The Group of Dementia Praecox Patients With an Increase of the Protein Content of the Cerebrospinal Fluid

Bruetsch, Walter L.; Bahr, MJ; SKOBBA, JOSEPH S.; Dieter, W.

doi:10.1097/00005053-194206000-00001

Cited by 19 publications

(7 citation statements)

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“…Across all CSF studies, cell counts ranged from normal [18, 19, 23, 30–36] to increased levels in up to 3.4% of the cases [20, 26] with no difference comparing to neurological controls [37]. Total protein levels varied from normal [18, 22, 30, 31] to increased in up to 42.2% of cases [6, 20, 26, 38, 39], with no difference in the studies comparing to neurological, psychiatric, surgical or healthy controls [32, 40–43]. Albumin levels ranged from normal [18, 22, 30, 31] to increased in up to 16% of cases [6, 24, 39], with no difference in the studies comparing with psychiatric controls [40] or a combined group of healthy and psychiatric controls [38].…”

Section: Primary Outcomesmentioning

confidence: 99%

“…Nonetheless, CSF studies have revealed increased CSF/serum albumin ratio in individuals with schizophrenia and affective disorders [6, 15–25] indicating increased blood–brain barrier (BBB) permeability. Other studies found elevated CSF cell count [15, 16, 20, 26, 27], IgG index [16, 21], and the presence of oligoclonal bands [15, 16, 18, 20, 21] which could be indicators of inflammation and intrathecal immunoglobulin production. Also, a meta-analysis found several specific infectious agents to be associated with schizophrenia; however, most studies were based on blood and not CSF, and control groups consisted typically of non-healthy subjects [28].…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis

et al. 2018

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Infections and inflammatory processes have been associated with the development of schizophrenia and affective disorders; however, no study has yet systematically reviewed all available studies on cerebrospinal fluid (CSF) immune alterations. We aimed to systematically review the CSF immunological findings in schizophrenia spectrum and affective disorders. We identified all studies investigating CSF inflammatory markers in persons with schizophrenia or affective disorders published prior to March 23, 2017 searching PubMed, CENTRAL, EMBASE, Psychinfo, and LILACS. Literature search, data extraction and bias assessment were performed by two independent reviewers. Meta-analyses with standardized mean difference (SMD) including 95% confidence intervals (CI) were performed on case-healthy control studies. We identified 112 CSF studies published between 1942-2016, and 32 case-healthy control studies could be included in meta-analyses. Studies varied regarding gender distribution, age, disease duration, treatment, investigated biomarkers, and whether recruitment happened consecutively or based on clinical indication. The CSF/serum albumin ratio was increased in schizophrenia (1 study [54 patients]; SMD = 0.62; 95% CI 0.24-1.00) and affective disorders (4 studies [302 patients]; SMD = 0.43; 95% CI 0.25-0.61, I = 0%), compared to healthy controls. Total CSF protein was elevated in both schizophrenia (3 studies [97 patients]; SMD = 0.38; 95% CI 0.12-0.65, I = 0%) and affective disorders (2 studies [53 patients]; SMD = 0.77; 95% CI 0.36-1.18, I = 0%). The IgG ratio was increased in schizophrenia (1 study [54 patients]; SMD = 0.60; 95% CI 0.23-0.98), whereas the IgG Albumin ratio was decreased (1 study [32 patients]; SMD = -0.62; 95%CI -1.13 to -0.12). Interleukin-6 (IL-6) levels (7 studies [230 patients]; SMD = 0.38; 95% CI 0.02-0.74; I = 64%) and IL-8 levels (3 studies [95 patients]; SMD = 0.46; 95% CI 0.17-0.75, I = 0%) were increased in schizophrenia but not significantly increased in affective disorders. Most of the remaining inflammatory markers were not significantly different compared to healthy controls in the meta-analyses. However, in the studies which did not include healthy controls, CSF abnormalities were more common, and two studies found CSF dependent re-diagnosis in 3.2-6%. Current findings suggest that schizophrenia and affective disorders may have CSF abnormalities including signs of blood-brain barrier impairment and inflammation. However, the available evidence does not allow any firm conclusion since all studies showed at least some degree of bias and vastly lacked inclusion of confounding factors. Moreover, only few studies investigated the same parameters with healthy controls and high-quality longitudinal CSF studies are lacking, including impact of psychotropic medications, lifestyle factors and potential benefits of anti-inflammatory treatment in subgroups with CSF inflammation.

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Section: Primary Outcomesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis

et al. 2018

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“…Nevertheless, the patients with increased CSF/serum albumin ratios should not simply be dismissed as "outliers", but may possibly represent a pathophysiologically distinct subgroup of patients. Increased blood-CSF permeability in some schizophrenic patients may explain earlier findings (Bruetsch et al, 1942) in large numbers of patients showing increased CSF total protein. In another recent quantitative analysis of CSF proteins in schizophrenia (Roos et al, 1985), the investigators did not specifically examine the albumin ratio.…”

Section: Blood-csf Barrier Permeabilitymentioning

confidence: 67%

“…Among the abnormalities reported at an early point in the course of biological investigations of schizophrenia was 220 D.G. Kirch et al an apparent increase in total CSF protein concentrations (Bruetsch et al, 1942), although subsequent studies of specific CSF proteins yielded divergent findings (Pearson, 1973;Bock and Rafaelson, 1974;Bock, 1978;Kirch et al, 1985;DeLisi and Crow, 1986;Torrey and Kaufmann, 1986).…”

Section: Introductionmentioning

confidence: 99%

Blood-CSF barrier permeability and central nervous system immunoglobulin G in schizophrenia

Kirch

Alexander

Suddath

et al. 1992

J. Neural Transmission

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The ratio of albumin in cerebrospinal fluid (CSF) to serum may serve as an index of the integrity of the blood-CSF barrier, with increases in this ratio indicating increased permeability. The ratio of immunoglobulin G (IgG) in CSF to serum (divided by the albumin ratio to correct for variance in blood-CSF permeability) represents an index of the endogenous production of IgG in the central nervous system (CNS), with increases reflecting a possible infectious and/or autoimmune process stimulating central IgG synthesis. We analyzed simultaneously collected CSF and serum samples from 46 schizophrenic subjects, 8 of whom were studied both on and off neuroleptic treatment, and samples from 20 normal controls. The data indicated increases in CSF/serum albumin ratios or CSF/serum IgG indices in 22% and 20%, respectively, of the schizophrenic patients. Only 3 patients showed elevations in both indices. Comparison of values on and off neuroleptics indicated no significant effect of neuroleptics on these indices.

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“…Studies of CSF total protein in patients with serious mental illness have consistently found a subset of patients with elevated values. The largest such study, done prior to the availability of antipsychotic medications, reported elevated values in 54 (4%) of 1,281 patients (26). A study by Hunter et al (86) reported elevated CSF total protein in 35 (14%) of 256 patients.…”

Section: Protein Abnormalitiesmentioning

confidence: 99%

Viruses, schizophrenia, and bipolar disorder

1995

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The hypothesis that viruses or other infectious agents may cause schizophrenia or bipolar disorder dates to the 19th century but has recently been revived. It could explain many clinical, genetic, and epidemiologic aspects of these diseases, including the winter-spring birth seasonality, regional differences, urban birth, household crowding, having an older sibling, and prenatal exposure to influenza as risk factors. It could also explain observed immunological changes such as abnormalities of lymphocytes, proteins, autoantibodies, and cytokines. However, direct studies of viral infections in individuals with these psychiatric diseases have been predominantly negative. Most studies have examined antibodies in blood or cerebrospinal fluid, and relatively few studies have been done on viral antigens, genomes, cytopathic effect on cell culture, and animal transmission experiments. Viral research on schizophrenia and bipolar disorder is thus comparable to viral research on multiple sclerosis and Parkinson's disease: an attractive hypothesis with scattered interesting findings but no clear proof. The application of molecular biological techniques may allow the identification of novel infectious agents and the associations of these novel agents with serious mental diseases.

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The Group of Dementia Praecox Patients With an Increase of the Protein Content of the Cerebrospinal Fluid

Cited by 19 publications

References 0 publications

Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis

Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis

Blood-CSF barrier permeability and central nervous system immunoglobulin G in schizophrenia

Viruses, schizophrenia, and bipolar disorder

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