Can depression cause a stroke?

When I asked my mother's neurologist what caused her stroke – she bore no evident cardiovascular risk – he said, "depression."

Depression, says Professor Craig Ritchie, the chief executive and founder of Scottish Brain Sciences, "may well be an upstream trigger for physical health". It might even have been a significant risk factor for the Alzheimer's disease that my mother suffered from in the last six years of her life.

People may present with depression later in life as a consequence of dementia but increasingly, research points to depression in early and midlife as a risk factor for developing dementia.

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They may, in fact, be twice as likely to be diagnosed with dementia if they battled with depression in early and midlife, according to a recent study, which followed 1.4 million Danish men and women for more than 40 years.

Holly Elser, a neurology resident at Penn Medicine and the lead author of the Danish study, says "There are lots of things happening in the brains of people with depression, including changing levels of serotonin, noradrenaline and dopamine, which all drive changes in the brain."

My mother's first episode of depression happened when she was 38. I remember this because I noted it in my 13-year-old diary in round, childish handwriting: "Mum doesn't feel well."

From then, until the time her dementia presented in her 70s, she was lucky to get away with an episode a year, and those lasted anything from three months to the two-year-long episode when "she sat too still for too long".

She continued to suffer throughout her life – her diagnosis, major treatment-resistant depression. She had treatment, which back in the 1970s, meant old-fashioned drugs and ECT.

My mother used to say depression was like living behind glass: you could see life, but you couldn't hear it or touch it. And it didn't touch you: she said everything abandoned her in depression, interest, joy, "even interest in my children", she said sadly.

There's a word for it that's used in the clinical diagnosis of depression: anhedonia. If she couldn't reach us, we couldn't reach her. She stopped cooking with us, stopped wanting to walk with us, just stopped. I grew to dread the mornings when she didn't get up, morning after morning for months at a time.

There was never any obvious trigger. They came, they went, apparently for no reason. We lost her to them. She always came back though.

Prof Ritchie elaborates on the pathology. When a person is battling with depression, he says, the stress hormones in their brains are at elevated levels that could result in "damage to nerve cells".

"There's an argument that not only does cortisol – the stress hormone – have a direct toxic effect on nerve cells, it also can underpin the development of Alzheimer's disease, by driving the production of the type of amyloid beta from the normal amyloid precursor protein (APP), which lays the foundation for amyloid plaques – the pathological marker for Alzheimer's."

But – and he is at pains to emphasise this – these processes don't happen overnight. A handful of depressive episodes are unlikely to have a lasting impact on the brain, he says. We're talking about "chronic exposure", months, years – for it takes years for the body's natural resilience to be overwhelmed, he says

As Gill Livingston, a professor of psychiatry of older people at UCL, says: "Depression is related to reduced self-care and social contact, so these may lead to an increased risk of dementia from illnesses and isolation."

Livingstone refers me to a large UK Biobank study of interventions for depression – 354,313 participants followed for 12 years – which found, yes, that people with a diagnosis of depression bear a higher risk of developing dementia but this risk is reduced if their depression is treated.

"It is important to energetically treat people with depression to improve mood, quality of life, ability to function and, for a few people, to save their life," says Prof Livingston. "The evidence is that people treated in midlife are less likely to develop dementia in the future and so treating now helps people avoid the illness which is most dreaded by people in midlife – dementia."






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