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Cerebrospinal fluid cytokines in geriatric patients with depressive disorders: A retrospective case-control study.

ABSTRACT: Central nervous system inflammation might play a role in patients with depressive disorders. This hypothesis is supported by studies reporting increased cerebrospinal fluid levels of the inflammatory markers interleukin (IL)-6, IL-8 and tumor necrosis factor alpha (TNF-α) in patients with ongoing depression. In this case-control study, we aimed to examine whether these findings also applied to depressed patients in a geriatric population. Cerebrospinal fluid cytokine analyses were performed on 15 patients (age >60 years) with depressive disorders and 45 age- and sex matched controls (patients with headache or idiopathic facial palsy). IL-6, IL-8, IL-10, TNF-α, monocyte chemoattractant protein-1 and transforming growth factor beta 1 were included in the statistical analyses. Patients with depression had significantly lower cerebrospinal fluid levels of IL-6 as compared to controls (p = 0.014) in the univariate analysis. The finding was, however, no longer statistically significant after correction for age and body mass index (p = 0.097). Overall, this study indicates that the cytokines included in this study are not significantly altered in geriatric patients with depression. Future studies exploring cerebrospinal fluid cytokine levels should include corrections for possible confounding factors.

SUBMITTER: Schou MB

PROVIDER: S-EPMC9510363 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Cerebrospinal fluid cytokines in geriatric patients with depressive disorders: A retrospective case-control study.

Schou Morten Brix MB Larsen Jeanette Brun JB Stunes Astrid Kamilla AK Sæther Sverre Georg SG

Frontiers in psychiatry 20220912

Central nervous system inflammation might play a role in patients with depressive disorders. This hypothesis is supported by studies reporting increased cerebrospinal fluid levels of the inflammatory markers interleukin (IL)-6, IL-8 and tumor necrosis factor alpha (TNF-α) in patients with ongoing depression. In this case-control study, we aimed to examine whether these findings also applied to depressed patients in a <i>geriatric population</i>. Cerebrospinal fluid cytokine analyses were perform ...[more]

PMID: 36172507

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Project description:In current international classification systems (ICD-10, DSM5), the diagnostic criteria for psychotic disorders (e.g. schizophrenia and schizoaffective disorder) are based on symptomatic descriptions since no unambiguous biomarkers are known to date. However, when underlying causes of psychotic symptoms, like inflammation, ischemia, or tumor affecting the neural tissue can be identified, a different classification is used ("psychotic disorder with delusions due to known physiological condition" (ICD-10: F06.2) or psychosis caused by medical factors (DSM5)). While CSF analysis still is considered optional in current diagnostic guidelines for psychotic disorders, CSF biomarkers could help to identify known physiological conditions. In this retrospective, partly descriptive analysis of 144 patients with psychotic symptoms and available CSF data, we analyzed CSF examinations' significance to differentiate patients with specific etiological factors (F06.2) from patients with schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F2). In 40.3% of all patients, at least one CSF parameter was out of the reference range. Abnormal CSF-findings were found significantly more often in patients diagnosed with F06.2 (88.2%) as compared to patients diagnosed with F2 (23.8%, p < 0.00001). A total of 17 cases were identified as probably caused by specific etiological factors (F06.2), of which ten cases fulfilled the criteria for a probable autoimmune psychosis linked to the following autoantibodies: amphiphysin, CASPR2, CV2, LGl1, NMDA, zic4, and titin. Two cases presented with anti-thyroid tissue autoantibodies. In four cases, further probable causal factors were identified: COVID-19, a frontal intracranial tumor, multiple sclerosis (n = 2), and neurosyphilis. Twenty-one cases remained with "no reliable diagnostic classification". Age at onset of psychotic symptoms differed between patients diagnosed with F2 and F06.2 (p = 0.014), with the latter group being older (median: 44 vs. 28 years). Various CSF parameters were analyzed in an exploratory analysis, identifying pleocytosis and oligoclonal bands (OCBs) as discriminators (F06.2 vs. F2) with a high specificity of > 96% each. No group differences were found for gender, characteristics of psychotic symptoms, substance dependency, or family history. This study emphasizes the great importance of a detailed diagnostic workup in diagnosing psychotic disorders, including CSF analysis, to detect possible underlying pathologies and improve treatment decisions.

Project description:BACKGROUND:Idiopathic intracranial hypertension (IIH) is a neurological disorder characterised by raised cerebrospinal fluid (CSF) pressure in the absence of any intracranial pathology. IIH mainly affects women with obesity between the ages of 15 and 45. Two possible mechanisms that could explain the increased CSF pressure in IIH are excessive CSF production by the choroid plexus (CP) epithelium or impaired CSF drainage from the brain. However, the molecular mechanisms controlling these mechanisms in IIH remain to be determined. METHODS:In vivo ventriculo-cisternal perfusion (VCP) and variable rate infusion (VRI) techniques were used to assess changes in rates of CSF secretion and resistance to CSF drainage in female and male Wistar rats fed either a control (C) or high-fat (HF) diet (under anaesthesia with 20 μl/100 g medetomidine, 50 μl/100 g ketamine i.p). In addition, CSF secretion and drainage were assessed in female rats following treatment with inflammatory mediators known to be elevated in the CSF of IIH patients: C-C motif chemokine ligand 2 (CCL2), interleukin (IL)-17 (IL-17), IL-6, IL-1β, tumour necrosis factor-α (TNF-α), as well as glucocorticoid hydrocortisone (HC). RESULTS:Female rats fed the HF diet had greater CSF secretion compared to those on control diet (3.18 ± 0.12 μl/min HF, 1.49 ± 0.15 μl/min control). Increased CSF secretion was seen in both groups following HC treatment (by 132% in controls and 114% in HF) but only in control rats following TNF-α treatment (137% increase). The resistance to CSF drainage was not different between control and HF fed female rats (6.13 ± 0.44 mmH2O min/μl controls, and 7.09 ± 0.26 mmH2O min/μl HF). and when treated with CCL2, both groups displayed an increase in resistance to CSF drainage of 141% (controls) and 139% (HF) indicating lower levels of CSF drainage. CONCLUSIONS:Weight loss and therapies targeting HC, TNF-α and CCL2, whether separately or in combination, may be beneficial to modulate rates of CSF secretion and/or resistance to CSF drainage pathways, both factors likely contributing to the raised intracranial pressure (ICP) observed in female IIH patients with obesity.

Dataset Information

Cerebrospinal fluid cytokines in geriatric patients with depressive disorders: A retrospective case-control study.

Publications

Cerebrospinal fluid cytokines in geriatric patients with depressive disorders: A retrospective case-control study.

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