Neuroticism

Neuroticism is the personality dimension that describes how readily someone experiences negative emotion: worry, self-consciousness, irritability, low mood. It is measured with a questionnaire, it is stable across adult life, and it is one of the strongest known predictors of later depression and anxiety.

It is also, as personality traits go, unusually well studied genetically — because a questionnaire is cheap and half a million people have filled one in.

The scale of it

A 2018 meta-analysis assembled 449,484 people and found 136 independent positions reaching genome-wide significance — 124 of them new at the time — implicating 599 genes.

Before it, sixteen loci were known. This is what happens to a heritable trait when the sample size crosses a few hundred thousand: the signal does not get stronger, it gets numerous.

Thirteen of those positions are on this page. Each one moves a questionnaire score by an amount too small to notice in a person.

Where the signal lives

The analysis did not stop at a list. It asked which tissues and cell types the implicated genes are active in, and got specific answers: dopaminergic neuroblasts (P = 3.49 × 10⁻⁸), medium spiny neurons (P = 4.23 × 10⁻⁸) and serotonergic neurons (P = 1.37 × 10⁻⁷).

The pathways that came up were neurogenesis (P = 4.43 × 10⁻⁹), axon part (P = 5.26 × 10⁻⁸) and — unexpectedly — behavioural response to cocaine (P = 1.84 × 10⁻⁷). That last one is not about drug use. It is a gene set defined by what those genes do in reward circuitry, and its appearance says the trait touches the machinery of reward as well as of mood.

The finding that matters most

Here is the part that changes how the trait should be thought about.

The genetic signal for neuroticism partly originates in two genetically distinguishable subclusters, which the authors label “depressed affect” and “worry”. They suggest distinct causal mechanisms.

Read that against how the trait is measured. A neuroticism score is a single number, produced by summing answers to a questionnaire that treats being low and being anxious as facets of one thing. The genetics says they are not quite one thing — they overlap, and they are separable.

That is a finding about the instrument as much as about the biology. When a measurement is a sum, the sum can hide that it is adding two different quantities together, and only something that can see beneath the score — like the genome — will notice.

What thirteen positions tell you

Nothing about your personality. With 136 loci and 599 genes, each individual position contributes a fraction of a fraction, and no combination of the thirteen here produces a meaningful score for a person.

There is also no diagnosis here. Neuroticism is a normal dimension of personality, not a disorder — everybody has a position on it. It is a risk factor for depression and anxiety in the same statistical sense that cholesterol is a risk factor for heart disease: real at the level of populations, and not a verdict on anyone.

And personality is not fixed by its heritability. That a trait is partly inherited says nothing about whether it can change, and neuroticism scores demonstrably do change — with age, with circumstances, and with treatment for the conditions it predicts.