Why are white people so anxious?

You’ve probably wondered this if you’re caucasian. Why so much anxiety?(1) Someone in your family is a “worrier.” or “has nerves”. You spend sleepless nights contemplating global warming, stock market collapse, overpopulation, asteroid strikes, supervolcanos, magnetic pole shifts, solar flares, to name a few. Billions of dollars are spent every year on prescription medications, illicit drugs, and alcohol to cope with a collective sense of impending doom. Safe spaces, trigger warnings. Where does it all come from?

The answer may lie in a simple transmembrane protein known as CFTR. This protein spans the walls of the cells in our body and allows the movement of chloride atoms across the cell membrane. But what does chloride (not to be confused with chlorine) have to do with anxiety?

Consider the following observations

1. Cystic fibrosis occurs due to a gene mutation that codes for CTFR. It is one of the most common gene mutations in northern Europeans. As many as 5% of Northern Europeans are carriers. As carriers, they still have one functioning copy of the CFTR gene and are largely unaffected. Those affected by cystic fibrosis have inherited two copies of the mutated CFTR gene. The lack of chloride secretion by cells lining the lungs causes a sticky mucus to form on their surface creating chronic respiratory problems among others. Why is this defective gene so prevalent in Caucasians? If one speculates high prevalence mutated genes in distinct populations offer some protection against endemic infections you’re usually on the right track.  Carriers of the cystic fibrosis gene appear to have some protection against infectious diarrheas like cholera, as well as the scourge of Europe, tuberculosis. Many infectious diarrhea-inducing pathogens secrete toxins that stimulate the secretion of chloride from cells lining the GI tract causing life-threatening dehydration.

2. Cystic fibrosis is the best characterized genetic defect in chloride atom transfer, but one could speculate any additional gene mutations or polymorphisms that alter the transfer of chloride may confer similar benefits against certain infectious diseases.

3. All brain function, including depression and anxiety, is ultimately mediated by chemicals called neurotransmitters. Neurotransmitters allow communication among neurons. Some neurotransmitters are excitatory, some are inhibitory. GABA is the main inhibitory neurotransmitter in the brain. It binds to the GABA receptor on brain neurons and has an inhibitory or calming effect on brain activity. Can’t turn your mind off? Probably mediated by GABA. Of interest, benzodiazepines (valium among others), gabapentin (Neurontin), pregabalin (Lyrica), and alcohol exert their sedating effect by binding to the GABA receptor.

4. What does this all have to do with anxiety? The CFTR protein is found in neurons as well. When the GABA receptor is activated, chloride channels temporarily open to allow the passage of chloride atoms into the neuron, decreasing the cell’s excitability. Therefore, any alteration or reduction in the flow of chloride across cell membranes may impair the function of GABA and increase anxiety. And Caucasians may be more vulnerable.

Just a theory, but if proven correct, you learned it here first.

References

1. Asnaani, et al.  A Cross-Ethnic Comparison of Lifetime Prevalence Rates of Anxiety Disorders. J Nerv Ment Dis. 2010 Aug; 198 (8): 551-555. 

2. Rodman, et al. The cystic fibrosis heterozygote - Advantage in surviving cholera? Medical Hypotheses. Volume 36, Issue 3, November 1991, Pages 253-258

3. Anderson, CM, Allan, J and Johansen, PG (1967) Comments on the possible existence and nature of a heterozygote advantage in cystic fibrosis. Mod. Probl. Pediat. 10: 381–387.

4. Meindl, et al. Hypothesis: A selective advantage for cystic fibrosis heterozygotes. American Journal of Biological Anthropology. September, 1987

5. Reznikov, et al. Cystic Fibrosis and the Nervous System. Chest.  2017 May; 151(5): 1147–1155.