Women more susceptible to PTSD

Women are more susceptible to Post-traumatic Stress Disorder (PTSD) even when the type of the stressful event is controlled for:

Males experience more traumatic events on average than do females, yet females are more likely to meet diagnostic criteria for Posttraumatic Stress Disorder (PTSD), according to a review of 25 years of research reported in the November issue of Psychological Bulletin, published by the American Psychological Association (APA).

The authors reviewed 290 studies conducted between 1980 and 2005 to determine who is more at risk for potentially traumatic events (PTE) and posttraumatic stress disorder (PTSD) � males or females? The results of the meta-analysis found that while males have a higher risk for traumatic events, women suffer from higher PTSD rates. PTSD is defined as an anxiety disorder precipitated by a traumatic event and characterized by symptoms of re-experiencing the trauma, avoidance and numbing and hyperarousal.

From the review, researchers David F. Tolin, PhD of the Institute of Living and Edna B. Foa, PhD, of the University of Pennsylvania School of Medicine found that female study participants were more likely than male study participants to have experienced sexual assault and child sexual abuse, but less likely to have experienced accidents, nonsexual assaults, witness death or injury, disaster or fire and combat or war. Sexual trauma, the authors conclude, may cause more emotional suffering and are more likely to contribute to a PTSD diagnosis than other types of trauma.

Women's higher PTSD rates were not solely attributable to their higher risk for adult sexual assault and child sexual abuse, explained Tolin. PTSD rates were still higher for women even when both sexes were compared on the same type of trauma.

"PTSD may be diagnosed more in women in part because of the criteria used to define it. Cognitive and emotional responses to traumatic events make a diagnosis of PTSD more likely. So even though men may experience more traumas, they don't seem to have the same emotional responses to traumatic events," said Tolin and Foa.

The research is published in the Psychological Bulletin.

There are two reasonable explanations for this discrepancy. First, the researchers suggest that there might be a problem with diagnosis in that males manifest the symptoms of PTSD differently. This may very well be true. However, I would argue that it may be the result of some intrinsic difference in susceptibility due to the way the disease affects the brain. We know a lot more than we used to about how PTSD gets set up in the brain, and much of the information we know suggests that women may have an increased hormonal susceptibility to PTSD.

With respect to the first, the common presentation of PTSD is below (from eMedicine):

-- The first criterion has 2 components, as follows:

• Experiencing, witnessing, or being confronted with an event involving serious injury, death, or a threat to a person's physical integrity
• A response involving helplessness, intense fear, or horror (sometimes expressed in children as agitation or disorganized behavior)

-- The second major criterion involves the persistent reexperiencing of the event in one of several ways. This may involve thoughts or perception, images, dreams, illusions, hallucinations, dissociative flashback episodes, or intense psychological distress or reactivity to cues that symbolize some aspect of the event. However, children reexperience the event through repetitive play, not through perception like adults.

-- The third diagnostic criterion involves avoidance of stimuli that are associated with the trauma and numbing of general responsiveness; this is determined by the presence of 3 or more of the following:

• Avoidance of thoughts, feelings, or conversations that are associated with the event
• Avoidance of people, places, or activities that may trigger recollections of the event
• Inability to recall important aspects of the event
• Significantly diminished interest or participation in important activities
• Feeling of detachment from others
• Narrowed range of affect
• Sense of having a foreshortened future

-- The fourth criterion is symptoms of hyperarousal, and 2 or more of the following symptoms are required to fulfill this criterion:

• Difficulty sleeping or falling asleep
• Decreased concentration
• Hypervigilance
• Outbursts of anger or irritable mood
• Exaggerated startle response

Particularly with things like anger or irritability or the manifestation of avoidance, it would not be unreasonable for men and women to culturally present differently. The authors mention this idea:

A reason that men may not fit the current diagnosable criteria of PTSD, said Tolin, is that their symptoms may manifest themselves differently. The male participants examined in this review were less likely to report anxiety or depression, but were more likely to report behavior and drug problems. They were also more likely to become irritable, angry or violent after traumas.

However, I would argue that there is also a mechanistic explanation that explains the greater susceptibility -- involving the action of hormones on the prefrontal cortex. This goes into what happens to the human brain after a traumatic event.

PTSD has been recognized in the neuropsychiatric field as a failure of fear extinction. The primary animal model that we have for fear conditioning is the rat. Conditioned fear is elicited by pairing of a tone with a foot shock leading to a freezing response. The animal associates the tone with a bad thing happening to it, so whenever it hears the tone it will anticipate the bad thing and freeze. This response is not permanent and can be extinguished, however, through a process neuroscientists call extinction. If you take that same animal and expose it to the tone over and over again without the foot shock, the animal will eventually forget the association between the two and stop freezing.

A great deal of research has gone into how extinction takes place. One of the things that we know about this extinction is that it is an active rather than a passive process. It requires the formation of a new memory to write over the old memory. Writing the new memory is in part achieved by the activation of a particular part of the brain called the prefrontal cortex. The prefrontal cortex does a lot of stuff, but one of things that it does is deactivate the associations of fear response during the process of extinction.

So far, so good. How does this have anything to do with PTSD? One of the problems in PTSD is that the prefrontal cortex may not be doing its job completely. Patients with PTSD show reduced activity and volume in the prefrontal cortex (reviewed here). If the prefrontal cortex is not suppressing the memories associated with fear responses, then the patients may not be able to let them go and will continue show exaggerated responses. Likewise, animal models where the prefrontal cortex is lesioned or prevented from functioning also show deficits in fear extinction (reviewed here). It has been speculated that PTSD may fundamentally represent a failure of fear extinction, leading us to be very interested in the things that affect prefrontal function.

Where does gender play a role in it? We know from animal models that female rats are more susceptible to stress during periods when estrogen is high (using a paradigm called restraint stress -- read the paper here). We also know that animal models of PTSD result in the contraction of the dendritic arbors of neurons in the prefrontal cortex. (The dendritic arbor retraction is associated with less function.) It is not unreasonable -- and has been suggested by others -- that the effects are related. I am not aware at this time of any published studies that show the direct association between estrogen and prefrontal dendritic contraction, but I am certain that they are ongoing.

How does this hypothesis work in practice? During periods with high estrogen -- and more generally throughout life -- women are more susceptible to stressors. This may be in part because stressors lead to dendritic arbor retraction in the prefrontal cortex, and hormones such as estrogen potentiate that effect. When dendritic arbors in the prefrontal cortex contract, the prefrontal cortex is no longer effective at inducing fear extinction, leading to PTSD.

This hypothesis has some interesting clinical predictions. If we can activate the prefrontal cortex, we should be able to substantially treat PTSD. (For more information about PTSD and where the research is going, here is an excellent review.)

Anyway, I was interested in seeing this article, because the idea that women may have some biologically greater risk for PTSD has been punted around the field for a while. Definitely an area to watch.