Schizophrenia and related disorders

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CHAPTER 5 Schizophrenia and related disorders

Schizophrenia is a disorder which affects roughly 1 in 200 people, and which can have a profound effect upon the individual and their families. The term schizophrenia refers to a ‘splitting of the psychic functions’, and not, as is commonly believed, to a ‘split personality’. Key aspects of the disorder are shown in Box 5.1.

Clinical features

The signs and symptoms of the disorder are most usefully divided into:

positive symptoms: delusions (fixed false beliefs held with tenacity and not understandable in terms of the sociocultural context) and hallucinations (false perceptions which can occur in any sensory modality, but with auditory hallucinations being most common)

negative symptoms: restricted or blunted affect (decreased range of facial expression); paucity of thought content; and apathetic social withdrawal

disorganisation symptoms: formal thought disorder (disorganised thoughts, manifested by disjointed speech); disorganised behaviour; and inappropriate affect (e.g. smiling when discussing a sad event), and

cognitive impairment (see below).

There is no specific laboratory or radiological test for schizophrenia, and none of the signs or symptoms outlined above are pathognomonic. However, the ‘first rank’ symptoms elucidated by Schneider (Box 5.2) have some degree of diagnostic specificity, and are useful to ask for in the clinical interview.

BOX 5.2 Schneider’s ‘first rank’ symptoms of schizophrenia

Auditory hallucinatory experiences

These include:

• third person auditory hallucinations: two or more voices discussing the individual in the third person (he, she, it); often derogatory/persecutory

• running commentary: a voice commenting on the person’s actual actions, in the third person, and

• audible thoughts (gedankenlaudwerten): hearing one’s own thoughts out loud.

Delusional perception

There is a normal percept to which an ‘un-understandable’ delusional attribution is given.

Passivity phenomena

This is a series of phenomena where the person experiences their will, actions, affect or bodily (somatic) functions being ‘taken over’ by some alien influence. It is an ‘as if’ phenomenon, such as: ‘It is as though my actions are controlled by a robot; I feel like a puppet on a string.’

Permeability of ego boundaries

This includes:

• thought insertion: not all thoughts in one’s mind are one’s own; thoughts are being ‘put into’ the person’s mind; there may be secondary elaboration (e.g. ‘An intergalactic machine is putting thoughts into my mind’)

• thought withdrawal: this is the reverse of thought insertion; it may be experienced as the mind transiently ‘going blank’, and

• thought broadcast: a feeling that thoughts dissipate out of the person’s mind, and are ‘shared’ by others; it is more than just feeling others can read their mind.

(Castle & Buckley 2008, with permission)

Negative symptoms can sometimes be ‘mimicked’ by depression, positive symptoms or the extrapyramidal side effects of antipsychotic medication. It is always important to treat the underlying cause, as shown in Table 5.1.

TABLE 5.1 Primary and secondary negative symptoms, and treatment

		Management
Primary		Use atypical antipsychotic; consider adjunctive treatments; if persistent, consider clozapine
Secondary	To depression	Antidepressant medication (SSRI or mirtazapine)
	To positive symptoms	Optimise treatment of positive symptoms: pharmacological and psychosocial approaches should be explored
	To D2 receptor blockade	Consider atypical antipsychotic; if persistent extrapyramidal side effects on atypical antipsychotic, consider adjunctive anticholinergic agent

(Castle & Buckley 2008, with permission)

Not all signs and symptoms occur in any one individual at any one time: different patients show different features and these might change over the course of the illness. Table 5.2 shows the cardinal features of schizophrenia according to DSM–IVTR and ICD–10. It will be noted that there is considerable overlap between these two constructs: the main difference is that DSM–IVTR requires a 6-month duration: disorders with the characteristic symptoms but shorter duration are labelled schizophreniform disorder.

TABLE 5.2 DSM–IVTR and ICD–10 diagnoses of schizophrenia

DSM–IVTR (synopsis)	ICD–10 (synopsis)
Symptoms (at least 1 month unless successfully treated): • delusions • hallucinations • disorganised speech • disorganised or catatonic behaviour, and • negative symptoms

Symptoms:

• at least one of: thought echo, insertion, withdrawal, broadcast

• passivity phenomena or delusional perception, and

• third person conversing or running commentary hallucinations

At least two symptoms required, unless:

• delusions are bizarre, and

• hallucinations are third person conversing or running commentary

At least two of:

• persistent hallucinations in any modality, with delusions

• disorganised speech

• catatonia, and

• negative symptoms (must be ‘primary’)

Social/occupational dysfunction:

• work

• interpersonal relations, and

• self-care

Duration: 6 months at least Duration: 1 month at least Exclusions:

• schizoaffective disorder

• bipolar disorder

• general medical condition, and

• substance-induced

Exclusions:

• mood disorder

• organic brain disease, and

• alcohol/drug-related intoxication

(Castle & Buckley 2008, with permission)

Differential diagnosis

‘Organic’ psychoses

Schizophrenia cannot be diagnosed if there are clear organic factors causing the symptoms and signs: this is labelled an organic psychosis. Exclusion of reversible organic causes (e.g. brain tumour) is obviously important in clinical practice, but it can be much more difficult to assess the role of illicit substances, which are commonly used by people with schizophrenia. A label of drug-induced psychosis is only appropriate if there is:

a clear temporal sequence between drug exposure and onset of symptoms

a resolution of symptoms on cessation of the drug, and

a relatively short duration of symptoms (certainly under 1 month).

People with established schizophrenia are vulnerable to relapse if they use drugs such as cannabis: the term drug-precipitated relapse is a more appropriate term in such cases.

Schizoaffective disorder

If there are clear affective and psychotic symptoms which occur at different times over the course of illness, a label of schizoaffective disorder is applied. There is some debate about the validity of this diagnosis and the boundaries are vague.

Delusional disorder

This group of disorders is characterised by well-circumscribed delusions in the absence of prominent hallucinations or negative or disorganisation symptoms. The delusional content is ‘understandable’, such as beliefs about having a disease (also termed monosymptomatic hypochondriacal delusions or delusional disorder, somatic subtype) or having an unfaithful partner (delusional jealousy, or Othello syndrome).

Pervasive developmental disorders

Pervasive developmental disorders (e.g. autism, Asperger’s syndrome (see Ch 16)) are characterised by abnormalities in social interactions, and a restricted and stereotyped range of interests and activities, evident from before 3 years of age.

Axis II disorders

Some of the cluster A DSM–IVTR Axis II (personality) disorders (see Ch 12) could be considered formes fruste of schizophrenia. The most obvious is schizotypal personality disorder, characterised by longstanding eccentricity, social withdrawal and odd beliefs. It is placed on Axis II in DSM–IVTR, but is probably genetically linked to schizophrenia, and sometimes evolves into full-blown schizophrenia.

Subtypes of schizophrenia

Many attempts have been made at subtyping schizophrenia, mostly on the basis of phenomenology and/or longitudinal course. DSM–IVTR and ICD–10 subtypes are shown in Box 5.3. Probably the best validated of these is the paranoid subtype.

BOX 5.3 DSM–IVTR and ICD–10 subtypes of schizophrenia

(Castle & Buckley 2008, with permission)

Subtypes include:

• paranoid: delusions and hallucinations, but no prominent negative or disorganisation symptoms

• disorganised (DSM–IVTR)/hebephrenic (ICD–10): prominent disturbance of affect, volition and thought stream; ICD–10 states adolescent/young adults only

• catatonic: prominent motoric disturbance

• undifferentiated: meet schizophrenia diagnostic criteria, but not one of the foregoing subtypes

• residual: prominent negative symptoms in absence of prominent positive symptoms, and

• simple: slow progression of negative symptoms in the absence of positive symptoms (ICD–10 considers this akin to schizotypal personality disorder).

Cognitive functioning in schizophrenia

Cognitive deficits are common in schizophrenia. They tend to affect mostly frontal lobe tasks such as executive function. These deficits tend to antedate the onset of illness, although they might show some progression. They are associated with impairment in work and social functioning. Current antipsychotic medications do not have powerful beneficial effects on cognition.

Comorbidity

Depression is common in people with schizophrenia. Recognition and treatment are critical, as depression is treatable, and if untreated can lead to an extra burden for the individual, and is associated with suicide (which itself is much more common in people with schizophrenia than the general population). Depression can be difficult to dis-entangle from negative symptoms and demoralisation. Features that suggest a depressive disorder include vegetative symptoms (e.g. anorexia, insomnia); functional shift symptoms (e.g. mood worse in the morning; early morning wakening); guilty feelings; and suicidality. Treatment of depression in schizophrenia follows roughly the same approach as for depression generally (see Chs 6 and 13).

Of the anxiety disorders, panic disorder, generalised anxiety disorder, agoraphobia, social phobia and obsessive-compulsive disorder (OCD) have all been shown to occur in excess in association with schizophrenia. OCD is particularly also associated with the use of atypical antipsychotics, notably clozapine. Anxiety disorder comorbidities can worsen the long-term course of schizophrenia, and need to be screened for and treated on their own merits: psychological and pharmacological treatments proven effective for these disorders not occurring comorbidly are often effective (see Ch 8).

Post-traumatic stress disorder also occurs in excess in people with schizophrenia. This relates in part to increased rates of child sexual abuse and other early disadvantage; the symptoms of psychosis themselves; and the trauma all too often associated with the treatment process (notably restraint and seclusion in acute hospital settings).

Substance abuse is common in schizophrenia (around 40–60%). Alcohol is the most widely used substance, followed by cannabis. The negative impacts of substance use in schizophrenia are shown in Box 5.4.

BOX 5.4 Impact of problematic substance use on outcomes in schizophrenia

(Castle & Buckley 2008, with permission)

Mental health issues

Issues include:

• increased psychotic symptoms

• greater relapse rates

• higher hospitalisation rates

• frequent emergency contacts with mental health services

• reduced adherence to treatment, and

• higher attempted and completed suicide rates.

Violence and crime

There is:

• increased violence

• an elevated crime rate, and

• an increased rate of incarceration.

Physical health

Impacts include:

• poorer overall healthcare and nutrition

• increased specific physical health risks, including HIV and hepatitis C, and

• overall increased mortality.

Finances and vocation

There may be:

• financial problems directly and indirectly related to drug use, and

• instability of work/studies.

Housing and families

There may be:

• unstable accommodation

• homelessness, and

• increased family conflict.

Treatment of substance use disorder (SUD) in schizophrenia is complex, but an integrated approach, with both problems being addressed at the same time, is preferred.

Physical comorbidity associated with schizophrenia is a major area of concern, and contributes substantially to lower life expectancy. Cardiovascular risk factors that are elevated in schizophrenia include obesity, hypertension, smoking, diabetes and hyperlipidaemia. These factors are fed, inter alia, by sedentary lifestyles, poor diet and some antipsychotic medications (notably clozapine and olanzapine). Cancer mortality rates are higher in people with schizophrenia, compared to the general population, notably breast and gastrointestinal malignancies. These cancers are often not screened for adequately nor treated as vigorously as in people without schizophrenia.

CASE EXAMPLES: schizophrenia and related disorders

First onset schizophrenia

A 17-year-old boy was brought for a medical consultation because he had been behaving oddly. Over the previous 8 months he had been spending most of his time alone in his room, his self-care had been poor, and he had been up all night on the internet. He had been sleeping most of the day and had abandoned his studies. Increasingly, he had been isolating himself and did not want to have anything to do with his friends. More recently, he had been talking to himself and had stopped eating prepared food, saying it is poisoned: he would eat only canned food, which he insisted on opening himself.

Chronic schizophrenia with negative symptoms

A 45-year-old man lived in a run-down boarding house. He spent most of his time alone, occasionally attending a local drop-in centre and coming for his depot injection at the mental health clinic. He had no particular hobbies or interests and no friends; he occasionally spoke with his mother on the phone but had no other contact with his family. He presented with restricted affect, gave only short unembellished answers to direct questions, and was generally evasive. His self-care was poor, he was malodorous, had rotting teeth, and wore many layers of clothing even though the weather was warm. On direct questioning, he said he believed that other people in the boarding house had been talking about him behind his back, and he could hear them even through brick walls.

Late onset schizophrenia

A 67-year-old woman came to the attention of psychiatric services because her neighbours complained she was abusive towards them and accused them of breaking into her apartment at night. She presented as suspicious and guarded, but eventually allowed the team into her apartment. She stated that her neighbours were plotting against her, that they broke through the window at night (despite it being closed) and left marks on the floor: she pointed to some innocuous-looking stains on the carpet. She said they had been pumping gas through the air conditioning, and that she could smell it at night.

Pathological jealousy (a form of delusional disorder)

A 50-year-old man was charged with assault after manhandling his wife. His wife reported that over the previous months he had become increasingly obsessed that she was having an affair with another man, although she denied this. She said he would check her mobile phone, her handbag, and even her underwear, whenever she had been out by herself. He was not amenable to reassurance, and became increasingly accusatory and threatening towards her, saying he was going to kill her and her ‘lover’.

Epidemiology

The World Health Organization (WHO) undertook two influential studies that showed rates of schizophrenia to be similar in a number of developed and developing countries; the incidence rates were between 7 and 14 new cases per 100,000 per year. Also of interest was an overall better outcome in developing countries. Prevalence studies (i.e. reporting the number of cases in a given population at a given point in time—point prevalence; or over a set period—period prevalence) have also been remarkably similar, when they have used appropriate methods, including operational criteria for diagnosis. Modern general population studies from the US, the UK and Australia have all reported prevalence rates of around 0.5–1.5%; the lower figure is more consistent with the total international literature. Another way of expressing these figures is that of lifetime morbid risk—that is, the risk at birth of anyone developing the illness, all else being equal. This is usually rounded to 0.5–1.0%.

Rates of schizophrenia do vary at a city or even neighbourhood level, with a well-established association with social deprivation. This is partly due to ‘drift’ of vulnerable people down the social strata, and partly to a ‘toxic’ effect of city upbringing. Also, migrants are at greater risk of schizophrenia: black migrants in predominantly white cultures are particularly at risk (e.g. African-Caribbeans in the UK). Interestingly, this elevated risk also pertains to British-born African-Caribbeans.

Overall, males and females appear roughly equally prone to schizophrenia across the whole life span, but males have an overall earlier onset (late teens) compared to females (early 20s, but with later peaks of onset in the 40s and 60–70s).

Females also tend to have better overall outcomes in terms of symptoms, recurrences and psychosocial parameters. Postulated reasons for these findings include a potential ‘protective’ effect of oestrogens, and/or that the sexes are differentially prone to different types of illness, notably males to an early-onset severe illness consequent upon neurodevelopmental deviance.

Outcome

Schizophrenia has a variable long-term course, with roughly a quarter of cases having a single episode and returning to good psychosocial functioning; around a third having an episodic course with reasonably good intermorbid functioning; and 40% tending to have a poor outcome. Certain factors do tend to be associated with a poor outcome in schizophrenia. Some of these are potentially remediable, while others are not (see Box 5.5). Particular recent interest has been shown in early intervention, but whether this ameliorates the long-term course is still unclear.

BOX 5.5 Factors associated with a poor outcome in schizophrenia

(Castle & Buckley 2008, with permission)

Factors potentially addressed by optimal clinical care

Factors include:

• long duration of untreated psychosis (debated)

• suboptimal treatment of psychotic symptoms

• suboptimal treatment of comorbid symptoms

• poor medication adherence

• medication side effects (e.g. neurolept-induced deficit syndrome)

• substance abuse, and

• high family expressed emotion.

Family environment can impact the course of the illness, notably those families that exhibit high expressed emotion (EE), characterised by hostility, critical comments and/or overinvolvement. Such families can benefit from specific family therapy interventions.

Life events are events that occur during the course of a person’s life and which might impact on risk of relapse. The individual can be taught strategies to deal more effectively with stressful life events, and thus reduce the chances of relapse.

Aetiology

Genetic factors

Genetic causality is well established in schizophrenia, with family studies and adoption studies all confirming an increased risk in biological relatives of people with schizophrenia (rates are roughly 10% in siblings, including dizygotic twins, 50% in monozygotic twins, 15% if one parent is affected, and around 50% if both parents are affected). Inheritance is certainly non-Mendelian, and there is no single schizophrenia gene, but rather multiple genes of small effect. Genes that have attracted attention and have shown some evidence of linkage in some samples include some associated with neurodevelopment (e.g. dysbindin, dysregulin) and with the metabolism of dopamine, notably catechol-O-methyltransferase (COMT).

Environmental factors

The fact that monozygotic twins are only 50% concordant for schizophrenia shows that non-genetic or ‘environmental’ factors must also operate to increase risk. The main putative factors are shown in Box 5.6. It should be stressed that none of these factors independently cause schizophrenia, and that they have only modest effects on risk: presumably they act on individuals who already carry some genetic vulnerability.

Schizophrenia as a brain disease

That some people with schizophrenia show subtle brain structural abnormalities is beyond doubt, with the most common findings of neuroimaging studies shown in Box 5.7. However, there is a great degree of overlap with ‘normals’ and no single neuroimaging finding is pathognomonic. These structural abnormalities seem to be evident even at the onset of illness, though some progression might occur over the course of the disorder.

People with schizophrenia tend to show functional brain abnormalities (e.g. ‘hypofrontality’ associated with negative symptoms, and increased blood flow to Broca’s area during auditory hallucinations). Various eye-tracking abnormalities and neurophysiological deficits (e.g. increased p-300 latency) have been found in both people with schizophrenia and their ‘unaffected’ relatives, suggesting these may be endophenotypic markers for the disorder.

The neurodevelopmental model

The neurodevelopmental model posits that schizophrenia has its roots in aberrant development of the brain, but that positive symptoms only manifest in late teens/early adulthood when the brain develops the capacity to produce such symptoms. This model is consonant with findings that even in early life people who later develop schizophrenia are at greater risk of delayed motor, verbal and social milestones. The model also gains support from findings that people with schizophrenia are more likely than ‘normals’ to have physical abnormalities such as high arched palate, low set ears, widely spaced eyes and unusual fingerprint patterns; these are thought to reflect early neurodevelopmental deviance.

Neurochemistry

There are a number of theories that address various aspects of schizophrenia in terms of perturbations of neurochemical balance. None of these theories is definitive, nor are they exclusive of each other: indeed, the complexity of the illness speaks to a number of different pathogenic mechanisms likely to be responsible for the various sets of signs and symptoms.

Management

With the worldwide move towards deinstitutionalisation, people with schizophrenia are preferentially treated in the community. Inpatient care is usually reserved for episodes of acute care, when the person is at risk to themselves or others and/or is unable to be safely managed in their own environment. Very few patients these days have protracted inpatient stays.

Treatment summary: schizophrenia

Always consider the patient as a person, not a label.

Consider the aspirations and goals of the individual in setting management plans.

Be vigilant about comorbidities such as depression and anxiety, and treat these effectively.

Be alert for suicidality, and make appropriate risk management plans.

Monitor the physical health of the patient as well as their mental health.

Monitor and address problematic substance use.

Engage families and carers as much as feasible.

Use the resources of the multidisciplinary team to effect comprehensive care.

Encourage engagement in social activities and hobbies.

Enhance opportunities for employed work, where appropriate.

To maintain them in the community, people with schizophrenia require a long-term treatment plan that encompasses biological and psychosocial domains. A multidisciplinary team is usually required, with each professional bringing their own expertise, but with a coordinating case manager who can ensure consistency and comprehensiveness of interventions. In those with severe illness and multiple problems, intensive case management, with the capacity to provide a high level of face-to-face contact (up to twice daily if required), can be beneficial and reduce hospitalisations.

Biological treatments

Antipsychotic medication is the mainstay of the treatment of people with schizophrenia. These drugs are described in Chapter 13. One of the major challenges for clinicians is to ensure patients (who often lack insight into their need for treatment) actually take their medication as prescribed. The provision of adequate information regarding the rationale for and potential side effects of the medication is key in this. Some patients benefit from more structured adherence therapy. For those who perennially do not adhere and thus continue to relapse, a long-acting injectable (‘depot’) form of antipsychotic can be considered.

Not all patients respond fully to the first prescribed antipsychotic. Negative symptoms and cognitive symptoms are often particularly underresponsive. Trial of another agent from a different class or, if that also fails, the use of clozapine, is suggested. Sometimes, use of adjunctive agents (e.g. another antipsychotic, or a mood stabiliser) is of benefit at an individual level, though monotherapy should be the preferred goal.