Psychiatry: The Interface of Psychiatry and Physical Illness
Psychiatry and Physical Illness
Comorbidity of psychiatric and physical illness
- Psychiatric morbidity (consisting mainly of dementia, delirium, depression and anxiety) is present in 25–45% of inpatients, irrespective of their primary diagnosis. Figure 27.1 shows the reasons for this high comorbidity.

Some personality traits may worsen outcomes from illnesses; for example, individuals with ‘Type D personalities’ (pessimism, worry, social inhibition) do worse following myocardial infarction.
- Psychological therapies such as cognitive behavioural therapy (CBT) may help people live with illness and its treatment.
- As many as 30% of acute medical patients have some cognitive deficits, reflecting in part the vulnerability of older people to both cognitive and physical disorders.
- Dementia may first become apparent during hospitalisation as patients reveal their inability to learn to cope in a novel environment and without family support. Dementia is associated with increased length of hospital stay, and early detection helps in planning discharge.
- Some symptoms of serious physical illness (such as lethargy, poor sleep and reduced appetite) can be difficult to distinguish from those of depression. It can help to focus on emotional features such as anhedonia, guilt and hopelessness. Antidepressants may be beneficial. Electroconvulsive therapy (ECT) can be lifesaving in severe or psychotic depressive illness in physically ill people, particularly where suicidal risk is high or where physical health is further threatened by poor food and fluid intake.
- Patients with pre-existing psychiatric illness may require urgent medical or surgical management. Such patients will need continued psychiatric management with careful monitoring of their mental state under stressful circumstances.
Liaison psychiatry
- The overlap of psychiatric and physical symptoms requires close cooperation between psychiatric and medical staff. In medical and surgical wards and clinics, this is managed through the liaison psychiatry team.
- Patients presenting with behavioural disturbance frequently have delirium (which must be excluded, or its underlying cause identified and treated as a matter of urgency) or dementia.
- Suicidal threats or acts may cause medical/surgical staff considerable anxiety; they may need advice on assessing and managing suicide risk.
- Multidisciplinary discussion of behavioural problems can identify triggers to undesirable behaviour and help find ways of defusing provocative situations.
Medically unexplained symptoms
Many people experience medical symptoms for which no cause is found. Here are the possible explanations.

- When treating medically unexplained symptoms, be as honest and open as possible with the patient, acknowledge the symptoms and try not to let frustration or anger affect your management.
Communication with the GP and other professionals involved in the patient’s care can prevent the replication of investigations and ensure consistency.
Somatoform disorders
A quarter of GP attendees have somatoform disorders. These include somatisation disorder and hypochondriacal disorder.
Somatisation disorder
- This is characterised in ICD-10 by at least two years of multiple physical symptoms with no physical explanation; patients persistently refuse to accept the advice of doctors that there is no physical explanation, and their social and family functioning is impaired as a result of the illness.
- Gastrointestinal and skin complaints are the most common.
- Somatisation disorder is much more common in women than in men, usually starting before the age of 30.

- It sometimes results in multiple operations despite the absence of organic disorder.
- Figure 27.3 explains how symptoms may arise. Patients are not consciously aware of the origin of their symptoms, no matter how clear and sometimes frustrating this might be to their families and carers.
- Treatment should begin by ruling out all organic illnesses.
Hypochondriacal disorder
- This is a non-delusional preoccupation with the possibility of serious illness such as cancer, heart disease, HIV or AIDS, despite medical reassurance.
- It is more common in men and people who have more contact with disease (e.g. health workers).
- Dysmorphophobia is related to hypochondriacal disorder. It is an excessive preoccupation with imagined or barely noticeable defects in physical appearance. For example, patients may become preoccupied by the size of their nose, believing an objectively normal nose to be ugly and deformed. This may lead to avoidance behaviour.
Many think it is on a spectrum with obsessive–compulsive disorder.
- Cognitive behavioural therapy (CBT) is the mainstay of treatment for somatoform disorders together with a focus on psychosocial and not physical symptoms. SSRIs can be helpful for dysmorphophobia.
Dissociative disorders (also termed ‘conversion disorders’)
- In dissociative disorders, physical (almost always neurological) symptoms occur in the absence of pathology and have a clear relationship with stressful events or disturbed relationships. Diagnoses include:

- The traditional psychoanalytic view suggests that in dissociative (conversion) disorders painful memories or thoughts (or the distress associated with them) are ‘cut off’ from the conscious self (Freud used the term ‘repressed memories’) and ‘converted’ into more acceptable and bearable physical symptoms.
This is called ‘primary gain’. Other psychological views see conversion disorders as resulting from ineffective communication. - Although rare in the general population, dissociative disorders affect between 4% and 30% of neurology outpatients; they are more common in women.
- Management involves ensuring that there really is no organic basis, treating any underlying mood disorder and exploring with the patient and the family any ‘secondary gain’ (such as sympathy or avoidance of family conflict) that might be maintaining symptoms.
- Dissociative disorders differ from somatisation in that they more often present with signs rather than only symptoms and are often acute in their presentation.
- Thinking about the distinction between dissociative and hypochondriacal and somatisation disorders can be confusing; here are some tips about how to tell them apart.


Factitious disorder
- In contrast to somatoform and dissociative disorders, people with factitious disorder deliberately feign or actually induce illness in themselves. Munchausen’s syndrome is another name for it.
- The patient’s reasons for feigning an illness are often complicated and may relate to
- the gaining of nurture from others,
- tangible benefit (e.g. avoiding criminal sanction, work or school).
Managing pain and fatigue
- Pain may trigger psychiatric referral even without clear evidence of somatoform disorder.
- Depression may underlie such pain or result from it, particularly if pain is inadequately treated for fear of causing opiate dependence. Chronic pain may respond to psychological therapy and antidepressants even in the absence of clear-cut depression.
- Chronic fatigue syndrome (also called ME or myalgic encephalomyelitis) is characterised by exhaustion after minimal physical activity, poor concentration and muscle tenderness. Recommended first-line treatment is CBT and/or graded exercise therapy.
DSM 5 categorises the disorders in this chapter somewhat differently, as shown in Table 27.2.
Neuropsychiatry I
- Neuropsychiatry concerns conditions in which mental disorder results from demonstrable structural or neurophysiological disturbance of the brain. Another definition is ‘the disorders which straddle the boundaries between neurology and psychiatry’ (e.g. Tourette’s Syndrome, Parkinson’s Disease, Huntington’s Disease, epilepsy).
- The psychiatric picture seldom bears a specific relationship to the type of underlying pathology, being more influenced by the site of brain involvement and the time course of the illness. It may include:
- personality and behavioural changes
- cognitive impairment and confusional states
- affective disturbances
- psychoses.
- An organic disorder can mimic functional disorders. The features below suggest organic problems.

- A history, mental state examination and full physical and neurological exams are all needed to make the diagnosis.
- Investigations should include a general screen.
- More specialised investigations may help to confirm or exclude specific diagnoses.
- Lumbar puncture should be undertaken with caution if raised intracranial pressure is suspected, in view of the risk of precipitating brainstem coning.
Focal neurological disorders: traumatic brain injuries and strokes
- The neuropsychiatric presentations of cerebrovascular accidents (CVA; strokes) and traumatic brain injuries (TBI) are similar so they are considered together. In both conditions, acute focal brain injuries result in neurological disability followed by a recovery period.
- Acute effects include disturbance of consciousness, amnesia and behavioural disorder. Worse cognitive outcomes are associated with:
- longer duration of post-traumatic amnesia (loss of memories about the injury and subsequent events), this is a more accurate prognostic indicator than retrograde amnesia (loss of memories from before the injury);
- duration of loss of consciousness greater than 24 hours.
- Figure 28.1 describes the psychiatric sequelae of CVAs and TBIs. The aetiology of these involves:
- direct neurophysiological effects (e.g. the cognitive disorders, temporal lobe injuries and psychosis);
- the psychosocial impact of sudden disability (important in anxiety and depression, although these may also relate directly to the injury).
- Lability of mood and apathy may be particularly prominent.

Post-concussional syndrome
- A ‘post-concussional syndrome’ has been described after head injury, characterised by:

- There may be an organic basis for the syndrome, but psychological and social factors are likely to play a major role.
- There is no specific treatment.
Epilepsy
- The prevalence of epilepsy is 0.5–1%, excluding febrile convulsions, single seizures and inactive cases.
- It is slightly more common in men.
- In most cases the cause is unknown.
- Known causes include:
- cerebrovascular disease (15%)
- cerebral tumours (6%)
- alcohol-related seizures (6%)
- post-traumatic seizures (2%).
- Onset is usually before the age of 30 (75%); however, the prevalence is increasing as the population ages because the prevalence of cerebrovascular disease is higher in older people.
- The most common seizure type is complex focal (60%), 60% of which arise in the temporal lobes.
- Epilepsy is present in around 25% of people with intellectual disability.
- Psychiatric aspects of epilepsy may be divided into:
- preictal (before the seizure)
- ictal (during)
- postictal (afterwards)
- interictal (disturbances are chronic and not related to the ictal electric discharge).
- Figure 28.2 shows when depression and psychosis usually occur in relation to seizures.

Depression
- Depression affects 30–50% of people with epilepsy at some time.
- Aetiological factors include:
- demoralisation, stigma;
- possibly lesion location (e.g. higher rates in temporal lobe epilepsy (TLE);
- anti-epileptic drugs (e.g. phenobarbitone and vigabatrin);
- a family history of depression;
- adverse life events, financial stress and unemployment.
- Depression can directly increase seizure frequency through the mechanism of sleep deprivation.
- Treatment includes careful use of antidepressants.
- Selective noradrenaline and serotonin reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) are recommended as least likely to lower the seizure threshold.
- Citalopram is also least likely to interact with anti-epilepsy drugs.
- Electroconvulsive therapy (ECT) may be given if necessary.
- Carbamazepine and lamotrigine are anti-epileptic agents that may also improve mood.
- Suicide is five times higher in people with epilepsy and 25 times higher in people with temporal lobe epilepsy compared with the general population.
Panic disorder
- Panic disorder has a lifetime prevalence of 21%. It can be interictal or peri-ictal; it is important not to mistake seizure activity for panic.
Psychosis
- Psychosis occurs in 3–7% of people with epilepsy.
- It is most commonly postictal.
- Postictal psychosis should be distinguished from delirium.
It occurs up to a week after the seizure and lasts from as little as a day up to three months. Symptoms may include delusions, depressive or manic psychosis, or bizarre thoughts and behaviour. Visual hallucinations are common. - Psychosis is more common with partial epilepsies and temporal lobe damage.
- Treatment is with antipsychotics, preferably those with least effect on seizure threshold (e.g. sulpiride, haloperidol).
Cognitive impairments
- Cognitive impairments are common in people with epilepsy and may be caused by:
- anti-epileptic medication (phenobarbitone, phenytoin),
- persistent abnormal electrical activity in the brain between seizures.
Sexual dysfunction
- Sexual dysfunction is common in people with epilepsy; causes include:
- anti-epileptic medication side effects,
- neurophysiological problems (more common in TLE),
- social problems.

Tumour
- Primary and secondary intracranial tumours can lead to behavioural, affective, psychotic, personality and cognitive disturbances via a number of mechanisms, including mass effects and obstructive hydrocephalus.
- Malignancy outside the cranium can also lead to neuropsychiatric disturbance as a result of tumour by-products or effects on renal, endocrine and other body systems.
Note: In ICD-10 depressive disorders due to another medical condition are coded under the specific physical disorder. DSM-5 has a code for Depressive Disorder Due to Another Medical Condition (293.83), and the name of the other medical condition is noted.
Neuropsychiatry II
Autoimmune and inflammatory disorders
Multiple sclerosis
- Multiple sclerosis (MS) is the most common cause of neurological disability in working-age adults. Episodes of demyelination result in central nervous system abnormalities.
- Aetiology is unknown, with genetic and environmental factors (e.g. virus) probably important.
- The table shows the psychiatric complications of MS.

- The suicide rate is doubled in MS compared with the general population; rates are higher in people with alcohol problems and depression and in those who live alone.
- The prevalences of depression (25–50% in lifetime) and bipolar affective disorder are increased, but non-affective psychosis is no more common. People with psychosis (affective or non-affective) and MS are more likely to have plaques in bilateral temporal horn areas.
- Emotional lability (20%), elation/euphoria (elevated mood without overactivity – in 25%) and pathological laughing or crying (exaggerated emotional responses without associated feelings of distress – in 10%) all occur.
- Cognitive deficits are present in up to half of people with MS.
- They arise early in the illness and usually progress slowly, although risk factors for a more rapid decline include more rapid disease progression and older age.
- Particular impairment is seen in:
– verbal fluency
– comprehension
– naming
– executive functioning
– memory.
- Particular impairment is seen in:
- They are usually associated with emotional lability and decreased information-processing speed.
- They arise early in the illness and usually progress slowly, although risk factors for a more rapid decline include more rapid disease progression and older age.
- Subcortical dementia also occurs, usually late in the illness.
Systemic lupus erythematosus
- Systemic lupus erythematosus (SLE) is an autoimmune disorder that often affects the brain and nervous system (>50%).
- The table shows the psychiatric complications and their likely causes.

- Psychosis due to lupus is uncommon. It usually occurs early in the disease and is associated with multisystem lupus activity.
Disorders of the basal ganglia
- Neural circuits linking the basal ganglia, frontal cortex and thalamus are involved in movement, attention, memory and reward processes. Basal ganglia disorders are characterised by movement, mental state and cognitive abnormalities.
Parkinson’s disease
- Parkinson’s disease (PD) affects over 1% of the population over 50 and results from deficient striatal dopaminergic activity.
- The table below shows the common psychiatric complications:
- The risk of dementia increases with age and duration of PD (78% after eight years). Symptoms are similar to those of dementia with Lewy bodies. Coexistent Alzheimer’s pathology is common.
- Cognitive deficits may be:
- frontal lobe and other isolated focal abnormalities (e.g. memory, visuospatial difficulties) due to neurodegeneration

- iatrogenic (e.g. antimuscarinic compounds and selegiline)
- related to depression.
- Psychosis most commonly presents with visual hallucinations and persecutory delusions and sometimes with pathological jealousy.
It is more common in people with cognitive impairment and on increasing anti-Parkinsonian medication. - Depression is associated with faster decline in cognitive function and activities of daily living and is a risk factor for dementia.
- A wide range of impulsive and compulsive behaviours, such as pathological gambling, hypersexuality, compulsive shopping and binge-eating, hypomania (in 2%) and euphoria (in 10%), are reported. They are almost always triggered by dopaminergic therapy.
- Treatment of depression and psychoses should be with drugs with a relatively low risk of extrapyramidal side
effects (e.g. the antipsychotic quetiapine, the antidepressant citalopram).
Huntington’s disease
- HD manifests at all ages, affects men and women equally, and prevalence is 4–7/100â•›000. It is characterised by cognitive decline, choreiform involuntary movements and personality change. Death usually occurs about 15 years after diagnosis.
- It is inherited as an autosomal dominant gene (100% penetrance) on chromosome 4. Rarely individuals have a negative family history, due to a new mutation or mistaken parentage.
Recent findings suggest that the HD aetiology is more complex than originally thought. For example, the length of the CAG repeat is inversely correlated with age of onset, while both environmental and genetic factors can further modulate this parameter. An exciting recent study demonstrated that increased dosage of the glucose transporter gene SLC2A3 delayed the age at onset in HD, and this correlated with increased levels of the neuronal glucose transporter in HD patient cells. - There is cerebral atrophy and reduced γ-aminobutyric acid (GABA), resulting in dopamine hypersensitivity.
- Cognitive impairments usually progress to subcortical dementia, with mental slowing, impaired executive functioning and a decline in memory; speech deteriorates faster than comprehension.
- Psychiatric disturbances are common in HD. Depression can also precede other symptoms.
- There is an increased risk of suicide in patients with HD and in those at risk (as high as 10%); this must be considered when planning predictive testing.
- Treatment is symptomatic, and depression and psychoses should be treated with standard medications. Atypical antipsychotics are preferred because they are less likely to exacerbate motor symptoms.
Hepatolenticular degeneration (Wilson’s disease)
- This is a rare autosomal recessive disorder (chromosome 13).
- Excess copper deposition occurs in the lenticular nuclei.
Timely treatment with penicillamine will usually reverse the neurologic symptoms and may ameliorate the psychiatric symptoms. - Depression (20%), emotional lability, personality and behavioural changes (irritability, antisocial behaviour, disinhibition), poor school performance and alcohol abuse have been reported.

Sleep disorders
- Narcolepsy has a prevalence of 0.025%. The symptoms are:
- excessive daytime sleepiness;
- cataplexy (falling down suddenly after losing body tone, often in response to strong emotions);
- sleep paralysis (paralysis on waking or going to sleep);
- hypnogogic hallucinations.
- Stimulants such as methylphenidate and modafinil are used in treatment.
- REM sleep behaviour disorder: individuals act out their dreams, with associated risk of harm to themselves and others. Disturbances occur during REM sleep. The normal atonia of REM sleep is lost. It can be idiopathic or associated with PD, Lewy body dementia or Guillain-Barré syndrome. Treatment involves clonazepam and making the sleep environment safe.
Tic disorders
- Tics are very common, affecting 4–28% of young people. Possible diagnoses include:
- transient tic disorder (tics lasting 1 year), (note: not included in DSM-5)
- chronic vocal or chronic motor tic disorder (>1 year)
- Tourette’s syndrome (TS, multiple motor tics and one or more vocal/phonic tics for >1 year). In ICD 10 this is Gilles de la Tourette syndrome; in DSM-5 is Tourette’s disorder.
- TS occurs in 1% of children aged 5–18 years. Males are more often affected (3–4:1).
- Recently it has been emphasised that there are many both neurological and psychiatric phenotypes: the only replicated phenotype is ‘Pure TS’ (tics only).
- The family history is frequently positive for tics, TS, obsessive–compulsive behaviour (OCB) and obsessive–compulsive disorder (OCD). No gene has been identified yet, but areas of interest have been demonstrated in some genetic studies (eg GWAS (Genome Wide Association Study).
- Both TS and tics are more common in people with learning disability and autistic spectrum disorders (ASD).
- Aetiology may include genetic vulnerability, pre- and perinatal problems (smoking, alcohol, cannabis, psychosocial stressors during pregnancy (may affect the severity/phenotype)): a suggestion of possibly infections (e.g. group A ß-haemolytic streptococcus), which gave rise to more plausible neuro-immunological hypotheses, and androgens. Little is known about aetiology and phenotype.
- TS usually begins with facial tics such as excessive blinking; the median age at onset is 7 years. Vocal/phonic tics usually begin later. Tics can be simple (eye blinking, nose twitching, throat clearing, coughing) or complex (e.g. raspberries or twirling). Tics usually improve in severity by age 18 but are normally lifelong (however, with reduced severity, distress, need for medication in adulthood). Associated symptoms include coprolalia (in 10% – involuntary swearing as a tic), copropraxia (involuntary rude sign as gesture), echolalia and echopraxia (copying what others say and do) and palilalia (repeating oneself), self-injurious behaviours and NOSI (non-obscene socially inappropriate behaviours, e.g. shouting ‘Bomb’ in an aeroplane/airport). TS is often comorbid with attention-deficit hyperactivity disorder (ADHD/Hyperkinetic Disorder), OCB/OCD and maybe ASD.
There are many coexistent psychopathologies (e.g. depression, anxiety, phobias, personality disorder etc). - Treatment is with:
- psychoeducation for the patient and the family;
- behavioural therapy, e.g. habit reversal training, CBIT (Comprehensive Behavioural Intervention for Tics);
- medication: antipsychotics (for tics), clonidine with or without stimulants (e.g. atomoxetine) (for ADHD).
Note: We kept tic disorders in this section: in DSM-5 they are grouped under Neurodevelopmental Disorders (307.23) and further subdivided into Motor Disorders.
Neuropsychiatry III

Infectious causes of neuropsychiatric symptoms
HIV and AIDS
- In the developed world, the prevalence of HIV is rising, in part because antiretroviral therapy prolongs life. In the UK there are around 7000 new diagnoses of HIV a year. In Western Europe, more than half of new diagnoses have been acquired through heterosexual contact, three-quarters in migrants or immigrants.
Intravenous drug abusers remain a high-risk group, despite harm-reduction strategies. - Regardless of treatment advances, HIV is still a stigmatising diagnosis in many sections of society.
The worried well
- People (not all of whom are at risk of HIV) may become preoccupied with the possibility of becoming infected. Repeated requests for HIV serological testing may reflect:
- depression or anxiety;
- hypochondriacal disorder;
- (more rarely) psychotic depression or schizophrenia, which may present with the delusion that the person is HIV-positive.
Psychological reactions to HIV infection
- Patients with HIV may undergo periods of crisis on first learning that they are infected, starting retroviral treatment, if tests indicate a problem with treatment (CD4 count falling or drug resistance) or when they first develop an HIV-related illness.
They may react to these crises with:- acute stress reactions or adjustment disorders;
- depression or anxiety;
- deliberate self-harm – suicide is increased more than 20-fold in HIV-positive individuals.
Mental illness and HIV
- Drug and alcohol misuse are associated with both HIV and mental illness.
- HIV increases the likelihood of mental illness, and impulsive behaviour associated with some mental illnesses may increase the likelihood of infection (see Figure 30.1). There is therefore a sizeable population living with both HIV and psychiatric illness.
- Once infected, people with mental illness may be less likely to adhere to the complicated regimens of retroviral treatment.
- The patient’s right to confidentiality may in rare cases need to be balanced against the need to protect others if health professionals become aware that the patient is putting others at risk (e.g. through unprotected sex).
- Depression is common at all stages of HIV and AIDS.
- The diagnosis of depressive illness may be difficult. Apathy and fatigue may be due to retroviral therapy. Fatigue and weight loss may also be caused by declining CD4 counts and rising viral loads, so advancing HIV infection must be considered in the differential diagnosis.
- AIDS-related dementia (now rare) may also present as a depression-like illness.
- Anhedonia, hopelessness and suicidal thinking are likely to reflect true depressive illness.
- Depression often reduces medication adherence and has been associated with an increase in CD4 count decline, so screening for it is an important part of HIV care.
- Depression may worsen the disabling effects of AIDS.
- HIV-positive patients may also present with acute mania or schizophrenia-like psychoses.
- These may have been present before HIV diagnosis.
- New onset cases are often associated with MRI/CT brain abnormalities, suggesting organic pathology.
- Caution is required when prescribing for HIV because of drug interactions and high sensitivity to side effects, especially extrapyramidal side effects.
- AIDS dementia complex occurs with a very low CD4 count (<200) and raised viral load. It is thought to be a direct manifestation of HIV infection within the brain, known as HIV-I associated dementia. This has become rare in the developed world since the introduction of highly active antiretroviral therapy (HAART). Opportunistic infections such as parvovirus, Toxoplasma gondii, cryptococcal meningitis, neurosyphilis, tuberculous meningitis, cytomegalovirus encephalitis, increased vascular risk factors and tumours (e.g. lymphomas) can also contribute to a dementia syndrome.
Viral encephalitis
- The most common cause of viral encephalitis in the West is herpes simplex.
- Presentation is usually with severe headache, vomiting and reduced consciousness, but occasionally with psychosis, seizures or delirium.
- At least 50% of survivors experience disturbed behaviour, concentration or social adjustment, some with chronic cognitive impairment.
Syphilis
- One type of tertiary syphilis (symptoms that occur some years after infection, often a decade) is general paralysis of the insane.
Symptoms include:- personality changes (disinhibition, irritability, lability);
- cognitive changes (poor concentration);
- dementia (20–40%);
- depression (25%);
- grandiosity (10%) and, more rarely, mania and schizophrenia-like psychoses.
- The main blood test for syphilis is VDRL. Intramuscular penicillin remains the first-line treatment.
Prion disease
- Human forms of spongiform encephalopathy (prion disorders, e.g. Creutzfeld–Jacob disease (CJD)) are rare (1/million per year) and are characterised by accumulation of an abnormal form of a normal host protease-resistant protein (PrP) in the brain.
- They present with a rapidly fatal dementia associated with myoclonic jerks.
- About 85% of cases are sporadic; the remaining cases of classical CJD are either familial (15%; sometimes autosomal dominant) or very rarely iatrogenic. A new form of CJD (variant CJD) was reported in younger adults (average age 27) in the UK in 1996 and appeared to relate to consumption of beef infected by bovine spongiform encephalopathy (BSE).
- Whereas classic CJD usually presents with physical symptoms, variant CJD most frequently starts with psychiatric symptoms (mood swings, fatigue, social withdrawal).
Metabolic disturbance
- Acute intermittent porphyria is the commonest type of porphyria (but still rare). Acute attacks occur spontaneously or may be precipitated by drugs (e.g. oral contraceptives, hypoglycaemics, alcohol), infections, pregnancy or low carbohydrate intake). Clinical presentation may be abdominal (colicky pain, vomiting, constipation) or neurological (peripheral neuropathy, bulbar palsies, epilepsy). Psychiatric disturbances include delirium (50%), depression, emotional lability and schizophrenia-like psychoses.
Endocrine
Table 30.1 lists some endocrine disorders and the psychiatric disorders they are associated with.

Nutritional disorders
- Vitamin B12 deficiency results in pernicious anaemia. This may be accompanied by subacute combined degeneration of the spinal cord, which is associated with signs of neuropathy and spinal cord involvement. Psychiatric symptoms include slowing of mental processes, confusion, memory problems, intellectual impairment, depression and paranoid delusions.
- Thiamine (B1) deficiency can result in Wernicke’s encephalopathy and Korsakoff’s psychosis. In the developed world, this is most commonly associated with alcohol dependence.
Acute Confusional States
- The acute confusional state (also known as delirium) is characterised by the rapid onset of a global but fluctuating dysfunction of the central nervous system (CNS) due to an underlying infectious, toxic, vascular, epileptic or metabolic cause.
- It may occur in as many as one-third of older patients admitted to hospital either at initial presentation or during hospitalisation.
- It represents one of the most important conditions encountered in liaison psychiatry and is seen by a wide range of specialities, including general and emergency medicine, general and orthopaedic surgery, and medicine for older people.
- It is associated with increased mortality and longer duration of hospitalisation.
Clinical features
The DSM5 /ICD-10 diagnosis of delirium requires:

- Based on the clinical presentation, delirium can be divided into two subtypes:
- hypoactive – characterised by withdrawn, quiet, sleepy behaviour, is less likely to be recognised;
- hyperactive – characterised by restless, agitated and aggressive behaviour.
- Mood and affect may fluctuate rapidly (lability) and be accompanied by irritability or perplexity; apathy and depression are also found.
- Poorly systematised, transient delusions are common. These may be secondary to abnormal perceptions and are often persecutory, with associated ideas of reference.
- Sweating, tachycardia and dilated pupils reflect underlying autonomic overactivity.
- There may be disturbance of the sleep/wake cycle (e.g. patients may be more alert during the evening and drowsy during the day).
Aetiology
- High-risk groups (who should be screened for delirium when admitted to hospital or care homes) include:
- people aged 65 and over,
- people with diffuse brain disease (dementia or Parkinson’s disease),
- people with a current hip fracture,
- the severely ill.
- Breakdown of the blood–brain barrier, dopaminergic excess and hypercortisolaemia have all been implicated.
- Figure 31.2 shows possible precipitants of acute confusional states.

Differential diagnosis
- Delirium can be difficult to distinguish from dementia since people with established dementia are particularly
vulnerable to delirium. - The distinction from dementia with Lewy bodies, in which cognition typically fluctuates, may be particularly difficult.
- Other conditions that may resemble delirium are:
- functional psychiatric conditions (mania, depression and late-onset schizophrenia);
- responses to major stress, particularly severe pain;
- dissociative disorders.
Here are some tips on telling delirium and dementia apart.

- The diagnosis depends on:
- the presence of the cardinal features of delirium (particularly fluctuation in both conscious level and cognitive impairment);
- the presence of a specific underlying cause;
- the lack of consistent features of affective or psychotic disorders.
Investigations
- It is imperative to obtain an informant history, focusing particularly on premorbid level of functioning, onset and course of the confusion, and use/abuse of drugs or alcohol.
- In the mental state assessment, particular attention should be paid to cognitive function (alertness, memory, language, visuospatial ability) and to fluctuation in behaviour.
- Physical examination is crucial in identifying focal neurological signs and evidence of infection or trauma.
- Appropriate blood investigations for confusion include:
- full blood count (FBC) (to exclude anaemia, macrocytosis, leucocytosis);
- erythrocyte sedimentation rate (ESR) (infection);
- urea and electrolytes (U&E) (dehydration, electrolyte imbalance);
- glucose;
- thyroid function tests (TFT);
- liver function tests (LFT);
- calcium;
- folate and B12;
- VDRL (i.e. syphilis serology).
- Midstream urine (MSU) is mandatory.
- Chest x-ray (CXR) may be informative.
- Structural brain imaging (computed tomography (CT) or magnetic resonance imaging (MRI)) can identify many intracranial causes.
- Consider electroencephalography (EEG) if epilepsy is a differential.

Prevention
Figure 31.3 shows measures that may help prevent delirium.
Management
- Specific management should be targeted at detection of the confusional state itself and at identification and subsequent treatment of underlying pathology. Patients should therefore usually be managed on general hospital (i.e. not psychiatric) wards.
- The preventative measures above are also good practice when treating delirium.
- If a person with delirium is distressed or considered a risk to him/herself or others and non-pharmacological measures are insufficient, medication may be needed.
- Consider short-term (<1 week) antipsychotic (e.g. haloperidol, risperidone (not recommended in dementia)) or short-acting benzodiazepines (e.g. lorazepam).
- Medication is preferable to physical restraint, but should be used sparingly.
- Hypotensive and anticholinergic side effects may precipitate falls or exacerbate the confusion.
- Longer acting benzodiazepines (e.g. diazepam or chlordiazepoxide) are used when the patient is withdrawing from alcohol or drug abuse.
Prognosis
- Delirium increases:
- risk of dementia
- mortality
- length of stay of people already in hospital
- risk of new admission to long-term care.
The Dementias
Definition and clinical presentation
- Dementia is a clinical syndrome rather than a diagnosis.
- It is acquired, progressive, usually irreversible global deterioration of higher cortical function in clear consciousness.
- Here are the diagnostic criteria and common symptoms:

- Presentation may occur months or years after the onset of symptoms and is often at family instigation because the person frequently has no insight into his or her deterioration. The clinical presentation may vary between different types of dementia.
Epidemiology
- Dementia is rare (<1%) before the age of 65 and becomes more common with increasing age. By the age of 90, the prevalence is 25%:

- As the ‘old’ population in the developing world and the ‘very old’ population in the developed world increase, the number of people with dementia is projected to rise steeply.
- Low educational attainment, obesity, untreated systolic hypertension, depression and mental, social and physical inactivity increase the risk of late-life dementia.
Classification
- Here are the approximate prevalences of the most common types of dementia:

- Dementias are sometimes classified as cortical or subcortical, although in reality pathology usually involves both cortical and subcortical tissue and the clinical features of both types overlap.


Alzheimer’s disease
- The onset of Alzheimer’s disease (AD) is gradual, usually with memory loss.
- Macroscopically, the brain is shrunken, with increased sulcal widening and enlarged ventricles.
- Microscopically, the key changes are neuronal loss and the presence (particularly in the cortex and the hippocampus) of neurofibrillary tangles and amyloid plaques. A protein called Aβ is the main constituent of amyloid plaques. It is cleaved from the amyloid precursor protein (APP) by a secretase enzyme. There is an association between dementia severity and the number of plaques in the brain. The amyloid cascade hypothesis states that AD is caused by an imbalance of (too much) brain Aβ production and (too little) Aβ clearance (see Figure 32.4).
- Mutations that increase the risk of AD have been identified in three genes: the APP gene and two genes coding for constituents of the secretase enzyme (presenilin 1 and presenilin 2). These account for most cases of familial (early-onset) AD, in which inheritance is autosomal dominant.
- Inheritance of late-onset AD is multifactorial and polygenic, the Apolipoprotein E (ApoE) gene contributing most to the genetic aetiological component. Three common alleles of ApoE exist (E2, E3, E4); the E4 allele (particularly if homozygous) indicates increased risk and likelihood of earlier onset.
- Neurochemically, there are deficits in several neurotransmitters, particularly acetylcholine, noradrenaline, serotonin and somatostatin, with corresponding loss of the cell bodies of neurones secreting these transmitters.
Vascular dementia
- This is associated with more patchy cognitive impairment than AD; focal neurological symptoms or signs appear in a ‘stepwise’ rather than a continuous deterioration.
- Many people with dementia have a mixed picture of AD and vascular pathology, and patterns of progression differ less than previously thought between these dementias.
- Pathologically, there is at least one area of cortical infarction.
There is a nine-fold increase in risk of dementia in the year after a stroke. Vascular risk factors such as hypertension, hypercholesterolaemia, diabetes and smoking are risk factors for both vascular dementia and AD.
Dementia with Lewy bodies
- Dementia with Lewy bodies (DLB) is characterised by fluctuating cognition and alertness, vivid visual hallucinations, spontaneous Parkinsonism, sensitivity to neuroleptic medication and a sleep disorder. It is associated with the presence of Lewy bodies and neurites in the basal ganglia and cerebral cortex. Pathological changes characteristic of AD are also often found.
- A quarter of people with Parkinson’s disease develop dementia, and 80% of patients with Parkinson’s disease still alive after 20 years of follow-up develop dementia. Where Parkinson’s disease predates the dementia by more than a year, the term ‘Parkinson’s disease dementia’ (2–4% of all dementias) is used.
Frontotemporal dementia
- Frontotemporal dementia (FTD) has a younger mean age of onset and accounts for up to 20% of early-onset dementias but <10% of older onset. It is characterised by early personality changes and relative intellectual sparing. It mainly affects the frontal and anterior temporal lobes; pathology is heterogeneous with most cases having ubiquitin or tau positive inclusions.
Alcohol-related dementia
This accounts for up to 10% of cases.
Normal pressure hydrocephalus
- This may be idiopathic or the result of subarachnoid haemorrhage, head injury or meningitis. It presents with marked mental slowness, apathy, wide-based gait and urinary incontinence. Ventriculoatrial shunting leads to frequent complications and tends to benefit only patients with prominent neurological signs and relatively mild dementia.
Dementia may occasionally be associated with repeated head trauma (e.g. boxers), subdural haematoma, Huntington’s chorea, motor neurone disease (always FTD) or infection (e.g. HIV, syphilis, prion disease). Dementias due to metabolic abnormalities (e.g. hyperparathyroidism, hypothyroidism) occur rarely.
Management
- Patients should have a full assessment to exclude treatable causes and identify specific problems.
The possibility of superimposed and treatable acute confusional states (commonly iatrogenic or secondary to infection) should be considered if a patient suddenly deteriorates. - Depression sometimes precedes or complicates established dementia and has a poor response to antidepressants. Controlling vascular risk factors in patients with vascular dementia and prescribing low-dose aspirin reduce the risk of further stroke-related deterioration.
- Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) can arrest or temporarily reverse cognitive and functional decline in people with mild to moderate AD and DLB, and may also improve behaviour.
- Memantine, which modulates glutamate neurotransmission, is used in moderate to severe AD.
- No currently available drugs can treat the underlying dementia, although these are targets of current research.
- Treatment of neuropsychiatric symptoms is important both for the patient’s direct benefit and because they predict caregiver distress and breakdown of care.
- Careful risk assessment and management is critical.
- Social support may include home care, day centres and intermittent respite organised by Social Services. Patients with severe dementia may require residential, nursing or continuing care (in hospital or other appropriate facility).
- Psychological techniques such as cognitive stimulation (group activities to actively stimulate and engage people with dementia) or teaching behavioural management techniques to carers may improve cognition and behaviour.
Prognosis
- The gradient of cognitive decline is variable and depends on the type of dementia and age. People with dementia die earlier than others of the same age, even taking into account physical health. Premature death may occur before the dementia becomes severe.
- Those who progress to severe dementia usually need full nursing care; death is often from bronchopneumonia. Skilled nursing care has greatly increased life expectancy.
- Patients with vascular dementia have a slightly worse prognosis than those with AD; progression is less consistent with vulnerability to sudden cardiovascular or stroke-related death.
Cognitive impairment in people without dementia
- The term ‘mild cognitive impairment’ (MCI) is used to describe deterioration in cognition that is insufficient to meet criteria for dementia. Around 15% of people with MCI develop dementia within a year and about 50% within three years.
- In subjective cognitive impairment (SCI), people report cognitive problems (e.g. difficulties remembering names and where they put things) but perform within the normal range on psychometric tests for their age and education.
- A third of the general population report being forgetful and most will not progress to dementia, although there is growing evidence that MCI is preceded by around 15 years of SCI.
- Severe depression in old age may present with a ‘pseudodementia’ with prominent forgetfulness and poor self-care. Such patients usually have a short history and are often aware of, and distressed by, their poor function.
- Slowly progressive acute confusional states (e.g. subdural haematoma, myxoedema and vitamin deficiencies) may present with a dementia-like picture.