S chizophrenia is a pervasive neuropsychiatric disease of uncertain etiology. In the United States, schizophrenia has a lifetime prevalence of greater than 1% and results in the annual expenditure of more than 65 billion dollars (1, 2). Family and adoption studies have demonstrated a significantly increased risk of schizophrenia in individuals who have a first-degree birth relative with this disease, indicating that there is a substantial genetic component in disease pathogenesis. Epidemiological studies have identified a number of environmental factors associated with the development of schizophrenia, including perinatal infections, winter-spring birth, household crowding, and upbringing in urban areas (3, 4). These genetic and environmental findings can be reconciled by the concept that the disease can result from infectious processes occurring in genetically susceptible individuals (5-8).Retroviruses have been hypothesized as one of the infectious agents involved in the pathogenesis of schizophrenia (9-11). Humans can be infected with retroviruses such as strains of human immunodeficiency virus (HIV) and human T-cell leukemia virus. These exogenous retroviruses can replicate within the central nervous system and cause neurological and psychiatric symptoms in some infected individuals. The clinical response to infection with HIV is determined, to some extent, by the genetic susceptibility of the infected individual (12-14).The human genome also contains many endogenous retroviral (HERV) elements, which have homology to known animal retroviruses. These elements probably arose from reverse transcriptase-mediated integration into the germ line of progenitors of Homo sapiens after exogenous retroviral infection. Many of the HERV sequences in the human genome are incomplete, although some full-length proviral genomic sequences have been identified. Some of these proviruses contain long open reading frames capable of encoding complete viral proteins and engendering viral particles (15)(16)(17)(18)(19)(20). The tissue-specific expression of HERVs has been associated with a number of chronic human diseases, including multiple sclerosis, diabetes, and autoimmune arthritis (21-23). We report the identification of retroviral sequences in cerebrospinal fluids (CSFs) obtained from individuals with recent-onset schizophrenia, and the differential transcriptional up-regulation of members of the HERV-W family of endogenous retroviruses in the postmortem frontal cortex of individuals with schizophrenia. Materials and Methods CSF Samples. Patients with new-onset schizophrenia.We obtained CSF samples from 35 previously healthy individuals (presenting to the Department of Psychiatry at the University of Heidelberg) with symptoms consistent with new-onset schizophrenia or schizoaffective disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. (25). These individuals had not been admitted previously to the hospital for schizophrenia and were without manifestations of acute infectious, inflammatory,...

Cytarabine administered either intravenously or intrathecally does not improve the prognosis of HIV-infected patients with progressive multifocal leukoencephalopathy who are treated with the antiretroviral agents we used, nor does high-dose antiretroviral therapy alone appear to improve survival over that reported in untreated patients.

Cerebral atrophy is a common radiologic manifestation of HIV dementia. To evaluate the relationship between cognitive impairment and cerebral atrophy, adjusting for age and immune status, we used standardized planimetry to measure the ventricle-brain ratio (VBR) and the bifrontal (BFR) and bicaudate (BCR) ratios, three measures of cerebral atrophy. We analyzed cranial MRIs of 23 HIV-1-seronegative controls (SN) and 116 HIV-1-infected individuals. Of the HIV-1-seropositive individuals, 37 had HIV dementia (DM group), 40 had neurologic or neuropsychological abnormalities insufficient for HIV dementia (NP+ group), and 39 were neurologically normal (NML group). We performed comparisons using analysis of covariance with correction for multiple comparisons. Both the VBR, a general measure of overall cerebral atrophy, and the BCR, a measure of atrophy in the region of the caudate nucleus, are significantly associated with dementia. The association is stronger for BCR enlargement than for VBR enlargement, suggesting that selective caudate region atrophy is associated with HIV dementia. These results indicate that overall cerebral atrophy and prominent caudate region atrophy are important radiographic features of HIV dementia.

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