Blood copper and psychiatric disorders- some correlational studies

Everyone has at least one hobby horse, I have a stable’s full. One of mine is the relationship between copper and psychiatric disorders. I first became interested in this connection when someone gave me a copper supplement to take and over a few days I became very anxious. The relationship is understudied, but what research there is has often found impressive effect sizes.

I’ve accumulated some studies that look at the relationship between various psychiatric disorders and copper. These weren’t gathered systematically, they’re just what I happened to run into, but nor have I excluded anything I found which was relevant. Unless I’ve forgotten something I’ve found only one negative result. I haven’t gathered these studies on the basis of any particular expertise in his area (quite the contrary) and I can’t vouch for their quality. I have calculated Cohen’s d myself where there is sufficient information to do so.

My understanding is that what motivated this research is that copper toxicity- a syndrome caused by extremely elevated blood copper levels is- associated with a variety of psychiatric problems including depression, anxiety, mood-swings, irritability, cognitive deficits & psychosis. But does a relationship between anxiety & copper hold outside extreme cases like copper toxicity?

Anxiety

Russo (2011) found significantly higher copper levels in anxiety patients compared to healthy controls (p= 0.0348, effect size using Cohen’s d =0.643575- “moderate”)

Islam et al. (2013) found an extremely large relationship between copper & anxiety (p=<0.0001, effect size using Cohen’s d= 1.566425- this is off the standard rating scale for Cohen’s d but we will call it “ginormous”).

Anxiety- OCD

One of only two negative results. Shohag et al. (2012) found no relationship between OCD and copper levels.

Ceruloplasmin is a protein with copper bound to it, indeed, a large majority of the copper in the blood is bound to ceruloplasmin. Virit et al. (2008) found that patients with OCD had more than twice the ceruloplasmin.

Depression

Młyniec (2014) reviews evidence relating Copper to depression, and finds a total of five studies, all of which indicated a relationship between copper & depression in some way- four by showing that blood copper is higher in those with depression or a history of depression by 14 to 22%, one by showing that blood copper fell post-treatment for depression.

Bipolar disorder

Mustak et al. (2008) found that across types and phases of bipolar disorder there is elevated copper levels. Bipolar type I, for example, was associated with  76.9% greater blood copper than healthy controls.

Schizophrenia

Yanik et al. (2004) found a large relationship (p= <0.001, d= >1.24 effect size well over the threshold for “large”) between schizophrenia and blood copper levels.

Vidović (2013) found a moderate relationship between schizophrenia and blood copper levels ( p = 0.001 d=0.634841, “moderate”)

Acik (2009) found that copper levels were even higher again among schizophrenics with a criminal record (no comparison between schizophrenics and non-schizophrenics was included however).

ADHD

Viktorinova et al. (2015) fails to do not find a positive relationship between copper and ADHD, although they report that there is a non-significant difference in that direction.

Autism

Faber et al. (2009) reports that autistic children generally have a lower (blood zinc/blood  copper) ratio than benchmark levels, though frustratingly they don’t seem to compare the mean blood copper in autistic children to the mean blood copper in non autistic children. It would seem the mean is likely to be above the normal range for copper because: “17% of the cohort displayed copper toxicity based on normal ARUP Laboratory ranges.”

Concluding remarks

A number of authors cited also look at other elements. A particularly popular candidate is Zinc, which is thought to be associated with reduced anxiety, and some authors suggest the copper/zinc ratio may be what determines symptoms, rather than either element in isolation. The quantity of the two elements does tend to be inversely related in he blood. Really then, all of the effect of copper might be mediated through its effect in lowering blood zinc.

It should go without saying, but none of this proves that copper causes anxiety. It could well be that elevated copper levels in the blood actually represent an adaptive response to anxiety.

Nonetheless, my own personal decision (and this is not medical advice) has been to avoid supplements that contain copper, unless advised to take them by a medical professional.

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