Hypothalamus and Post-Traumatic Stress Disorder: A Review

Abstract

Humans have lived in a dynamic environment fraught with potential dangers for thousands of years. While fear and stress were crucial for the survival of our ancestors, today, they are mostly considered harmful factors, threatening both our physical and mental health. Trauma is a highly stressful, often life-threatening event or a series of events, such as sexual assault, war, natural disasters, burns, and car accidents. Trauma can cause pathological metaplasticity, leading to long-lasting behavioral changes and impairing an individual’s ability to cope with future challenges. If an individual is vulnerable, a tremendously traumatic event may result in post-traumatic stress disorder (PTSD). The hypothalamus is critical in initiating hormonal responses to stressful stimuli via the hypothalamic–pituitary–adrenal (HPA) axis. Linked to the prefrontal cortex and limbic structures, especially the amygdala and hippocampus, the hypothalamus acts as a central hub, integrating physiological aspects of the stress response. Consequently, the hypothalamic functions have been attributed to the pathophysiology of PTSD. However, apart from the well-known role of the HPA axis, the hypothalamus may also play different roles in the development of PTSD through other pathways, including the hypothalamic–pituitary–thyroid (HPT) and hypothalamic–pituitary–gonadal (HPG) axes, as well as by secreting growth hormone, prolactin, dopamine, and oxytocin. This review aims to summarize the current evidence regarding the neuroendocrine functions of the hypothalamus, which are correlated with the development of PTSD. A better understanding of the role of the hypothalamus in PTSD could help develop better treatments for this debilitating condition.

Post-traumatic Stress Disorder: The Influence of the Environmental Context and Analysis of Oxidative Stress and Inflammatory and Glycemic Markers in Women Living in Kurdistan Regional Government-Iraq

“…PTSD is associated with elevated levels of inflammatory markers, including CRP, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), that could exacerbate insulin resistance [ 22 , 23 ]. In addition, PTSD is linked to changes in the hypothalamic-pituitary-adrenal axis and cortisol level [ 24 ], which have been demonstrated to be associated with visceral obesity and insulin resistance [ 25 ]. Furthermore, PTSD is connected to a higher body mass index (BMI), disrupted sleep patterns, and lifestyle modifications, such as prolonged inactivity and unhealthy dietary choices, all of which collectively contribute to the onset of diabetes [ 26 ].…”

E-Cigarette Exposure Alters Neuroinflammation Gene and Protein Expression in a Murine Model: Insights from Perinatally Exposed Offspring and Post-Birth Mothers

“…In the context of the hypothalamus, where an increase in AMPAR protein levels was observed in offspring in the present study, neuroinflammation could further exacerbate excitatory signaling and contribute to disruptions in normal neural function [ 42 ]. Such an alteration could potentially lead to dysregulation in hormonal balance, appetite control, and stress responsiveness, as well as negative alterations in neural circuits governing food intake and body weight [ 43 , 44 ]. Further research in this area will contribute to a better understanding of the complex mechanisms underlying the impact of E-cigs on neural development and function, as well as guide future studies of less well-understood crosstalk between cognitive (hippocampal) brain signals in mothers and developing hypothalamic pathways in their offspring.…”

Neuroanatomical and functional correlates in post‐traumatic stress disorder: A narrative review

“…In fact, during exposure to chronic stress, the hypothalamicpituitary-adrenal (HPA) axis responds with an altered and continuous production of glucocorticoids and cortisol, and it has been repeatedly shown how excessive and persistent levels of these molecules are capable of reducing the activity of hippocampal and cortical neurons while hyperactivating amygdala and brainstem neurons. 23 In general, albeit with some differences related especially to gender, age, and severity of the disorder as well as the trauma suffered, in adult patients with PTSD, significantly reduced volumes and altered function can be found in the cerebral white matter 24 and structures such as medial frontal, lateral dorsal and orbital cortex, insula, 25 hippocampus-sometimes bilaterally, 26 amygdala, especially left, 27 hypothalamus, 28 and cingulate cortex. 29 In children under 6 years of age, on the other hand, such abnormalities are significantly rarer; however, it is not uncommon to observe reduced than normal volumes of the corpus callosum and frontal lobes along with enlarged brain ventricles.…”

“…In general, albeit with some differences related especially to gender, age, and severity of the disorder as well as the trauma suffered, in adult patients with PTSD, significantly reduced volumes and altered function can be found in the cerebral white matter 24 and structures such as medial frontal, lateral dorsal and orbital cortex, insula, 25 hippocampus‐sometimes bilaterally, 26 amygdala, especially left, 27 hypothalamus, 28 and cingulate cortex. 29 In children under 6 years of age, on the other hand, such abnormalities are significantly rarer; however, it is not uncommon to observe reduced than normal volumes of the corpus callosum and frontal lobes along with enlarged brain ventricles.…”

“…Precisely because of its characteristics and functions, abnormalities in it may contribute to the pathophysiology of PTSD. 27 However, concerning the effects of hormonal dysregulation resulting from stress, the literature reports that numerous evidences, 38 , 39 studies regarding possible neuroanatomical alterations of the hypothalamus in PTSD are still relatively scarce. However, a recent paper 40 analyzed by MRI the hypothalamic volume in adult subjects with a diagnosis of PTSD who had experienced one or more adverse childhood experiences (ACEs) during childhood, showing a significant reduction in this brain structure compared with that found in the control sample and subjects without PTSD.…”