The Science of Fear: Probing the Brain Circuits That Link ADHD and PTSD
Research increasingly reveals a strong relationship — and reciprocal risk factors — between ADHD and PTSD. What explains this mutual comorbidity? PTSD is associated with dysfunction in areas of the brain implicated in fear extinction learning. New studies reveal that individuals with ADHD have similarly deficient fear circuitry, which could begin to explain the disorders’ link.
Is there a relationship between attention deficit hyperactivity disorder (ADHD) and post-traumatic stress disorder (PTSD)? Absolutely. A growing body of research has documented a robust link between the two conditions, suggesting that individuals with ADHD are at elevated risk for PTSD — and vice versa. Clinically, the implications of such a relationship are vast, as are the questions: What makes ADHD an antecedent risk factor for PTSD?
One theory posits that abnormal neural fear circuitry connects individuals with ADHD and PTSD. Individuals with ADHD appear to have dysfunctional activation of the same brain structures implicated in fear, which is also true for individuals with PTSD. This overlap may underscore the strong statistical association between the disorders — and help explain why individuals with ADHD are more likely to suffer the long-lasting psychological aftershocks of PTSD after experiencing a severe jolt of trauma.
ADHD and PTSD: Risk Factor Research
By definition, PTSD is preceded by a major traumatic event. Though half the population may experience some lifetime trauma, the majority of people do not develop PTSD. The condition has a lifetime incident rate of 8.7 percent in the United States1. The issue of interest, then, is vulnerability — specifically, identifying the factors that make an individual more likely to develop PTSD following trauma.
ADHD, while not the only risk factor for PTSD, emerges as an incredibly intriguing one for these reasons:
- ADHD is a prevalent neurobiological disorder with early-life onset, while PTSD develops later in life, suggesting that the former is a precursor for the latter.
- ADHD is associated with high levels of risk-taking behaviors and impulsivity that could lead to traumatic events.
- Deficits in attention and prefrontal cortical function resembling those in ADHD brains have been identified in people with PTSD as well. In rodents, prenatal nicotine exposure leads to both an ADHD-like phenotype as well as fear circuitry abnormalities like those seen in PTSD. In addition, both conditions are characterized by irregularities in dopaminergic neurotransmission.
- Both ADHD and PTSD have common specific genetic risk factors, including polymorphisms in the dopamine transporter gene and cannabinoid receptor gene.
Our systematic review and meta-analysis of several studies examining the relationship between ADHD and PTSD reveals a bidirectional association between the two disorders2:
- The relative risk for PTSD in individuals with ADHD is four times greater compared to normal controls; it is close to 2 against psychiatric controls, and 1.6 against traumatized controls.
- The risk for ADHD in individuals with PTSD is twice that observed in normal controls. Against trauma controls, the risk ratio is more than 2 (highly significant); against psychiatric controls, it is about 1 (not very elevated).
In addition to statistical associations, our review found a significant positive correlation between the severity of symptoms when both ADHD and PTSD are present.
ADHD and PTSD: Understanding Fear and Neural Circuitry
If ADHD is an antecedent risk factor for PTSD, it could be due to a neurological vulnerability – specifically, abnormal fear circuitry – that may predispose individuals with ADHD to develop PTSD after trauma. To understand this relationship, we must first review the processes involved in fear, including how fear is developed and extinguished, and how the process might be compromised in individuals with PTSD.
Pavlovian Conditioning and Fear in PTSD Brains
Individuals with PTSD often experience intense distress and physiological reactions to cues related to the preceding traumatic event(s). These cues carry emotional salience and significance that are difficult to regulate or change in context and meaning.
Consider a military veteran, now based in Texas, who relives the trauma of his Humvee exploding in Iraq every time he sees a pigeon – the last thing he remembers seeing before the blast. This soldier is unable to distinguish the context of the pigeon in Iraq versus at home in Texas. Why? Translational models of fear conditioning and extinction help us understand this response.
In basic Pavlovian auditory conditioning, an animal is placed in a cage and hears a tone (a neutral stimulus). The tone is then paired with a mild electric shock (an aversive stimulus). The animal forms an association between the tone and the shock. Eventually, the animal becomes afraid of the tone because it has become conditioned to expect a shock as well. To begin to extinguish the fear (i.e. fear extinction learning) the tone is presented without any shocks. After time, this learning is consolidated in the brain as a new memory and recalled when the tone is heard.
For the soldier in Texas, for example, fear extinction learning would occur with each pigeon he sees without an accompanying explosion. The fear associated with seeing a pigeon to gradually decrease so as to eventually extinguish. (Such is the case for the majority of people exposed to traumatic events.)
It’s important to note that extinction learning does not “erase” the initial fear memory. After extinction learning, there are two types of competing memories – a “fear” memory and a “fear not” memory – that are gated by context.
The Neurobiology of Fear
A comparable two-day fear conditioning and extinction paradigm was developed to study these processes in humans3 where subjects received mild shocks when seeing blue and red lights (two conditioned stimuli) in a specific environmental context. Subjects underwent fear extinction learning for the blue light, but not the red, which was left as an unextinguished stimulus. Functional MRI was used to measure brain activation during conditioning, as well as extinction learning (blue light versus control) and extinction recall (blue light versus red light, measured on day two).
In fear learning, several areas of the brain, including the dorsal anterior cingulate cortex (dACC), the amygdala, and the hippocampus, are more activated. In extinction learning, the brain “cools,” though the amygdala is still implicated. In late extinction learning, the ventromedial prefrontal cortex (vmPFC), which was not activated in conditioning and early extinction, is activated. In extinction memory retrieval, this same area is even more activated. The hippocampus, meanwhile, is key in context gating the conditioning and extinction memory. The insular cortex is another important area, especially in the formation of fear memories.
Combined, these brain areas are what we refer to as the fear circuit, interacting with each other during different phases of this paradigm, be it fear acquisition, extinction learning, consolidation of the learning, or extinction of memory expression.
Extinction Recall in PTSD Brains
PTSD is associated with impairment in fear extinction learning, especially recall4. Results from a 2009 study show that individuals with PTSD and trauma-exposed individuals who did not develop PTSD have comparable responses during fear conditioning and early extinction, but differ considerably in recall, when PTSD patients do not retain extinction learning. In PTSD subjects, the vmPFC (implicated in late extinction learning) is less active, and the dACC (involved in fear learning) is hyperactivated compared to controls. This balance explains the exaggerated fear responses in individuals with PTSD, and why fear can’t be extinguished.
Fear Circuitry in ADHD Brains
Given the established neurobiological links and other connections between ADHD and PTSD, might there be dysfunctional activation in brain structures mediating fear extinction in individuals with ADHD that could explain their high risk for PTSD? Our research indicates that there are similar deficits here, too.
In our study on fear circuitry in ADHD5, we had medication-naive young adults with ADHD and young adults without ADHD, all without trauma history, undergo the aforementioned two-day fear conditioning paradigm. A mild shock was delivered through electrodes in the fingers of the participants’ hand, and electrodes attached to the palm measured skin conductance response as an index of fear conditioning. Functional MRI was used to study brain activation.
We observed significant differences in brain activation for the two groups during extinction recall and extinction memory consolidation. Compared to ADHD subjects, controls showed greater activation in the left hippocampus, the vmPFC, and the right prefrontal cortex (PFC) in this phase. ADHD subjects compared to healthy controls, showed deficient vmPFC, hippocampus, dACC, and insula activation, which are implicated in fear extinction learning and extinction recall. This points to deficient fear circuitry in ADHD brains.
The deficient vmPFC and hippocampus activation in ADHD subjects during extinction recall, furthermore, is similar to deficit findings in individuals with PTSD. (Important to note and clarify, however, is that ADHD subjects, unlike those with PTSD in previous studies, did retain extinction memory when tested on day two in this study. Their fear responses did not look like people with trauma, although we found decreased activation in these implicated brain structures.) These results start to explain the strong association between the disorders.
ADHD and PTSD: Implications of Relationship
Our study on fear circuitry in ADHD brains is the first research demonstrating deficits during late extinction learning and recall. More work, however, is needed to better understand neurological vulnerability to PTSD and even trauma. Perhaps our findings, for example, are not specific to ADHD, as studies have also identified impaired fear circuitry in other psychiatric disorders. As for medication treatment for ADHD, we can hypothesize that it would be beneficial for PTSD prevention, but we do not have data to support this.
Overall, clinicians should consider ADHD as a very important risk factor for PTSD. It may be important to screen for ADHD in individuals with high-trauma-exposure positions, like first responders, firefighters, police, and military personnel, to minimize their risk for PTSD and provide appropriate supports.
In children, PTSD is a very serious disorder, and emphasis should be on prevention when possible. Clinicians should screen for trauma and PTSD in their patients with ADHD, and screen for ADHD in their patients with PTSD. Treating comorbidities are often important to improved functioning in children with multiple psychiatric disorders, and so clinicians should focus on identifying and treating both conditions when present.
The content for this article was derived with permission from the “ADHD and PTSD” symposium presented by Andrea Spencer, M.D., Joseph Biederman, M.D., and Mohammed Milad, Ph.D., as part of the 2021 APSARD Annual Virtual Meeting.
ADHD and PTSD: Next Steps
- Read: ADHD and Trauma – Untangling Causes, Symptoms & Treatments
- Read: What Anxiety Disorders Look Like in Adults
- Read: When It’s Not Just ADHD – Symptoms of Comorbid Conditions
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3 Linnman, C., Zeidan, M. A., Furtak, S. C., Pitman, R. K., Quirk, G. J., & Milad, M. R. (2012). Resting amygdala and medial prefrontal metabolism predicts functional activation of the fear extinction circuit. The American journal of psychiatry, 169(4), 415–423. https://doi.org/10.1176/appi.ajp.2011.10121780
4 Milad, M. R., Pitman, R. K., Ellis, C. B., Gold, A. L., Shin, L. M., Lasko, N. B., Zeidan, M. A., Handwerger, K., Orr, S. P., & Rauch, S. L. (2009). Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biological psychiatry, 66(12), 1075–1082. https://doi.org/10.1016/j.biopsych.2009.06.026
5 Spencer, A. E., Marin, M. F., Milad, M. R., Spencer, T. J., Bogucki, O. E., Pope, A. L., Plasencia, N., Hughes, B., Pace-Schott, E. F., Fitzgerald, M., Uchida, M., & Biederman, J. (2017). Abnormal fear circuitry in Attention Deficit Hyperactivity Disorder: A controlled magnetic resonance imaging study. Psychiatry research. Neuroimaging, 262, 55–62. https://doi.org/10.1016/j.pscychresns.2016.12.015