Neurobiology of Stress and Mental Illnesses

Stress responses are activated by situations perceived as less life-threatening.
Reference: Frankenhauser (1978) discusses how stress can arise in seemingly benign scenarios.
Commuting in crowded trains leads to increased production of epinephrine; longer and more crowded rides correlate with even higher levels of epinephrine.
Sympathetic hormones, such as epinephrine (E) and norepinephrine (NE), also see elevation in the days preceding significant examinations (e.g., graduate exams).

Two critical factors influencing how stress is perceived:
- Predictability: The extent to which an individual can anticipate a stressful event.
- Controllability: The degree of control one has over the stressor or situation.

Conducted on baboons in Kenya living in a resource-abundant environment without natural predators.
Observed high levels of community stress despite no immediate threats.
Stress primarily arises from competition over mating opportunities and dominant positioning in social hierarchies.
Key Finding: Cortisol levels are inversely related to social status within the group; alpha males exhibit lower cortisol levels than subordinates.
Chronic stress in monkeys results in persistently elevated cortisol levels.

Short-Term Adaptations include:
- Mobilization of energy reserves.
- Increased cardiovascular output.
- Suppression of digestion, growth, and reproductive functions.
- Altered immune function leading to heightened awareness and cognition.
Long-Term Pathology results in:
- Myopathy and fatigue.
- Type 2 diabetes and hypertension.
- Gastric ulcers and irritable bowel disorders.
- Psychosocial dwarfism (growth failure due to psychological factors).
- Amenorrhea, impotency, and loss of libido.
- Immunosuppression and increased risk for infections.
- Synaptic pruning in regions like the cortex and hippocampus driven by elevated cortisol levels.

Growth failures in children linked to psychological and social stressors are mediated through Central Nervous System (CNS) interactions with hormone systems (Green et al., 1984).
Removal from stressful conditions can trigger rapid growth in affected children.
Prolonged cortisol secretion from hyperactivity of the Hypothalamic-Pituitary-Adrenal (HPA) axis may inhibit the release of Growth Hormone (GH), detrimental to growth and physical development.

Early life stress, such as maternal separation during crucial developmental stages, enhances stress reactivity in adult rats (e.g., heightened HPA activity and anxiety-like behaviors).
Epigenetic changes stemming from early maternal experiences have been observed to alter adult stress reactivity.
In humans, early life trauma correlates with a greater propensity for major depressive disorder later in life, believed to have an epigenetic foundation.

Elevated cortisol levels in rats lead to atrophy of pyramidal neurons, effectively destroying excitatory synapses in critical brain regions: the hippocampus and prefrontal cortex.
Conditions like Cushing’s disease, characterized by chronically high cortisol levels, result in significant shrinkage and cell loss in the hippocampus, with probable implications for the prefrontal cortex as well.

Prolonged elevation of cortisol disrupts negative feedback mechanisms of the HPA axis.
The hippocampus and prefrontal cortex, which are critical for regulating this feedback, may become compromised, potentially leading to a negative feedback loop exacerbated by stress.

PTSD may develop after traumatic events leading to:
- Frequent intrusive recollections or flashbacks.
- Nightmares related to the event.
- Avoidance of reminders linked to the trauma.
- Heightened arousal to stimuli such as noises.

PTSD patients exhibit reductions in hippocampal and prefrontal cortical volumes, coupled with increased amygdala size.
Autonomic/sympathetic output sensitivity is heightened in PTSD, which is less evident in depressive symptoms.
The disorder is perceived as rooted in amygdala hyperactivity and prefrontal cortex underactivity.

Major categories include:
- Major depressive illness.
- Reactive depression.
- Anxiety disorders.
- Post-traumatic stress disorder (PTSD).
A significant overlap exists between these disorders, indicating comorbidity.
Interactions between genetic predispositions and environmental Stressors enhance susceptibility to these disorders.

An estimated one-third of the US population experiences symptoms resembling major psychiatric disorders at some point in their lives.
Prevalence rates are similar across genders, although some disparities exist—higher rates of depression in women, and greater substance dependence in men.

Various methods of treating mental illness have evolved, often reflecting societal beliefs and understanding of the brain.
Early treatments included trephination, where a hole was drilled into the skull to release perceived demonic forces.

The biological basis for mental disorders began gaining traction in the early 20th century with findings related to paralytic dementia and its links to bacterial infections such as syphilis
- Hideyo Noguchi's work uncovered the biological underpinnings of mental disorders leading to improved treatments.

The 1930s saw the rise of psychosurgery, first through frontal lobe lesion studies in chimpanzees, leading to human applications by Egas Moniz.
Lobotomy was widely practiced but later fell out of favor due to adverse effects (e.g., mood swings, personality changes).
Walter Freeman became infamous for promoting lobotomies inappropriately.