As part of Depression Detectives, we’re holding weekly Q&As with scientists and experts who work on depression or related topics. Our Q&A last week was with Charlotte Huggins, a  researcher with Generation Scotland.

Charlotte is currently working on a project called TeenCovidLife, examining how the well-being of young people age 12 to 17 in Scotland has been affected by the COVID-19 pandemic. If you’re aged 12-17 and living in Scotland, you can get involved here.

Q&A

Hi Charlotte!

Charlotte: Evening all! I’m Charlotte, a researcher with Generation Scotland. I work on the impact of the pandemic on mental health, particularly in teens. I’m also really interested in mental health in autism, and the role of emotion. Before the pandemic, I also worked in Japan for a couple of months! Now I’m working at University of Edinburgh.

 

Depression Detectives member C (DD C): We had a bit of a discussion in our group about what’s the worst for kids in Covid-times, and some felt the rhetorics around “falling behind” education-wise is impacting kids more than anything else these days. Is that something you’ve found in your studies?

Charlotte: That’s an interesting point! We don’t have data on that exactly, but I do personally think the relentless doom-and-gloom around young people’s education might be counter-productive. After all, especially for teenagers, the standards they should be ‘at’ at every stage are something we invented! I think instead of frightening young people with prophecising, we should focus on making positive changes to support their education and mental health in these difficult times.

 

DD I: From the main group:

Are there links between autistic traits and depression (and/or autoimmune conditions and/or somatic conditions)? Autism being the particular point of interest.

Charlotte:  I can’t speak to autoimmune conditions/somatic conditions (not something I’ve ever looked at!) but there are definitely associations between autistic traits and depression. Autistic people have much higher rates of anxiety and depression compared to non-autistic people. And in non-autistic people, higher autistic traits is likewise associated with mental health difficulties.

DD C: Do you know anything about reasons for these higher rates? For example, does it have something to do with how the mind is wired, or how much difficulty people with autism experience in daily life through stigma, etc.?

DD S: And do we know anything about whether that is something intrinsic to autism, or does it come from the difficulty of navigating the neurotypical world as an autistic person? I don’t even know how you would do research to try to separate those two things!

DD M: My guess would be that society disables autistic people. Everything is geared towards neurotypicals.

It’s still called a disorder, which in itself is stigmatising. I think that professionals in particular need to listen to autistic people

Charlotte: I personally think it’s more to do with being an autistic person in a neurotypical world! Autistic people experience much lower rates of employment and education, suffer from lower self-esteem, and often have difficulties forming and maintaining good social relationships (which are a great protective factor against mental ill health). If the world was made more accessible to autistic people (including improving attitudes towards and understanding of autistic people), I believe much of these issues would improve.

 

DD S: What are the ‘headline findings’ that Generation Scotland has been seeing in relation to the pandemic and mental health?

Charlotte: This is some analysis I’ve not quite finished yet (so please take with a grain of salt!), but we’ve been finding a definite increase in depressive symptoms during the strictest lockdown measures, which improve as lockdown measures ease. However, anxiety seems to have risen in February, which I wonder if relates to uncertainty around the new variants and vaccine rollout. I’m doing some really exciting stuff with other UK cohorts to find out exactly more about how it’s changed over time, and how it compares to pre-pandemic.

DD C: Really interesting. I’m not very familiar with cohort studies. Do you take “random” things into account such as, say, the weather/time of the year (my mental health is the worst in February)?

Charlotte: It depends on the type of analysis being done! Since we have such big data, many people work on it, and different types of questions require different types of analyses to answer. I’ve personally never used weather/time of year (I imagine pulling in all that data would be difficult) but I’m sure there’d be some fascinating analysis to do there.

DD S: Something came out recently that seemed to show that depression was twice as as high as normal in the first few months of this year. Would your research agree with that? If yes, does it look like people who have previously experienced depression all getting depressed at once? Or is it new people getting depressed?

Charlotte:  I’m not sure! We’re working on analysis that is looking at this change over time more closely, but it’s not quite ready yet, so I don’t want to jump the gun. I’d hazard a guess that there was an increase at the start of this year, between the gloomy weather, the increased restrictions, and the fatigue of almost a year under the pandemic. But whether depression rates have doubled, I wouldn’t be able to say!

 

DD M: What do you think are the differences between children/young people and adults when it comes to how they are affected by the pandemic? Is there anything additional to look at here that might be different?

DD E: I’m wonder if there was any distress apparent in the teens of either Covid or lockdown and the disruption to their education?

Charlotte: I think for young people, the impact on schooling is the biggest issue. Many older teens are experiencing a lot of uncertainty and stress about how this will affect their future job prospects and getting into university. And just getting the placement often isn’t the end of the issues – making friends, forming long-term relationships, settling into your adult life…all of that becomes more difficult when done remotely. I think people in transitionary life periods are probably experiencing very particular challenges.

 

DD M: Some autistic people might have felt relieved by some of the restrictions during the pandemic. Is there anything we can take from this to aid mental health going forward?

Charlotte: That’s definitely something I’ve seen as well! I think the changes we’ve made in response to the pandemic can be wonderful for autistic people (and many other people beside!) – such as more options for remote working/schooling and reduced crowding in public places. I think moving forward, it would be great to keep these accessibility options in place. We’ve proven now that it is possible to make these changes, and a lot of places now have infrastructure to do so!

 

DD E: Did you find it more onerous to collect data during lockdowns or was it actually easier to find participants because of lockdowns?

Charlotte: The CovidLife projects (Check out this link for more detail: https://www.ed.ac.uk/…/generation…/covidlife-volunteers) have seen really good returns! I think particularly for Covid-related research, people are keen to participate and have their voice heard.

For projects that can’t be done online, though, it gets much difficult. Just before the first lockdown in March, I was planning a study about interoception (the ability to identify your own bodily sensations). This would have involved me passing the same objects back and forth to participants over the course of an hour! As you can imagine, that never quite came to fruition 😄

 

DD C: I heard that teenagers’ eating disorders increased a lot during Covid. Have you seen a reduction in this now, since there are less restrictions on kids’ sports and they can go back to school?

DD N: Potentially might be linked to the control element of EDs? With so little control over all the external factors of the pandemic.

DD M: my thoughts too

 

DD S: Can I just check about how Generation Scotland works. You have a load of people signed up, and you ask them lots of questions at the beginning, and you get access to their medical records? And you also send them more questionnaires from time to time? And then you can basically ask questions of all this data? Like, you could ask it ‘Are people who live near the sea more likely to get depression?” And if they are, you’ve found something out.

And I know the list must be super-long, but could you give us an idea of the kind of data you have about people?

DD E: My question is firstly how you collate your data and when you have gathered it in how you design the data? Hope that makes sense.

Charlotte: Yes, Generation Scotland is a cohort study, so a lot of it is about collecting detailed data. We have some of the most detailed data on our participants in the UK! When GenScot started (back in 2006, while I was preoccupied with being in primary school), participants took part in a clinic visit which involved taking a lot of detailed measurements, and provide genetic samples for analysis. We also link to NHS data. The exciting thing about GenScot is that we’re a family study – meaning people join up as part of families, so we can link their genetic data together. We even have neuroimaging data!

This year, we’re planning a new wave of recruitment. This time, the initial measurements will be done completely online, in our new system. Participants will be sent a kit in the post so they can submit a saliva sample to us for genetic testing.

And yes, the benefit of having such a big bank of data to work with is that we can address many different research questions. Other researchers can apply to use our data (without any identifying data of course!) and answer research questions. There are over 250 publications in academic journals using Generation Scotland data. Here’s a great link if you want to see a bit more: https://www.ed.ac.uk/generation-scotland/what-found

DD S: So what kind of data do you have about people? What questions do you ask them?

I mean, I’m assuming postcode, parents occupations, obv all these samples, but do you give them personality tests? IQ tests? Do you ask them about their hobbies? Pastimes? Diets? Sexual activities? Jobs?

Charlotte: We have a lot of this! We have personality data, cognitive ability data, diet and exercise habit, employment, health history and health behaviours, I don’t think we have data about sexual activity or past-times though.

 

DD I: We hear alot about young people and social media. Did this come up in your study? I guess it has positives and negatives during lockdown?

Charlotte: We didn’t spend many questions on social media in TeenCovidLife, unfortunately! We didn’t want the survey to be too long. In the first lockdown, about 54% of teens said their social media use had increased. But, after lockdown ease, 50% said they used it less than during lockdown!

DD C: Do you check whether self-reports tie up with other measurements?

 

DD E: I came across a graphics timeline (link) on Twitter which was amazing.

How many hours and people would be involved in that?

Charlotte: It’s fantastic isn’t it! Amazingly, the majority of that was done by just one of my colleagues. I will definitely pass on your appreciation to her 🙂

 

DD N: And that’s all we’ve got time for! Thanks so much again for coming Charlotte, this has been really great

DD E: Thank you Charlotte for a very interesting Q&A. Let’s hope we all don’t have anymore lockdowns to contend with even if researchers produce very interesting facts. 😊

Charlotte: Thank you so much! Would it be at all cheeky if I plugged the ongoing work we’re doing for TeenCovidLife?

DD S: Please go ahead!

Charlotte: We’re currently collecting data for our next sweep of TeenCovidLife! If you have or know a 12 to 17 year old living in Scotland, we’d appreciate it immensely if you passed the word! The survey can be accessed here. Questions about exams, school, mental health, and how pets help us in the pandemic (the latter I’m very excited to get data on) 

May 20, 2021

As part of Depression Detectives, we’re holding weekly Q&As with scientists and experts who work on depression or related topics. Our Q&A last week was with Mark James Adams, a statistical geneticist from the University of Edinburgh.

Q&A

Hi Mark!

Mark: Hi, everyone. I’m a researcher in the psychiatry department at the University of Edinburgh. My background is in computing, genetics, and psychology. I mostly work with population health datasets doing genome-wide association studies (abbreviated “GWAS”), where I look across the whole genome to find parts of our DNA that increase or decrease the risk of having depression.

 

Depression Detectives member E (DD E): Can the symptoms of depression lie dormant, for eg teens/adulthood then manifest at say 40 due to change of life and hormonal imbalance?

Mark: Yes, we do see differences like that. Some people seem to be at risk for having depression but have not yet experienced a life event stressful enough. For example, childbirth is a very stressful time for many people, especially mothers.

Here is a figure from a paper by one of our researchers showing different trajectories of depressive symptoms from adolescence to adulthood. The higher the number in the figure, the more depression symptoms a person has, and each line represents a different trajectory that the burden of symptoms can take.

DD N: Do most people who experience depression fall into one of the groups on the graph?

Mark: Yes, the “stable low” trajectory is the most common, followed by the “early-adult onset” type. The “childhood persistent” was the least common.

DD M: That childbirth can be a very stressful time is in itself rather depressing!

DD S: I feel like becoming a parent is the really stressful thing…!

DD M: both? 🤷‍♀️

DD S: Yes, both I guess. And on top of childbirth itself, the hormone changes are huge. But becoming a parent is an earthquake in your life that never goes away, if you know what I mean.

DD I: Being a parent means you are ‘always on duty’. No longer can you just go off for a walk for example.

 

DD A: Can you tell us about the kind of projects you’re working on at the moment?

Mark: My big project at the moment is part of the Psychiatric Genomics Consortium to do a large genetic study of depression. https://www.med.unc.edu/pgc/

One thing we have learned about genetics for depression is that each part of your DNA makes only a tiny contribution to making you vulnerable or protecting you, so it takes data from a very large number of people to identify those differences. In the study I am working on now, we are combining data from 3.5 million people from all across the world.

My other main project is a genetic study of symptoms of depression. Most of our data are just based on yes/no assessments of depression, so I want to see if there are genetic and environmental factors that influence specific symptoms. I have found that there is a genetic difference between somatic symptoms (like fatigue or changes in appetite or sleep) and psychological symptoms (like low mood or lack of interest in pleasurable activities).

DD S:  That’s interesting. What portion of the risk is genetic?

Mark: About 30% of the differences between people is genetic, and about 10% is from differences between family environments.

DD S: I don’t know if this is within your remit to know, but how does that compare to other risks? I know we were talking in the group the other day about how big an influence poverty and precarity are. They seem much bigger than I had quite realised.

Mark: Yes, the genetic portion of depression is low compared to other psychiatric traits like schizophrenia or bipolar disorder. In terms of genetic risk, depression is more like heart disease or diabetes. I think the environment is hugely important and we are still trying to find good ways to measure it, since what each person finds stressful can be very different.

 

DD N: How are the environmental factors measured at the moment? Or have they just not been studied much?

Mark: We collect lots of data on childhood experiences, strength of family connections, community involvement. This is from asking people about their lives, but we also pull in information based on where people live (for example, is there a lot of green space around).

DD S: So is it you, or colleagues, who analyses the rest of that data? I mean, if we wanted to find out if living near a chip shop affected your chance of getting depression, how easy or hard would that be to do? (Living near a chip shop is just a random example off the top of my head…)

DD I: Yes, if we chose a question like that, Mark Adams is the first person I would turn to!

DD S: Awesome. In that case, I have a lot more questions I’d like to ask. Can Mark come again?:-)

 

DD N: Really interesting about different symptoms having different genetic causes! In Stella’s Q&A she talked about the idea that maybe depression might not be all one illness but a group of different things, do you think that different symptoms having different genetic causes is evidence for that being true?

Mark: Yes, I agree with Stella. While there does seem to be something common genetically across all types of depression, there are probably differences that drive how depression is expressed as different symptoms.

 

DD A: Can you tell us what the GWAS is (in simple terms 🙂)

Mark: In every part of your DNA, you have two copies of each variant or gene, one from each parent. What we do is we pick one of the variants as a baseline, and then count how many copies of the other variant each person has. So for a simple 1 letter change in your DNA, there are usually two alternative variants, such as A and C. So the four genotypes are AA, AC, CA, and CC. If “A” is the baseline, then we count how many “C”s each person has (which will be either 0, 1 or 2). We then run a statistical test (called a “logistic regression”) that checks if people with more “C”s are more likely to be depression. We do this test for several million places in the genome and find which ones are robustly associated with depression.

 

DD S: If the genetic risk is relatively small, compared to other factors, why study it? Why not put all our resources towards, for example, relieving poverty?

Mark: There are a few reasons. One is just to understand the biology of depression. Even if the ultimate cause is in the environment, it’s the ultimate impact is in the body (how the brain reacts and overcomes stress, for instance).

Another main reason has to do with understanding causality. Did the poverty cause the depression, or did the depression cause job loss or breakdowns in relationships that resulted in poverty? With genetics, we know that the causal arrow always has to flow from DNA → Depression. We can use this to identify modifiable behaviors that can help alleviate depression. For example, this type of analysis was used to show that exercise really does help alleviate depression rather than the connection just being that people or aren’t depressed exercise more.

DD I: So maybe if we understand the biology, we might be able to intervene? (e.g. new drugs to treat or prevent depression) is that what you mean Mark?

DD S: Thanks Mark. That makes sense. But can you explain a bit more what you mean when you say this kind of analysis was used to show that exercise does alleviate, rather than depressed people exercising less?

Mark: The type of analysis is called “Mendelian randomisation” There is a good short Youtube video on it: The type of analysis is called “Mendelian randomisation” There is a good short Youtube video on it: https://www.youtube.com/watch?v=LoTgfGotaQ4

 

DD M: What is it hoped these data might be useful for deriving?

Mark: I hope the data can contribute to finding treatments It would be useful to know ahead of time whether a person is more likely to respond to talking therapy or medication, for instance.

DD N: Is the difference between someone responding better to medication or better to talking therapy something you can see in the data currently?

Mark: We’re still looking into this. The limitation we are currently are having with our analysis is getting good data on talking therapy and how people respond to it. This is easier with medication since we can look directly at prescribing records to see if people are switching from one medication to another, or not filling their full course of prescriptions.

In some cases it might not be that the medication wasn’t working, but that the side effects were intolerable. So we hope to understand this better.

DD I: In the group it was discussed that people may move off medication and onto talking therapy (or something else) that they pay for privately.

Mark: I’m very thankful to this group for that insight. It will help our research tremendously.

 

DD S: Another tricky question. Are there any downsides to finding these genes? I mean, is it possible that in a future dystopia people selectively abort babies with depression genes? Or people with depression genes get denied health insurance, or whatever?

Mark: I’m much more concerned about implications for health insurance than designer babies!

One thing we know about genes is that they have influence many processes in the body. So tinkering with depression might have other consequences that we don’t know about yet.

The International Society of Psychiatric Genetics recently made a statement on the ethics of embryo screening: https://ispg.net/ethics-statement/

DD S: Like maybe the depression genes are useful for some things? Like sickle cell anaemia protecting people against malaria…

Mark: Yes, that’s what I’m thinking about. The genes can probably have a positive effect as part of the stress response. For example, rumination can be good if it helps you make a better decision or get out of a bad situation

DD S: So they remain in the population, because they are useful in small amounts, or certain circumstances. But if you have too many of them they can cause problems.

 

DD E: There is exciting news of a new DATAMIND national research hub being led by researchers/scientists based in England. How will this impact on MHSUs /researchers/scientists based in Scotland.

Mark: I hope DATAMIND helps Scottish researchers use data from England, where this type of project will have more of an impact since their data come from so many places. In Scotland everyone has a single unique identifier (called a Community Health Index number) that makes it easier to link our research participants’ data with their health records.

 

Mark: There was a question asked ahead of time about the DATAMIND research hub, which you can read about here: https://www.hdruk.ac.uk/helping-with-health-data/our-hubs-across-the-uk/datamind/

The background to efforts like DATAMIND is that the UK has a very long and rich history of health research studies where the same group of people are followed up over time. These started with birth cohorts in the 1940s and subsequent decades, which were set up to study health and social mobility. There is a lovely book about this history called “The Life Project” by Helen Pearson. https://helenpearson.info/book/the-life-project/

While these studies were hugely important, for decades they struggled with funding. It has only been in the last 10 years or so that their value has been widely recognised. DATAMIND is an effort to build on these research cohorts.

A similar project to see what these kinds of efforts are all about is Catalogue of Mental Health Measures. These research cohorts can look impenetrable from the outside, so one of the biggest barriers to using them is just being able to quickly see what kind of data they contain and to see how they can be used together (for example, I work with the Generation Scotland data set and it is useful to be able to see what other studies have similar measures of depression) https://www.cataloguementalhealth.ac.uk/

This catalogue is very useful for researchers, but my hope is that projects like DATAMIND can turn these resources into a dialogue between study participants, researchers, and the public. In Scotland we are fortunate that it is a lot easier to link between different data sets since, for example, we only have one NHS authority. I’m looking forward to DATAMIND so that we can also better use data from the other nations.

 

DD N: That’s all we’ve got time for! Thanks so much Mark, this has been really interesting!

Mark: Thanks everyone for the great questions!

May 18, 2021

As part of Depression Detectives, we’re holding weekly Q&As with scientists and experts who work on depression or related topics. Our Q&A last week was with Andrew McIntosh, a psychiatrist from the University of Edinburgh.

Hi Andrew!

Andrew: Hello everyone. My name is Andrew McIntosh. I’m a professor of psychiatry from the University of Edinburgh and an NHS Psychiatrist in the Royal Edinburgh Hospital. I’m happy to answer any questions you have about treatments for depression. I’ll be here from 9pm until 10pm

 

Depression Detectives member E (DD E): I would like to ask you about the long term effects of psychotropic medication (lithium and amitriptyline), by which I mean 3 decades or more?

DD A: My question is similar to E’s. What does current research say about patients using an SSRI like Sertraline long term? >3 years.

Andrew: Not very much. The side effects of SSRIs are thought to be greatest at the very start of treatment and with every increase in dose. You tend to break them down more effectively over time, as your liver tries to eliminate them.

As you age however, other illnesses may develop that impact how you deal with the SSRIs. These illnesses (e.g. of the kidney) can mean that the blood levels of SSRIs rise over time and you might get worse side effects whilst remaining on the same dose.

There are long term side effects from lithium with continued use. There are 2 in particular – hypothyroidism and diabetes insipidus. 

Hypothyroidism, a common condition is where the thyroid doesn’t produce enough thyroxine. It can be treated by giving thyroxine in a tablet every day. Not ideal, but that’s what many people choose to do. Diabetes insipidus is a condition where the kidneys find it progressively difficult to concentrate your urine. It can be quite disabling and can lead to people drinking and urinating many many times a day. It can’t currently be reversed.

DD M: that’s a bit of a bugger considering I’ve been taking SSRIs (and a few years of SNRI in the middle) for over 20 yrs 😬

DD A: So does that mean you will eventually need higher and higher doses to get the same effect?

Andrew: That could be the case. However (and sorry to complicate this) but the levels of SSRI in your blood aren’t a very good indicator of your response. So the link between dose over time and your response to the treatment isn’t very clear and differs between people

DD M: That’s really interesting.

Andrew: I think so too. If it were as simple as a lack of serotonin, it should be more straightforward. In practice, research suggests that its your brain adaptation to the SSRI that leads to the treatment response. So its fascinating, but there’s still much we don’t know

DD C: Would you be able to explain a bit more what it means that your brain adapts to the SSRIs?

Andrew: I’ve just see your comment. It’s really interesting- after a week or two of treatment, your serotonin returns to normal, and your depression starts to get better. We don’t understand why- but isn’t it fascinating?

There have been some reports of other types of issue arising with long term treatment, such as abnormal movements. These don’t seem to be very common and they are more controversial

DD M: Is there likely to be any permanent changes to neurobiology with long term use at all?

Andrew: Probably not – on 2 counts

1. We would like treatment with long term antidepressants to eliminate the need for treatment years later, by altering the neurobiology. Unfortunately I don’t think that’s what we really see. We DO see treatment effects continuing with sustained treatment over 2 years however.
2. We don’t see convincing changes in long term brain structure or function many many years out from treatment. There are some studies that have shown this, but its not convincing yet in my opinion.

Note from Andrew: As I look through my comments, I’m reflecting on the response I gave saying that there were no convincing long term changes in the brain with antidepressants. While that may be true, it’s more difficult to study than you’d think and there’s still work to be done there.

 

DD E: I am interested in things people do to ease their depressive symptoms – how much evidence is there that they help, and how much can they help relative to (or even in addition to) antidepressants? Things people might choose to do themselves without medical input like smoking marijuana or regular exercise or cutting off unhelpful relationships.

DD M: Well, there’s eating excessively or drinking alcohol too?

DD E: Maybe another way of phrasing it is “how effective can behaviour change be versus antidepressants?

Andrew: Lots of good evidence for this… CBT – people often attend to the ‘C’ – cognition/thought aspect. Changing ways of behaving was one of the core components of CBT – the ‘B’ if you like.

 

DD S: Based on discussions on the group, when a person first goes to their GP with depression, it seems they are likely to be prescribed antidepressants, and perhaps some short term CBT. Is that because these are the best treatments? Or are they what is most available?

Are there other treatment options?

Andrew: There are lots of treatment options, but these are some of the ones for which we have really good evidence. The advantages of antidepressants are you can start right away. There are advantages for CBT too (such as its effective, and you don’t need to take a medication at all potentially)- but you can rarely start straight away.

DD S: Thanks Andrew. Some people in discussions had felt they would have benefitted from longer term CBT, or from other talking therapies. Are those difficult to come by because they are expensive, and GPs don’t have the funding? Or is it because the HCP genuinely believes they won’t help?

What are the constraints on doctors when prescribing treatments?

DD M: Do you think IAPT is helpful as part of the treatment options?

DD I: For others IAPT = The Improving Access to Psychological Therapies (IAPT) programme (talking therapies) which began in England in 2008 – https://www.england.nhs.uk/mental-health/adults/iapt

Andrew: I think there aren’t enough clinical psychologists to meet the number of people who could want therapies and waiting lists are significant. IAPT was an NHS England initiative that helped to expand psychological treatments in England. It didn’t make it north of the border. There aren’t any constraints on doctors prescribing treatments, but someone has to be available to provide them.

Doctors usually refer to clinical psychology – who do an assessment and decide on the best talking treatment. I don’t generally refer for CBT, although I know that CBT and/or mindfulness based therapies are the more likely treatments that people will recieve. They both have solid evidence for their efficacy and lots of people find them helpful

DD S: I would say availability of providers is a constraint then:-).

Is that another advantage of CBT then? It doesn’t take a qualified clinical psychiatrist to do it, and it can be given by a nurse with some extra training.

Andrew: It can also be delivered by computer.

DD M: Do you think it is different in England, and in Wales in practice? And also for large cities e.g. London? I live in Greater London.

Andrew: I’m not sure, sorry. I think accessing psychological treatments is perhaps easier in England. I don’t know very much about Wales. I know lots of psychiatrists and psychologists in E&W and they seem to be facing similar challenges

 

DD N: Hi Andrew, thanks for joining us. I’d be really interested to know about the different types of antidepressants – what are the main similarities/differences and what’s the best way to find the right option?

Andrew: Different antidepressants work by affecting 2 main chemicals (serotonin and/or noradrenaline) in the brain, but in fairly subtly different ways

Some cause the brain to stop recycling them in the brain cells (e.g. SSRIs), some do this for both chemicals (tricyclic antidepressants like amitriptyline) others working in complimentary ways …. but they are more similar that they are different in a way

The *real* difference between them is in their side effects. Some medications are slightly more effective than others (e.g. amitriptyline) – but come with worse side effects. The side effects differ a lot, but their efficacy differs by less.

It’s mostly a matter of choosing your side effects initially (when I see people in clinic). For the first episode, docs generally treat with SSRIs as these are generally effective and have some of the best side effect profiles

DD T: Thanks Andrew McIntosh What is happening with these 2 main chemicals when someone has depression? You mentioned they are recycled in brain cells, can you talk about why that happens and what we know about how that changes with depression?

Andrew: The brain is designed to send signals using these chemicals from one nerve cell to another. When a message arrives at the end of one brain cell, it may be passed onto the next one using a chemical signal.

Once the chemical has done its job, the nerve cells then hover it up again, so that it can be sent again when it’s needed

Disclaimer: this is the gist, but an oversimplification

 

DD L: Hi Andrew, do you think antidepressants are over-prescribed?

Andrew: That’s a tricky question! I would guess that there must be some people who are receiving an antidepressant when another treatment would suit them better. However, I do not think that they are generally overprescribed.

I think the idea that antidepressants are overprescribed has been created by 2-3 things:

1. When SSRIs came on the market, you could achieve the recommended dose (the defined daily dose, or DDD) immediately. Whereas earlier drugs had more side effects and people often didn’t get to the usual effective dose. This led to an apparent spike in antidepressant prescriptions
2. The recognition of depression in GP when I was training was understood to be grossly inadequate/under-recognised. Over the last 20 years GPs have been better at spotting depression, and of course that has led to more prescriptions.
3. In my opinion – when someone is treated for migraine, cancer, MS etc — people rarely question whether this is appropriate or not. When antidepressants are mentioned, it’s often in the context of ‘mind altering drugs’ or ‘masking the underlying issues’. I personally believe that this is a kind of shaming/stigmatisation of people taking antidepressants that you don’t see elsewhere.

DD S: That’s really interesting. Would you say then that there was a lot of under-diagnosed depression which was sending people repeatedly to the doctors with other things? (Or, indeed, that people were just miserable a lot, without even going to the doctors…)

Andrew: There’s a lot of undiagnosed depression out there. We know that, because we’ve done studies of the general population, and we see people with depression who have never been to their GP or a psychologist or counsellor

One of the first people I treated for depression had MS. They hadn’t been given treatment I believe because sometimes people see the symptoms as understandable. I think there are a lot of people with cancer who don’t receive treatment that could help them

DD M: I was talking to a friend who worked in the pharmacy industry years ago who thought they were pushed rather forcefully by reps.

I’m guessing also that some GPs prescribed inappropriately at that point?

Andrew: I think that’s true…it’s very different now (for the better)

 

DD A: How do you differentiate between depression, depression from stress, depression in the context of autism, and negative symptoms of schizophrenia? Sorry, probably a weird question.

Andrew: Not weird at all. In each case, depression has to meet the same general criteria. Sometimes, it can be difficult to tell whether someone is depressed in each of these situations however as some of the features of depression overlap with that of the other condition (eg schizophrenia and lack of motivation, autism and social withdrawal). However, I think it is usually possible to tell because of the *change* in mood and behaviour in a person. It really helps to have a friend/relative there, or someone who knows the person very well.

DD A: That does make good sense, but seems not so defining. For instance, I typically have social withdrawal when depressed and lack of motivation generally. I wonder in the context of my daughters, who have been diagnosed with autistic spectrum disorder and learning disorder (learning disorder for me as well, but forgotten until I was in my thirties). In part, it is why I supported the finding a diagnosis for them, as I did not feel the treatment I received was helpful, though people meant mostly well. I will be briefly honest and say that some were not so helpful.

 

DD N: If money/resource/capacity were not a factor (or we lived in an ideal world with a fully funded NHS for mental health treatments) what would treatment look like? Would there be more time taken to diagnose causes of depression meaning more bespoke treatment options, for example?

Andrew: Great question! I think many issues would be the same and antidepressants would be used a lot. However, I think there would be a more rapid access route to refer people to trained therapists (e.g. nurses, other caring professionals) for straight from the GP than coming to hospital.

I’d like to think that we would also have what I’d call a learning health service.

That’s where information on your treatment is continually fed back for research and other purposes routinely so that we continue to learn what treatments work best for each individual, and we are in a cycle of continuous improvement.

DD N: yes – that makes a lot of sense! Would help the individual and the wider thoughts on best treatment practice.

DD A: massage. every. day. and trees everywhere! And government pays musicians!

 

DD E: Also, I have heard it said that antidepressants are like a sticking plaster over a gaping wound. It might hold you together but can never heal the underlying problems. Is that fair to say? Or part of stigmatising narrative?

Andrew:  I can see that in the case of a particular individual, this narrative might make some sense. I can see people in abusive or unhappy marriages, and while they *are* helped by the antidepressant, I’m not persuaded that’s all they need to do

In some cases I think that people in very difficult circumstances can be helped to find the motivation to change their situation through antidepressant treatment.

There’s a theory of depression called learned helplessness

It’s based on human and animal research, but it states that depression happens when you no longer believe you have the agency to change your current circumstances.

You can test this model in humans and (and I’m sorry if this offends) in animals (usually rats). It turns out that there is some evidence from the animal studies that antidepressants tend to ameliorate learned helplessness

So – long answer. In summary, its complicated and its difficult to know. I don’t conclude that antidepressants are a sticking plaster however. They can be highly effective and help people help themselves out of some very intractable problems

 

DD A: Has there been any recent research on EMDR as a treatment for depression or anxiety?

Andrew: EMDR has been studied for Post Traumatic Stress Disorder, but has received relatively little attention as a treatment for depression as far as I know.

I did a very quick pubmed search here, and you can see there are people actively thinking about this: https://pubmed.ncbi.nlm.nih.gov/?term=EMDR+depression+random

DD A: thank you! I’ll check it out.

 

DD C: What is the evidence for/against the view that antidepressants might be depressogenic (causing depression) over the long term?

Andrew: I don’t think there’s any good evidence to suggest that is the case.

 

DD E: Having just watched the leaders debate only one, William Rennie made any reference to funding mental health. Do you have a viewpoint on mental health funding and how it could be increased. I would happily pay a bit more in tax if I was assured it went to mental health.

Andrew: I’ve just watched some of it too! I think if funding was tied to the suffering and years lived with disability in a rational way, mental health would receive more funding. I think we all need to make the case repeatedly – and write to our MP/MSPs. I wrote to Christine Jardine recently on a matter relating to mental health (she’s my local MP, this isn’t an endorsement btw!). She was surprisingly responsive and it’s worth doing if politicians think they will lose votes by not supporting mental health.

 

DD A: I was wondering a bit about personalized medicine. I have a sister with a CYP and serotonin transporter variant that makes her very sensitive to some SSRIs who was subsequently diagnosed with bipolar II. Do you think that guidelines to check for these types of differences will become (or should become) incorporated into guidelines? Though I know that some see it as possibly unmasking bipolar disorder, to me it seems more like feeding someone with prediabetes doughnuts.

Andrew: Interesting question – let me answer the first part

I do think that routine genetic testing will come one day. I think it is already justifiable in learning disability diagnosis and will become useful in a number of conditions soon.

I think that it will also be helpful for depression treatment targeting too. Highlighting people more likely to have a good response, as well as people likely to have side effects.

The evidence for these tests isn’t quite there yet (although there are some disreputable companies who are already offering testing)

This is an area of research we’re investigating

My hope is that genetic testing research for depression and depression treatment will be brought along and developed further as this becomes more commonplace for other conditions. I think genetics will be part of a learning health system eventually

DD A: My sister was encouraged to be tested by her psychiatrist, because of a history of developmental disorders (though not exactly descriptive, since vs IQ tends to be very high in my family, though generations, and verbal IQ catches up to normal or above). And the commentary on her genetic variations came from a phd in neuroscience (friend of mine) who said a person with these variations should never be given an SSRI. For context, they felt that my quick response to SSRI might indicate that I was a good candidate, and they had taken SSRIs in the past, so they were not anti-medication.

 

DD N: That’s all we’ve got time for! Thanks so much again for coming and answering so many questions Andrew.

Andrew: Thanks for inviting me along today. I hope you’re finding all of the discussions interesting and I’m looking forward to hearing more about your experience of this group some time

May 10, 2021