Inflammatory Biomarkers and Risk of Schizophrenia. A 2-Sample Mendelian Randomization Study. Fernando Pires Hartwig et al. JAMA Psychiatry, doi:10.1001/jamapsychiatry.2017.3191
Key Points
Question What is the effect of increased inflammatory biomarkers on the risk of developing schizophrenia?
Findings In this 2-sample mendelian randomization study using summary gene-biomarker association results estimated in pooled samples ranging from 1645 to more than 80 000 individuals, 2-fold increments in circulating levels of C-reactive protein and soluble interleukin-1 receptor levels were associated with a 10% reduction and a 6% increase in the lifetime odds of developing schizophrenia.
Meaning We found that blockade of interleukin-6 effects and low C-reactive protein levels might increase schizophrenia risk, possibly due to increased susceptibility to early life infection.
Abstract
Importance Positive associations between inflammatory biomarkers and risk of psychiatric disorders, including schizophrenia, have been reported in observational studies. However, conventional observational studies are prone to bias, such as reverse causation and residual confounding, thus limiting our understanding of the effect (if any) of inflammatory biomarkers on schizophrenia risk.
Objective To evaluate whether inflammatory biomarkers have an effect on the risk of developing schizophrenia.
Design, Setting, and Participants Two-sample mendelian randomization study using genetic variants associated with inflammatory biomarkers as instrumental variables to improve inference. Summary association results from large consortia of candidate gene or genome-wide association studies, including several epidemiologic studies with different designs, were used. Gene-inflammatory biomarker associations were estimated in pooled samples ranging from 1645 to more than 80 000 individuals, while gene-schizophrenia associations were estimated in more than 30 000 cases and more than 45 000 ancestry-matched controls. In most studies included in the consortia, participants were of European ancestry, and the prevalence of men was approximately 50%. All studies were conducted in adults, with a wide age range (18 to >80 years).
Exposures Genetically elevated circulating levels of C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1Ra), and soluble interleukin-6 receptor (sIL-6R).
Main Outcomes and Measures Risk of developing schizophrenia. Individuals with schizophrenia or schizoaffective disorders were included as cases. Given that many studies contributed to the analyses, different diagnostic procedures were used.
Results The pooled odds ratio estimate using 18 CRP genetic instruments was 0.90 (random effects 95% CI, 0.84-0.97; P = .005) per 2-fold increment in CRP levels; consistent results were obtained using different mendelian randomization methods and a more conservative set of instruments. The odds ratio for sIL-6R was 1.06 (95% CI, 1.01-1.12; P = .02) per 2-fold increment. Estimates for IL-1Ra were inconsistent among instruments, and pooled estimates were imprecise and centered on the null.
Conclusions and Relevance Under mendelian randomization assumptions, our findings suggest a protective effect of CRP and a risk-increasing effect of sIL-6R (potentially mediated at least in part by CRP) on schizophrenia risk. It is possible that such effects are a result of increased susceptibility to early life infection.
34 Inspiring Quotes on Criticism (and How to Handle It) -- EXTRACT
- – Dale Carnegie
- “The pleasure of criticizing takes away from us the pleasure of being moved by some very fine things.”
– Jean de La BruyĆØre - – Aristotle
- – John Wooden
- “Criticism is an indirect form of self-boasting.”
– Emmet Fox - “When virtues are pointed out first, flaws seem less insurmountable.”
– Judith Martin - – Neil Gaiman
- – Norman Vincent Peale
- “When we judge or criticize another person, it says nothing about
that person; it merely says something about our own need to be
critical.”
– Unknown - “It is much more valuable to look for the strength in others. You can gain nothing by criticizing their imperfections.”
– Daisaku Ikeda - “The artist doesn’t have time to listen to the critics. The ones who
want to be writers read the reviews, the ones who want to write don’t
have the time to read reviews.”
– William Faulkner - “If we judge ourselves only by our aspirations and everyone else
only their conduct we shall soon reach a very false conclusion.”
– Calvin Coolidge - “I have yet to find the man, however exalted his station, who did
not do better work and put forth greater effort under a spirit of
approval than under a spirit of criticism.”
– Charles Schwab - “I criticize by creation, not by finding fault.”
– Marcus Tullius Cicero - “Let me never fall into the vulgar mistake of dreaming that I am persecuted whenever I am contradicted.”
– Ralph Waldo Emerson - “Don’t criticize what you don’t understand, son. You never walked in that man’s shoes.”
– Elvis Presley - – Frank A. Clark
- “People tend to criticize their spouse most loudly in the area where they themselves have the deepest emotional need.”
– Gary Chapman - “Criticism is the disapproval of people, not for having faults, but having faults different from your own.”
– Unknown - “It is not the critic who counts; not the man who points out how the
strong man stumbles, or where the doer of deeds could have done them
better.
The credit belongs to the man who is actually in the arena, whose face is marred by dust and sweat and blood, who strives valiantly; who errs and comes short again and again; because there is not effort without error and shortcomings; but who does actually strive to do the deed; who knows the great enthusiasm, the great devotion, who spends himself in a worthy cause, who at the best knows in the end the triumph of high achievement and who at the worst, if he fails, at least he fails while daring greatly.
So that his place shall never be with those cold and timid souls who know neither victory nor defeat.”
– Theodore Roosevelt - “Before you go and criticize the younger generation, just remember who raised them.”
– Unknown - “Who do you spend time with? Criticizers or encouragers? Surround
yourself with those who believe in you. Your life is too important for
anything less.”
– Steve Goodier - “Criticism may not be agreeable, but it is necessary. It fulfills
the same function as pain in the human body. It calls attention to an
unhealthy state of things.”
– Winston Churchill - “He has a right to criticize, who has a heart to help.”
– Abraham Lincoln - – Antoine de Saint-Exupery
- – Eleanor Roosevelt
- “One mustn’t criticize other people on grounds where he can’t stand perpendicular himself”
– Mark Twain - “That was excellently observed’, say I, when I read a passage in an
author, where his opinion agrees with mine. When we differ, there I
pronounce him to be mistaken.”
– Jonathan Swift - “Any fool can criticize, condemn and complain and most fools do.”
– Benjamin Franklin - “Flatter me, and I may not believe you. Criticize me, and I may not
like you. Ignore me, and I may not forgive you. Encourage me, and I will
not forget you. Love me and I may be forced to love you.”
– William Arthur Ward - “A man interrupted one of the Buddha’s lectures with a flood of abuse.
Buddha waited until he had finished and then asked him:
If a man offered a gift to another but the gift was declined, to whom would the gift belong?
To the one who offered it, said the man.
Then, said the Buddha, I decline to accept your abuse and request you to keep it for yourself.” - – Joseph Joubert
- – Abraham Lincoln
- – Michel de Montaigne