Psychoneurological aspects

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16 Psychoneurological aspects

image Clinical cases for thought

Historical development of emotional theories

Plato’s model of emotion was essentially dualist in nature. The dualism involved the existence of a soul and an earthly body it inhabited. Plato placed the emotions as a direct function of the soul, which was composed of three forces: reason, desire, and appetite. Plato envisioned the emotions as wild, uncontrollable forces in continual opposition to the controlling powers of reason. Two distinct ideas emerge from Plato’s theory of emotion. Firstly, emotions are to be contrasted with that which is rational and, secondly, that emotions play a role in psychological conflict. The second concept implies that there must also exist processes to defend against the powers of emotions.

The view that the emotions should be the slaves of reason and that reason dwelled in the divine soul made the ‘feeling’ or Platonic theory of emotion very popular among the Christian and Islamic scholars who dominated Western thinking until the late nineteenth century. René Descartes elaborated on the Platonic theory in a pamphlet entitled On the Passions of the Soul. Descartes describes the soul as the ‘switch master’ or control that allows the movement of the spirits through the body via the pineal gland in the brain. The body then experiences these movements as emotions. Emotions to Descartes were simply the experience of awareness of the spirit movements through the body. Emotions had no function, but were simply a phenomenon that occurred in response to a stimulus. For example, the movement of bodily spirits may produce the experience of fear excited by the recognition of external danger, but cannot be influenced by a cognitive appraisal of the danger or produce an appropriate behavioural response. These are two of the major criticisms of the Platonic or ‘feeling’ theory: that it can give no explanation as to how emotions can result in behaviours, and it can give no explanation as to how cognitive processes can appraise the external stimuli to alter or modify the fear response (Lyons 1992).

Regardless of the criticisms of Descartes, he was the first to suggest that some emotions might be more basic or primitive than others and listed six primary ‘passions’: wonder, joy, sadness, love, hatred, and desire. He was also the first to suggest that emotions may exist on more than one level at the same time, for example, fear and excitement (Powers & Dalgleish 1997).

William James added to the ‘feeling’ theory of emotion in his classic work Principles of Psychology in which he emphasised the physiological aspects of emotions and outlined the distinctions of each emotion which cleared the way for psychological experimentation. James was the last influential psychologist to present the feeling theory of emotion with such conviction, and with his death came the decline of the feeling theory in psychology (Powers & Dalgleish 1997).

With the decline of the dualist theory came the emergence of Darwin’s ‘survival of the fittest’ concept outlined in his Origin of Species monograph in 1859. It was Darwin’s view that emotions were a carryover from primitive man and were no longer of any use to modern humans. This theory was not widely accepted as far as it applied to the emotions, but other parts of his theory shocked most of upper society and ironically stimulated a fury of investigation that renewed interest in the biological theory of emotion.

In contrast to Darwin’s view that emotions were no longer of use but were vestigial like the appendix, and the Platonic or dualistic view that emotions were irrational, others such as Aristotle took the view that emotions have important short- and long-term functions that enable individuals to adapt to changes in their social and physical environment. Aristotle was probably the first to propose a functionalist model of emotional development. Aristotle’s theory was not widely accepted in his day, as it was overshadowed by his teacher Plato’s theories, which were much more amenable to contemporary religious leaders.

Aristotle’s most comprehensive discussion of the emotions occurs in The Art of Rhetoric. In this monograph, he outlines the relationship between an emotion and the behaviour that it produces. He also describes ten specific emotions: four positive (calm, friendship, favour, pity) and six negative (anger, fear, shame, indignation, envy, jealousy). Aristotle argued that for any emotion to arise it was necessary for three conditions to be satisfied. First, the individual must be in the appropriate ‘state of mind’ to experience the emotion; second, there must be a ‘stimulus’ to elicit the emotion; third, there must be an ‘object’ for the emotion. For example, if an individual is in a state of mind that something dangerous may happen to them, and then he/she is confronted by an assailant, they might evaluate the situation as one of impending danger. This evaluation may, in turn, result in a stimulus that produces fear. It is the evaluation of the situation and not the situation itself that stimulates the emotion. In the above example, if the assailant was not perceived as threatening to the individual, the resulting emotion may have been completely different, such as anger. Aristotle’s theory laid the foundation for the functionalist’s approach to emotions and their development.

Behavioural and social learning theories

Social learning theory emphasises the importance of modelling others’ emotional reactions as a means of developing emotional patterns and responses. The behaviourists have developed a number of various classifications of behavioural theory, depending largely on the degree to which they refer to metaphysical or epistemological claims in their explanations of emotion. The two main categories of behaviour theory are psychological behaviourism and philosophical behaviourism. The psychological behaviourist approach to emotions can best be exemplified by the theories of James Watson and B. F. Skinner. Watson, in 1919, described emotion as ‘a hereditary pattern-reaction involving profound changes in bodily mechanisms as a whole, but particularly of the visceral and glandular systems’.

In Watson’s model of emotion, only three emotions can be distinguished: fear, rage, and love. He further states that these primary emotions can only by demonstrated in the newborn. Watson’s major contribution was his finding that emotional reactions could be learned through classic conditioning (Watson & Raynor 1920).

In 1967, Etzel and Gewirtz demonstrated that operant conditioning could have an impact on emotional development. Skinner refined Etzel and Gerwirtz’s work into a complex model where emotions evolve from an operant conditioning framework, where emotion is defined by the sets of operants and reinforcers that one optimises in any given setting (Skinner 1974). One of the major criticisms of Skinner’s theory is that some emotions exhibit little or no operant behaviour. For example, grief, especially when about a loss or death, does not result in any operant behaviour because no behaviour can bring about the desired results (Lyons 1992).

One of the most influential philosophical behaviourists was Gilbert Ryle. In 1949, his work The Concept of Mind outlined that emotion can be described in four different ways: inclination, moods, agitations, and feelings. Ryle viewed inclinations as the permanent disposition state of personality. Moods, agitations, and feelings were short-term displays overlying the main inclination theme. For example, if a person has the inclination to be kind, he may still experience short-term occurrences of irritability or cruelty, which would be attributed to his mood or feeling swings.

Further expansion of the social learning theory in recent years has been accomplished by Albert Bandura, who has added a cognitive component. According to Bandura, as a person’s representational ability improves, he/she can engage in emotional self-arousal by thinking about their own emotionally charged past experiences or even by recalling the experiences of others (Bandura 1986, 1989, 1991).

One of the main criticisms of social learning/behavioural theory is that it cannot explain the emergence of emotions that have not been acquired through modelling or conditioning, but seem to appear spontaneously.

Cognitive theories

Instead of viewing emotions as central forces in the development of social interaction, cognitive psychologists view emotions as by-products of cognitive processes (Berk 1994). Several examples of cognitive theories follow, including Hebb’s discrepancy theory, Alder’s style of life theory, Epsteins cognitive-experiential self theory, and Apler’s reversal theory.

Donald Hebb (1947, 1949) explained in his discrepancy theory how distress reactions are elicited by novel stimuli. According to Hebb, when a person encounters a new stimulus, they compare it to a scheme or internal representation of a familiar object. The discrepancy between the stimulus and the internal representation determines the emotional response. Other researchers have modified Hebb’s theory, suggesting that a wide variety of emotional reactions could be explained by Hebb’s theory. For example, they argue that a positive emotion such as happiness could result from only moderate discrepancies between current stimuli and the internal scheme. Negative emotions, such as anxiety and fear, could result as the discrepancy between the present stimuli and the interval scheme widens (McCall & McGhee 1977; Kagan et al. 1978). This theory falls short when it is observed that people sometimes willingly seek out activities that are new and not in agreement with their internal scheme.

Alfred Adler, in his 1954 work Understanding Human Nature, was probably the first to integrate emotions, motivations, and cognition into one theory (Epstein 1993). According to Adler, individuals construct a belief system and a way of relating to the world which he termed a ‘style of life’. At the centre of a person’s style of life is a fictional goal which guides the individual in his attempts to overcome inferiority to gain social approval, a goal to which all humans strive. Emotions enter into Adler’s theory in two ways. Firstly, the quest for overcoming the feelings of inferiority provides an incentive for developing a style of life. Secondly, once the style of life has been developed, the emotions corresponding to that style of life are encouraged to develop. In other words, the style of life that one develops is a major determinant of the emotions that a person experiences, much like Aristotle’s ‘state of mind’ (Epstein 1993).

In the cognitive-experiential self theory (CEST), emotions are considered to be both influencing and being influenced by a person’s implicit theory of reality. The theory considers the primary emotions to be anger, sadness, joy, and affection. Cognitive affective units are constructed around the nuclei of the primary emotions. These cognitive units direct the development of critical adaptive behaviour patterns such as fighting, withdrawing, exploring, and showing affection. The development of these behavioural patterns results in emotionally rewarding experiences when they are consistent with a beneficial outcome to the individual (Epstein et al. 1992).

Apter’s reversal theory is explained in some detail here because it is one of the few theories that has a theoretical construct for encompassing changes over time in the individual which are clinically relevant for the functional neurologist. The centrepiece of reversal theory is a typology of distinct psychological states of mind. When people are in one of these states they want to experience a particular kind of emotion. The states are meta-motivational because they determine what types of experiences people want. In different states, people may react to the same stimuli in different ways, and experience distinctly different emotions. This theory focuses on how a person differs over time rather than on differences between people. Reversal theory suggests that there are eight different meta-motivational states, four pairs of opposite states. The reversal from one state to its opposite is the key feature of the theory. The two states of a pair are mutually exclusive and exhaustive; for example, a person is always in one state or the other, never both at the same time or neither state. The eight states of the reversal theory are serious–playful, compliant–defiant, power-oriented–affection-oriented, and self-oriented–other-oriented (Apter 1988). The first pair of meta-motivational states is composed of the telic and paratelic states. When in the telic state the person is primarily goal-oriented. Conversely, when a person is in the paratelic state they are best described as being playful. In this state the person does not attach much significance to what they are doing; they could not care less. The lability of a person, how readily they reverse back and forth between opposite states, varies at different times. The actual reversal process is dependent on one of three reasons: contingency, satiation, and frustration. Contingency is any change in the environment that instigates or necessitates a reversal. Satiation occurs when, in the absence of an environmental change, a reversal will eventually occur. Frustration–motivated reversals occur when a person remains in a particular state too long without achieving satisfaction (Frey 1997).

Reversal theory takes the approach of starting with motivation and experience and then interpreting the behaviour generated in light of these. Reversal theory emphasises that people are inconsistent and self-contradictory and goes so far as to say that healthy people are characterised by instability, not stability (Murgatroyd 1987).

Developing a theoretical construct for emotion

How are changes in emotional states brought about by changes or alterations in neuraxial function in humans? Can how we feel influence the function of the neuroimmune system? Emotional factors have been linked to a variety of diseases including Grave’s disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), asthma, and diabetes (Koh 1998). Could these diseases be caused or precipitated by emotional factors? Several psychological states have been linked to alterations in neural activity in the limbic circuits of the brain involving the amygdala and hippocampus, which are areas historically associated with emotional response generation (Pribram & McGuinness 1975). Imbalances in emotional activation and reaction have been investigated in a number of studies (Sackeim et al. 1982; Robinson et al. 1984; Flor-Henry 1986). The advances made by these researchers have led to the discovery that cells of the immune system (lymphocytes) produce stress-associated peptides thought only to be produced in the brain and pituitary. When this finding is coupled with the discovery of neurotransmitter receptors and hormone receptors on neurons and immune cells (Blalock 1984), the existence of a bidirectional communication relationship between emotion and neuroimmune systems seems unavoidable.

How do we define and measure emotional states or changes in those states? To what extent does the interaction determine health?

What is the connection between emotion, mood, affect, and neurological function?

Campos et al. (1994) define emotion as those processes which establish, maintain, change, or determine the relation between the person and the environment on matters of significance to the person. A person’s mood may be determined by a complex interplay of the emotions that they are experiencing at any one time as per the reversal theory. ‘Mood’ therefore can be defined as the way that we feel, while ‘affect’ can be defined as how we behave as a result of our mood. Neurologically, mood and affect depend on the complex interplay among diffuse networks of the frontal lobes and subcortical circuits. They can be influenced by genetic and environmental factors, similar to any form of activity in the nervous system. Long-term changes in mood and behaviour may occur because of ‘plastic’ changes in these networks. This refers to the moulding of nerve excitability and interconnectivity referred to as neural plasticity that occurs following repeated or essential exposure to an environmental stimulus, and subsequent alteration of gene expression in the associated nerves.

Other probably genetically determined neural systems seem primed to perform a variety of innate activities called ‘fundamental functions’ in the cortex. Fundamental functions comprise diffuse, overlapping, or parallel units that contribute to more complex interactions and multimodal processing in the nervous system. The more recent definition of fundamental functions applies to frontal-subcortical and limbic circuits, which are largely intact from birth. Executive/integrative functions apply to the prefrontal circuitry, which also comprise diffuse, overlapping, or parallel influences that contribute to more complex interactions and multimodal processing in the nervous system. Fundamental functions are generally less modularised than motor or sensory functions. In other words, they are less dependent on one single area within the brain, and instead receive their input from multiple sources and generate an output that can influence the entire state of the individual. These wide-ranging functionally connected areas are often receiving similar information at the same time and are often referred to as parallel distributed processing circuits. Dysfunction associated with these networks can therefore lead to so-called ‘circuit-related disorders’ affecting complex aspects of cognition or leading to mood and behavioural changes. Therefore, abnormalities associated with fundamental or executive regions of the brain may result in either ‘negative’ or ‘positive’ symptoms. Negative symptoms or deficits generally refer to decreased expression of a normal function, whereas positive symptoms refer to release of primitive functions or new behaviours. An example of a negative symptom is depression, where a patient may exhibit withdrawal from normal activities and social interaction and less expression in their face and body movements. An example of a positive symptom can be seen clinically in paranoid schizophrenia where environmental stimulus is amplified and taken out of context of reality. Positive symptoms may also be referred to as productive symptoms, release or escape phenomena. A classic example of ‘escape’ phenomena is the exaggerated autonomic reactivity that may be observed in patients with panic or anxiety disorders. Primitive areas of the brain and brainstem are allowed to summate or increase their firing more easily because of a loss of descending reticular inhibition from the more developed frontal areas of the brain. Obsessive–compulsive disorder (OCD) can also be viewed as an example of a release phenomena. The patient develops an irresistible urge to perform a specific action that will bring about relief of tension. While not purely seen as a ‘disinhibition’ syndrome, the patient often feels compelled to carry out an action that interferes with their daily lives. Cortical and subcortical areas implicated in mood and behavioural functions receive tonic influences from a large array of different neuronal circuits, some of which involve parallel distributed processing circuits that utilise a wide variety of neurotransmitters including dopamine, serotonin, noradrenalin, and acetylcholine. Thus the cumulative activity of these various circuits results in a temporal variation in the relative concentrations of the neurotransmitters utilised in each circuit.

The concept of parallel distributed processing is essential for healthcare practitioners to gain an understanding of the link between psychological and somatic or visceral health complaints. Not only may somatic health complaints affect the ability of an individual to exercise their normal daily routines, thus leading to altered mood and behaviour, but direct physiological connections exist that involve somatic and visceral afferents and the limbic system or ascending reticular activating systems of the brainstem and hypothalamus. One example of parallel distributed processes is outlined below, involving the rostral cingulate cortex as the limbic motor response area that responds to parallel afferent information also received by the sensory cortex. The rostral cingulate motor area (area 24) is responsible for primitive motor behaviours (fear, avoidance, etc.) mediated via the corticospinal and reticulospinal pathways. Activity in this region is also dependent on activation of the caudal cingulate motor area (area 25), which orientates the body in space. These cingulate motor areas and receptive regions of the cingulate and insular cortex that project to it are not only influenced presynaptically by subcortical and spinal neurons carrying sensory information, but they are also heavily modulated by monoaminergic neurons from the brainstem. The influence of dopamine, noradrenalin, and serotonin on sensory modulation, arousal, and orientation is complex in nature and discussed in further detail in Chapter 9.

Chronic pain and emotional responses

Functional neuroimaging using quantitative EEG (qEEG) suggests similar mechanisms between chronic pain syndromes and mood disorders in that similar areas appear to be activated in these patients. A strong tendency for overactivation of the right hemisphere or decreased left hemisphere activation has been identified in patients who demonstrate negative behaviour or affect (Davidson 1992). Similar findings are often present in patients with chronic pain syndromes suggesting that pain, stress, and negative emotions may share common influences on association areas of the cortex concerned with contextual processing. Pain-related circuits in the brain, particularly those associated with ‘older’ pathways, tend to adapt and undergo plastic changes when closely associated with a behaviour or an emotion. Functional magnetic resonance imaging of the brain has been used to identify the neural networks involved in aversive conditioning, and anticipation of visceral pain. Actual and anticipated visceral pain elicited similar cortical responses. This demonstrates similarities with the principle that imagined movements through visual imagery can strengthen learning of new motor sequences. At some point in the sequencing of neural activity, motor execution is inhibited or restrained during motor imagery. However, actual, imagined, and perhaps anticipated movements or perceptions may share the same neural networks up until this point of restraint. With respect to mood and affective disorders the anticipation of negative consequences associated with illness, injury, or social and environmental stimuli may therefore induce a new ‘virtual reality’ that bears all the hallmarks of ‘actual’ disease and disability.

The amygdala receives direct synaptic connections from thalamic and spinal cord neurons that are involved in aversive conditioning and fear-potentiated behaviour. Approximately half of the neurons projecting to limbic or striatal regions terminate in the hypothalamus. This suggests that somatic and visceral afferents to the spinal cord are intrinsically linked to higher limbic centres and may profoundly affect behaviour. Since mood and behaviour are inextricably dependent on the central integrated state of both limbic and higher cortical centres, presynaptic influences on these areas may have a central role in the aetiology of mood and behavioural disorders. Increased activation of pain pathways has already been mentioned, particularly with respect to activation of the ‘older’ pain pathways. However, other sensory systems share similar relationships with the limbic system, including the visual, auditory, vestibular, olfactory, and gustatory systems. An overview of the relationship between the auditory system and mood and behaviour is detailed below.

Brain imaging studies have shown similar activation patterns in chronic tinnitus sufferers and chronic pain sufferers who also suffer from depression. Plastic changes in receptors associated with brain-derived neurotrophic factor and neurokinins have also been identified in the hippocampus of these patients.

Mood and behavioural problems may be associated with altered ascending inputs from various subcortical circuits such as those in the dorsal cochlear nucleus (DCN) and somatic or vestibular processing pathways. It has been postulated that the cause of tinnitus may represent a distributed phenomenon with the possibility of dysfunction in a variety of pathways individually or simultaneously rather than damage at one location. Thus, interactions between many brain regions may be the cause. The same principle is likely to apply to mood and behavioural problems. The auditory portions of the DCN and vestibular nucleus share some similarities with respect to their apparent influence on limbic/reticular nuclei and therefore mood. The output from both of these nuclei may be heavily influenced via interactions with cervical spine afferents. In a detailed review of the literature concerning the effect of rehabilitation exercises on vestibular adaptation, Black and Pesznecker (2003) found that vestibular rehabilitation outcome is negatively affected by anxiety, depression, and cognitive dysfunction, suggesting a role for mood, affect, and cognition in modulating balance and/or spatial processing. A number of mechanisms linking balance control and anxiety have been found:

The most likely mechanism for these interactions is that the serotonergic pathways mediated by the raphe nuclei and receptors of targets of the parabrachial nucleus calibrate the sensitivity of affective responses to aversive aspects of motion.

When alterations in emotion are related to changes in the neuroimmune system, many variables arise. Researchers have attacked the problem by breaking the broad concept of emotion into smaller, more manageable sections, mainly positive and negative emotional states. Knapp et al. (1992) asked subjects to recall and relive maximally disturbing situations in their lives which they classified as negative emotions and maximally pleasurable situations in their lives which they classified as positive emotions. They found that negative emotional states promoted significant declines in mitogenic lymphocyte reactivity followed by a return to pre-emotional levels. They also found a similar decrease in cytotoxic T-cell function with negative emotional stimuli. Modulation of the immune system in these studies was thought to have occurred via nervous system function. Psychotic disorders such as schizophrenia have repeatedly been shown to have altered immune system function, and some investigators have suggested that immunological dysfunction may, in fact, contribute towards the multifactorial aetiology of schizophrenia via bidirectional parallel circuit feedback systems (Kirch 1993; Syvalahti 1994; Rothermundt et al. 1998). Several clinical conditions are outlined below with some discussion of their neuroimmunological relationships.

Mania

Affect, which is another way to describe emotion, gives richness and meaning to our experience of the world around us and many would say is an indispensable dimension of our humanism. When the behaviours or feelings produced by emotions become inappropriate or extreme they can be the source of overwhelming psychological distress (Bootzin & Acocella 1984). Disturbances in mood which result in intense feelings of sadness or elation that are unrealistic and last over a prolonged period of time result in depression or mania, respectively.

The affective disorders or disorders of feeling have been recognised and written about since the history of medicine has been recorded. Melancholia, which is another term for depression, was noted by Hippocrates in the fourth century BC and has been found referenced as early as the first century AD. Some very famous people have fallen victim to depression including Abraham Lincoln and Winston Churchill. Even though these conditions have been investigated for centuries they still remain something of a mystery. Some disturbances in affect can be caused by inappropriate responses to intense or chronic mental stress.

How do people usually respond to mental stress? Some of us try to distract our attention from the effects of the stress by becoming feverishly active and energetic; others accomplish the distraction by surrounding themselves with people or by constantly going out to parties or social events. Doing unusual amounts of work is another tactic. In short, many of us respond to stress in a way that resembles manic behaviour. When does this behaviour become pathological in nature?

Overactivity becomes manic when it becomes extreme, prolonged, and uncontrollable. Manic individuals are hyperactive, talkative, and endlessly energetic and usually perform these behaviours in bursts of activity that eventually result in a burnout period of exhaustion. They find great superficial pleasure in people and things that never interested them before until their attention is turned to another more interesting topic. In the process of these bursts of mania, their self-image becomes grossly inflated. They tend to ignore their limits, believing they can do anything. They love and admire themselves without reservation and ironically they are often irritable, unhappy, and reckless in their actions (Bootzin & Acocella 1984).

Depression

Most people report that they have gone through periods of depression or extreme dejection at some point in their lives. They admit to ‘feeling sorry for themselves’ and may report the following symptoms:

These symptoms that most people have reported experiencing are similar to the symptoms of pathological depression. It is essential to grasp the concept that most psychological dysfunctions, including pathological depression, are determined based on the degree of symptom expression. Pathologically depressed patients often show a degree of utter despair and hopelessness that is foreign to the experience of most people (Bootzin & Acocella 1984).

People with depression live in a state of sheer hopelessness, in which there exists no source of pleasure, and in some, no reason for living. Some people who are depressed do, in fact, kill themselves. They may experience delusions and hallucinations which do not occur in ‘normal’ periods of depression. For example, they fear the imminent destruction of the world, or that terrible tragedies are in store for them or their loved ones.

Persons who undergo one or more major depressive episodes with no intervening manic episodes are classified as major depressive in nature. In the United States the prevalence of major depression is about 3% for men and about 9% for women and the lifetime risk, which is defined as the chance of experiencing at least one episode of major depression, is 12% for men and 26% for women (Boyd & Weissman 1981). Depression is second only to schizophrenia as the primary condition for admissions to mental hospitals (Woodruff et al. 1975).

Some groups of people, such as low socioeconomic classes, of both sexes, middle-aged and elderly, and women in general are more susceptible than others to developing depression. It is distressing to note that young people have recently started to increase their prevalence of depressive episodes. Even the incidence in infants has been reported to be on the increase.

In about 50% of the cases the first episode is also the last episode. They have no recurrence. However, for the remaining 50% the depression will come and go many times (Bootzin & Acocella 1984). The episodes may occur in clusters or be separated by many years of normal function. In most cases adjustment back to a normal life occurs relatively quickly. However, in about 20% of people, return to their normal premorbid state following a major depressive episode does not occur. Why these people do not return to their normal or premorbid state becomes understandable to a certain extent when consideration is given to the effects that a depressive episode can have on their lives. A major episode of depression often erodes self-confidence, disrupts family and marital relationships, interferes with progress at school or work, and alters other people’s expectations of the depressed individual. Thus, the event itself sets up a vicious circle of reoccurrence by the state in which it leaves the individual.

Classification

Several classifications of depression have been developed. The following classification is based on the age or stage of development of the individual.

Depression and neuroimmune function

Depression has been shown to be related to schizophrenia (Crow 1984), herpes simplex virus (Halonen et al. 1974), Ebstein–Barr virus (Amsterdam et al. 1986), human immunodeficiency virus (HIV) type I (Levy & Bredesen 1989), several autoimmune diseases (Johnstone & Whaley 1975), leukaemia (Greene 1954), and a variety of cancers (Persky et al. 1987). These relationships suggest disorders of the neuroimmune system in some fashion or other.

The role of neuroimmune function in depression has attracted attention for many years (Calabrese et al. 1987). Depressive illness poses a major public health problem with 2% to 3% of the population hospitalised or seriously afflicted at any one time; in this light, many investigators have approached depression from a neuroimmunological prospective (Stein et al. 1991). Many studies document that patients with depression show reduced immune function throughout a wide variety of immune function measures. Stein et al. (1985) found that in-patients with depression have poorer blastogenic responses than non-depressed controls. Depressed patients have also been shown to have a lower percentage of helper T-lymphocytes than non-depressed controls (Krueger et al. 1984). Irwin et al. (1990) showed that when compared to normal controls, men with major depressive disorder were associated with a 50% reduction in T-cell cytotoxicity. Not all research supports the above findings. Stein et al. (1991) reported in a comprehensive review that out of eight studies that they looked at only one found lymphopenia to be significant in depressive patients studied. Out of five additional studies examined by the same authors, again only one showed an alteration in neutrophil counts in depressed patients. Immune function studies in patients with depression have also been explored. Irwin et al. (1987b) found a decrease in cytotoxicity of natural killer cells in depressed patients as compared to controls. Other studies relating to natural killer cell cytotoxicity did not find any significant difference between controls and depressed patients (Mohl et al. 1987; Schleifer et al. 1989

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