Study uncovers 300 new genetic links to depression

Breakthrough international research has provided a deeper understanding of depression by finding close to 700 genetic variants linked to the condition, as well as identifying more targeted and effective treatments.
 
The world’s largest and most diverse genetic study into depression to date examined the genetic component behind the condition and aimed to identify what genes play a role in increasing risk.
 
The Australian and UK-led research team identified 697 variants and 308 genes associated with higher risk of depression – a significant increase on what was previously known.
 
Although each genetic variant has a small impact on the overall risk of someone developing depression, multiple variants can add up to increasing a person’s risk.
 
Dr Cathy Andronis is Chair of RACGP Specific Interests Psychological Medicine. She told newsGP it is important to remember genetics are not the only risk factor, and that ‘association is not causation’.
 
‘Genetics is the coding for our human operating system, and it is logical that if we go looking we will find the genes associated with various conditions including depression,’ she said.
 
‘However, we also know that genes are expressed as needed and are turned on and off according to the environment and context of an individual’s life, so every person will have their own unique pattern of genetic code that can be potentially measured, but these genes are not sole causes of their depression.’
 
The study authors highlight that previous research into the genetics of depression has primarily involved white, higher socioeconomic populations, but this genome-wide association study enabled a more diverse sample of people from whom to identify new risk factors.
 
A meta-analysis of 688,808 people with major depression was compared to four million without depression from 29 countries across diverse and mixed ancestries, including East Asian, South Asian, African and Hispanic. One in four participants were from a non-European background.
 
Co-author Dr Brittany Mitchell said this diverse sample showed a remarkable increase on what was previously known and will help to improve outcomes for people with depression, regardless of ethnicity.
 
‘While depression is a growing major health issue, we lack the insights needed to better treat and prevent it,’ she said.
 
‘Larger, more inclusive studies like this will help us develop better treatments and interventions, ultimately improving lives and reducing the global impact of the condition.
 
‘It will also reinforce the evidence that mental health conditions are as biologically based as other conditions like heart disease.’
 
Dr Andronis says just as conditions like heart disease are prevented and managed, at the core of GPs’ role in depression management is tailored lifestyle advice and ongoing support.
 
‘As GPs we need to assist patients to manage what they can change and this is almost always lifestyle related,’ she said.
 
‘Good psychotherapy supports patients to recognise what they can do to manage their mood more effectively. Medication certainly benefits some patients at some times but attention to good sleeping patterns, supportive relationships, diet and exercise are vital for everyone and especially for depressed individuals.  
 
‘GPs are able to support patients by providing psychoeducation and counselling, for instance motivational interviewing regarding lifestyle changes and improved problem-solving skills.’
 
She says because depression is a clinical diagnosis the symptoms and goals of each patient are different.
 
‘Diagnosing depression is all about taking a good holistic biopsychosocial history and making a careful formulation of the patient’s symptoms, risk factors, associated conditions as well as their strengths to collaboratively plan treatments specific to that patient’s needs,’ she said.
 
‘We are not robots so can’t be treated with algorithms.’
 
In the study, biological markers of depression linked with genetics also demonstrated new drug targets and more effective therapies, highlighting potential drug repurposing opportunities.
 
More than 1600 medications were examined to determine if they had an impact on the 308 genes linked with higher risk of depression.
 
While the research team says further studies and clinical trials are needed, anti-cancer medicines and those used to treat chronic pain and narcolepsy such as Pregabalin and Modafinil, could potentially be repurposed for treatment of depression.
 
Highlighting opportunities for repurposing medicines, the study comes as novel treatments for depression emerge, including psychedelics and ketamine.
 
Depression effects around one in five Australians at some point in their lifetime, which is expected to increase over the next decade, while globally the condition is estimated to impact around 280 million people.
 
Dr Mitchell says the ‘landmark study’ is expected to act as a springboard for many different studies to better understand depression.
 
‘These findings mean we’ve made a really big leap forward in what we understand about the causes of depression and starting to move towards a more personalised treatment at the right time,’ she said.
 
‘The study shows there is a strong biological basis to depression and it’s time we started moving away from a stigmatised society … where we take it as seriously as other medical conditions.’
 
Echoing calls for a non-stigmatised approach, Dr Andronis circles back to one of the fundamental parts of being a GP.
 
‘Our humanity and capacity for trust and a safe doctor–patient relationship is usually the best treatments for patients,’ she said.
 
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