Wednesday, May 27, 2015

I felt a funeral, in my brain

"I just didn't want it to hurt any more"
Mark Henick, mental health advocate who attempted suicide

Suicide is the leading cause of death in young males in Ireland. Not everyone who experiences major depression will attempt suicide, and indeed not everyone who attempts suicide is depressed. Nonetheless, the spectre of suicide hangs over major depression. Even where major depression is not so extreme, it takes a terrible toll; a WHO report has identified it as the world's leading cause of disability.

In our discourse on depression, one sometimes sees an attitude that people need to snap out of it, sometimes even that depression doesn't exist. Without wanting to pander to the view that mental disorder is just the fictitious cousin of physical illness, we can counter the non-existence argument by simply pointing out how depression has pervasive effects on the body.

A biological marker of biomarker can be decribed as a "an indicator of a physiological or pathological state that can be objectively measured and evaluated" (Spiller, 2011). A biomarker may reach the status of surrogate endpoint if it can be used as a substitute for more direct clinical outcomes (e.g. reduced quality of life or worsened apathy in depression). We're probably a long way off identifying a surrogate endpoint for depression. Depression is still identified using the person's self-report, although for various reasons people may deny or minimise their experience of depression if questioned about it. Nonetheless, a number of physiological variables do seem to be affected by major depression.

Brain derived neurotrophic factor is one example. It is a protein that is associated with the development of neurons, and with learning and memory. There is increasing evidence that BDNF levels in the blood are lowered in depression, and successful antidepressant treatment can restore BDNF levels. Not only is circulating BDNF reduced, but there is post mortem evidence from suicide victims that BDNF is indeed reduced in the central nervous system (although this finding did not appear to be specific to depression). Not surprising then that there's evidence that depression can have a negative effect on cognition, with worse severity of depression being associated with worse episodic memory and executive function.

So it seems depression is bad for the brain, but it is also bad for the rest of the body. Major depression can also have an impact on the immune system. It can increase inflammatory cytokines-these moderate the immune system by increasing its defences. This is useful for fighting infection, but may not be so hot if it is occurring chronically in the absence of infection. Furthermore, these cytokines can also moderate neurochemical signalling in the central nervous system, potentially exacerbating the depressive state. The immune system may be involved in the development of depression-chronic stress is associated with the development of depression, and stress can activate the types of immune system activity involved in depression.

But one shouldn't make the scenario seem simpler than it is. Part of the difficulty in identifying biomarkers if that, of course, depression hits differently for different people. Although every person's experience is unique, there are some consistencies in diversity. Melancholic depression is associated with anhedonia (a lack of enjoyment or positive response to things that used to cheer one up), early waking time, feeling worse in the morning, weight loss and agitation. There is evidence that the hypothalamic-pituitary-adrenal axis (HPA axis) is more highly activated in people suffering from melancholic depression, compared to those with non-melancholic depression. In the HPA axis, the hypothalamus (a region of the brain) initiates a chain reaction of neurochemical processes, resulting in the release of cortisol from the adrenal gland. Cortisol is a hormone released in response to stress, helping to mobilise the body for the so-called "fight or flight" response. It can permeate to tissues throughout the body, so whatever affects cortisol release can have pervasive effects on our physiology, including the immune system.

So, different sub-types of depression can guide the study of its biological effects. In the future, it may be the case that the search for biological changes in major depression will lead to depression being broken down into further sub-categories. If these categories don't line up with some aspect of the depressive experience, they will have to be evaluated against some other yardstick, such as predicting effectiveness of treatment for depression. Genetic and neurological technologies are developing all the time-perhaps the data sometimes comes in too fast for researchers to analyse and understand in its full depth. For the foreseeable future we will probably still be relying on the person's experience to identify depression and what goes with it. It's important as individuals and communities that we encourage people to seek help if they need it.

If you are or think you may be suffering from depression, whether or not you are suicidal, please do seek help. You could speak to family/friends, to a counsellor/your GP, or get in touch with the Samaritans by phone at 116123 (Republic of Ireland) or by email at

Sunday, May 10, 2015

The hangover

The brother was over for a visit to my current home city of Cork. At a certain craft-beer establishment I partook of a few imperial stouts. Although not overly drunk when I returned home, on waking the next day I found it unusually difficult to keep anything in my stomach. Thankfully it was a Sunday, so there was no need to drag my sorry carcass into the workplace. The most complex thing I could handle was gawking at a movie with the brother. ("Reincarnated", the moving tale of Snoop Dogg's transition to Snoop Lion-truly the "Citizen Kane" of hip-hip to raggae crossover movies). Had I been that bad on a Monday morning I've little doubt my performance would have suffered.

The full economic cost of hangover is difficult to estimate-although sickies will lead to obvious losses, when asked to think of an example of presenteeism (turning up for work when you're not capable of working to your usual capacity) many of us will think of a hangover incident.

But what's the hard evidence for hangover effects? An interesting review by Richard Stephens and colleagues has discussed the impact of hangover on cognition. A majority of studies in this area have NOT shown an effect of hangover on cognitive performance, although Stephens contends this may sometimes be due to the use of insensitive measures. One study that did show an effect administered alcohol or placebo in the evening, and the next morning found worse delayed recall for a word list during hangover, despite an absence of an effect on a vigilance task, suggesting the memory effect was not simply due to fatigue. The other study found that psychomotor speed was slowed in addition to memory performance, suggesting sluggishness might have been at least part of the problem. This latter study used the more naturalistic approach of studying people after a normal night's drinking.

Stephens et al. suggest that the spectre of demand characteristics may hang over (heh heh) this research area. As mentioned above, one may study hangover in a controlled manner by giving a fixed amount of alcohol in a hangover condition. However, one may instead get some participants to come into the lab when they are hungover (after a night's drinking in a pub) and some to come in when they are not hungover. This second approach appears to more successful in demonstrating cognitive effects of hangovers. However, if invited to take part in such a study, one is essentially taking part in an "open-label" investigation. One may perform worse on cognitive tests during hangover, simply because this is what the experimental situation suggests to you.

However, Stephens et al. suggest an ingenious way around this. One can schedule some students to take part in your study on a morning after a popular drinking evening, and other students on a day when they are less likely to be drunk on the job. With enough numbers, you are likely to have a substantial proportion of the study participants attending while hungover (although perhaps the more severe cases will stay at home).

Even where performance is relatively preserved, the nauseous and draining subjective impact of heavy hangover does beg the question of whether we owe our future selves a lighter night's drinking. In many cases, I dare say a good behavioural medicine would be learning how to be a little less socially inhibited without having to resort to a few too many bevvies.

Stephens, R.; Ling, J.; Heffernan, T.M.; Heather, N. & Jones, K. (2008). A review on the cognitive effects of alcohol hangover. Alcohol & Alcoholism, 43(2), 163-170.