Post-Traumatic Stress Disorder Pathophysiology Essay (Critical Writing)

Introduction

Post-traumatic stress disorder, commonly abbreviated as PTSD, refers to a severe anxiety disease whose onset is influenced by the exposure to a traumatic life episode. This disorder occurs in around 8-14% of the US populace, and its prevalence among females (12-18%) in the country is about twice higher than that of their counterparts (Togay and El-Mallakh, 2020). PTSD has been associated with a substantial burden on the wider society and individuals. Furthermore, Togay and El-Mallakh (2020) underscore the increased likelihood of PTSD patients to utilise drugs and sustaining psychological functioning impairments. Most of the individuals with this illness typically match the diagnostic criteria for other mental conditions; this includes anxiety and major depression. The paper highlights the disorder’s pathophysiology to foster the understanding of its underlying aetiology.

Noradrenergic System

Adrenoreceptors, typically abbreviated as ARs, relate to a grouping of receptors, particularly the G protein-coupled ones, which consist of three primary categorisations: β, α1 and α2 with related subtypes. This system prompt sympathetic autonomic reaction and CNS activity via cell bodies situated within the coeruleus locus. It later extends towards the structures of the limbic system and prefrontal cortex, implicating it in discriminatory response to fear and stress-related feedbacks and aversive and rewarding stimuli (Sakellariou and Stefanatou, 2017). Through physiological processes’ dysregulation, hyperadrenergic actions trigger mental illnesses, such as anxiety, traumatic brain injuries and major depression. Its impact on pertinent fear signalling and amygdala functioning further play a crucial role in PTSD’s onset.

Recent ongoing research reveals the involvement of NET (noradrenaline transporter) in PTSD manifestation. Studies demonstrate the interconnection between severe distress exposure and the increased availability of noradrenaline synaptic within cortical regions, reduced presence of NET within coeruleus locus and the AR system’s dysfunction (Togay and El-Mallakh, 2020). Reboxetine, a selective NRI (noradrenaline reuptake inhibitor) medication has been shown to antagonise the availability of noradrenaline synaptic and minimise the reaction of foot shock distress (Kelmendi et al., 2016). The aforementioned outcome has also been demonstrated by human PET (positron emission tomography) surveys that reveal a reduced NET availability in PTSD patients (Kelmendi et al., 2016). The delineated modification in the response of homeostatic distress could trigger phenotypes related to depression and anxiety, which typify PTSD.

A study aimed to ascertain the efficacy of various PTSD therapies in veterans diagnosed with alcohol dependence and PTSD uncovered the effectiveness of using an amalgamation of naltrexone and NRI desipramine in minimising these conditions. This treatment approach was compared with the combination of naltrexone with either paroxetine or SSRI (Salellariou and Stefanatou, 2017). The latter proved to be slightly inefficient in improving the clinical manifestation associated with this disorder.

Exposure to trauma may trigger emotional dysregulation and decreased impulse control. Studies indicate that atomoxetine, a medication typified by an increased NET affinity, aids in minimising symptoms related to ADHD with concomitant PTSD and anxiety diagnoses and elevating inhibitory reaction control (Kelmendi et al., 2016). The aforementioned medication can be efficient in managing phenotypes demonstrating noticeable impulsive and hyperarousal deportments. Studies also reveal the clinical utility of venlafaxine, a drug categorised as an SNRI, in decreasing numbing/avoidance and recurring symptoms, as well as fear extinction (Kelmendi et al., 2016). This underscores its efficacy as a supplement therapy for PTSD exposure. NET’s interaction with other distress systems, for example, dopaminergic emphasise the effectiveness of amalgamating medicines such as SNRIs and integrated therapies which influence NET functions to enhance better PTSD management outcomes.

Serotonergic Receptors: 5-HT_1B, 5-HT_1A

5-HT – serotonergic receptors relate to a grouping of receptors, particularly the G protein-linked ones and 5-HT3, a distinguished ligand-gated channel of ion, which consists of several categorisations, i.e., 5-HT1 to 5-HT7 with their correlated subclasses. According to Ayers et al. (2016), the 5-HT framework is implicated in the regulation of behaviour or deportment, processing of emotions, and cognition. Studies involving humans and animals exhibit this system’s role in triggering various mental illnesses’ pathophysiology; this includes PTSD, alcoholism and depression (Sakellariou and Stefanatou, 2017). Sakellariou and Stefanatou, (2017) further link threat responsiveness and fear regulation with the signalling of 5-HT within the amygdala; this is an area within the brain deemed essential in comprehending the reaction to fear and aetiology of PTSD. Furthermore, they reveal the selective role assumed by 5-HT agonists in inducing flashbacks associated with trauma and anxiety attacks among individuals with PTSD. The reaction triggered by this agonist fosters the understanding of 5-HT’s role in the disorder’s aetiology.

5-HT1A refer to a type of receptors situated on the cell bodies of 5-HT within the raphe presynaptically and in other regions of the brain, postsynaptically. 5-HT1A postsynaptic receptors are commonly found in the limbic and frontal cortices’ astroglia, and they trigger trophic-factor S-100β’s release, consequently fostering cytoskeletal maintenance and serotonergic system growth (Sakellariou and Stefanatou, 2017). The neuropathological deviations demonstrated in the paralimbic and limbic cortical regions with regard to mood disorders may be ascribed to the impaired functioning of the 5-HT1A receptor. These presentations facilitate their capacity to influence various PTSD-related symptoms.

On the other hand, 5-HT1B receptors are highly expressed within the ventral tegmental region, substantia nigra, nucleus accumbens, pallidum, and striatum. They function as autoreceptors presynaptically on the terminals of the axon linked to 5-HT receptors that consist of neurons and on non-5-HT-bearing neurons as heteroreceptors (Kelmendi et al., 2016). The 5-HT1B receptor operates as a heteroreceptor by regulating the action of several neurobiological components within the brain; this includes GABA, glutamate, acetylcholine, dopamine and noradrenaline in regions interlinked to PTSD pathogenesis. Therefore, this means that the alteration in the levels of this component may trigger PTSD.

Patients diagnosed with PTSD and those exposed to trauma often exhibit the decreased binding potential of 5-HT1B. This occurs within the cingulate cortex, particularly the anterior one, amygdala, and caudate with observable incontestable interconnections linked to symptom severity and trauma history. Recent surveys link density modifications in 5-HT1B to certain PTSD-related symptomologies, implying that these alterations may account for specific elements of PTSD clinical phenotypes (Ayers et al., 2016). Therapies that target the action of 5-HT1B can foster clinical utility in PTSD treatment; this includes appropriate medications for comorbid illnesses that affect one’s mood.

Corticotropin-Releasing Factor – CRF and 5 Hypothalamic-Pituitary-Adrenal Axis – HPA

The HPA axis relates to a neuroendocrine distress-response system, which connects the CNS (central nervous system) to the endocrine structure; its dysfunction triggers several psychiatric and psychosomatic illnesses. The CRF, on the other hand, refers to a neuronal signalling component generated by hypothalamus cells in retaliation to mental or physical distress (Togay and El-Mallakh, 2020). High CRF levels within the hypothalamus typically cause the HPA axis’ activation or stimulation and the elevated cortisol secretion. Researchers argue that the increased CRF levels during trauma can enhance the traumatic evocation encoding procedure and anxiety-related effects. Patients with PTSD often demonstrate aberrations in systems linked to the HPA axis and elevated CRF levels in the cerebrospinal fluid. This, in turn, reveals the efficacy of medications that enhance the dampening of the hormones linked to the HPA axis and CRF system in PTSD therapy (Kelmendi et al., 2016). Studies aimed to assess the CRF-1 antagonists’ is necessary to determine the efficacy of this medication on PTSD therapy.

Opioid System

Several studies implicate opioid-related systems in PTSD’s pathophysiology. According to Sakellariou and Stefanatou (2017), opioid receptors, commonly abbreviated as ORs are classified under receptors of the G protein-linked category. They are categorised further into three subtypes: μ (morphine preferring), κ (dynorphin choosing) and δ (encephalin preferring) (Sakellariou and Stefanatou, 2017). Empirical surveys implicate dynorphin OR in multiple brain diseases, for instance, Alzheimer’s disorder, Tourette’s syndrome, epilepsy and substance abuse, especially psychostimulants. It has also been linked to the manifestation of distress-triggered deportments.

Established preclinical findings identify k-ORs as therapy development targets for clients diagnosed with phenotypes linked to anxiety and depression. A particular survey revealed the efficacy of dynorphin OR antagonists in managing learned and involuntary fear due to their antidepressant-anxiolytic features compared to fluoxetine, an SSRI subtype. There is a threefold scientific proof suggesting the involvement of opioid systems in PTSD’s aetiology:

• Victims of violence, particularly those involving intimate partners, can demonstrate pain-related syndromes.
• An interconnection exists between exaggerated opioid use rate in adulthood and sexual trauma in childhood.
• Morphine’s use in trauma-linked cases may decrease the probability of consequent PTSD development following traumatic injuries, especially among adult patients, children, burn survivors and military experts.
• Additional research on k-OR’s role in PTSD will play a crucial role in fostering the comprehension of its circuity and therapy implications.

Conclusion

The essay highlights the recent developments in studies related to the pathophysiology of PTSD and the relevancy of these findings on understanding the disease’s aetiology. Current practices involving PTSD diagnosis depend on clinical interviews and screening approaches. Therapy is restricted to the management of symptoms instead of the pertinent biological aetiology. Therefore, there is an increasing need to foster a detailed comprehension of PTSD’s pathophysiology and its clinical presentations to promote the development of effective therapeutic strategies.

Reference List

Ayers, S. et al. (2016) ‘The aetiology of post-traumatic stress following childbirth: a meta-analysis and theoretical framework’, Psychological Medicine, 46(6), pp. 1121-1134.

Kelmendi et al. (2016) ‘PTSD: from neurobiology to pharmacological treatments’, European Journal of Psychotraumatology, 7(1), pp. 1–11.

Sakellariou M.O. and Stefanatou, A. (2017) ‘Neurobiology of PTSD and implications for treatment: an overview’, Current Research: Integrated Medicine, 2(1), pp. 50-53.

Togay, B. and El-Mallakh, R. S. (2020) ‘Posttraumatic stress disorder: from pathophysiology to pharmacology’, Current Psychiatry, 19(5), pp. 33-39.