Sex differences in the blood-brain barrier: Implications for mental health, 2022, Dion-Albert et al

First sentence, and it's not starting well for me. Seriously? 1 in 4 people are affected by mental disorders? - and they make it sound as though that ratio is at this point in time, rather than 1 in 4 people will suffer from a mental disorder in their lifetime. That suggests to me that the diagnosis criteria for these various conditions is medicalising very common human conditions of grief, sadness and worry.

With "mental health" or more accurately, "mental illness" covering such a diverse range of mood disorders, behaviours, 'stress', and illnesses such as schizophrenia which must surely have a biological basis, and with so little known about what is causing each of the conditions, to me it doesn't make sense to try to propose some overarching biological mechanism.

 

Yeah, I just find a lot of this stuff (things to do with gender and mental illness and links with cardiovascular issues) a bit questionable - there's so much scope for prejudices to colour what is studied and the interpretation of any results. Take for example that section on learned helplessness. I don't think that mice study set-up really creates a 'depressive-like phenotype'. What the researchers have done is trained some mice to know that there is no escape from a specific stressful event (electric shocks) and so it needs to be endured as it will eventually stop. So, when those mice are put back in that same specific situation, they know that it is probably not worth running around, and they wait it out. It's quite a leap to extrapolate from that one specific situation to suggesting that the mice have a 'depressive-like phenotype'. What's the bet that those same mice, when exposed to a different challenge, would try to find a way to avoid it?

The authors cite one old study in rats as proving that short antidepressant treatment reverses this learned helplessness. I haven't bothered to look to see what anti-depressant was used, but to me it's extremely unlikely that the drug was 'curing depression caused by a series of electric shocks'.

And then there's that amazing last paragraph: the validity of the learned helpless paradigm has been questioned, not because it's been done in mice, nor because it's a very specific set-up that hardly equates to human life, or even because mice waiting out a series of electric shocks is really nothing like depression. No. The thing that makes the paradigm questionable is that female mice supposedly don't express this helpless 'depressive-like' behaviour as much as the male mice do. I presume the problem is that the female mice should be cowering like proper damsels in distress, while the male mice should be showing greater resilience and initiative in the face of a painful challenging situation?

Given what we know about how common problems with studies are, a lot of this stuff becomes very much like a house of cards. We've seen flimsy constructions built on unreliable research findings and prejudices before.


There may well be something true in this paper, but I'm pretty sure there are plenty of things that are not. I'd much rather see the authors study a single mental health condition and critically review the literature for it, rather than mashing all sorts of information together.

I rather doubt the finding of sickness behaviour differences, but it might be worth having a look at that cited Girard-Joyal paper.

 

I've read a bit more, and I have to note that this discussion about the natural experiments created by changes in female hormones over a woman's life is interesting:

If female hormones affect BBB permeability and vascular function, and these are relevant to ME/CFS pathology, then we might expect to see some changes in symptoms aligned with the menstrual cycle, and/or some major changes during pregnancy and at menopause. I'm not sure that we do see these changes, but there hasn't been much investigation, as far as I know. There are studies there begging to be done that might produce clues.