPECT observation of thalamic and widespread cortical hypoperfusion in the adult case of MLD, above.…”

Low Arylsulphatase A Activity in the Development of Psychiatric Disorders

“…MLD very often occurs with various psychiatric symptoms [3]. There are numerous reports in the literature, showing that deterioration of cognitive functions, personality changes, psychosis and dementia are common clinical manifestations of the disease [4][5][6][7][8].…”