Organic psychiatric disorders lie at the apex of the diagnostic hierarchy (see Figure 3.2). In other words, they should be excluded before a diagnosis of a ‘functional’ psychosis, neurosis or personality disorder is entertained. For example, if a young man were to present for the first time with symptoms typically seen in schizophrenia, such as Schneiderian first-rank symptoms (see Chapter 8), it would be important to exclude the possibility that the symptoms resulted from an organic psychiatric disorder or psychoactive substance abuse, before treating the patient for schizophrenia. It could be that his symptoms were the result, for instance, of temporal lobe epilepsy or amphetamine abuse. Similarly, a middle-aged woman presenting with low mood may in fact be suffering from a brain tumour, hypothyroidism or Addison’s disease, rather than a depressive illness. When such a primary organic cause is found, it should be the primary focus of treatment; in many cases it may be reversible.

To exclude an organic psychiatric disorder (including psychoactive substance abuse), it is necessary to take a detailed history, perform thorough mental state and physical examinations, and carry out appropriate investigations.

Mental state examination

Pointers from the mental state examination that might indicate the presence of an organic psychiatric disorder (including psychoactive substance abuse) include:

• Appearance – e.g. the body build may suggest recent weight loss (as in malignancy and the AIDS-related complex); the facial appearance may suggest an endocrine disorder (such as hypothyroidism or Cushing’s syndrome).

• Behaviour – e.g. bradykinesia, resting tremor, stooped flexed posture and festinant gait in Parkinson’s disease; unsteady gait in normal-pressure hydrocephalus.

• Speech – e.g. aphasias (such as receptive or sensory aphasia resulting from a lesion in Wernicke’s area).

• Mood – e.g. elevated mood in frontal lobe lesions.

• Thoughts – e.g. perseveration (common in both generalized and localized disorders of the brain), concrete thinking.

• Perceptions – visual hallucinations are usually caused by organic psychiatric disorders; hallucinations in other modalities may also occur (e.g. olfactory and auditory hallucinations in temporal lobe epilepsy, formication following cocaine use).

• Orientation – e.g. disorientation in time and place in delirium.

• Attention – e.g. impaired attention in dementia.

• Memory – e.g. loss of memory for recent events in dementia.

• General information and intelligence – e.g. there is impairment in these cognitive functions in dementia.

If an organic disorder is suspected it is important to carry out a detailed cognitive assessment including tests for apraxias, agnosias and language ability (see Chapter 5).

Physical examination

A detailed physical examination should be carried out if an organic psychiatric disorder is suspected. Together with the history and mental state examination, this may give a strong indication of the nature of the underlying pathology before any investigations are performed. For example, the presence of increased pigmentation in the mouth, skin creases and pressure points of a patient complaining of an insidious onset of low mood and lassitude points to Addison’s disease. Similarly, in a young person presenting for the first time with auditory hallucinations, the presence of venepuncture marks points to the possibility that illicit drug abuse may be the underlying cause, although the relationship between drug use and psychiatric illness is not straightforward (see Chapter 7).

Investigations

The routine investigations detailed in Chapter 5 should be carried out: i.e. further information should be obtained from the GP, relatives and the case notes from any previous hospital treatment; routine haematological and biochemical tests, such as thyroid function tests; other blood tests as cited in Chapter 5 (such as syphilitic serology). In addition, other investigations should be carried out as appropriate: for example, cortisol assay in suspected Addison’s disease, electroencephalography (EEG) in suspected epilepsy, magnetic resonance imaging (MRI) or computed tomography (CT) in suspected brain malignancy, and neuropsychological testing in suspected dementia or pseudodementia.

Introduction

• Organic psychiatric disorders cause psychological dysfunction in cognitive functioning, the sensorium, thinking, perception and/or emotion/mood.

• In order to exclude an organic psychiatric disorder, a detailed history, mental state examination, physical examination and appropriate investigations should be carried out.

Delirium

Delirium is characterized by acute generalized psychological dysfunction that usually fluctuates in degree. There is impairment of consciousness, often accompanied by abnormal perceptions (illusions and/or hallucinations) and mood changes (anxiety, lability or depressed mood). This is probably the most common psychiatric disorder encountered by medical students when first ‘on the wards’.

Clinical features

The clinical features of delirium are summarized in Figure 6.2. Prodromal symptoms include:

• perplexion

• agitation

• hypersensitivity to light and sound.

Figure 6.2 • Clinical features of delirium.

Features of delirium itself include the following:

• Impairment of consciousness. The level of consciousness fluctuates, often being worse at night.

• Mood changes. The patient may be anxious, perplexed, agitated or depressed, with a labile affect.

• Abnormal perceptions. Transient illusions and visual, auditory and tactile hallucinations may occur.

• Cognitive impairment. Disorientation in time and place, poor concentration and impaired new learning, registration, retention and recall may all occur. Language disturbance may also occur.

• Temporal course. The disturbance develops over a short period (usually hours to days) and tends to fluctuate.

Aetiology

Delirium can result from poisoning, psychoactive substance-use withdrawal, intracranial causes, endocrinopathies, metabolic disorders, systemic infections and postoperatively. Details of these causes, including psychoactive substance use (see Chapter 7), are summarized in Table 6.2. This is an appropriate place to consider briefly the more important clinical features of some of these endocrinopathies, particularly those that often present with psychiatric symptoms other than delirium.

Table 6.2 Causes of delirium

Drugs and alcohol	Drug toxicity – antimuscarinic (anticholinergic) drugs, anticonvulsants, antihypertensives, anxiolytic-hypnotics, cardiac glycosides, cimetidine, insulin, levodopa, opiates, salicylate compounds, steroids; industrial poisons (e.g. organic solvents and heavy metals); carbon monoxide poisoning
Intracranial causes	Infections – encephalitis, meningitis
	Head injury
	Subarachnoid haemorrhage and space-occupying lesions – e.g. brain tumours, abscesses, subdural haematomas
	Epilepsy and postictal states
	Drug and alcohol withdrawal – withdrawal of anxiolytic-sedative drugs, amphetamine
Metabolic and endocrine disorders	Endocrinopathies – Addison’s disease, Cushing’s syndrome, hyperinsulinism, hypothyroidism, hyperthyroidism, hypopituitarism, hypoparathyroidism, hyperparathyroidism
Systemic infections	Hepatic failure, renal failure, respiratory failure, cardiac failure, pancreatic failure
Postoperative states	Hypoxia
	Hypoglycaemia
	Fluid and electrolyte imbalance
	Errors of metabolism – carcinoid syndrome, porphyria
	Vitamin deficiency – thiamine, nicotinic acid, folate, vitamin B₁₂

Primary hypoadrenalism (addison’s disease)

There is destruction of the adrenal cortex in this relatively uncommon endocrine disorder, leading to reduced production of glucocorticoids, mineralocorticoids and sex steroids. This condition often presents with symptoms similar to those that occur in depression, including weakness, tiredness, weight loss, depressed mood and anorexia. Important clinical features are shown in Figure 6.3(a) and (b).

Figure 6.3 • Clinical features of primary hypoadrenalism (Addison’s disease).

(A) Bold type indicates signs of greater discriminant value.

(Reproduced with permission from Kumar P, Clark M (eds) 1998 Clinical medicine. WB Saunders, Edinburgh.)

(B) (a) Facial pigmentation. (b) Buccal pigmentation. (c) Skin crease pigmentation. (d) Vitiligo, which is particularly striking owing to Addisonian pigmentation of the ‘normal’ skin.

(Reproduced with permission from Douglas G, Nicol F, Robertson C (eds) 2009 Macleod’s clinical examination, 12th edn. Churchill Livingstone, Edinburgh.)

Cushing’s syndrome

This describes the clinical state of increased free circulating glucocorticoid and occurs most commonly following the administration of synthetic steroids. Causes include:

• glucocorticoid administration

• pituitary-dependent (Cushing’s disease)

• ectopic ACTH-producing tumours

• ACTH administration

• adrenal adenomas

• adrenal carcinomas

• alcohol-induced pseudo-Cushing’s syndrome.

Cushing’s syndrome may present with symptoms similar to those seen in depression, mania and schizophrenia (including mood changes, delusions, hallucinations and thought disorder). Important clinical features are shown in Figure 6.4(a) and (b).

Figure 6.4 • Clinical features of Cushing’s syndrome.

(A) Bold type indicates signs of most value in discriminating Cushing’s syndrome from simple obesity and hirsuties.

(Reproduced with permission from Kumar P, Clark M (eds) 1998 Clinical medicine. WB Saunders, Edinburgh.)

(B) (a) Cushingoid facies. (b) After curative pituitary surgery. (c) Typical features: facial rounding, central obesity, proximal muscle wasting and skin striae. (d) Skin thinning: purpura caused by wristwatch pressure.

(Reproduced with permission from Douglas G, Nicol F, Robertson C (eds) 2009 Macleod’s clinical examination, 12th edn. Churchill Livingstone, Edinburgh.)

Hypothyroidism

This is one of the most common endocrine disorders (particularly in women). Causes include:

• congenital causes – agenesis, ectopic thyroid remnants

• atrophic thyroiditis

• Hashimoto’s thyroiditis

• iodine deficiency

• dyshormonogenesis

• antithyroid drugs

• other drugs – lithium, amiodarone, interferon

• postinfective thyroiditis

• postsurgery

• postirradiation

• radioiodine therapy

• tumour infiltration

• peripheral resistance to thyroid hormone

• secondary hypopituitarism.

Hypothyroidism may present with symptoms similar to those seen in depression, mania and schizophrenia (myxoedema madness). Important clinical features are shown in Figure 6.5(a) and (b). Note that these features may not be seen in children and young women. The former often have slowed growth and perform poorly at school; pubertal development may be arrested. This condition should be excluded in any young non-pregnant, non-postpartum woman presenting with:

• hyperprolactinaemia (e.g. manifesting with lactation).

Figure 6.5 • Clinical features of hypothyroidism.

(A) Bold type indicates signs of greater discriminant value.

(Reproduced with permission from Kumar P, Clark M (eds) 1998 Clinical medicine. WB Saunders, Edinburgh.)

(B) (a) Before treatment. Note the marked periorbital myxoedema, which may be particularly evident in older patients, and loss of eyebrow hairs. (b) After levothyroxine replacement.

(Reproduced with permission from Douglas G, Nicol F, Robertson C (eds) 2009 Macleod’s clinical examination, 12th edn. Churchill Livingstone, Edinburgh.)

Note also that the clinical features of hypothyroidism may be difficult to recognize in the elderly as some of them are similar to those that occur with normal ageing.

Hyperthyroidism

This is one of the most common endocrine disorders (particularly in women). Causes include:

• Graves’ disease

• toxic solitary adenoma/nodule (Plummer’s disease)

• toxic multinodular goitre

• de Quervain’s thyroiditis

• postpartum thyroiditis

• thyrotoxicosis factitia

• exogenous iodine

• drugs – amiodarone

• metastatic differentiated thyroid carcinoma

• thyroid stimulating hormone (TSH)-secreting tumours

• human chorionic gonadotropin (HCG)-secreting tumours

• ovarian teratoma.

Hyperthyroidism may present with symptoms similar to those seen in mood disorders, panic disorder, generalized anxiety disorder and, in children, attention-deficit hyperactivity disorder (behavioural problems such as hyperactivity). Important clinical features are shown in Figure 6.6(a) and (b). Note that these features may not be seen in children, in whom hyperthyroidism may instead manifest as excessive growth or behavioural problems.

Figure 6.6 • Clinical features of hyperthyroidism.

(A) Bold type indicates signs of greater discriminant value.

(Reproduced with permission from Kumar P, Clark M (eds) 1998 Clinical medicine. WB Saunders, Edinburgh.)

(B) Clinical features of Graves’ hyperthyroidism. (a) Typical facies. (b) Severe inflammatory thyroid eye disease. (c) Thyroid acropachy. (d) Pretibial myxoedema.

(Reproduced with permission from Douglas G, Nicol F, Robertson C (eds) 2009 Macleod’s clinical examination, 12th edn. Churchill Livingstone, Edinburgh.)

Management and prognosis

Appropriate investigations are carried out in order to determine the underlying cause of the delirium, which is then treated. In such cases, the episode of delirium usually lasts about a week, although it may sometimes last as long as a month. The prognosis is that of the underlying cause.

Good, calming nursing care is essential, preferably in a quiet single room. In general, it should be ensured that the delirious patient has an adequate fluid and electrolyte balance. The nature of the condition should be explained to the patient for reassurance and to reduce the effects of illusions, hallucinations and/or delusions (which may be persecutory in nature). The effects of disorientation can be reduced by, for example, allowing the patient to know the time, placing a television in the room and allowing visitors. A low level of lighting should be used at night, sufficient to reassure the patient of orientation in place, but not enough to interfere with much-needed sleep.

In patients who are very agitated, anxious or frightened, oral or intramuscular haloperidol can be used; if there is hepatic failure then benzodiazepines can be given. Benzodiazepines can also be given for their hypnotic effect at night. The treatment of alcohol withdrawal is described in Chapter 7.

Dementia

Dementia is characterized by generalized psychological dysfunction of higher cortical functions without impairment of consciousness. In fully developed dementia the higher cortical functions affected include memory, thinking, orientation, comprehension, calculation, learning capacity, language and judgement. Dementia is an acquired and usually chronic or progressive disorder, although sometimes it may be reversible. In most sufferers the cause (e.g. Alzheimer’s disease) is currently incurable; management strategies are discussed in Chapter 20.

Clinical features

The impairment of higher cortical functions mentioned above, which together form the cardinal feature of dementia, may be preceded, or more commonly accompanied, by impairment of:

• emotional control – anxiety, lability of mood, depression

• social behaviour – restlessness, inappropriate behaviour, e.g. shoplifting, sexual disinhibition

• motivation – the patient sinks into a set of rigid routines, with a loss of interest in new activities and reduced motivation; under stress the patient is unable to cope and becomes markedly agitated, angry or upset (this is known as a catastrophic reaction).

Case history: postoperative delirium

Following a cardiac bypass operation, a 57-year-old man, while recovering in an intensive care unit, suddenly became very agitated and started shouting at the staff. He complained that the leads and tubes attached to his body were moving like snakes and he believed the nurses and doctors were trying to kill him. He was diagnosed as suffering from postoperative delirium. His fluid and electrolyte balance was normal. He was calmed by the nursing staff, who explained what was happening, and he agreed to take oral haloperidol (this was in order to prevent an accident, such as the intravenous tubing being pulled out and the monitoring equipment being disconnected). The haloperidol was given in syrup form to ensure compliance, as the patient was still somewhat suspicious and might have hidden tablets under his tongue, believing them to be poisonous. A night-time sleeping regime was instituted using benzodiazepines. At night, the lighting in the room was dimmed. By the fourth day the patient had made a full recovery from the episode of delirium, and had little memory of what had taken place.

Higher cortical functions

Higher functions that may become impaired in dementia include:

• Memory. Registration, storage and retrieval of new information are typically affected. Forgetfulness is a typical presenting feature. As the dementia advances, remote memory tends to be better than recent memory, which can result in confabulation. In advanced severe dementia even remote memory is affected, with the patient no longer remembering the names of spouse and children, for example.

• Thinking and judgement. Thinking becomes slower, with a reduced flow of ideas and impaired concentration. Judgement is impaired from early on and leads to poor insight. Paranoid thoughts and ideas of reference are common and may develop into delusions.

• Orientation. Disorientation for time, which may be present in early dementia, occurs in almost all cases of advanced dementia and precedes disorientation for place and person.

• Comprehension and learning capacity. The brain’s ability to process incoming information is impaired.

• Calculation. This cognitive skill is usually impaired from early on in dementia.

• Language. Impairment in language manifests as difficulty in word finding and a reduced functional vocabulary in speech; a much greater use of clichés and set phrases; concretization; increasingly poor sentence construction and perseveration (e.g. echolalia). Careful examination may be needed to elicit nominal aphasia (e.g. by asking the patient to name objects), which may not otherwise be obvious.

In order to elicit the above clinical features it is particularly important to carry out a detailed mental state examination, including a full cognitive assessment (see Chapter 5), and to obtain further information from informants. Table 6.3 compares the features of delirium with those of dementia.

Table 6.3 Comparison of features of delirium and dementia

Delirium	Dementia
Acute onset	Insidious onset
Disorientation, bewilderment, anxiety, poor attention
Clouding of/impaired consciousness, e.g. drowsy	Clear consciousness
Perceptual abnormalities (illusions, hallucinations)	Global impairment of cerebral functions (e.g. recent memory, intellectual impairment and personality deterioration with secondary behaviour abnormalities)
Paranoid ideas/delusions (term delirium sometimes only used if delusions and/or hallucinations present)
Fluctuating course with lucid intervals	Progressive course (static course in head injury and brain damage)
Reversible	Irreversible

Epidemiology

The prevalence of dementia increases with age. In Western countries dementia afflicts at least 5% of the population aged over 65 and 10% of those aged over 80.

Aetiology

The causes of dementia are summarized in Table 6.4. Alzheimer’s disease and vascular (including multi-infarct) dementia together account for approximately three-quarters of all cases of dementia. They are described in more detail in this section, with other specific causes of dementia: Lewy body dementia, frontotemporal dementia, Pick’s disease, Huntington’s disease (chorea), Creutzfeldt–Jakob disease and normal-pressure hydrocephalus. Other disorders that can result in dementia, for example Parkinson’s disease, are described in the next section of this chapter and in Chapter 7.

Table 6.4 Causes of dementia

Degenerative diseases of the CNS	Alzheimer’s disease
	Pick’s disease
	Huntington’s disease (or chorea)
	Creutzfeldt–Jakob disease
	Normal-pressure hydrocephalus
	Parkinson’s disease
	Multiple sclerosis
	Lewy body disease
Intracranial causes	Space-occupying lesions – tumours, chronic subdural haematomas, chronic abscesses, aneurysms
	Infections – encephalitis, meningitis, neurosyphilis, AIDS and AIDS-related complex (ARC), cerebral sarcoidosis
	Trauma – head injury, punch-drunk syndrome
Metabolic and endocrine disorders	Endocrinopathies – Addison’s disease, Cushing’s syndrome, hyperinsulinism, hypothyroidism, hypopituitarism, hypoparathyroidism, hyperparathyroidism
	Hepatic failure, renal failure, respiratory failure
	Hypoxia
	Renal dialysis
	Chronic uraemia
	Chronic electrolyte imbalance – hypocalcaemia, hypercalcaemia, hypokalaemia, hyponatraemia, hypernatraemia
	Porphyria
	Hepatolenticular degeneration (Wilson’s disease)
	Vitamin deficiency – thiamine, nicotinic acid, folate, vitamin B₁₂
	Vitamin intoxication – vitamin A, vitamin D
	Paget’s disease
	Remote effects of carcinoma or lymphomas
Vascular causes	Multi-infarct dementia
	Cerebral artery occlusion
	Cranial arteritis
	Arteriovenous malformation
	Binswanger’s disease
Intoxication	Alcohol
	Heavy metals – lead, arsenic, mercury, thallium
	Carbon monoxide
	Drug and alcohol withdrawal – withdrawal of anxiolytic-sedative drugs, amphetamine

Alzheimer’s disease

Alzheimer’s disease is the most common cause of dementia in people over the age of 65. The same pathological changes take place in both the senile (onset over the age of 65) and the presenile forms (onset under the age of 65). A 39–43 amino acid fragment of β-amyloid precursor protein (APP), Aβ, accumulates in the brain parenchyma to form the typical lesions associated with Alzheimer’s disease.

Pathological features

Macroscopically there is global atrophy of the brain, which is shrunken with widened sulci and ventricular enlargement. The atrophy is usually most marked in the frontal and temporal lobes, as shown in Figure 6.7. The structural neuroimaging appearances seen are shown in Figure 6.8.

Figure 6.7 • Alzheimer’s disease.

• The coronal section shows gross atrophy, affecting in particular the temporal lobes, and associated lateral ventricular enlargement.

(Reproduced with permission from Graham DI, Nicoll JAR, Bone I (eds) 2006; see Further reading.)

Figure 6.8 • Alzheimer’s disease seen on CT scan.

(Reproduced with permission from Suohami RL, Moxhum J (eds) 1994 Textbook of medicine, 2nd edn. Churchill Livingstone, Edinburgh.)

Histologically there is neuronal loss, shrinkage of dendritic branching and a reactive astrocytosis in the cerebral cortex. Other neuropathological features include the abundant presence, particularly in the cerebral cortex, of neurofibrillary tangles; the presence, mainly in the cortex, of silver-staining neuritic plaques (senile plaques) (Figure 6.9); granulovacuolar degeneration, particularly in the middle pyramidal layer of the hippocampus; and eosinophilic rod-shaped filamentous intracytoplasmic neuronal inclusion bodies known as Hirano bodies. Neurofibrillary tangles are silver-staining highly insoluble neuropathological structures of the neuronal perikaryon, made up of thick bundles of neurofibrils. The numbers of neurofibrillary tangles and neuritic plaques correlate with the degree of cognitive impairment.

Figure 6.9 • Alzheimer’s disease.

• There are many silver-staining neuritic plaques in the cerebral cortex which can be seen to be granular and filamentous. Some of the plaques have dense cores.

(Reproduced with permission from Graham DI, Nicoll JAR, Bone I (eds) 2006; see Further reading.)

Electron microscopy reveals that each neuritic plaque contains an amyloid core made of Aβ. Abnormal neurites surround the amyloid. The gene coding for Aβ has been localized to the long arm of chromosome 21.

Biochemically, in the post-mortem brain there is reduced activity of both acetylcholinesterase and choline acetyltransferase. These enzymes are involved in the metabolism and biosynthesis, respectively, of the neurotransmitter acetylcholine. Other neurotransmitters, for example γ-aminobutyric acid (GABA), may also play a role.

Clinical features

Alzheimer’s disease is more common in women and in those with a family history of:

• Alzheimer’s disease

• Down’s syndrome

• lymphoma.

It usually presents with memory loss. Other clinical features may include: apathy or lability of mood; progressive impairment of intellectual function; progressive deterioration of personality; features typical of parietal lobe dysfunction (see below); paranoid features; parkinsonism; the mirror sign, in which individuals may fail to recognize their own reflection; disorders of speech such as logoclonia and echolalia; epilepsy; and aspects of the Klüver–Bucy syndrome, which includes hyperorality, hypersexuality, hyperphagia and placidity.

Patients with Down’s syndrome are very likely to develop the neuropathology and clinical features of Alzheimer’s disease by the time they reach the fourth decade (see Chapter 17). This is probably related to the fact that Down’s syndrome results from trisomy 21.

Lewy body dementia

The generic term ‘dementia with Lewy bodies’ was proposed at the first International Workshop on Lewy Body Dementia in 1995. (It was described in 1923 by Frederick H. Lewy in a large proportion of his patients with paralysis agitans who had coincident plaques and neurofibrillary tangles.) It includes various types of dementia such as:

• diffuse Lewy body disease

• senile dementia of Lewy body type

• Lewy body variant of Alzheimer’s disease.

Lewy body dementia is the second most common neurodegenerative cause of dementia.

Pathological features

The histological appearance of a typical Lewy body is shown in Figure 6.10. A Lewy body is an intracytoplasmic concentrically laminated round to elongated eosinophilic inclusion, which often has a dense central core surrounded by a paler peripheral rim.