Abnormal cerebrospinal fluid total protein and gamma-globulin levels in 256 patients admitted to a psychiatric unit

doi:10.1016/0022-510X(69)90056-2

Journal of the Neurological Sciences

Volume 9, Issue 1, July–August 1969, Pages 11-38

https://doi.org/10.1016/0022-510X(69)90056-2 Get rights and content

Abstract

Cerebrospinal fluid total protein and γ-globulin levels were measured in 256 unselected patients admitted to a mental hospital unit using the method of Papadopouloset al. (1959). Sixty-eight patients (26.5%) showed abnormalities: 35 (14%) had raised total protein levels and in 9 of these the γ-globulin was also raised; and 33 (13%) had raised γ-globulin levels in the presence of normal total protein.

Serial punctures were performed in 43 patients. In 22 patients with CSF abnormalities initially, and with depressive, schizophrenic or paranoid-hypochondriacal syndromes, the abnormalities disappeared more frequently in patients whose clinical condition improved than in those whose condition showed no change or deteriorated.

Abnormalities were commoner among the men of whom 24 (16%) had raised total protein levels and 20 (14%) raised γ-globulin levels in the presence of normal total protein, as against 11 (10%) and 13 (12%), respectively, of the women.

Among younger patients there was a group with depressive illness and raised total protein levels; and a group with a schizophrenic picture who had raised γ-globulin levels associated with extrapyramidal disturbances and skin eruptions. There was a group of men of middle age or older who developed paranoid syndromes and were found to have persistently-raised total CSF protein levels. Exacerbation of post-encephalitic Parkinsonism was found to be accompanied by changes in the CSF proteins.

In 18 patients the finding of abnormal CSF proteins provided corroborative evidence of systemic or neurological disease; in the remaining 50 it was the most direct evidence of nervous system involvement and in 3 of these led directly to the identification of an organic cause for the illness.

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Immune Cell Alterations in Psychotic Disorders: A Comprehensive Systematic Review and Meta-Analysis
2024, Biological Psychiatry
A comprehensive meta-analysis on the composition of circulating immune cells from both the myeloid and the lymphoid lines including specialized subsets in blood and cerebrospinal fluid (CSF) of patients with psychotic disorders compared with healthy control participants has been lacking.
Multiple databases (PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov, and PsycINFO) were searched for eligible studies up until October 18, 2022. All studies investigating circulating immune cells in the blood and CSF from patients with psychotic disorders (ICD-10: F20 and F22-29) compared with healthy control participants were included.
A total of 86 studies were included in the meta-analysis. In the blood, the following categories of immune cells were elevated: leukocyte count (31 studies, standardized mean difference [SMD] = 0.35; 95% CI, 0.24 to 0.46), granulocyte count (4 studies, SMD = 0.57; 95% CI, 0.12 to 1.01), neutrophil granulocyte count (21 studies, SMD = 0.32; 95% CI, 0.11 to 0.54), monocyte count (23 studies, SMD = 0.40; 95% CI, 0.23 to 0.56), and B lymphocyte count (10 studies, SMD = 0.26; 95% CI, 0.04 to 0.48). Additionally, the neutrophil/lymphocyte ratio (23 studies, SMD = 0.40; 95% CI, 0.19 to 0.60), the monocyte/lymphocyte ratio (9 studies, SMD = 0.31; 95% CI, 0.04 to 0.57), and the platelet/lymphocyte ratio (10 studies, SMD = 0.23; 95% CI, 0.03 to 0.43) were elevated. The CSF cell count showed a similar tendency but was not significantly elevated (3 studies, SMD = 0.14; 95% CI, −0.04 to 0.32).
The results indicate a broad activation of the immune system in psychotic disorders, with cells from both the myeloid and the lymphoid line being elevated. However, CSF analyses were lacking in most of the studies, and many studies were hampered by insufficient adjustment for confounding factors such as body mass index and smoking.
Evidence of cerebrospinal fluid abnormalities in patients with depressive syndromes
2016, Journal of Affective Disorders
Citation Excerpt :
In Table 2, we summarize studies that performed CSF basic diagnostics in patients with depressive syndromes. The main finding in these studies was the relevant BBB dysfunction (Hunter et al., 1969; Bayard-Burfield et al., 1996; Gudmundsson et al., 2007; Bechter et al., 2010). Only one study analyzed cell counts, which were slightly increased in 10% of the patients (Bechter et al., 2010).
Depression is the most prevalent psychiatric disease. In addition to primary, idiopathic depression, there are multiple secondary organic forms. However, distinguishing the two can be difficult, information about cerebrospinal fluid (CSF) basic findings in patients with depressive syndromes is sparse. Therefore, we investigated CSF alterations in so far the largest sample of patients with depressive syndromes. We hypothesized that increased prevalence of CSF pleocytosis, blood-brain-barrier (BBB) dysfunction, and oligoclonal bands (OCBs) would be observed as possible markers of underlying immunological processes.
From January 2006 until October 2013, we performed CSF basic diagnostics in 125 patients with depressive syndromes. We also performed serum and CSF autoantibody measurements, cerebral magnetic resonance imaging (cMRI) and electroencephalography (EEG).
Four % of the patients displayed increased CSF white blood cell counts (WBC), 46.4% had increased protein concentrations, and 19.4% had pathological albumin quotients. OCBs in the CSF were detected in 6.5%. Overall, CSF basic diagnostics were abnormal in 56%. Including instrument-based diagnostics, we found alterations in 80.8% of patients. Suicidal tendencies correlated with an increased WBC count (r=0.276, p=0.002).
In this open, uncontrolled study, we investigated mainly CSF samples of depressive patients with signs of organic features. Therefore, the study cohort is not representative of idiopathic depression.
The main findings of this study are the high rates of pathological (although mainly unspecific) CSF findings. We discuss the findings regarding possible immunological mechanisms and the vascular depression hypothesis. If these findings are associated with low-level inflammation of the central nervous system, new treatment alternatives could be considered. More and better controlled research is necessary.
Cerebrospinal fluid total protein in patients with affective disorders
1995, Psychiatry Research
Cerebrospinal fluid (CSF) total protein was evaluated in 240 patients with affective disorders and compared with findings in 55 normal comparison subjects. Subtype diagnoses were as follows: bipolar I (n = 108, 47 men, 61 women); bipolar type II (n = 67, 26 men, 41 women); and unipolar (n = 65, 22 men, 43 women). Men had significantly elevated values compared with women. In men with bipolar I disorder, mean CSF protein levels were found to be significantly elevated over those in normal subjects, with 31.9% above the traditional normal range cutoff of 45 mg/dl. Moreover, CSF protein levels in male bipolar I patients were found to be positively correlated with severity of depression at the time of the lumbar puncture and with duration of illness. It thus appears that increased protein levels may be associated with illness severity or progression in male patients with bipolar I disorder. Although elevated CSF protein is a nonspecific marker of cerebral pathology, further search for the potential underlying pathophysiological mechanisms related to this finding would now appear to be warranted.
Elevated cerebrospinal fluid protein in men with unipolar or bipolar depression
1994, Biological Psychiatry
We studied a large sample of rigorously diagnosed, generally unmedicated patients with major depressive disorder (n = 179), bipolar affective disorder (n = 102), or schizophrenia (n = 125) to determine if increased cerebrospinal fluid (CSF) protein is associated with a particular diagnosis or gender. Men had a higher mean CSF protein level than women across all diagnoses (p < 0.001). There were no differences across diagnosis among the female patients. Men with unipolar depression had a higher mean CSF protein content than other male patients (n = 0.029), but depressed bipolar males had an equivalently elevated mean level. Considered apart from unipolar or bipolar diagnosis, the depressive syndrome was strongly associated with increased CSF protein in men (p = 0.004); again, there was no difference across type of illness (depression versus mania) among women. Elevated CSF protein content seems to be associated with illness syndrome rather than diagnosis, and may represent an important finding among men with depression.
Elevated CSF protein in male patients with depression
1990, Biological Psychiatry
Elevation of total protein is the most frequent pathologic finding in the cerebrospinal fluid (CSF) examination. It occurs in a variety of situations such as inflammation or tumors of the central nervous system (CNS), degenerative disorders, and subarachnoid hemorrhage, or as a result of traumatic taps. It has also been reported, for unknown reasons, in patients with psychiatric disease. In a study of hormone changes in depression, 9 of 24 (38%) patients (13 male, 11 female) were found to have elevated CSF protein levels (>45 mg/dl), whereas no elevations were found in healthy controls (8 male, 9 female). Eight of the patients with the elevated CSF protein levels were male (62%) and one was female (9%). Depressed patients had significantly higher CSF protein levels (44.7 ± 18.0 mg/dl) than controls (31.5 ± 6.0 mg/dl) (t = 3.32, df = 30.37, p = 0.002). No relationship was found between CSF protein levels and (1) the use of medication (tricyclic antidepressants, lithium carbonate, or monoamine oxidase inhibitors) or (2) post-dexamethasone suppression test cortisol levels. Female controls, however, tended to have lower protein levels than male controls, whereas female patients had significantly lower levels than male patients. Protein electrophoresis was performed on 21 of the 41 subjects (13 patients, 8 controls). Male patients had nonsignificantly higher absolute concentrations of CSF albumin and the globulin fractions when compared to male controls. These differences in CSF protein do not suggest monoclonal CSF protein production, nor are they the result of this elevated peripheral protein. They suggest increased polyclonal production of CSF protein and/or increased blood-brain barrier permeability in male depressed patients, and a tendency to such in female depressed patients.
Depression, Stress, and Immunity
1987, The Lancet

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Abnormal cerebrospinal fluid total protein and gamma-globulin levels in 256 patients admitted to a psychiatric unit

Abstract

Lancet

J. neurol. Sci.

J. neurol. Sci.

Amer. J. Med.

Immunoelektrophoretische Erfahrungen bei Liquores mit erhöhten Gamma-Globulinen

Depression. Clinical, Experimental, and Theoretical Aspects

Dementia Praecox

Forschungen zur Schizophrenielehre 1951 bis 1955

Forschungen und Begriffswandlungen in der Schizophrenielehre 1941–1950

Über den Liquor bei Schizophrenen

Allg. Z. Psychiat.

Subacute encephalitis of later adult life, mainly affecting the limbic areas

Brain

Een Onderzoek van den Liquor Cerebrospinalis bij Schizophrenen

The group of dementia praecox patients with an increase of protein content of the cerebrospinal fluid

J. nerv. ment. Dis.

Studies in schizophrenia

J. ment. Sci.

Panel discussion of “proposed standardization of analysis of cerebrospinal fluid proteins”

Periodic hypersomnia and megaphagia in adolescent males

Brain

Physiology of the Cerebrospinal Fluid

Der Liquor Cerebrospinalis bei den sogenannten Hirnatrophien

Fortschr. Neurol. Psychiat.

Das Eiweissbild des Liquor Cerebrospinalis

Fortschr. Immunitätsforsch.

Clinical Value of Protein Analysis in Cerebrospinal Fluid

Sex differences in total protein content of cerebrospinal fluid

Acta psychiat. scand.

Spinal fluid changes in patients treated with ataractic drugs

Amer. J. Psychiat.