58 Long-range connectivity Multiple models of white matter disorders can be found in neurology. These are the best models of disordered long-range connectivity

and they mimic in some way, although to a much larger extent, what has been described in schizophrenia. Most white matter (WM) diseases are associated with a higher occurrence of psychosis than in the normal population (Table Inhibitors,research,lifescience,medical I).59-82 This increased prevalence appears to be independent of the etiology, albeit differing largely according to the cause. Late-onset adrenoleukodyst.rophy (ALD) and metachromatic leukodystrophy (MLD) present a higher occurrence of psychosis.61,62,83 Inhibitors,research,lifescience,medical Moreover, in such cases psychoses are more likely to occur without confusion. Table I. Prevalence of psychosis, mania, and depression in several white matter diseases, classified

according their etiologies.61-82 See text for comments. DAI, diffuse axona! injury; A!DS, acquired immune deficiency syndrome; ADC, AiDS dementia complex; Inhibitors,research,lifescience,medical AD, … Is psychosis a specific feature of white matter diseases? Unfortunately, this docs not appear to be the case. Mania and depression are also very frequent in many WM diseases60 This illustrates once again the spectrum ranging from bipolar disorder to schizophrenia. However, against such a proposal, it is worth mentioning that late-onset ALD and MLD seem to have some specificity for psychosis. We were not able to find any find more reports of mania or depression in ALD or MLD through our reading or through Medline searches. Are white matter diseases more likely to specifically Inhibitors,research,lifescience,medical trigger psychosis, Inhibitors,research,lifescience,medical or is this feature common whatever the type of encephalopathy? In many neurodegenerative diseases, eg, metabolic or vascular diseases, psychosis can precede dementia. Some WM. diseases also evolve toward a dementia. Thus,

it is questionable whether WM diseases have a selective role in provoking psychosis, or whether psychosis is just an early reaction to a nonspecific encephalopathy. Indeed, the Thymidine kinase comparison with Alzheimer’s disease shows a similar degree of psychosis (a mean of 41 % but up to 60%).81 However, the clinical features are very different from the psychosis of schizophrenia: Delusions are mostly persecutory (non-bizarre). There are typically misidentifications, and if hallucinations occur they are mostly visual. This is not the case of WM diseases where psychotic symptoms are more similar to schizophrenia (multiple sclerosis, metabolic diseases such as ALD and MLD)62: Bizarre delusions leading to odd behavior. Verbal hallucinations. Nevertheless, these psychotic symptoms are not specific to all WM diseases.