Tuesday, January 5, 2010

Physiology of anxiety

Historical Development

Descartes saw the mind & body as different units and noticed the direct effect of emotions on the body reactions. He proposed that pineal body was the main mediating centre between the body and the soul.
The Cannon-Baird theory named thalamus as the centre initiating emotional reactions. It was held responsible for receiving sensory information. It also communicated with cortex & body organs to bring about behavioural changes. Cannon also described the characteristic ‘fight / flight’ stress reaction and the role of sympathetic nervous system in it.
The modern basis of emotional expression in the biology of the brain began with the work of the American neuroanatomist James Papez. Papez described an "ensemble of structures" in the lower, subcortical areas of the brain (as the hypothalamus, the hippocampus and the amygdala) or the limbic system as brain sites associated with emotion. He emphasized the role of hypothalamus rather than thalamus as control centre in initiating emotional response.
Recent evidence highlights the role of genetic influences in the causation of anxiety disorders. Studies have shown that the prevalence of anxiety and related disorders is higher among the relatives of affected subjects than among control families.


Recent studies suggest that three brain sites are responsible for regulating anxiety, i.e. prefrontal area of cortex, amygdala and hypothalamus in sub cortex.
▪ The higher brain or cortex is responsible for:
Identifying and interpreting stressors and Initiating / coordinating the voluntary action.
▪ The lower brain or sub cortex is responsible for:
Beginning and controlling states of physiological excitement and for involuntary homeostatic functions.

When exposed to stress, following processes happen:

▪The cortex first perceives the stressor.
▪The prefrontal cortex is involved in the cognitive evaluation of the stressor.
▪The subcortical structures are then called into play.
▪The amygdala is responsible for generating the fear response.
▪The hypothalamus regulates the stress response and activates the autonomic and the endocrine systems. It mediates between these two systems and is involved with limbic cortex in regulating emotions.

The Amygdala
The amygdala is believed to serve as a communication hub between the parts of the brain that process incoming sensory signal and the parts that interpret them. It signals that a threat is present and triggers a fear response or anxiety.
Hippocampus is another brain structure that is responsible for processing threatening or traumatic stimuli. The hippocampus plays a key role in the brain by helping to encode information into memories.
Studies have shown that the hippocampus appears to be smaller in people who have undergone severe stress because of child abuse or military combat. This reduced size could help explain why individuals with PTSD have flashbacks, deficit in clear memory, and fragmented memory for details of the traumatic event.

The Hypothalamus
The hypothalamus helps the body in controlling body temperature. It also contains centres involved with hunger and pleasure. Its main function during stress is to activate and regulate the autonomic and endocrine systems.
The hypothalamus, on stimulation produces emotional and behavioural responses, both autonomic and skeletal. Three main reactions have been observed on experimental stimulation of hypothalamus. They are Alarm, Flight and Rage.

The two lobes of hypothalamus are concerned with the regulation of arousal. The anterolateral lobe inhibits sympathetic nervous system activity and the release of activating hormones from the pituitary. The posteromedial lobe has the opposite effect.
It has direct links with the pituitary gland, the limbic structures, the cortex and the thalamus. Neural pathways from hypothalamus also link it to the brainstem and the spinal cord.

The Autonomic nervous system and anxiety

It has an important part in instigation and maintenance of appropriate levels of physiological arousal. It has two main branches –
Sympathetic nervous system (SNS). It is responsible for the ‘stress’ response. During ‘stress’ states, the SNS prepares the individual for ‘fight or flight’ response. The flow of blood from digestive organs is directed to the fighting muscles and the heart rate increases.
Parasympathetic nervous system (PNS). It is responsible for ‘relaxation’ response. During ‘relaxed’ states, the PNS prepares the individual for digestion, recuperation and sleep.
The two branches of ANS work partly in concert. While most organs are under control of both, some sites & symptoms are under the sole control of SNS, i.e. the sweat glands, lung muscles, blood glucose levels and the basal metabolic rate. Others, such as the ciliary muscles of the eye, are under exclusive control of PNS.
Individual responses and ANS
While the SNS is usually predominant during stress, some individuals may respond to stressors with PNS dominance. It causes a fall in blood pressure and blood glucose levels. Other symptoms may be cold sweating, dizziness, reduced respiratory action and fainting.
Lacey proposed that persons do not respond with simple PNS or SNS dominance under stress. It suggested that individuals might react strongly on one physiological measure and very little on another.
The nature of reaction profile might be determined by the total life experience of the individual as well as genetically determined physiological factors. Several studies on physiological arousal patterns in anxiety neurosis have demonstrated consistent sympathetic hyperactivity.
Anxiety disorders have been correlated with a pattern of raised heart rate levels, frontalis muscle tension, forearm blood flow, skin conductance, respiration rates and blood pressure.
Each individual has a base line norm of autonomic arousal, or starting point. It has been shown that a high baseline norm will lead to a smaller reaction under stress while a low baseline norm will lead to a larger reaction.

The Endocrine system and Anxiety

This system has an important role in total stress response.
During stress, the ‘master gland’ pituitary is stimulated by hypothalamus to release several chemical messengers to the slave glands directly into bloodstream. These include vasopressin, adrenocorticotrophic hormone (ACTH) and thyrotrophic hormone (TTH). Vasopressin contracts the arteries and causes the blood pressure to rise. ACTH and TTH pass on to adrenal and thyroid glands. They work together to increase circulation and basal metabolic rates.
The Adrenal glands

Adrenalin & noradrenalin from medulla and corticoids from cortex are directly released into blood stream.
Adrenalin stimulates the production of glucose from glycogen in liver. The glucose is released in blood increasing the carbohydrate metabolism. It also dilates coronary and skeletal muscle arteries, increases heart rate, blood volume and body temperature.
Gaseous exchange is facilitated by bronchial dilatation and shallow breathing results. Smooth (visceral) muscles tend to relax while the sphincters are constricted. Noradrenalin constricts the peripheral arterioles and increases blood pressure. It has been suggested that adrenalin is the major hormone in states of fear while noradrenalin is predominant in anger. Glucocorticoids from cortex tend to raise blood sugar levels and inhibit inflammation.
Thyroid gland

Thyrotrophic hormone acts on thyroid causing release of thyroxine. The rise of thyroxine in stress conditions causes increased sweating, muscle tremor, heart rate and exaggerated breathing. These effects are similar to adrenalin. Adrenalin tends to predominate in short term stress while thyroxine is released in large quantities in prolonged stress.

General Adaptation Syndrome

Selye used the term ‘stress’ instead of ‘strain’ in its relation to human psychophysiology. He coined the term ‘general adaptation syndrome’ or GAS. GAS has three phases:
• Alarm reaction (involving shock and counter shock phases).
• Resistance (adaptive response).
• Exhaustion.
The Alarm phase: In this phase, mobilization takes place following the detection of a stressor. The stressor can either be psychological or physiological in nature. Increase in adrenocortical hormones also takes place in this phase.
The Resistance phase: It involves selection of an appropriate organ or system to deal with the particular stressor. Adrenocortical hormones diminish once a specific system is delegated. All the internal resources are then directed towards the support of this system, leaving others susceptible. This may reduce the resistance of the organism to disease.
The Exhaustion phase: When the system assigned the job becomes overloaded, the exhaustion phase is reached. At this point, the adrenocortical hormone levels increase again and the alarm phase is induced again. A different system may then be delegated to handle the continuing stress.

The GAS is useful in mobilising protective resources in emergency situations. In prolonged situations, it may lower resistance. The energy for adaptive reaction to stress is provided by suppressing immune reactions and inflammatory responses to invading pathogens. It is suggested that the ‘weakest link’ or most vulnerable part of the body breaks down first under stress. Therefore, factors including heredity and prior disease may predispose an organism towards a specific somatic disorder.
Allergies may also be associated with stress. Allergic reactions involve high levels of inflammatory corticoids for destruction of pathogens. Under stressful conditions the allergic response may be aggravated.
Selye based his conclusions on experimental work in which rats were subjected to prolonged stress. It resulted in drastic body changes including irreversible organ damage. The rats showed enlargement of adrenal cortex and atrophy of thymus, spleen and lymph nodes. A severe reduction of white cells and bleeding ulcers in stomach and duodenum were observed.
According to Selye, ACTH plays an important role in GAS. In acute stress, adrenalin and noradrenalin from the adrenal medulla are most important. In chronic stress the corticoids are the primary agents.
The kidney also plays an important role in GAS, as it is responsible for maintaining a chemical and water balance in the blood and tissues.

In chronic stress conditions, when corticoids are raised for a prolonged period, blood pressure may rise and damage the kidney.
Damage to arteries associated with atherosclerosis may also occur. Continued stress can produce increased hydrochloride acid secretion in stomach leading to formation of ulcers.
Selye also added some suggestions on ways of dealing with stress as:
• Removal of unnecessary stressors from lifestyle.
• Do not allow neutral events to become stressors.
• Develop skill in dealing with stressors.
• Seek relaxation.
Neurotransmitters and anxiety
The nerve cells communicate with one another with the help of neurotransmitters. Some of these play a significant role in anxiety and other psychiatric disorders. Examples of these are noradrenalin, adrenalin, serotonin, GABA, dopamine, acetylcholine and histamine.
The dysfunction of neurotransmitter activity is the cause of the most psychiatric disorders. The excessive activity may lead to anxiety and psychosis while under activity may cause depression.
Recent developments support the view that noradrenalin and serotonin have a central role in mechanisms underlying anxiety in the central nervous system.

By Dr. Dushyant kamal Dhari
M.D. (Hom).

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