I am not neurotic, but I occasionally worry that dreadful things will happen, caused by a lamentable oversight on my part, such as an un-returned Christmas greeting provoking justifiable depression in a former acquaintance who then turns to drink, and crashes his car into a pedestrian who happens to be the only person capable of saving us from a world-wide bird-flu pandemic, thus leading to the end of humanity.
Now an explanation for my slight tendency to worry arrives in the form of a mammoth study on the genetics of neuroticism. Has my affliction been tracked down, and is it attributable to my genes, rather than the slings and arrows of outrageous fortune? Let us see.
The status quo ante was that a nervous disposition, mostly concerned with worry and guilt, was associated with 11 genetic loci. Now the Deary gang have crunched the genetic data on 329,821 Biobank participants, and in a GWAS identified 116 significant independent loci related to neuroticism, an order of magnitude increase in our understanding of the genetic basis of the condition. 15 of these loci replicated at P < 0.00045 in an unrelated cohort (N = 122,867). In fact, it is a bit better than that, as 111 out of 116 were found in the replication cohort, with 51 nominally significant, and only 15 after Bonferroni correction. As one might expect, the genetic signals of neuroticism correlated with the genetic signals of depressive symptoms (0.82) major depressive disorder (0.69) and subjective well-being (-0.68).
Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism. Nature Genetics. https://doi.org/10.1038/s41588-017-0013-8
Far from being a random collection of signals that happen to have got through even the most rigorous controls for multiple comparisons, this bunch make sense in terms of their molecular function, biological process and protein class. There are some demonstrated links with anxiety and depression, and psychiatric disorder generally. Among the 15 replicated SNPs 9 were associated with significant regulation of 60 genes expressed in a variety of tissues. Of the 30 brain expression associations, half were in the cerebellum, with 4 SNPs regulating 10 genes. Notably, magnetic resonance imaging (MRI) studies have shown associations between cerebellar volume and neuroticism as well as cerebellar blood flow in response to negative emotional cues.
Yes, the effect sizes are still small, and other studies will be required to confirm these findings, and to extend them.
In the current climate of genetic research, this will be correctly seen as a big advance in understanding the causes of personality differences. However, earlier in the 20th Century, this would have been dynamite, because the prevailing ideology, fuelled by psycho-analytic theory, was that variously, trauma, seduction and repressed sexuality were the root causes of neuroticism. With rather more evidence, and far less impact on popular culture, Pavlov was on the right track when he surmised that a different balance of excitation and inhibition in the nervous system was what determined the resilience of dogs under stress. Dogs have temperaments, and Pavlov noticed that. Hans Eysenck and Jeffrey Gray extended those insights.
The authors conclude:
There was also support for neuroticism having causal effects on socioeconomic markers. These discoveries promise paths to understanding the mechanisms whereby some people become depressed and broader human differences in happiness, and they are a resource for those seeking novel drug targets for major depression.
After millennia in which scholars and researchers have sought the sources of individual differences in proneness to dysphoria, the present study adds to explanations of the (genetic) anatomy of melancholy.
I wonder if these sorts of research results might one day bring about a cultural change, in which it is accepted that while some people experience more negative events than others, people also differ in their sensitivity to emotional issues.