Evaluate the biological evidence for depression

Unipolar depression is a disorder involving great sadness, feelings of worthlessness and guilt, withdrawal from others, a loss of sleep, appetite and sexual desire and lack of interest or pleasure in usual activities. It is often associated with other disorders, such as panic attacks, substance abuse, sexual dysfunction and personality disorders, and the average episode lasts for around 5 months, although it may also become chronic. Given the high prevalence of depression in the population, estimated as between 5.2% and 17.1%, and the fact that it is up to three times more common in women, a biological basis for this disorder has long been postulated. There is evidence that depression is associated with both low levels of, or dysfunctioning of, serotonin, and high levels of cortisol, and although this is a too simplistic view, it is clear that biological processes play an important role in depression and several interconnected brain regions are likely to be implicated in the disorder.

The distinction between endogenous, or biologically mediated, depression and reactive depression is an old one, and it has been suggested that the former is characterised by an absence of precipitating factors, a prominent vegetative state, including weight loss and insomnia, a tendency to recur, a good response to somatic therapy and a tendency to be familial. As far as aetiology is concerned, therefore, it has been proposed (Weissenburger and Rush, 1996), that it is the cortisol level found to relate to the "vegetative symptoms" which is involved in endogenous depression, while in reactive depression it is serotonin which causes the "cognitive" symptoms, such as suicide and guilt. Although there is much evidence in support of the role of biology in the disorder, there seems little reason to assume that there are two different types of depression. Heredity has often been used to provide evidence for an endogenous variation of the disorder, but when the hypothesis that patients with endogenous depression should have higher rates of familial affective illness than those with non-endogenous depression was tested (Andreasen et al, 1986), no evidence for this was found. It seems likely, then, that depression is a disorder in which both biological and cognitive factors combine, and that both are important in its aetiology and maintenance.

The evidence for a biological aspect to depression is clear from the changes in both limbic forebrain function and cortical activity which have been observed in patients (Checkley, 1995). Widespread and severe neuroendocrine disturbances have been cited, with increased activation of the HPA axis and therefore increased cortisol excretion, as well as reduced secretion of the thyroid stimulating hormone TSH. Prolactin responses to indirectly acting 5-HT (serotonin) agonists are also impaired, and there is strong evidence for sleep disturbances, including changes in REM sleep and reduced slow-wave sleep, also occurring in depression. Changes in cortical activity have also been observed, with elderly depressives having enlarged lateral ventricles and a widening of the cerebral sulci (Rabins et al), and areas of increased MRI signal density in subcortical regions such as the basal ganglia and the thalamus. Finally, Mayberg et al (1999), suggested that there are also functional connections between the limbic structures and the neocortex involved in depression. They targeted interregional interactions and regional reciprocity of function in the brain activity present during transient and sustained changes in affective state. They found that sadness increased blood flow to the limbic-paralimbic area, especially the subgenual cingulate and the anterior insula, and decreased flow to regions in the neo-cortex, such as the right dorsolateral prefrontal cortex and the inferior parietal lobe. The reverse pattern was seen in depression recovery, indicating that there are reciprocal changes occurring in the cingulate and the right prefrontal cortex with both transient and chronic changes in negative mood. This implies that these regional interactions may mediate the well-recognised relationships between mood and attention that are often found in depression.

It is clear from these studies that biological factors play an important role in depression, but exactly which mechanisms are involved? The serotonin hypothesis stemmed for the accidental discovery that two types of drug are successful in treating depressed mood - Tricyclic drugs, which prevent the re-uptake of norepinephrine and serotonin, and Monoamine oxidase (MAO) inhibitors, which prevent the MAO enzyme from deactivating these neurotransmitters. Both, therefore, compensate for the abnormally low levels of serotonin and norepinephrine in the brains of depressed patients. This led to the hypothesis that a serotonin deficiency lies at the root of depression, and the finding that selective serotonin re-uptake inhibitors (SSRIs) are also effective in treating the disorder, was taken to be further evidence of the crucial role of serotonin. The evidence for the serotonin hypothesis does not end there, however, with support coming from tryptophan depletion studies, neuroendocrine function tests and neuroimaging of the brain regions involved.

If low serotonin levels are important in depression, then the lowering of 5-HT's amino acid precursor, tryptophan, should be able to provoke depressive symptoms in individuals already vulnerable to the disorder. To test this, recovered patients were given either a nutritionally balanced drink containing tryptophan, or one not containing tryptophan. They were then scored on the Hamilton scale for depression, as well as self-rated measures of mood, before and 7 hours after drinking. It was found (Smith et al, 1997) that the tryptophan-free mixture resulted in a 75% decrease in plasma tryptophan concentration, and 10 out of 15 patients experienced a clinically significant relapse. This strongly suggests that the rapid lowering of brain serotonin function precipitates depressive symptoms, although it is important to remember that this may only be the case with individuals already vulnerable to depression.

Further evidence for the role of serotonin in depression comes from neuroendocrine 5-HT tests. The hypothalamus receives dense innervation from the raphe nuclei, and activation of the 5-HT pathways results in reliable increases in the plasma concentrations of various anterior pituitary hormones. This causes an increase in cortictrophine and a resultant elevation in the plasma levels of cortisol which can be used as a marker of 5-HT neuroendocrine responses. This, therefore, provides evidence that brain serotonin function is impaired in depressed patients, since they exhibit a reliably lowered prolactin response to drugs which enhance 5-HT function through actions on the presynaptic serotonin neurons. This further suggests that the impairment in 5-HT mediated prolactin release in depression is due to abnormalities in the 5-HT pathways and not due to alterations in pituitary regulation of prolactin secretion. In other words, decreased 5-HT mediated prolactin release is a state marker of depression, implying that depressive disorders are associated with reversible impairment of brain serotonin function.

The serotonin hypothesis does not specify, however, exactly where the fundamental deficit occurs, but PET imaging has been used to examine serotonin receptor binding as a possible stage of abnormality (Sargent et al, 2000). In this method, the radioligand binds to one sub-type of the 5-HT receptor, and then the level of receptor binding can be estimated as a measure of receptor number. This approach was used to determine whether depressed patients have reduced 5-HT receptors as compared with controls, and it was found that this is indeed the case, suggesting that a significantly decreased number of serotonin receptors may be at least part of the deficit behind depression. Despite the amount of evidence supporting the role of serotonin in depression, however, there are still problems with the serotonin hypothesis (Cowen, 1996). The decreased brain 5-HT function proposed to underlie depression, has also been found to be implicated in a number of different disorders, including OCD, eating disorders and PMS, so how can the same biochemical abnormality cause such a wide range of conditions? The answer to this may lie in the fact that serotonin has such a diverse range of behavioural functions, but this is nonetheless a problem for the hypothesis. Similarly, it is difficult to consider serotonin neurons in isolation because of the many important interconnections they have with other neurotransmitter pathways whose functions may also be abnormal in depression. Most crucially, however, is the fact that antidepressants usually take two weeks to have an effect, even though their biochemical impact is almost immediate. It is possible, therefore, that it is not a direct effect of serotonin which causes depression, but of another, mediating neurotransmitter. The suggestion that it is a desensitisation of the autoreceptors which causes the delay in antidepressant action is also a plausible explanation for this phenomena. Clearly, then, the serotonin hypothesis, although necessary, is not sufficient to explain the biological basis of depression, and this is where the role of life events comes in.

The limbic area of the brain is closely linked to emotion and also effects the hypothalamus, which in turn controls the hormones produced by the pituitary gland. It has been suggested, therefore, that this hypothalamic-pituitary-adrenocortical (HPA) axis is overactive in depressed patients. Evidence to support this comes from finding that levels of cortisol are high in depression, which led to a biological test for the condition - the dexamethasone suppression test (DST) - demonstrating that depressed individuals do indeed fail to suppress cortisol due to over-activity of the HPA axis. Cushing's syndrome, characterised by abnormal growths on the adrenal gland leading to over-secretion of cortisol, also results in depression, providing further support for the role of the HPA axis in this disorder. It has also been proposed (Checkley, 1995), that the biological basis of environmental influences on depression lies in the HPA axis, with the main biological response to stress being the activation of the adrenal medulla and therefore increased secretion of cortisol. Social support may be the protective factor which reduces the liklihood of depression following a given life event or stressor. Evidence for the role of life events in HPA activation comes from the finding that cortisol secretion is increased by life events (Willis et al, 1987), that social support buffers the cortisol response to stress in children (Gunnar et al, 1992) and that sexual abuse leads to lasting neuroendocrine changes similar to those seen in depression (de Bellis et al, 1994). It seems, then, that corticosteroid responses to environmental stress makes a convenient model of how life events contribute to depression.

Attempts to combine the roles of decreased serotonin function and increased levels of cortisol due to HPA activation into a complete theory of the biological basis of depression have not always been successful, but they at least provide a framework for future research. Curzon (1988), studied the behavioural effects of a 2 hour immobilisation on the rat, suggesting that since this results in increased cortisol levels, it might be a useful way of looking at depression. After immobilisation, when the rat was placed in an open field it displayed abnormal behaviours such as decreased locomotion and increased defecation. On repeating the stress every day, however, the rat adapted and its behaviour became normal. Interestingly, this model also conforms to the sex differences seen in human depression, with higher corticosterone responses and a lack of increased 5-HT functioning on repeated stress seen in females. This apparent defective behavioural adaptation may explain why women are much more likely to suffer from depression. It is proposed, therefore, that a failure to adapt to stress in this way, might be a rational model for depression in humans, since adaptation is also associated with increased post-synaptic 5-HT function. Depression, could therefore, stem from a combination of a high corticoid response to environmental stress and low 5-HT functional activity which opposes adaptation and predisposes the individual to depression.

In conclusion, the biological evidence for depression, although far from complete, provides consistent support for the role of decreased serotonergic function in predisposing individuals to depression, and for the role of HPA axis over-activation in leading to maladaptation to stressful life events. Since CRH neurons project to the regions modulating noradrenaline and serotonin, it is likely that changes in cortisol levels following early life stress are affected by serotonin functioning. In general, this suggests that there exist complex inhibitory interactions between serotonin and the HPA system in depression.

COMMENTS
You have an impressive grasp of the subject and a clear way of presenting it. Well done again. I cannot find much to add other than perhaps to mention the new issues raised by genetic findings that we discussed in the tutorial.

Here are some additional notes on genetics in case you want to include them:

Preliminary reports from a study of an Amish population with an extensive history of manic-depression once raised the possibility that chromosome 11 (see below) held one or more genes producing vulnerability to bipolar disorder, but the finding did not hold up. A gene somewhere on the X chromosome could play a role in some cases of that condition, but the connection is not evident in most people who have been studied. Most recently, various regions of chromosome 18 and a site on chromosome 21 have been suggested to participate in vulnerability to bipolar illness, but these findings await replication.

In a pioneering study of 680 female homozygous and heterozygous twins, Kendler and associates found that the strongest predictors of liability to major depression were, in descending order: (1) stressful life events, (2) genetic factors, (3) previous history of major depression and (4) neuroticism. The authors concluded that major depression is a multifactorial disorder, and understanding its aetiology will require the rigorous interaction of genetic, temperamental and environmental risk factors. For more details see: Kendler KS, Kessler RC, Neale MC, et al. The prediction of major depression in women: Toward an integrated etiologic model. Am J Psychiatry. 1993;150:1139-1148.

McGuffin and Katz (1997) reviewed 12 family studies of bipolar illness and found the average morbidity risk among first-degree relatives to be 7.8% for bipolar and 11.4% for unipolar illness. This is a substantial increase over the respective population rates of approximately 1% and 3%, cited by the same authors. Probandwise monozygotic twin concordance rates for bipolar illness range from 62 to 72 percent, and an additional 18 to 25 percent have unipolar illness. Comparative dizygotic concordance rates range from zero to 8 percent for bipolar illness with an additional unipolar range from zero to 11 percent. The role of genes in depressive illness is further supported by observations on adoptees. Increased rates of depressive illness are seen in biological parents but not in adoptive parents, indicating that the family and twin data indeed reflect the action of genes. Collectively, the evidence points to a genetic predisposition with a relatively high penetrance and a range of expression including bipolar and unipolar affective disorder.
The most extensive observations on the bipolar phenotype and its transmission come from a comprehensive family study of bipolar I, bipolar II, schizoaffective, unipolar and control probands. The first four disorders, with the possible addition of cyclothymic personality disorder, aggregate in the families of schizoaffective and bipolar probands. Genetic analyses of these pedigrees indicate that a multifactorial-threshold model provides a plausible explanation of the transmission and that a single locus model can be excluded. According to the model, schizoaffective disorder is the most severe form of the illness, followed by bipolar I, bipolar II and unipolar depressive disorder.
The discovery of large bipolar pedigrees among the Old Order Amish provides a rare opportunity to study manic-depressive illness in a population isolate with an apparently autosomal dominant form of the disease. Such genetically isolated populations are ideal for linkage studies because their gene pools are typically more homogeneous than those of the general population. Indeed, a gene appeared to have been found when linkage was reported between bipolar illness and two DNA markers (HRAS and INS) on the short arm of chromosome 11.
In retrospect, failures to replicate the finding should have sounded a note of caution, but at the time, the discrepancy between the studies was felt to be evidence of genetic heterogeneity. This explanation seemed plausible because of the isolated nature of the Amish population; the linkage could represent a rare gene that would be difficult to replicate outside of that group. Therefore, the pedigree was extended to include two new branches and, at the same time, the diagnoses were updated. Linkage analyses based on these revisions resulted in a decisive erosion of the original score to the point that a disease locus for bipolar illness could now be excluded from the region in question.
How can the steep fall in the scores be reconciled with the strong original evidence of linkage? One possibly is the inclusion of unipolar depression in the affected phenotype. Though unipolar depression is an expression of the bipolar genotype, the high population prevalence of depression could introduce cases into the pedigree that are unrelated to the bipolar gene. Indeed, it was unipolar depressives in the new pedigree extensions that were most responsible for the changes.
The linkage studies just reviewed have tested the hypothesis that a major gene contributes to vulnerability to depressive illness. A major gene may be thought of as necessary for the development of the disease, at least in the pedigree or pedigrees being studied. A locus of this nature would be expected to produce a large lod score and to be easily replicable in other pedigrees transmitting the disease at the same locus. Now that a number of genome scans of manic-depressive illness have been completed without identifying a major locus, it has become increasingly apparent that a different genetic mechanism must be anticipated. Most likely, the genetics will be explained by multiple genes of small effect acting in concert to cause the disease-oligogenic inheritance. Unlike major genes, each locus individually has a small effect on liability, no locus is necessary for the disease, and the statistical evidence of linkage at any locus is likely to be modest. An important consequence is that linkages will be difficult to replicate. The statistical power to detect any one locus is low; therefore, only a proportion of studies will detect it and non-replications will be common.

Source: Raymond R. Crowe, MD, Neuropsychopharmacology, 2001.



"Men are not moved by things, but by the views they take of them." Discuss with relation to depression.

The idea that it is not objects or events themselves which cause negative emotions and responses, but the interpretation which the individual makes of them which results in maladaptive behaviour, is central to cognitive theories of almost all psychological disorders, including unipolar depression. Cognitive approaches have demonstrated that depressed people are more likely to make a triad of negative interpretations of the self, the world and the future, and studies into learned helplessness and hopelessness have supported this conclusion by showing that the tendency of depressed individuals to attribute stable, global and internal causes to negative events is an important part of the disorder. Finally, behavioural research has also found that depressed people interpret usually pleasant activities in a negative manner, but it is also important not to forget the role of social factors such as life events and negative childhood experiences in depression vulnerability and maintenance.

Beck's (1987) cognitive theory of depression asserted that people suffer from the disorder because their thinking is biased toward negative interpretations, and the way they think affects the way they feel. He also suggested that some of this thinking takes the form of negative automatic thoughts, that is they are repetitive, unintended and not easily controllable. One of the most important parts of the theory is that depressed individuals all exhibit a triad of such thoughts about themselves, the world and their future and that this trend is specific to depression and necessary for the disorder to occur. In this way, depression is seen as resulting from the interaction between dysfunctional beliefs about the significance of certain kinds of experience, a high subjective evaluation of the importance of that experience and the occurrence of an apt stressor. These descriptive features of the theory have not been consistently supported, however (Haaga, Dyck and Ernst, 1991). The idea that all subtypes of depression are associated with increased negative thinking is supported, but positive thoughts are not, as Beck claimed, by necessity excluded from the disorder. Depressed people do appear to think negatively about themselves, their future and their aptitude for coping with the world, but this may be a single dimension rather than a triad, and may also not be necessary for depression to occur. Information processing research has, however, confirmed a further aspect of the theory, by finding that depressed individuals show biased attentional deployment, in that they demonstrate more self-focused attention of negative content (Ingram et al, 1987), and biased recognition, in that they show greater recollection of negative words (Dunbar and Lishman, 1984). It is clear then, that it is how individuals interpret and view events which determines how they feel about them, and depressed people tend to make negative interpretations.

Beck's theory forms a framework for another approach to depression - learned helplessness. In 1967, Overmeier and Seligman found that dogs exposed to inescapable and unavoidable shocks in one situation failed to learn to escape a shock in another situation in which escape was possible. Seligman and Maier (1967), then suggested that this effect was caused by the uncontrollability of the original shocks, and that this learned helplessness might be used to explain depression in humans. It was suggested that there are three aspects to the learned helplessness phenomenon - motivation, which is reduced by the expectancy of uncontrollability, cognition, which is interfered with by the organism's tendency to perceive contingent relationships between its behaviour and outcomes, and emotion, which is also disrupted by aversive events. According to the theory, then, when an organism is faced with an outcome that is independent of his responses, he learns that nothing he can do will have any effect on that outcome. This tends to produce a lack of response initiation to control the outcome, and produces a belief in the inefficacy of responding in general. Crucial to the theory is that information about the contingency between behaviour and outcome must be processed and transformed into a cognitive representation of the expectation that responding and the outcome are independent. Confirmation that it is the expectation of uncontrollability and not actual controllability which is important comes from the finding that students told they could switch off noise if they had to did not become helpless (Glass and Singer, 1972). Further support for the theory comes from a study by Thornton and Jacobs (1971), in which college students sat through a second shock following a first inescapable one. When asked why, 60% responded that they had no control over the shock so why bother trying to avoid it? It certainly seems that learning that an outcome is independent of a response makes it harder to later learn that responses can control an outcome, but how exactly does this relate to depression?

There are several problems with the original learned helplessness theory, the main one being that it does not distinguish between cases in which outcomes are uncontrollable for all people and cases in which they are uncontrollable only for some people. It also does not explain when helplessness is general and when it is more specific, and when it is chronic and when it is acute. Abramson, Seligman and Teasdale (1978) reformulated the learned helplessness theory in order to make it more relevant to depression in humans. They placed it in an attributional framework, suggesting that when an individual finds himself helpless he makes a causal attribution which determines the generality and chronicity of the helplessness deficits and the impact on his self-esteem. Once people perceive a non-contingency between their responses and outcomes, therefore, they attribute their helplessness to a cause, and this can be stable or unstable, global or specific and internal or external. It has been demonstrated (Rizley, 1978), that depressed individuals possess a striking attributional style, with depressed students attributing their failure at a cognitive task to incompetence on their side (internal, global and stable) and success to task ease (external, stable, and specific). Non-depressed students, on the other hand, attributed failure to task difficulty (external, specific, stable) and success to their ability (internal, global and stable). It does appear, therefore, that depressed people see failures as being their fault and something that will always be present, and successes as being down to luck or some other external factor, and that this negative interpretation constantly undermines their own self-esteem and maintains their feeling of helplessness and depression.

The helplessness theory has been somewhat usurped by the notion that it is not uncontrollable events which are important in depression, but specifically negative events and how they are interpreted. The hopelessness theory (Abramson et al, 1989), postulates the existence of an as-yet unidentified sub-type of depression in which the main cause is the expectation that no response will change the liklihood of an aversive outcome. The theory suggests that the perceived occurrence of a negative life event serves as an "occasion setter" for people to become hopeless. It is proposed that there are three parts to hopelessness depression - causes are inferred as stable and global, and there is much importance attached to the outcome of the negative event, the inferred consequences are seen as important, not remediable, unlikely to change and affecting many areas of life, and the inferred negative characteristics about the self are also believed to be not remediable or likely to change and it is believed that possession of them will preclude the attainment of important outcomes in many areas of life. The theory implies that those with a depressive attributional style are more likely to become hopeless, but also that in the absence of negative events or the presence of positive ones, such individuals are no more likely to become hopeless than those who do not possess this style of attribution. This can, therefore, be seen as a specific vulnerability factor for hopelessness depression, rather than a cause. Evidence for this theory comes from a study into the attribution of poor grades by students (Metalsky et al, 1987). Only the students who attributed poor grades to global and stable factors became depressed, and this was also only the case with students with low self-esteem. Furthermore, this effect was mediated by an increase in feelings of hopelessness. Whether or not hopelessness is a sub-type of depression or is more widespread across the disorder, it does seem evident that it is the way individuals respond to events, not the events themselves, which are crucial in depression.

This has also been demonstrated by a study into how mood affects judgements of happiness and satisfaction with life (Schwartz and Clore, 1983). Moods were first induced by asking subjects for vivid descriptions of recent happy or sad events, and then induced by interviewing subjects on either rainy or sunny days. In both conditions it was found that more happiness and satisfaction was reported when participants were in a good mood, but the negative impact of bad moods could be eliminated by inducing them to attribute their feelings to a transient external source (such as the weather) which was irrelevant to evaluations of their lives. Subjects in a good mood, however, were not affected by these misattribution manipulations. This study neatly shows that people use affective states as information sources in making judgements about how happy and satisfied they are with their lives, and that people in depressed states are more likely to search for and use information to explain their affect than people in happy states. This demonstrates the importance of causal attributions in depression, with patients tending to actively look for reasons for their negative feelings. Coupled with a bias towards making global, internal and stable attributions, this is clearly crucial to the maintenance of the disorder.

Behavioural studies have also shed light on the cognitive processes underlying depression. Hammen and Glass (1975) tested the operant theory that depressive behaviours are the result of reduced response-contingent positive reinforcements and that there should, therefore, be a relationship between an individual's participation in pleasurable activities and his mood. In the first study, depressed subjects were induced to increase their level of participation in activities they deemed enjoyable. In the second study, depressed and non-depressed participants' subjective evaluations of the reinforcements they received were examined. It was found that inducing depressed subjects to increase their participation in enjoyable, and therefore reinforcing, activities did not necessarily reduce their depression. In fact depressed subjects who increased their activity rate actually evaluated the activities more negatively than other subjects. This shows clearly that simply making depressed patients do more "fun" things will have little positive effect on their mood, since it is the way they view those things and not the things themselves which determines how they feel.

It is evident from cognitive and behavioural studies that negative interpretation is key in depression, but it is also important to remember that social aspects may provide vulnerability and maintaining factors which it would be imprudent to overlook. Life events are often cited as a causal factor in depression, but a prospective study of 400 women with children at home found that only 1 in 5 women experiencing a severe, life-threatening event developed depression. It is obvious, therefore, that again it is not the event itself, but how it is perceived which is crucial. Factors mediating the impact of stress may be the level of social support and coping skills available to the individual. Nolen-Hoeksema et al (1994), found that ruminative coping, a tendency to focus on and worry about things, was more common in women, and that bereaved adults with more a ruminative style at 1 month were more depressed at 6 months. The experience of marked adversity, increased externality and the endorsement of irrational beliefs was also shown to be related to depression in Alzheimer's disease caregivers (McNaughton et al, 1994). It is also possible that different types of depression have different social causes, and this is supported by the finding that there is a difference in the proportion of those with at least one severe event in the 6 months before the onset of depression between patients with endogenous depression and patients with other types of depression (Frank et al, 1994). In support of this, Brown et al (1994) found that patients with melancholic depression are less likely to have suffered a severe event if they had had a previous episode of depression. If it was their first episode, however, it was nearly as often preceded by a life event as with neurotic depressive episodes.

Distal causes such as childhood experience may also play an important role in adult depression. Parental divorce has been found to be positively associated with depression in women but not in men, and neglect and abuse consistently double the rate of depression in adulthood (Bifulco, Brown and Harris, 1994). Since women are more likely to have been sexually abused as children, this may be one reason why they are also more likely to suffer from depression as adults. The chronicity of depression may also be determined by social factors. Brown and Moran (1994) found that the experience of childhood adversity or severe interpersonal difficulties greatly increases the odds of a depressive episode becoming chronic, and Lam et al (1994) showed that recovery is positively associated with emotional support and negatively associated with the experience of a severe life event or ongoing difficulties.

It seems, then, that people are moved to responses by the views they take of things, and not by the things themselves, and in depression this takes the form of negative thinking, global, internal and stable attributions to negative events and a general cognitive bias towards negative interpretations of life. Treatment for depression should, therefore, focus on how patients perceive themselves and the world, rather than on negative events themselves, since cognitions are clearly a crucial component of the disorder.

This is a first class essay.

Natural to start off with Beck and then move into the learned helplessness bits; keeping a close tab on the question (referring back to it). Mentioning at least two refs per paragraph like you do, keeps the text tight and to the point.

Crucial link in the conclusion to consequences for treatment. Well done!

Enough flattery. Here are a few more points to consider:

Beck viewed deviant cognitive processes as intrinsic to the depressive disorder, not a cause or a consequence these negative cognitions are functionally related to depressive schemata (basic beliefs) that have been activated in response to certain stressors dysfunctional beliefs are thus hypothesised to be diatheses (predisposing) for depression before activation be specific experiences, they are thought to be latent, not directly influencing mood or cognition and not necessarily readily available to awareness stressors congruent with one's personality are expected to activate dysfunctional beliefs about the meaning of the stressful event and hence precipitate depression.

Beck also suggested that although the negative cognitive processing is similar for all types of depression, the factors precipitating the various disorders vary widely: negative cognitions are found to be equivalent in unipolar and bipolar, primary and secondary, endogenous and non-endogenous, and melancholic and non-melancholic depressions.Furthermore, Beck proposed a key difference between subclinical and clinical conditions subclinical affective responses were said to be associated with accurate perceptions of events, whereas psychopathology was said to be associated with a poor correspondence of conceptualisation and external reality

Depression Short Notes

DEPRESSION
· range of conditions - severe depression = psychotic depression - accompanied by hallucinations and delusions
symptoms of depression
· emotional symptoms:
- misery, apathy and pessimism
- low self-esteem: feelings of guilt, inadequacy and ugliness
- indecisiveness, loss of motivation
· biological symptoms
- retardation of thought and action
- loss of libido
- sleep disturbance and loss of appetite

(mania)
· opposite of depression in most respects
· characterised by excessive exuberance, enthusiasm and self-confidence, accompanied by impulsive actions
· often combined with irritability, impatience and aggression
· sometimes grandiose delusions

UNIPOLAR DEPRESSION:
· mood swings are always in the same direction
· 75% reactive depression: non-familial, clearly associated with stressful life-events, and accompanied by symptoms of anxiety and agitation
· 25% endogenous depression: familial pattern, different symptamotology

-a clinical distinction: little evidence that antidepressent drugs show selectivity; may be of some value regarding ancilliary treatment

BIPOLAR AFFECTIVE DISORDER:
· much less common
· depression alternates with mania
· strong hereditary tendency (but failed genetic linkage studies so far)
· usually appears in early adult life

Clinicans have long suggested that depression is not a single disorder but rather a group of disorders heterogeneous with respect to symptoms, cause, course, therapy, and prevention

comorbidity
· research has shown that in adulthood both anxiety and depressive conditions are frequently provoked by a severely threatening event occuring not long before onset
:a study of a Regent's Park general practice documented that a severe event involving loss was more often involved in depression, and in anxiety one involving danger (Finlay-Jones & Brown, 1981)
- consistent with this are findings that there is a tendency for the onset of a mixed condition to be preceded by both loss and danger

· women selected for a study because of the death of a spouse experienced mixed depression and anxiety, remitting to depression w/o anxiety at follow-up, whereas among women whose spouse had suffered a cardiac arrest depression w/o anxiety was rare
- consistent with findings of the tendency of loss to produce depressive syndromes and danger events to produce anxiety

beck's cognitive theory of depression
· developed by Beck in 1963
· Beck postulated several cognitive concomitants of depression
:depressed people are thought to show automatic thoughts reflecting themes of loss and revealing negative views of self, the world, and the future

- studies show that depressed people rate themselves, their prospects for the future, and their fitness for meeting life's demands more negatively

:the degree of negative thinking is believed to relate directly to the severity of other depressive symptoms

· the greater negativity of depressed patients' cognitions is confirmed by many studies using such negative thinking measures as the Crandell Cognitions Inventory and the Automatic Thoughts Questionnaire
- compared to nondistressed people, nonpsychiatric medical patients, depressed patients in remission or themselves when in remission

· research indicates that depressed people rate at least as many positive adjectives as self-descriptive as they do negative ones indicating that positive thinking is not excluded in depression

· studies show that depressed people appear to be more self-critical, report lower self-esteem, more hopeless about the future, and rate themselves as further away from their ideal selves

· Beck viewed deviant cognitive processes as intrinsic to the depressive disorder, not a casue or a consequence
· these negative cognitions are functionally related to depressive schemata (basic beliefs) that have been activated in response to certain stressors
· dysfunctional beliefs are thus hypothesised to be diatheses (predisposing) for depression
- before activation be specific experiences, they are thought to be latent, not directly influencing mood or cognition and not necessarily readily available to awareness
· stressors congruent with one's personality are expected to activate dysfunctional beliefs about the meaning of the stressful event and hence precipiate depression

· Beck suggested that although the negative cognitive processing is similar for all types of depression, the factors precipitating the various disorders vary widely
:negative cognitions are found to be equivalent in unipolar and bipolar, primary and secondary, endogenous and nonendogenous, and melancholic and nonmelancholic depressions

· schemata are thought to become importanr during depression, dominate the thought processes, and lead to cognitive distortions but are relatively inactive during the nondepressed period

· Beck proposed a key difference between subclinical and clinical conditions
:subclinical affective responses were said to be associated with accurate perceptions of events, whereas psychopathology was said to be associated with a poor correspondance of conceptualisation and external reality

helplessness and hopelessness theories

learned helpelessness theory of depression
· Maier & Seligman (1976)

a person's passivity and sense of being unable to act to control his or her own life is acquired through unpleseant experiences and traumas that the he or she tried unsuccessfully to control, bringing on a sense of helplessness, which leads to depression

· supported by Seligman study (1974) on dogs which received inescapable electric shocks
:soon after receiving the first shocks, the dogs were reported to 'give up' and passively accept the painful stimulation. later, when the shocks could be avoided, these dogs did not acquire the avoidance response as efficiently and effectively as control animals. Most were observed to lay down in a corner and whined

\ interpreted that animals acquire a sense of helplessness when confronted with uncontrollable aversive stimulation as they appeared to lose the ability and motivation to learn to respond in an effective way to painful stimuli

but if you were able to communicate to the dogs that the shocks became avoidable, perhaps they would respond as effectively as control animals; perhaps this helplessness response is not due to lack of motivation to avoid the response but a realisation of the futility of trying to avoid a shock that is unavoidable

· concluded that learned helplessness in animals could provide a model for at least certain forms of human depression
· many depressed people also appear passive in the face of stress, failing to initiate actions that might allow them to cope
· physiological evidence: noradrenaline was depleted in Seligman's animals and is a neurotransmitter implicated in depression

attribution and learned helplessness
· revised helplessness theory (Abramson, Seligman, & Teasdale, 1978) after inadequacies of original theory were made evident
many depressed people hold themselves responsible for their failures - if they regard themselves as helpless, how can they blame themselves?

· some studies indicated that helplessness inductions in humans sometimes led to subsequent facilitation of performance (eg. Wortman & Brehm, 1975)

· the attributional revision postulates that the way in which a person explains failure will determine the subsequent effect of failure

global attributions ('i never do anything right') increase the generality of the effects of failure

attributions to stable factors ('i usually fail tests') prolong the effects of failure

attribution of failure to internal characteristics ('i am stupid') is more likely to diminsh self-esteem, particularly if the personal fault is global and persistent

\ people become depressed when they attribute negative life events to stable and global causes

· diathesis: the individual prone to depression is thought to show a depressive attributional style: a tendency to attribute bad outcomes to personal, global, stable faults of character

· Seligman et al. (1979) devised the Attributional-Style Questionnaire which found that mildly depressed college students often attributed failure to personal, global, and persistent inadequacies
NB college-student populations probably do not provide a good analogue of a clinical population: accumulating evidence indicates that selecting subjects soley on the basis of elevated BDI scores does not yield a group of people who can serve as a good analogue for those with clinica depression

· depressive attributional style does not appear to be specific to depression but is related to anxiety and to general distress

· when depressed persons were asked about the five most stressful events of their lives, their attributions did not differ from those supplied by normal people (Hammen & Cochran, 1981)
:suggests that attributions may not be relevant in causing depression

learned hopelessness theory of depression
· Abramson, Metalsky, & Alloy (1989)
· a theory-based classification of a subset of the depressive disorders

depressed persons have negative expectations about the occurence of highly valued outcomes and expectations of helplessness about changing the likelihood of occurence of these outcomes

there is a generalised hopelessness : people exhibit the negative-outcome/helplessness expectancy about many areas of life (as opposed to circumscribed pessimism)

supported by...
· longitudinal study reported that college students' levels of hopelessness predicted their levels of depression 5 weeks later (Rholes et al, 1985)
· pessimists were found more likely to develop postpartum depression than were optimists (Carver et al, 1987)
· reported that hospitalised unipolar depressive patients were more hopeless than both hospitalised nondepressed control and nondepressed schizophrenic subjects (Garber et al. 1978)

contributory causes to hopelessness
· the hypothesised causal chain begins with the perceived occurence of negative life events (or nonoccurence of positive events)
· epidemiological research has shown that the occurence of negative life events is involved in the development of depression (eg. Brown & Harris)
- however, people do not always become hopeless and depressed when confronted with negative life events

· the kinds of inferences people make for negative events and the degree of importance they attach to these events are important factors
- hopelessness is more likely to occur when negative life events are attributed to stable (ie. enduring) and global (ie. likely to affect many outcomes) causes

inferences about why the event occured
:events are more likely to be attributed to internal, stable, and global causes when people are confronted with situational information that suggests the event is low in concensus (eg. others do well in an anatomy exam that you failed), high in consistency (eg. typically failing anatomy exams), and low in distinctiveness (eg. typically failing exams in other subjects)
:other factors such as expectations of success and failure, and motivation to protect or enhance one's self-esteem, probably influence inferences about why an event occured

inferences about consequences of the event
:events are more likely to be attributed to internal, stable, and global causes if negative consequences are viewed as important, unlikely to change and as affecting many areas of life

infered negative characteristics about the self, given these events
:inferences concerning worth, abilities, personality, desirability, etc
:likely to lead to hopelessness when the person believes the negative characteristic is not remediable or likely to change
:probably not independent of causal attributions for these events

· individual differences in how much people tend to infer negatively about events are obviously important
- these negative styles of thinking = cognitive diatheses
ie. cognitively vulnerable

· supported by study which found that college students who showed a style to attribute negative achievement events to stable, global causes experienced a longer depressive mood reaction to a low grade than other students (Metalsky et al. 1987)
- subsequent study confirmed these findings and also demonstrated that low self-esteem correlates better with a longer depressive mood than hopelessness does (Metalsky et al. 1987)

- this may be interpreted as extending the hopelessness theory by viewing low self-esteem as an additional vulnerability factor that, in combination with the attributional diathesis and negative life events, ought to result in hopelessness

· Abramson & Seligman (1984) found that students who typically attribute negative life events to global causes showed a wider generalisation of learned helplessness to new situations when they were exposed to uncontrollable events
· Sacks & Bugental (1987) found that attributional style predicted short-term depressive reactions to a stressful social experience
· Wise & Barnes (1986) reported that a normal sample of college students who were cognitively vulnerable (high Dysfunctional Attitudes Scale scores) and exposed to negative life events during the past year were more depressed than were cognitively vulnerable subjects but were not exposed to a high rate of negative life events, as well as students who were not cognitively vulnerable regardless of life events

· in addition to cognitive factors, interpersonal, developmental and genetic facotrs may modulate the likelihood that hopelessness will develop

· maintenance of depression may be influenced by the consequences the individual infers from the fact that he or she is depressed or infers about himself or herself given that he or she is depressed

explaining symptoms
· motivational symptoms: retarded initiation of voluntary responses, lack of energy, apathy
if a person expects that nothing he or she does matters, why try?

· emotion symptoms: sad affect
- a likely consequence of the expectation that the furture is bleak

· suicidal ideation: Beck and others have demonstrated that hopelessness is a key factor in serious suicide attempts
:of 141 hospitilised suicide ideators, the 10 who committed suicide during a 5 to 10 year follow-up had received higher clinican ratings of hopelessness (Beck et al. 1989)

· disturbed sleep and difficulty in concentration: ruminations about hopelessness

· low self-esteem: if a negative event is attributed to an internal, stable, global cause
NB internal attributions per se are not maladaptive and, in some cases, may be very adaptive (eg. attributing failure to lack of effort leads to increased trying)
if people expect that others could attain the outcomes about which they feel hopeless
=> leads to feelings of inadequacy

hence, the hopelessness theory is a conceptual reorganisation of the various characteristics associated with depression. It reorganises these characteristics into a hypothesised causal sequence, giving some features previously viewed as symptoms causal status

a number of theories of depression organise the features of depression into different hypothesised causal sequences (eg. Beck)

psychosocial causes of depression

stressful life events
· the Life Event and Difficulty Schedule (LEDS) has consistently shown large associations between life events and the development of clinical depression (Brown & Harris, 1978)
· LEDS ignores self-reports about meaning \ various potential sources of bias stremming from the respondent can be excluded
- the presence of depression or the recent experience of loss may inflate the reported amount to previous attachment to the lost object

· a review of onset of depression in 10 population studies of women in the general population, using the LEDS and similar measures, indicates that the majority of women experienced a provoking agent before onset
· only about one in five women experiencing a provoking agent goes on to develop depression

· Brown & Harris study and research in Camberwell concluded that it is the meaning of particular events that tends to be crucial for depression

· results from a patient and community series (Price & Gardener, 1994) showed that once humiliation and entrapment events were taken into account, only deaths of close others showed much of a link

:loses such as redundancy, where there is no basis for feelings of shame because the whole firm is closing, had a low risk, and danger events, without any element of humiliation and entrapment had a lower risk

-these findings were related to the theory that low self-esteem, and particularly negative self-evaluation, is a key mediating pathway between stress and depression - humiliations is such an experience which lowers self-esteem

· use of life-event instrument to assess many stressors suggested that the impact of material factors on depression is usually through their effect on interpersonal relationships (Brown & Moran, 1995)
· longitudinal study in which confinement to a bed or chair and poverty status were independently associated with increased risk (Bruce & Hoff, 1994)
- the association was substantially reduced when controlling for the degree of isolation from friends and family

· it is a common experience that great deprivation, hardship and disappointment can be shifted more or less permanently to some peripheral part of consciousness - one role of life events can be to tell us something central about our lives that we have known in one sense all along

interpersonal characteristics, social support, and coping
· depressed individuals tend to have sparse social networks and to regard them as providing little support
:reduced social support may lessen an individuals ability to handle negative life events

· depressed persons elicit negative reactions from others (Coyne, 1976)
· the roommates of depressed college students rated social contacts with them as low in enjoyment and reported high levels of aggression toward them (Joiner et al. 1992)
· depression and marital discord frequently co-occur
:critical comments of spouses of depressed people are a significant predictor of recurrence of depression (Hooley & Teasdale, 1989)

· several studies have demonstrated that depressed people are low in social skills across a variety of measures
:interpersonal problem solving
:speech patterns: speaking very slowly, with silences and hesitations, and more negative self-disclosures
:maintenance of eye contact

· suggested that depressed people constantly seek reassurance about themselves from others, but even when reassured are only temporarily satisfied. their negative self-concept causes them to doubt the truth of the feedback they have received, and their constant efforts to be reassured come to irritate others

· ruminative coping - a tendency to focus on and worry about an existing depressed mood
:bereaved adults with a more ruminative styles at 1 month were found to be more depressed at 6 months
· poor social support no longer had direct effects on depression once ruminative coping and other psychosocial factors were controlled for, suggesting that this may be the mechanism by which these factors affect depression
- poor social support could result in more personal coping such as ruminative coping

adverse experiences in childhood and adolescence
· many studies indicate that it may be the quality of parental care after loss of a parent rather than the actual loss that is important
:evidence from general population samples suggests that parental death generally has little effect on the occurence of adult depression

· studies using the Parental Bonding Instrument (Parker et al. 1979) and interview-based ratings
· adverse experiences in childhood and adolescence involving parental indifference, and sexual or physical abuse, were related to a considerably raised risk of both depression and anxiety in adult life (Brown & Harris, 1993)
· survey of women living in the inner-city area of Islington (Brown & Harris, 1993)

:an index of childhood adversity comprising the components of parental indifference (physical or emotional neglect) physical abuse and sexual abuse has been shown to be related to depression

:poor parental care - similar to the measure of parental indifference - has shown a large association
· Brown & Harris (1993) reported a similar marked association of anxiety disorders with negative experience in childhood and adolescence and
· suggested that all of these childhood experiences are likely to contain both elements of loss and danger: abuse may involve not only an inducement to vigilance against future damage but also a loss of self worth

Schematic outline of psychosocial factors leading to depression and anxiety disorders (Brown & Harris, 1993)

comparing the theories

· Beck's theory, Brown & Harris's theory and the hopelessness theory all highlight the importance of maladaptive inferences about negative events
· these theories are all diathesis-stress theories
· whereas the hopelessness theory emphasises negative cognitive styles as diatheses for depressive symptoms, Brown & Harris's theory emphasises low self-esteem as the diathesis