Man crossing street with large manipulator looming above tethering him to PTSD symptoms

Inside the anatomy of PTSD and the potential role of neurotransmitters

Evolving research suggests that the dysregulation of neurotransmitter systems associated with PTSD, including norepinephrine (N), serotonin (S), and dopamine (D), may contribute to the symptoms of PTSD^1-11

Brain icon showing various brain regions

Amygdala
Hippocampus
PFC
Striatum

The amygdala, hippocampus, prefrontal cortex (PFC), and striatum are key brain regions involved in the balance between the approach and avoidance systems in PTSD.^3,12-14

The avoidance system is linked to fear-related processes¹²
The approach system is closely related to reward processes¹²

Neurotransmitters, including N, S, and D, can alter the activity of key brain regions associated with the approach and avoidance systems.^1-4,9,15-18

Healthy cognitive behavior requires balance between the approach and avoidance systems.¹² Neurotransmitters may be linked to the pathophysiology of PTSD and its associated symptoms.

An Expert’s Insights

Dr. Javanbakht discusses neurotransmitters associated with the pathophysiology of PTSD

Dysregulation of neurotransmitters in these brain regions may be associated with PTSD symptoms^1-11,16

Norepinephrine

Hyperarousal and  intrusion^5-7

Serotonin

Mood and hyperarousal^7,9-11

Dopamine

Mood and
avoidance⁴

Brain icon showing norepinephrine pathway

Norepinephrine system hyperactivity associated with PTSD may contribute to hyperarousal and intrusion symptoms^5-7

High levels can increase amygdala activity and fear conditioning^1-3
Hyperactivity can impair PFC function, leading to restricted control of emotions^1-3

Serotonin deficits associated with PTSD may contribute to negative mood and hyperarousal symptoms^7,9-11

Hyperactivity of the amygdala may contribute to excessive fear responses and reactivity¹⁶
Stress can alter activity in the hippocampus, which can affect mood^10,11

Dopamine dysfunction associated with PTSD may contribute to negative mood and avoidance symptoms^4,8

Striatal dopamine dysfunction may contribute to negative mood symptoms, such as anhedonia and emotional numbing⁸
High dopamine levels in the medial PFC may contribute to avoidance⁴

Research continues into the pathophysiology of PTSD

It may be helpful to discuss the pathophysiology that could be associated with PTSD with your patients.

Behind the numbers
Understanding the impact of PTSD

Explore the impact

Shedding light
Confronting the challenges of PTSD

Discover the PTSD landscape

Beyond the trauma
Navigating the symptoms and course of PTSD

See the symptoms

1.
Arnsten AFT. Stress signalling pathways that impair prefrontal cortex structure and function. Nat Rev Neurosci. 2009;10(6):410-422.
2.
Arnsten AFT. Stress weakens prefrontal networks: molecular insults to higher cognition. Nat Neurosci. 2015;18(10):1376-1385.
3.
Giustino TG, Maren S. Noradrenergic modulation of fear conditioning and extinction. Front Behav Neurosci. 2018;12:43.
4.
Vander Weele CM, et al. Dopamine tunes prefrontal outputs to orchestrate aversive processing. Brain Res. 2019;1713:16-31.
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Strawn JR, Geracioti TD Jr. Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder. Depress Anxiety. 2008;25(3):260-271.
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Lewis MW, et al. Exploring the impact of trauma type and extent of exposure on posttraumatic alterations in 5-HT_1A expression. Transl Psychiatry. 2020;10(1):237.
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Mahar I, et al. Stress, serotonin, and hippocampal neurogenesis in relation to depression and antidepressant effects. Neurosci Biobehav Rev. 2014;38:173-192.
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Stein MB, Paulus MP. Imbalance of approach and avoidance: the yin and yang of anxiety disorders. Biol Psychiatry. 2009;66(12):1072-1074.
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Kredlow MA, et al. Prefrontal cortex, amygdala, and threat processing: implications for PTSD. Neuropsychopharmacology. 2022;47(1):247-259.
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Liberzon I, Abelson JL. Context processing and the neurobiology of post-traumatic stress disorder. Neuron. 2016;92(1):14-30.
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Bocchio M, et al. Serotonin, amygdala and fear: assembling the puzzle. Front Neural Circuits. 2016;10:24.
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Krystal JH, Neumeister A. Noradrenergic and serotonergic mechanisms in the neurobiology of posttraumatic stress disorder and resilience. Brain Res. 2009;1293:13-23.
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Li X, et al. 5-HT_1A receptor agonist affects fear conditioning through stimulations of the postsynaptic 5-HT_1A receptors in the hippocampus and amygdala. Eur J Pharmacol. 2006;532(1-2):74-80.
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Balbino de Paula B, et al. Distinct effect of 5-HT_1A and 5-HT_2A receptors in the medial nucleus of the amygdala on tonic immobility behavior. Brain Res. 2016;1643:152-158.

Inside the anatomy of PTSD and the potential role of neurotransmitters