The aftermath

THE AFTERMATH We think of PTSD primarily as something caused by the horrors of war. The reality is very different, finds Jessica Hamzelou

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HINK of the most scared you’ve ever been, and imagine that happening all the time,” says Kerry Ressler. “You have intrusive terror and nightmares, and the threat of imminent death starts to take over your life.” That is the horrific reality of post-traumatic stress disorder. But while we tend to think of PTSD primarily as a condition that afflicts soldiers – most of whom are men – more than two-thirds of people with the condition are women. So what puts women at greater risk? Now, by looking at genetics, hormones, early childhood experiences and even the type of trauma, we are starting to find some answers. These insights are not only shedding light on how PTSD affects everyone, but opening avenues to better treatment – and even ways to prevent it. As many as 24 million adults in the US have PTSD at any one time. Most people will face trauma at some point, but for roughly one in 13 of us that will lead to PTSD. These types of events tend to be unpredictable and uncontrollable, and the person often feels their life is threatened. But Ressler, who studies the condition at Harvard Medical School, says there is no precise formula. “Anything horrible can trigger PTSD.” People with PTSD often have intrusive thoughts, as memories come back to haunt them during waking hours and in nightmares. They tend to start avoiding people, places and things that remind them of the trauma. They

can feel anxious, stressed, depressed, isolated or even dissociated from reality. Many are prone to panic attacks. But not all people with PTSD have the same symptoms. Some may feel nothing at all, just numb. It is normal to experience some of these symptoms after an ordeal. But in PTSD, they persist for at least a month, and with chronic PTSD they go on for many months, sometimes years. “You’re imprisoned by your memories,” says Karestan Koenen, who studies PTSD at Harvard University. “The horrible event may be over, but you’re held hostage by what happened to you.” Chronic PTSD has been linked to a range of physical maladies, from a higher risk of heart attack, stroke and type 2 diabetes to chronic pain and dementia. And people with PTSD are at higher risk of suicide: 20 US veterans with PTSD take their own lives each day. For many, though, the trauma that leads to PTSD doesn’t happen on a battlefield. Psychiatrists commonly see the condition in people who have been subjected to violence, especially at the hands of someone they know. “As humans, so much of our lives is based on being able to trust other people,” says Koenen. “If another human attacks you, it violates your trust in humanity.” Not everyone is equally vulnerable. Though men are more likely to experience trauma during their lives, women are more than twice as likely to get PTSD when they do. In part, that’s due to the types of trauma >

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Estelle Lagarde/Millennium Images, UK

experienced. Sexual violence is more likely to cause PTSD than many other types of trauma. Both men and women face a similar risk of developing PTSD after such crimes, and men may actually be more vulnerable: one study found 65 per cent of men who experienced sexual violence developed PTSD, compared with 46 per cent of women. But women are much more likely to be raped or sexually assaulted. Around the world,

“The horrible event may be over, but you’re held hostage by what happened to you” one-third of women have experienced physical or sexual violence. In the US, one in six women has been raped or experienced attempted rape, compared with one in 33 men. Women are also more likely to have been sexually abused during childhood: worldwide, one in five women and one in 13 men report child sexual abuse. All of these figures make a stark point about the types of violence girls and women face. Koenen understands this grim reality too well. She developed PTSD after being raped. “My research career came completely from my own experience,” she says. But the nature of trauma isn’t the whole story. Even in cases of accidents, physical assaults, disaster or fire, women are more prone to PTSD than men. This could be because pre-existing anxiety and depression can increase the risk of developing PTSD, and more women than men are diagnosed with either or both of these conditions. But there could be a genetic component too. Several genes have been linked to PTSD, and the condition runs in families. Research in identical twins suggests that about 30 per cent of the variance in risk is down to genetics. Pinning down which genes are behind this effect is proving difficult, however. One line of enquiry is into the genes that code for neurotransmitters, which enable our brain cells to communicate. For instance, PTSD may be more prevalent in people with certain variations of a receptor gene for serotonin – a neurotransmitter important for mood and stress. But so far, no major differences have been found between men and women. Attention has also turned to a protein known as PACAP, which regulates our response to stress, influencing everything from pain 40 | NewScientist | 17 September 2016

sensitivity to blood pressure and metabolism. Ressler and his colleagues found that women with higher levels of the protein in their blood had more symptoms of PTSD, such as being easily startled and struggling to distinguish between signals of fear and safety. But surprisingly, this wasn’t seen in men. Ressler also found that women with one variant of the gene that codes for the PACAP receptor on cells were more vulnerable to PTSD, but those with another seemed to be protected. In fact, even after experiencing similar types of trauma, women with the protective variant showed fewer symptoms of PTSD than men. The difference seems to be down to oestrogen: the bit of DNA that the hormone can bind to is different in the vulnerable gene variant. “It kind of links stress to oestrogen,” says Vasiliki Michopoulos, who studies genetics and PTSD at Emory University in Atlanta, Georgia. That may help explain why women with PTSD report feeling more anxious when they have low levels of the hormone, such as just before a period. Oestrogen could also influence PTSD recovery. Many people with the condition learn to fear objects, smells and sounds they associate with the traumatic events – a car backfiring can trigger memories of gunfire, for example, while the smell of grass might remind someone of an outdoor assault. Treatment often involves re-imagining aspects of the traumatic environment in a safe space to “extinguish” fear memories by learning that, on their own, those sounds and smells are safe. But women are less able to do this when they have low levels of oestrogen. Further evidence for the hormone’s role comes from the finding that women who take an oestrogen-containing emergency

Primed for PTSD Women are more than twice as likely to get post traumatic stress disorder (PTSD) as men. In part, that is down to a greater chance of experiencing sexual violence 13.6

Sexual violence

13.3

Assault

11.5

Motor vehicle crash

7.6

Tragic death

7.3

Any trauma

6.4

Fire

6.0

Robbery Combat

2.2 Risk for PTSD by trauma type

SOURCE: WWW.NCBI.NLM.NIH.GOV/PUBMED/1619095

contraceptive after rape go on to develop fewer PTSD symptoms than those who don’t. What’s going on? It seems this powerful hormone may actually be reshaping the brain – specifically the hippocampus, thought to be involved in learning, memory and anxiety. Having a large hippocampus appears to protect both men and women from PTSD, and is linked to a better chance of recovery. Its response to oestrogen can be seen in how the brain changes during a woman’s menstrual cycle. Brain scans of 21 women taken just after their period – when oestrogen levels are high – show that the hippocampus is larger compared with just before their period, when levels are at their lowest. Similar changes have been seen in other areas of the brain, including the amygdala, thought to be important in shaping our emotional responses. One small study showed that a woman’s oestrogen levels can affect how strongly the amygdala is connected to other parts of the brain; when levels are high, for instance, connections to the part of the brain responsible for decision-making increase. Testosterone might also play a role in PTSD and anxiety more generally. Injections of the hormone seem to reduce anxiety in rats, and men with high levels appear to be better able to extinguish fearful memories. It may be that testosterone has similarly protective effects in men as oestrogen appears to have in women.

TIM WILKINSON/MILLENNIUM IMAGES, UK

Sex hormones may also help explain why PTSD can look different in men and women. While both sexes can develop any of the symptoms, men are more likely to be irritable, angry and drink to excess and women are more likely to be jumpy. “At the biological level, some risk factors interact with oestrogen and others interact with testosterone,” says Ressler. “We’re just at the tip of the iceberg.” As well as genetics and hormones, epigenetics – the study of how our environment and experiences can modify the way our genes work – could hold clues to why some people have a higher risk of PTSD. Childhood abuse seems to prime adults for the condition in this way. In a study of people who developed PTSD after several traumatic experiences as adults, those who were abused in childhood had more epigenetic changes related to immune regulation and central nervous system development. They also had more changes overall: 12 times as many as those who faced trauma only as adults. Other research supports the idea that preexisting changes to how our genes work could set us up for PTSD. Michopoulos and colleagues took blood samples from 39 women in hospital just after a traumatic event and looked for modifications to genes that have been linked to PTSD, including one thought to help control the way we respond to stress. Women who developed a PTSD-like

condition one month later had a different pattern of changes to those who didn’t experience any lasting stress. PTSD can also modify the expression of genes involved in cognition and immune function, which may underlie symptoms such as difficulty concentrating and poor health. Now Michopoulos is following people for several months after they have experienced a trauma, with the aim of pinpointing biomarkers associated with increased risk for PTSD, and also tracking changes caused by the condition itself. Together, these threads of research are changing the way we see PTSD. As we discover how the condition differs between people, there is a growing realisation that our approaches to treatment should differ too. “Our job now is not to think of PTSD as a monolithic disorder, but to figure out what kinds of different responses there are so we can personalise treatments,” says Rachel Yehuda at Mount Sinai School of Medicine in New York City. Once we have uncovered mechanisms by which trauma leads to PTSD, we could develop genetic tests to help identify the most effective treatments. “We have a number of different psychotherapies, but we don’t know which is the best for each person,” says Koenen. “In the next five or 10 years we’ll get closer to that.” She is running the largest ever study into the genetics of PTSD, and is halfway to her goal of getting data from at least 50,000 people. The ultimate goal is to find a way to prevent PTSD. For soldiers, who know they may face a traumatic incident, playing video games to promote hyper-awareness before combat has been shown to reduce the risk of PTSD. Few people can anticipate traumatic events, however. So preventing the condition from

SEEKING HELP FOR PTSD Two-thirds of people with PTSD will recover with treatment – even if they have had the condition for years. To get help, talking to a doctor is a good first step, but there are also online resources available: The International Society for Traumatic Stress Studies istss.org The Association for Behavioural and Cognitive Therapies (US) findcbt.org Assist Trauma Care (UK) assisttraumacare. org.uk

developing means interception after an ordeal – which may be most effective within about six hours. For most people, the first port of call after an assault or accident is a hospital. That provides a unique opportunity: “Because of this contact with the health service, we could in theory prevent PTSD,” says Koenen. If further research confirms that oestrogen and testosterone can help mitigate the harms of PTSD, one strategy for prevention could be

“As we discover how PTSD differs between people, we realise treatments should differ too” to administer these in the immediate aftermath of a trauma – much as emergency contraception is currently given to women who have been raped. But understanding the influence of hormones won’t be straightforward. Paradoxically, there is also some evidence that giving drugs that mimic the effects of stress hormones shortly after trauma could reduce the risk of PTSD. Another strategy is to try to disrupt the memory consolidation process. Giving people a blood pressure drug called propranolol may enable them to disentangle the memories of the trauma from the associated feelings, and other medications are being investigated with similar aims. “In the future, we will probably have drugs that more specifically target the fear system or the threat system,” says Ressler. For the time being, it is important to remember that PTSD is treatable (see “Seeking help for PTSD”, left). Don’t shut yourself off from normal life activities, says Ressler. “Although the instinct is to stay at home and avoid everything you’re afraid of, that avoidance is often the first step in having more problems,” he says. “For recovery, it’s critical to re-engage.” It is also vital to seek help. With existing treatments – which include medications for certain symptoms and cognitive behavioural therapies – more than two-thirds of people with PTSD will recover. Even after a long time, there is still hope for improvement. “I’ve seen people who have had PTSD for decades,” says Koenen. “With treatment, they got better.” n Jessica Hamzelou is a reporter for New Scientist. Links to the studies mentioned in this article are included in the online version 17 September 2016 | NewScientist | 41