Psychological Trauma and Brain

Psychological TRAUMA and BRAIN

Trauma is a deeply distressing or disturbing experience that overwhelms an individual’s ability to cope. Childhood trauma, in particular, can have long-lasting effects on our mental health. It can arise from various events such as abuse, neglect, violence, accidents, or natural disasters. When we experience trauma, our body and mind react to protect us from harm. These reactions are natural, but when the trauma is severe or prolonged, it can have lasting effects on our mental health. Psychological trauma and brain are thus very importantly intertwined with each other to produce a variety of mental health conditions.

Trauma significantly affects cognitive functions, including memory, attention, and executive functions. Individuals who have experienced trauma often exhibit difficulties in concentrating, learning, and making decisions. These cognitive impairments are linked to changes in brain structure and function.

The normal brain undergoes changes in structure and function across lifespan from early childhood to late life. Cortisol and norepinephrine are the two neurochemicals that significantly mediate stress response. The three areas most vulnerable to trauma and stress during brain development are hippocampus, amygdala, and medial prefrontal cortex¹.

Stress

Hans Selye, a pioneering physician and endocrinologist known in many circles as the founder of stress theory, defined stress as “the state manifested by a specific syndrome which consists of all the nonspecifically-induced changes within a biologic system” ²(6, p. 64).

Amid these complexities, however, there is general consensus in the neuroscientific literature, that stress can be considered as a stimulus, a reaction to a stimulus, or the physiological effects of that reaction^3,4

Since then, it was discovered that the response to stressful stimuli is elaborated and triggered by the, now known, stress system, which integrates a wide diversity of brain structures that, collectively, are able to detect events and interpret them as real or potential threats. However, different types of stressors engage different brain networks, requiring a fine-tuned functional neuroanatomical processing. This integration of information from the stressor itself may result in a rapid activation of the Sympathetic-Adreno-Medullar (SAM) axis and the Hypothalamus-Pituitary-Adrenal (HPA) axis, the two major components involved in the stress response.⁴

In Nepal

In Nepal one in every third (33%) of children were spanked, hit or slapped on the bottom, 25% were hit or slapped on the face and approximately 3% were beaten up hard. Odds of facing physical punishment were higher among children aged 3-5 years (odds ratio [OR] 2.9, 95% confidence interval [CI]: 2.0-4.3), aged 6-8 years (OR 2.8, 95% CI: 2.2-3.7), engaged in child labour activities (OR 1.4, 95% CI: 1.1-1.7), with mother that accepted wife beating by husband is justified (OR 1.2, 95% CI: 1.1-1.4), whose father is currently abroad (OR 1.5, 95% CI: 1.2-1.9) and whose father is away from home but in the same country (OR 1.60, 95% CI: 1.1-2.3). The risk was also higher among children living in households that believe physical punishment of children is necessary (OR 3.5, 95% CI: 2.9-4.3) and from lower caste/indigenous (dalit/janajati) ethnicity (OR 1.3, 95% CI: 1.1-1.7). Those less likely to experience physical punishment included female children (OR 0.7, 95% CI: 0.6-0.9) and children with an older mother (34-49 years; OR 0.5, 95% CI: 0.3-0.9). Conclusions: Our results suggest that physical punishment of children is common across Nepal with varying severity. Prevention efforts should focus on designing and promoting interventions that support parents to adapt alternative forms of parenting practices⁵.

The Stress Response Cycle

Corticotropin-releasing factor (CRF) and the Hypothalamic-pituitary-adrenal (HOA) axis plays an important role in stress response. CRF is released from the hypothalamus, with stimulation of adrenocorticotropic hormone (ACTH) release from the pituitary, resulting in glucocorticoid (Cortisol in man) release from the adrenal, which in turn has a negative feedback effect on the axis at the level of the pituitary, as well as central brain sites including hypothalamus and hippocampus.

Studies in animals showed that early stress has lasting effects on the HPA axis and norepinephrine. A variety of early stressors resulted in increased glucocorticoid response to subsequent stressors^1,6. Maternally deprived rats had decreased numbers of glucocorticoid receptors in the hippocampus, hypothalamus, and frontal cortex^7,8. Stressed animals demonstrated an inability to terminate the glucocorticoid response to stress⁹, as well as deficits in fast-feedback of glucocorticoids on the HPA axis, which could be related to decreased glucocorticoid receptor binding in the hippocampus¹⁰. Exposure to chronic stress results in potentiation of noradrenergic responsiveness to subsequent stressors and increased release of norepinephrine in the hippocampus and other brain regions¹¹.

Effects on Memory

Preclinical and clinical studies have shown alterations in memory function following traumatic stress¹², as well as changes in a circuit of brain areas, including hippocampus, amygdala, and medial prefrontal cortex, that mediate alterations in memory¹³. The hippocampus, a brain area involved in verbal declarative memory, is very sensitive to the effects of stress. Stress in animals is associated with damage to neurons in the CA3 region of the hippocampus (which may be mediated by hypercortisolemia, decreased brain-derived neurotrophic factor (BDNF), and/or elevated glutamate levels) and inhibition of neurogenesis¹. High levels of glucocorticoids seen with stress were also associated with deficits in new learning^14,15.

Reversal (Neuroplasticity) and neurogenesis

The hippocampus demonstrates an unusual capacity for neuronal plasticity and regeneration¹. In addition to findings noted above related to the negative effects of stress on neurogenesis, it has recently been demonstrated that changes in the environment, eg, social enrichment or learning, can modulate neurogenesis in the dentate gyrus of the hippocampus, and slow the normal age-related decline in neurogenesis^16,17. Rat pups that are handled frequently within the first few weeks of life (picking them up and then returning them to their mother) had increased type II glucocorticoid receptor binding which persisted throughout life, with increased feedback sensitivity to glucocorticoids, and reduced glucocorticoid-mediated hippocampal damage in later life¹⁸. These effects appear to be due to a type of “stress inoculation” from the mothers’ repeated licking of the handled pups¹⁹.

Cortisol

Cortisol is a glucocorticoid hormone that is synthesized and secreted by the cortex of adrenal glands. The hypothalamus releases a corticotrophin-releasing hormone and arginine vasopressin into hypothalamic-pituitary portal capillaries, which stimulates adrenocorticotropic hormone secretion, thus regulating the production of cortisol²⁰. Cortisol regulates metabolism, blood glucose levels, immune responses, anti-inflammatory actions, blood pressure, and emotion regulation. Cortisol is a glucocorticoid hormone that is synthesized and secreted by the cortex of adrenal glands²⁰. Glucocorticoids are a major class of stress hormones released by activation of the hypothalamic-pituitary-adrenal (HPA) axis. When an organism is exposed to a stressful situation, the HPA axis is activated. This cascade is first initiated by the release of corticotropin releasing factor (CRF) from the paraventricular nucleus of the hypothalamus. This leads to the secretion of adrenocorticotropin hormone (ACTH) from the pituitary and the release of GCs (mainly corticosterone in animals and cortisol in humans) from the adrenal glands then ensues. It is important to note that basal GC secretion follows a circadian rhythm characterized by a peak reached approximately 30 to 60 minutes after awakening followed by a progressive decline throughout the day ²¹. Following an increase in GCs, the organism needs to return to a homeostatic basal state. In order to do so, GCs cross the blood-brain-barrier exploiting their liposoluble properties, and bind to the pituitary and the hypothalamic regions to exert negative feedback. Importantly, other brain structures are rich in GC receptors. There are two types of GC receptor: mineralocorticoid receptors (MR or Type I) and glucocorticoid receptors (GR or Type II). They differ from each other with respect to their affinity and their distribution throughout the various brain structures. GCs bind with a much higher affinity to MRs than GRs²²1 This means that in the morning period, GCs occupy more than 90% of MRs, but only 10% of GRs. However, when facing a stressor and/or during the circadian peak of GC secretion, MRs are saturated and approximately 70% of the GRs are occupied²³.² Moreover, the two categories of GC receptors differ with regards to their distribution in the brain. In fact, the MRs are exclusively present in the limbic system whereas GRs are present in both subcortical and cortical structures, with a preferential distribution in the prefrontal cortex²⁴.³ Elevation of GC is seen during the time of memory consolidation whereas the opposite is true for memory retrieval. Higher level of GC decrease the ability to retrieve previously consolidated memory²⁵.

Chronic high cortisol causes functional atrophy of the hypothalamic-pituitary-adrenal axis (HPA), the hippocampus, the amygdala, and the frontal lobe in the brain²⁶. Stress activates cortisol which in turn increases brain activity and Frontal Activity Asymmetry. Cortisol increased the relative right frontal activity and reduces approach motivation²⁷.  Interestingly, cognitive impairment subjects exhibited high cortisol levels that were associated with low brain activity, but negative emotions with high cortisol were associated with high brain activity(20). Cortisol has a number of effects which facilitate survival. In addition to its role in triggering the HPA axis, CRF acts centrally to mediate fear-related behaviors²⁸, and triggers other neurochemical responses to stress, such as the noradrenergic system via the brain stem locus coeruleus²⁸. Noradrenergic neurons release transmitter throughout the brain; this is associated with an increase in alerting and vigilance behaviors, critical for coping with acute threat²⁹. A variety of early stressors resulted in increased glucocorticoid response to subsequent stressors(6). Maternally deprived rats had decreased numbers of glucocorticoid receptors in the hippocampus, hypothalamus, and frontal cortex(7). Stressed animals demonstrated an inability to terminate the glucocorticoid response to stress,47,48 as well as deficits in fast-feedback of glucocorticoids on the HPA axis, which could be related to decreased glucocorticoid receptor binding in the hippocampus³⁰.

Sexually abused girls (in which effects of specific psychiatric diagnosis were not examined) had normal baseline Cortisol and blunted ACTH response to CRF³¹, while women with childhood abuse-related PTSD had hypercortisolemia³². Another study of traumatized children in which the diagnosis of PTSD was established showed increased levels of Cortisol measured in 24-hour urines³³. Emotionally neglected children from a Romanian orphanage had elevated Cortisol levels over a diurnal period compared with controls³⁴. Maltreated school-aged children with clinical level internalizing problems had elevated Cortisol compared with controls³⁵. Depressed preschool children showed increased Cortisol response to separation stress ³⁶. Adult women with a history of childhood abuse showed increased suppression of Cortisol with low-dose (0.5 mg) dexamethasone ³⁷. Women with PTSD related to early childhood sexual abuse showed decreased baseline Cortisol based on 24-hour diurnal assessments of plasma, and exaggerated Cortisol response to stressors (traumatic stressors ³⁸ more than neutral cognitive stressors)³⁹. We also found that patients with PTSD had less of an inhibition of memory function with synthetic Cortisol (dexamethasone) than normal subjects ⁴⁰. Adult women with depression and a history of early childhood abuse had an increased Cortisol response to a stressful cognitive challenge relative to controls⁴¹, and a blunted ACTH response to CRF challenge ⁴². These findings show long-term changes in stress responsive systems. Early in development, stress is associated with increased Cortisol and norepinephrine responsiveness, whereas with adulthood, resting Cortisol may be normal or low, but there continues to be increased Cortisol and norepinephrine responsiveness to stressors. In addition, early stress is associated with alterations in hippocampal morphology which may not manifest until adulthood, as well as increased amygdala function and decreased medial prefrontal function ¹.

Post Traumatic Stress Disorder (PTSD)

Multiple studies have demonstrated verbal declarative memory deficits in PTSD^12,43,44. Patients with PTSD secondary to combat⁴⁵, and childhood abuse⁴⁶ were found to have deficits in verbal declarative memory function based on neuropsychological testing. Studies, using a variety of measures (including the Wechsler Memory Scale, the visual and verbal components of the Selective Reminding Test, the Auditory Verbal Learning Test, Paired Associate Recall, the California Verbal New Learning Test, and the Rivermead Behavioral Memory Test), found specific deficits in verbal declarative memory function, with a relative sparing of visual memory and IQ^45,47.

Important Brain Connectivity

DMN:   Default Mode Network

CEN:    Central Executive Network

SN:       Salience Network

References

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