First Glance

Most information has been accumulated in relation to neurological diseases, particularly cerebrovascular disease. Depression is common after a stroke and approximately a quarter of patients experience severe depression while another quarter experience minor degrees of depression. At first sight these are not unexpected observations, given the major disabilities which stroke patients experience. But several studies have shown little correlation between post- stroke depression and the degree of physical disability in the weeks immediately after the stroke. However, the association becomes more pronounced with time so that a complex interaction between mood and physical impairment is established.

Major depression is more frequent in patients with left anterior lesions, especially lesions involving the left frontal cortex and left basal ganglia. Non-fluent aphasia also occurs after left frontal lesions but this does not seem sufficient to explain the development of depression because a similar degree of depression occurs with left frontal lesions not complicated by aphasia. Subcortical atrophy, as shown by ventricular enlargement, may be a predisposing for post-stroke depression. Some studies have found no difference in the frequency of depression between patients with left and right hemisphere lesions so this issue needs further investigation.

Patients with cerebrovascular disease can experience mood disturbances which are too brief to justify the diagnosis of organic mood syndrome. These disturbances are referred to as pathological emotionalism, or emotional ability, and their defining features are an increase in tearfulness with sudden episodes of crying which are not under normal social control.

Endocrine Disorders

There is a close relationship between the endocrine systems and emotions. Endocrine diseases as a cause of organic reaction are well known. They can also present with symptoms suggesting an affective disorder. Anxiety symptoms are prominent in hyperthyroidism, pheochromocytoma and hypoglycemia due to an insulinoma. The anxiety may be persistent or episodic and in the case of pheochromocytoma the onset is so abrupt that it resembles an acute panic attack. Depression is a common accompaniment of hypothyroidism, Cushing's syndrome, Addison's disease and hyperparathyoidism. It is occasionally seen hyperthyroidism in the elderly ('apathetic thyrotoxicosis') and in hypoparthyroidism.

Depression in Cancer

There have been intriguing reports of depression as a prodromal manifestation of cancer although not all studies have found an association between the two conditions. Several explanations have been proposed to account for the hypothetical link, the most likely being that the generalized debiliating effects of cancer mimic the symptoms of depression to such an extent that a diagnosis of depression is made before the tumour becomes manifest. This would account for the alleged association between depression and pancreatic carcinoma, a tumour which is notoriously difficult to diagnose in its early stages. Depression may present as a feature of a primary or secondary cerebral tumour especially if located in the frontal region. There is also the possibility of mental changes due to non-metastatic mechanisms.

Several non-metastatic neuropsychiatric syndromes have been described and they are believed to result from the effects on the nervous system of peptide substances secreted by the tumour. Depression is likely when there is a subacute diffuse encephalopathy. Non-metastatic metabolic changes can also be responsible for depressive symptoms: carcinoma of the lung is known to secrete ectopic ACTH or parathormone, giving rise to the clinical features of Cushing's syndrome or hyperparathyroidism.

It is also possible that an antecedent depressive illness can alter the patient's immunological competence thus allowing the development and proliferation of malignant cells.

Collagen Disease

Neuropsychiatric features are being increasingly recognised in this group of conditions which include systemic lupus erythematosus (SLE), rheumatoid arthritis, polyarteritis nodosa and temporal arthritis. Particular attention has been given to SLE. Organic mental disturbances are the commonest psychological changes but depression and 'functional' psychotic syndromes can also occur. Changes in cerebral blood flow in these patients and episodes of cerebral vasculitis altered flow and allowed leakage of autoantibodies into brain tissue.

Drug induced depression

Depression symptoms comprise one group of adverse drug reactions which account for considerable degree of psychiatric morbidity.

Drug-induced psychiatric disorders may be divided as follows :

• Behavioural toxicity: irritability, aggressive outbursts, hostility and hypersexuality,
• Delirium : acute confusional state
• Depressive reactions : varying from mild mood changes to severe psychotic depression
• Paranoid and schizophrenia like psychoses : delusions of persecution with or without auditory hallucination; also thought disorders of the schizophrenic type
• Hallucinatory states: usually visual without other features of delirium
• Dementia and pseudodementia: cognitive changes usually reversible on stopping the drug but some drugs can produce irreversible brain damage
• Neuropsychiatric states: combination of psychological symptoms with involuntary movements, ataxia, dysarthria or convulsions

The list of drugs causing affective symptoms is lengthy. For convenience they can be grouped into the following categories :

• Antihypertensives,
• Corticosteroids,
• Major tranquilizers,
• Levodopa,
• Stimulants (withdrawal).

In most cases the mood change takes the form of mild depression. Some drugs are particularly likely to cause euphoria, occasionally amounting to mania. These are steroids, isoniazid, levodopa and fenfluramine.

Aetiological Considerations

If affective symptoms can be produced by a wide range of physical disorders which have not yet manifested themselves in other ways it must be asked whether the physical process has a casual or precipitating effect. Structural brain damage could have a direct causal effect.

In contrast, where depression or mania occurs as a result of drug, toxic or metabolic effects, the patients are likely to have a genetic or constitutional disposition to depression. In these cases the physical disorder appears to precipitate episodes of mood disturbance which may have arisen spontaneously or in response to other adverse factors.