Cannabis use is associated with increased levels of soluble gp130 in schizophrenia but not in bipolar disorder

ABSTRACTThe complex effects of plant cannabinoids on human physiology is not yet fully understood, but include a wide spectrum of effects on immune modulation. The immune system and its inflammatory effector pathways are recently emerging as possible causative factors in psychotic disorders. The present study aimed to investigate whether self-administered cannabis use was associated with changes in circulating immune and neuroendocrine markers in schizophrenia (SCZ, n=401) and bipolar disorder patients (BD, n=242). A screening of 13 plasma markers reflecting different inflammatory pathways was performed in SCZ and BD patients after subdividing each group into cannabis user and non-user subgroups. We found that i) soluble gp130 (sgp130) concentrations were significantly elevated among cannabis users in the SCZ group (p=0.002) after multiple testing correction, but not in BD. ii) Nominally significant differences were observed in the levels of IL-1RA (p=0.0059), YKL40 (p=0.0069), CatS (p=0.013), sTNFR1 (p=0.031), and BDNF (p=0.020), where these factors exhibited higher plasma levels in cannabis user SCZ patients than in non-users. iii) These differences in systemic levels were not reflected by altered mRNA expression of genes encoding sgp130, IL-1RA, YKL40, CatS, sTNFR1, and BDNF in whole blood. In sum, our results show that cannabis self-administration is associated with markedly higher sgp130 levels in SCZ, but not in BD, and that this phenomenon is independent of the modulation of peripheral immune cells. These findings warrant further investigation into the potential neuroimmune, anti-inflammatory, and biobehavioral-cognitive effects of cannabis use in SCZ.

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Exploring Phenotypic and Genetic Overlap Between Cannabis Use and Schizotypy

Twin Research and Human Genetics ◽

10.1017/thg.2020.68 ◽

2020 ◽

Vol 23 (4) ◽

pp. 221-227 ◽

Cited By ~ 1

Author(s):

James Vaissiere ◽

Jackson G. Thorp ◽

Jue-Sheng Ong ◽

Alfredo Ortega-Alonso ◽

Eske M. Derks

Keyword(s):

Multiple Testing ◽

Association Studies ◽

Genetic Correlations ◽

Cannabis Use ◽

Exact Nature ◽

Social Anhedonia ◽

Multiple Testing Correction ◽

Phenotypic Correlations ◽

Genetic Overlap ◽

Heritability Estimates

AbstractThere is a well-established relationship between cannabis use and psychosis, although the exact nature of this relationship is not fully understood. Recent studies have observed significant genetic overlap between a diagnosis of schizophrenia and lifetime cannabis use. Expanding on this work, the current study aimed to examine whether genetic overlap also occurs for subclinical psychosis (schizotypy) and cannabis use, as well as examining the phenotypic association between the traits. Phenotypic correlations were calculated for a variety of schizotypy and cannabis phenotypes in the UK Biobank (UKB), and single nucleotide polymorphism (SNP)-based heritability estimates and genetic correlations were calculated for these UKB phenotypes as well as for several other variables taken from recent genomewide association studies. Positive phenotypic correlations were observed between 11 out of 12 pairs of the cannabis use and schizotypy phenotypes (correlation range .05–.18), indicating a robust association between increased symptoms of schizotypy and cannabis use. SNP-based heritability estimates for two schizotypy phenotypes remained significant after multiple testing correction: social anhedonia (h2SNP = .08, SE = .02, N = 4025) and ever seen an unreal vision (h2SNP = .35, SE = .10, N = 150,717). Finally, one significant genetic correlation was observed between schizotypy and cannabis use, a negative correlation between social anhedonia and number of times used cannabis (rg = −.30, p = .012). The current study suggests the relationship between cannabis use and psychosis is also seen in subclinical symptoms of psychosis, but further research with larger samples is needed to determine the biological mechanisms underlying this association.

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Cannabis Use Is Associated With Increased Levels of Soluble gp130 in Schizophrenia but Not in Bipolar Disorder

Frontiers in Psychiatry ◽

10.3389/fpsyt.2020.00642 ◽

2020 ◽

Vol 11 ◽

Author(s):

Attila Szabo ◽

Ibrahim A. Akkouh ◽

Thor Ueland ◽

Trine Vik Lagerberg ◽

Ingrid Dieset ◽

...

Keyword(s):

Bipolar Disorder ◽

Cannabis Use ◽

Soluble Gp130

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C-reactive Protein and Parathyroid Hormone in Acute Severe Psychotic Disorders (Schizophrenia, Bipolar Disorder and Methamphetamine-induced Psychotic Disorder)

10.26226/morressier.5885d719d462b8028d892863 ◽

2017 ◽

Author(s):

Shahrzad Arya

Keyword(s):

Bipolar Disorder ◽

Parathyroid Hormone ◽

Psychotic Disorder ◽

Psychotic Disorders ◽

C Reactive Protein ◽

Reactive Protein

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Cortical thickness, cortical surface area and subcortical volumes in schizophrenia and bipolar disorder patients with cannabis use

10.26226/morressier.5971be84d462b80290b52671 ◽

2017 ◽

Author(s):

Cecilie Bhandari Hartberg

Keyword(s):

Bipolar Disorder ◽

Surface Area ◽

Cortical Thickness ◽

Cannabis Use ◽

Cortical Surface ◽

Cortical Surface Area ◽

Subcortical Volumes

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Faculty Opinions recommendation of How does multiple testing correction work?

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.720491212.793520593 ◽

2016 ◽

Author(s):

Robert Powers

Keyword(s):

Multiple Testing ◽

Multiple Testing Correction

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Genetic biomarkers in the VEGF pathway predicting response to anti-VEGF therapy in age-related macular degeneration

BMJ Open Ophthalmology ◽

10.1136/bmjophth-2019-000273 ◽

2019 ◽

Vol 4 (1) ◽

pp. e000273

Author(s):

Irina Balikova ◽

Laurence Postelmans ◽

Brigitte Pasteels ◽

Pascale Coquelet ◽

Janet Catherine ◽

...

Keyword(s):

Visual Acuity ◽

Macular Degeneration ◽

Treatment Response ◽

Multiple Testing ◽

Age Related Macular Degeneration ◽

Patient Specific ◽

Multiple Testing Correction ◽

Anti Vegf ◽

Age Related ◽

Vegf Pathway

ObjectiveAge-related macular degeneration (ARMD) is a leading cause of visual impairment. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard treatment for wet ARMD. There is however, variability in patient responses, suggesting patient-specific factors influencing drug efficacy. We tested whether single nucleotide polymorphisms (SNPs) in genes encoding VEGF pathway members contribute to therapy response.Methods and analysisA retrospective cohort of 281 European wet ARMD patients treated with anti-VEGF was genotyped for 138 tagging SNPs in the VEGF pathway. Per patient, we collected best corrected visual acuity at baseline, after three loading injections and at 12 months. We also registered the injection number and changes in retinal morphology after three loading injections (central foveal thickness (CFT), intraretinal cysts and serous neuroepithelium detachment). Changes in CFT after 3 months were our primary outcome measure. Association of SNPs to response was assessed by binomial logistic regression. Replication was attempted by associating visual acuity changes to genotypes in an independent Japanese cohort.ResultsAssociation with treatment response was detected for seven SNPs, including in FLT4 (rs55667289: OR=0.746, 95% CI 0.63 to 0.88, p=0.0005) and KDR (rs7691507: OR=1.056, 95% CI 1.02 to 1.10, p=0.005; and rs2305945: OR=0.963, 95% CI 0.93 to 1.00, p=0.0472). Only association with rs55667289 in FLT4 survived multiple testing correction. This SNP was unavailable for testing in the replication cohort. Of six SNPs tested for replication, one was significant although not after multiple testing correction.ConclusionIdentifying genetic variants that define treatment response can help to develop individualised therapeutic approaches for wet ARMD patients and may point towards new targets in non-responders.

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DSM-III criteria for affective disorders and schizophrenia : A preliminary appraisal using family interview findings

Psychiatry and Psychobiology ◽

10.1017/s0767399x00001723 ◽

1988 ◽

Vol 3 (3) ◽

pp. 159-169

Author(s):

H.G. Pope ◽

B.M. Cohen ◽

J.F. Lipinski ◽

D. Yurgelun-Todd

Keyword(s):

Bipolar Disorder ◽

Affective Disorder ◽

Schizoaffective Disorder ◽

Psychotic Disorders ◽

Diagnostic Interview ◽

Diagnostic Categories ◽

Family Interview ◽

Small Test ◽

Test Retest Reliability ◽

Interview Studies

SummaryWe performed a blind family interview study of 226 first-degree relatives of 63 probands meeting DSM-III criteria for schizophrenia, schizoaffective disorder, and bipolar disorder, as diagnosed by the National Institute ot Mental Health Diagnostic Interview Schedule (DIS). A small test-retest reliability study demonstrated good agreement between the proband interviewer and the principal family interviewer for the major diagnostic categories of psychotic disorders. Excellent compliance was obtained, with 85% of living relatives interviewed personally.Three principal findings emerged front the study. First, as expected, bipolar disorder, as defined by DSM-III, displayed a strong familial comportent, comparable to that found by many studies using criteria other than those of DSM-III. Second, patients meeting DSM-III criteria for schizophrenia and schizoaffective disorder displayed a low familial prevalence of schizophrenia. Although initially suprising, this finding is in agreement with the results of several other recent lantily studies of schizophrenia. Upon comparing our results with those of other recent family studies of schizophrenia, it appears that the familial component in schizophrenia tnay be less than was estimated by earlier studies using older and “broader” definitions of schizophrenia.Third, we found that patients meeting DSM-III criteria for schizophrenia appeared genetically heterogeneous. Those who had displayed a superimposed full affective syndrome at some tinte in the course of their illness, together with those probands meeting DSM-III criteria for schizoaffective disorder, displayed a high familial prevalence of major affective disorder, similar to that found in the families of the bipolar probands. On the other hand, “pure” DSM-III schizophrenie probands, who had never experienced a superimposed full affective syndrome, displayed a low familial prevalence of major affective disorder, similar to that found in the general population. These findings favor the possibility that probands meeting DSM-III criteria for schizophrenia, but displaying a superimposed full affective syndrome, may in sonie cases have a disorder genetically relatcd to major affective disorder.Further prospective family interview studies, using DSM-III criteria and larger samples, will be necessary to test these preliminary impressions.

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2dFDR: a new approach to confounder adjustment substantially increases detection power in omics association studies

Genome Biology ◽

10.1186/s13059-021-02418-8 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Sangyoon Yi ◽

Xianyang Zhang ◽

Lu Yang ◽

Jinyan Huang ◽

Yuanhang Liu ◽

...

Keyword(s):

Multiple Testing ◽

Statistical Power ◽

Association Studies ◽

Control Procedure ◽

Multiple Testing Correction ◽

New Approach ◽

False Discovery ◽

Traditional Procedure ◽

Extensive Evaluation ◽

Confounder Adjustment

AbstractOne challenge facing omics association studies is the loss of statistical power when adjusting for confounders and multiple testing. The traditional statistical procedure involves fitting a confounder-adjusted regression model for each omics feature, followed by multiple testing correction. Here we show that the traditional procedure is not optimal and present a new approach, 2dFDR, a two-dimensional false discovery rate control procedure, for powerful confounder adjustment in multiple testing. Through extensive evaluation, we demonstrate that 2dFDR is more powerful than the traditional procedure, and in the presence of strong confounding and weak signals, the power improvement could be more than 100%.

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