Schizophrenia Part II

 

Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, paranoia, and disorganized thinking. Other symptoms include social withdrawal, decreased emotional expression, and apathy. Symptoms typically come on gradually, begin in young adulthood, and in many cases never resolve. There is no objective diagnostic test; the diagnosis is used to describe observed behavior that may stem from numerous different causes. Besides observed behavior, doctors will also take a history that includes the person's reported experiences, and reports of others familiar with the person, when making a diagnosis. To diagnose someone with schizophrenia, doctors are supposed to confirm that symptoms and functional impairment are present for six months (DSM-5) or one month (ICD-11). Many people with schizophrenia have other mental disorders, especially substance use disorders, depressive disorders, anxiety disorders, and obsessive–compulsive disorder.

About 0.3% to 0.7% of people are diagnosed with schizophrenia during their lifetime. In 2017, there were an estimated 1.1 million new cases and in 2019 a total of 20 million cases globally. Males are more often affected and on average have an earlier onset, although some large reviews have not found gender differences in the prevalence of the disorder. The likely causes of schizophrenia include genetic and environmental factors. Genetic factors include a variety of common and rare genetic variants. Possible environmental factors include being raised in a city, cannabis use during adolescence, infections, the ages of a person's mother or father, and poor nutrition during pregnancy.

About half of those diagnosed with schizophrenia will have a significant improvement over the long term with no further relapses, and a small proportion of these will recover completely. The other half will have a lifelong impairment. In some cases people may be repeatedly admitted to hospitals. Social problems such as long-term unemployment, poverty, homelessness, exploitation, and victimization are commonly correlated with schizophrenia. Compared to the general population, people with schizophrenia have a higher suicide rate (about 5% overall) and more physical health problems, leading to an average decrease in life expectancy by 20 years. In 2015, an estimated 17,000 deaths were linked to schizophrenia.

The mainstay of treatment is antipsychotic medication, along with counseling, job training, and social rehabilitation. Up to a third of people do not respond to initial antipsychotics, in which case the atypical antipsychotic clozapine may be used. In a network comparative meta-analysis of 15 antipsychotic drugs, clozapine was significantly more effective than all other drugs, although clozapine's heavily multimodal action may cause more side effects. In situations where doctors judge that there is a risk of harm to self or others, they may impose short involuntary hospitalization. Long-term hospitalization is used on a small number of people with severe schizophrenia. In some countries where supportive services are limited or unavailable, long-term hospital stays are more common.

Signs and symptoms

Schizophrenia is a mental disorder characterized by significant alterations in perception, thoughts, mood, and behavior. Symptoms are described in terms of positive, negative, and cognitive symptoms. The positive symptoms of schizophrenia are the same for any psychosis and are sometimes referred to as psychotic symptoms. These may be present in any of the different psychoses, and are often transient making early diagnosis of schizophrenia problematic. Psychosis noted for the first time in a person who is later diagnosed with schizophrenia is referred to as a first-episode psychosis (FEP).

Positive symptoms

Positive symptoms are those symptoms that are not normally experienced, but are present in people during a psychotic episode in schizophrenia. They include delusions, hallucinations, and disorganized thoughts and speech, typically regarded as manifestations of psychosis. Hallucinations occur at some point in the lifetimes of 80% of those with schizophrenia and most commonly involve the sense of hearing (most often hearing voices) but can sometimes involve any of the other senses of taste, sight, smell, and touch. The frequency of hallucinations involving multiple senses is double the rate of those involving only one sense. They are also typically related to the content of the delusional theme. Delusions are bizarre or persecutory in nature. Distortions of self-experience such as feeling as if one's thoughts or feelings are not really one's own, to believing that thoughts are being inserted into one's mind, sometimes termed passivity phenomena, are also common. Thought disorders can include thought blocking, and disorganized speech. Positive symptoms generally respond well to medication, and become reduced over the course of the illness, perhaps related to the age-related decline in dopamine activity.

Negative symptoms

Negative symptoms are deficits of normal emotional responses, or of other thought processes. The five recognized domains of negative symptoms are: blunted affect – showing flat expressions or little emotion; alogia – a poverty of speech; anhedonia – an inability to feel pleasure; asociality – the lack of desire to form relationships, and avolition – a lack of motivation and apathy. Avolition and anhedonia are seen as motivational deficits resulting from impaired reward processing. Reward is the main driver of motivation and this is mostly mediated by dopamine. It has been suggested that negative symptoms are multidimensional and they have been categorized into two subdomains of apathy or lack of motivation, and diminished expression. Apathy includes avolition, anhedonia, and social withdrawal; diminished expression includes blunt affect, and alogia. Sometimes diminished expression is treated as both verbal and non-verbal.

Apathy accounts for around 50 percent of the most often found negative symptoms and affects functional outcome and subsequent quality of life. Apathy is related to disrupted cognitive processing affecting memory and planning including goal-directed behavior. The two subdomains have suggested a need for separate treatment approaches. A lack of distress – relating to a reduced experience of depression and anxiety is another noted negative symptom. A distinction is often made between those negative symptoms that are inherent to schizophrenia, termed primary; and those that result from positive symptoms, from the side effects of antipsychotics, substance use disorder, and social deprivation – termed secondary negative symptoms. Negative symptoms are less responsive to medication and the most difficult to treat. However, if properly assessed, secondary negative symptoms are amenable to treatment.

Scales for specifically assessing the presence of negative symptoms, and for measuring their severity, and their changes have been introduced since the earlier scales such as the PANNS that deals with all types of symptoms. These scales are the Clinical Assessment Interview for Negative Symptoms (CAINS), and the Brief Negative Symptom Scale (BNSS) also known as second-generation scales. In 2020, ten years after its introduction, a cross-cultural study of the use of BNSS found valid and reliable psychometric evidence for the five-domain structure cross-culturally. The BNSS is designed to assess both the presence and severity and change of negative symptoms of the five recognized domains, and the additional item of reduced normal distress. BNSS can register changes in negative symptoms concerning psychosocial and pharmacological intervention trials. BNSS has also been used to study a proposed non-D2 treatment called SEP-363856. Findings supported the favoring of five domains over the two-dimensional proposition.

Cognitive symptoms

Cognitive deficits are the earliest and most constantly found symptoms in schizophrenia. They are often evident long before the onset of illness in the prodromal stage, and may be present in early adolescence, or childhood. They are a core feature but not considered to be core symptoms, as are positive and negative symptoms. However, their presence and degree of dysfunction is taken as a better indicator of functionality than the presentation of core symptoms. Cognitive deficits become worse at first episode psychosis but then return to baseline, and remain fairly stable over the course of the illness.

The deficits in cognition are seen to drive the negative psychosocial outcome in schizophrenia, and are claimed to equate to a possible reduction in IQ from the norm of 100 to 70–85. Cognitive deficits may be of neurocognition (nonsocial) or of social cognition. Neurocognition is the ability to receive and remember information, and includes verbal fluency, memory, reasoning, problem solving, speed of processing, and auditory and visual perception. Verbal memory and attention are seen to be the most affected. Verbal memory impairment is associated with a decreased level of semantic processing (relating meaning to words). Another memory impairment is that of episodic memory. An impairment in visual perception that is consistently found in schizophrenia is that of visual backward masking. Visual processing impairments include an inability to perceive complex visual illusions. Social cognition is concerned with the mental operations needed to interpret, and understand the self and others in the social world. This is also an associated impairment, and facial emotion perception is often found to be difficult. Facial perception is critical for ordinary social interaction. Cognitive impairments do not usually respond to antipsychotics, and there are a number of interventions that are used to try to improve them; cognitive remediation therapy is of particular help.

Onset

Onset typically occurs between the late teens and early 30s, with the peak incidence occurring in males in the early to mid twenties, and in females in the late twenties. Onset before the age of 17 is known as early-onset, and before the age of 13, as can sometimes occur, is known as childhood schizophrenia or very early-onset. A later stage of onset can occur between the ages of 40 and 60, known as late-onset schizophrenia. A later onset over the age of 60, which may be difficult to differentiate as schizophrenia, is known as very-late-onset schizophrenia-like psychosis. Late onset has shown that a higher rate of females are affected; they have less severe symptoms and need lower doses of antipsychotics. The tendency for earlier onset in males is later seen to be balanced by a post-menopausal increase in the development in females. Estrogen produced pre-menopause has a dampening effect on dopamine receptors but its protection can be overridden by a genetic overload. There has been a dramatic increase in the numbers of older adults with schizophrenia. An estimated 70% of those with schizophrenia have cognitive deficits, and these are most pronounced in early onset and late-onset illness.

Onset may happen suddenly or may occur after the slow and gradual development of a number of signs and symptoms, a period known as the prodromal stage. Up to 75% of those with schizophrenia go through a prodromal stage. The negative and cognitive symptoms in the prodrome stage can precede FEP (first episode psychosis) by many months and up to five years. The period from FEP and treatment is known as the duration of untreated psychosis (DUP) which is seen to be a factor in functional outcome. The prodromal stage is the high-risk stage for the development of psychosis. Since the progression to first episode psychosis is not inevitable, an alternative term is often preferred of at risk mental state. Cognitive dysfunction at an early age impacts a young person's usual cognitive development. Recognition and early intervention at the prodromal stage would minimize the associated disruption to educational and social development and has been the focus of many studies. It is suggested that the use of anti-inflammatory compounds such as D-serine may prevent the transition to schizophrenia. Cognitive symptoms are not secondary to positive symptoms or to the side effects of antipsychotics.

Cognitive impairments in the prodromal stage become worse after first episode psychosis (after which they return to baseline and then remain fairly stable), making early intervention to prevent such transition of prime importance. Early treatment with cognitive behavioral therapies is the gold standard. Neurological soft signs of clumsiness and loss of fine motor movement are often found in schizophrenia, which may resolve with effective treatment of FEP.

Risk factors

Schizophrenia is described as a neurodevelopmental disorder with no precise boundary, or single cause, and is thought to develop from gene–environment interactions with involved vulnerability factors. The interactions of these risk factors are complex, as numerous and diverse insults from conception to adulthood can be involved. A genetic predisposition on its own, without interacting environmental factors, will not give rise to the development of schizophrenia. The genetic component means that prenatal brain development is disturbed, and environmental influence affects the postnatal development of the brain. Evidence suggests that genetically susceptible children are more likely to be vulnerable to the effects of environmental risk factors.

Genetic

Estimates of the heritability of schizophrenia are between 70% and 80%, which implies that 70% to 80% of the individual differences in risk to schizophrenia is associated with genetics. These estimates vary because of the difficulty in separating genetic and environmental influences, and their accuracy has been queried. The greatest risk factor for developing schizophrenia is having a first-degree relative with the disease (risk is 6.5%); more than 40% of identical twins of those with schizophrenia are also affected. If one parent is affected the risk is about 13% and if both are affected the risk is nearly 50%. However, the DSM-5 indicates that most people with schizophrenia have no family history of psychosis. Results of candidate gene studies of schizophrenia have generally failed to find consistent associations, and the genetic loci identified by genome-wide association studies explain only a small fraction of the variation in the disease.

Many genes are known to be involved in schizophrenia, each with small effect and unknown transmission and expression. The summation of these effect sizes into a polygenic risk score can explain at least 7% of the variability in liability for schizophrenia. Around 5% of cases of schizophrenia are understood to be at least partially attributable to rare copy number variations (CNVs); these structural variations are associated with known genomic disorders involving deletions at 22q11.2 (DiGeorge syndrome) and 17q12 (17q12 microdeletion syndrome), duplications at 16p11.2 (most frequently found) and deletions at 15q11.2 (Burnside–Butler syndrome). Some of these CNVs increase the risk of developing schizophrenia by as much as 20-fold, and are frequently comorbid with autism and intellectual disabilities.

The genes CRHR1 and CRHBP are associated with the severity of suicidal behavior. These genes code for stress response proteins needed in the control of the HPA axis, and their interaction can affect this axis. Response to stress can cause lasting changes in the function of the HPA axis possibly disrupting the negative feedback mechanism, homeostasis, and the regulation of emotion leading to altered behaviors.

The question of how schizophrenia could be primarily genetically influenced, given that people with schizophrenia have lower fertility rates, is a paradox. It is expected that genetic variants that increase the risk of schizophrenia would be selected against due to their negative effects on reproductive fitness. A number of potential explanations have been proposed, including that alleles associated with schizophrenia risk confers a fitness advantage in unaffected individuals. While some evidence has not supported this idea, others propose that a large number of alleles each contributing a small amount can persist.

A meta-analysis found that oxidative DNA damage was significantly increased in schizophrenia.

Environmental

Environmental factors, each associated with a slight risk of developing schizophrenia in later life include oxygen deprivation, infection, prenatal maternal stress, and malnutrition in the mother during prenatal development. A risk is also associated with maternal obesity, in increasing oxidative stress, and dysregulating the dopamine and serotonin pathways. Both maternal stress and infection have been demonstrated to alter fetal neurodevelopment through an increase of pro-inflammatory cytokines. There is a slighter risk associated with being born in the winter or spring possibly due to vitamin D deficiency or a prenatal viral infection. Other infections during pregnancy or around the time of birth that have been linked to an increased risk include infections by Toxoplasma gondii and Chlamydia. The increased risk is about five to eight percent. Viral infections of the brain during childhood are also linked to a risk of schizophrenia during adulthood.

Adverse childhood experiences (ACEs), severe forms of which are classed as childhood trauma, range from being bullied or abused, to the death of a parent. Many adverse childhood experiences can cause toxic stress and increase the risk of psychosis. Chronic trauma can promote lasting inflammatory dysregulation throughout the nervous system. It is suggested that early stress may contribute to the development of schizophrenia through these alterations in the immune system. Schizophrenia was the last diagnosis to benefit from the link made between ACEs and adult mental health outcomes.

Living in an urban environment during childhood or as an adult has consistently been found to increase the risk of schizophrenia by a factor of two, even after taking into account drug use, ethnic group, and size of social group. A possible link between the urban environment and pollution has been suggested to be the cause of the elevated risk of schizophrenia.

Other risk factors of importance include social isolation, immigration related to social adversity and racial discrimination, family dysfunction, unemployment, and poor housing conditions. Having a father older than 40 years, or parents younger than 20 years are also associated with schizophrenia. It has been suggested that apart from gene-environment interactions, environment-environment interactions also be taken into account as each environmental risk factor on its own is not enough.

Substance use

About half of those with schizophrenia use recreational drugs, including cannabis, tobacco, and alcohol excessively. Use of stimulants such as amphetamine and cocaine can lead to a temporary stimulant psychosis, which presents very similarly to schizophrenia. Rarely, alcohol use can also result in a similar alcohol-related psychosis. Drugs may also be used as coping mechanisms by people who have schizophrenia, to deal with depression, anxiety, boredom, and loneliness. The use of cannabis and tobacco are not associated with the development of cognitive deficits, and sometimes a reverse relationship is found where their use improves these symptoms. However, substance use disorders are associated with an increased risk of suicide, and a poor response to treatment.

Cannabis use may be a contributory factor in the development of schizophrenia, potentially increasing the risk of the disease in those who are already at risk. The increased risk may require the presence of certain genes within an individual. Its use is associated with doubling the rate. The use of more potent strains of cannabis having a high level of its active ingredient tetrahydrocannabinol (THC), increases the risk further. One of these strains is well known as skunk.

Mechanisms

The schizophrenia diagnosis is not made by using an objective diagnostic test; rather the diagnosis is used to describe observed behavior stemming from numerous different causes. A number of models have been put forward to explain links between altered brain function and schizophrenia. The prevailing model of schizophrenia is that of a neurodevelopmental disorder, and the underlying changes that occur before symptoms become evident are seen as arising from the interaction between genes and the environment. Extensive studies support this model. Maternal infections, malnutrition and complications during pregnancy and childbirth are known risk factors for the development of schizophrenia, which usually emerges between the ages of 18–25, a period that overlaps with certain stages of neurodevelopment. Gene-environment interactions lead to deficits in the neural circuitry that affect sensory and cognitive functions.

The common dopamine and glutamate models proposed are not mutually exclusive; each is seen to have a role in the neurobiology of schizophrenia. The most common model put forward was the dopamine hypothesis of schizophrenia, which attributes psychosis to the mind's faulty interpretation of the misfiring of dopaminergic neurons. This has been directly related to the symptoms of delusions and hallucinations. Abnormal dopamine signaling has been implicated in schizophrenia based on the usefulness of medications that affect the dopamine receptor and the observation that dopamine levels are increased during acute psychosis. A decrease in D1 receptors in the dorsolateral prefrontal cortex may also be responsible for deficits in working memory.

The glutamate hypothesis of schizophrenia links alterations between glutamatergic neurotransmission and the neural oscillations that affect connections between the thalamus and the cortex. Studies have shown that a reduced expression of a glutamate receptor – NMDA receptor, and glutamate blocking drugs such as phencyclidine and ketamine can mimic the symptoms and cognitive problems associated with schizophrenia. Post-mortem studies consistently find that a subset of these neurons fail to express GAD67 (GAD1), in addition to abnormalities in brain morphometry. The subsets of interneurons that are abnormal in schizophrenia are responsible for the synchronizing of neural ensembles needed during working memory tasks. These give the neural oscillations produced as gamma waves that have a frequency of between 30 and 80 hertz. Both working memory tasks and gamma waves are impaired in schizophrenia, which may reflect abnormal interneuron functionality. An important process that may be disrupted in neurodevelopment is astrogenesis – the formation of astrocytes. Astrocytes are crucial in contributing to the formation and maintenance of neural circuits and it is believed that disruption in this role can result in a number of neurodevelopmental disorders including schizophrenia. Evidence suggests that reduced numbers of astrocytes in deeper cortical layers are associated with a diminished expression of EAAT2, a glutamate transporter in astrocytes; supporting the glutamate hypothesis.

Deficits in executive functions, such as planning, inhibition, and working memory, are pervasive in schizophrenia. Although these functions are separable, their dysfunction in schizophrenia may reflect an underlying deficit in the ability to represent goal related information in working memory, and to utilize this to direct cognition and behavior. These impairments have been linked to a number of neuroimaging and neuropathological abnormalities. For example, functional neuroimaging studies report evidence of reduced neural processing efficiency, whereby the dorsolateral prefrontal cortex is activated to a greater degree to achieve a certain level of performance relative to controls on working memory tasks. These abnormalities may be linked to the consistent post-mortem finding of reduced neuropil, evidenced by increased pyramidal cell density and reduced dendritic spine density. These cellular and functional abnormalities may also be reflected in structural neuroimaging studies that find reduced grey matter volume in association with deficits in working memory tasks.

Positive symptoms have been linked to cortical thinning in the superior temporal gyrus. Severity of negative symptoms has been linked to reduced thickness in the left medial orbitofrontal cortex. Anhedonia, traditionally defined as a reduced capacity to experience pleasure, is frequently reported in schizophrenia. However, a large body of evidence suggests that hedonic responses are intact in schizophrenia, and that what is reported to be anhedonia is a reflection of dysfunction in other processes related to reward. Overall, a failure of reward prediction is thought to lead to impairment in the generation of cognition and behavior required to obtain rewards, despite normal hedonic responses.

It has been hypothesized that in some people, development of schizophrenia is related to intestinal tract dysfunction such as seen with non-celiac gluten sensitivity or abnormalities in the gut microbiota. A subgroup of persons with schizophrenia present an immune response to gluten differently from that found in people with celiac, with elevated levels of certain serum biomarkers of gluten sensitivity such as anti-gliadin IgG or anti-gliadin IgA antibodies.

Another theory links abnormal brain lateralization to the development of being left-handed which is significantly more common in those with schizophrenia. This abnormal development of hemispheric asymmetry is noted in schizophrenia. Studies have concluded that the link is a true and verifiable effect that may reflect a genetic link between lateralization and schizophrenia.

Bayesian models of brain functioning have been utilized to link abnormalities in cellular functioning to symptoms. Both hallucinations and delusions have been suggested to reflect improper encoding of prior expectations, thereby causing expectation to excessively influence sensory perception and the formation of beliefs. In approved models of circuits that mediate predictive coding, reduced NMDA receptor activation, could in theory result in the positive symptoms of delusions and hallucinations.

Diagnosis

Criteria

Schizophrenia is diagnosed based on criteria in either the Diagnostic and Statistical Manual of Mental Disorders (DSM) published by the American Psychiatric Association or the International Statistical Classification of Diseases and Related Health Problems (ICD) published by the World Health Organization (WHO). These criteria use the self-reported experiences of the person and reported abnormalities in behavior, followed by a psychiatric assessment. The mental status examination is an important part of the assessment. An established tool for assessing the severity of positive and negative symptoms is the Positive and Negative Syndrome Scale (PANSS). This has been seen to have shortcomings relating to negative symptoms, and other scales – the Clinical Assessment Interview for Negative Symptoms (CAINS), and the Brief Negative Symptoms Scale (BNSS) have been introduced. The DSM-5, published in 2013, gives a Scale to Assess the Severity of Symptom Dimensions outlining eight dimensions of symptoms.

DSM-5 states that to be diagnosed with schizophrenia, two diagnostic criteria have to be met over the period of one month, with a significant impact on social or occupational functioning for at least six months. One of the symptoms needs to be either delusions, hallucinations, or disorganized speech. A second symptom could be one of the negative symptoms, or severely disorganized or catatonic behaviour. A different diagnosis of schizophreniform disorder can be made before the six months needed for the diagnosis of schizophrenia.

In Australia the guideline for diagnosis is for six months or more with symptoms severe enough to affect ordinary functioning. In the UK diagnosis is based on having the symptoms for most of the time for one month, with symptoms that significantly affect the ability to work, study, or to carry on ordinary daily living, and with other similar conditions ruled out.

The ICD criteria are typically used in European countries; the DSM criteria are used predominantly in the United States and Canada, and are prevailing in research studies. In practice, agreement between the two systems is high. The current proposal for the ICD-11 criteria for schizophrenia recommends adding self-disorder as a symptom.

A major unresolved difference between the two diagnostic systems is that of the requirement in DSM of an impaired functional outcome. WHO for ICD argues that not all people with schizophrenia have functional deficits and so these are not specific for the diagnosis.

Changes made

Both manuals have adopted the chapter heading of Schizophrenia spectrum and other psychotic disorders; ICD modifying this as Schizophrenia spectrum and other primary psychotic disorders. The definition of schizophrenia remains essentially the same as that specified by the 2000 text revised DSM-IV (DSM-IV-TR). However, with the publication of DSM-5, the APA removed all sub-classifications of schizophrenia. ICD-11 has also removed subtypes. The removed subtype from both, of catatonic has been relisted in ICD-11 as a psychomotor disturbance that may be present in schizophrenia.

Another major change was to remove the importance previously given to Schneider's first-rank symptoms. DSM-5 still uses the listing of schizophreniform disorder but ICD-11 no longer includes it. DSM-5 also recommends that a better distinction be made between a current condition of schizophrenia and its historical progress, to achieve a clearer overall characterization.

A dimensional assessment has been included in DSM-5 covering eight dimensions of symptoms to be rated (using the Scale to Assess the Severity of Symptom Dimensions) – these include the five diagnostic criteria plus cognitive impairments, mania, and depression. This can add relevant information for the individual in regard to treatment, prognosis, and functional outcome; it also enables the response to treatment to be more accurately described.

Two of the negative symptoms – avolition and diminished emotional expression – have been given more prominence in both manuals.

Comorbidities

Many people with schizophrenia may have one or more other mental disorders, such as panic disorder, obsessive–compulsive disorder, or substance use disorder. These are separate disorders that require treatment. When comorbid with schizophrenia, substance use disorder and antisocial personality disorder both increase the risk for violence. Comorbid substance use disorder also increases risk for suicide.

Sleep disorders often co-occur with schizophrenia, and may be an early sign of relapse. Sleep disorders are linked with positive symptoms such as disorganized thinking and can adversely affect cortical plasticity and cognition. The consolidation of memories is disrupted in sleep disorders. They are associated with severity of illness, a poor prognosis, and poor quality of life. Sleep onset and maintenance insomnia is a common symptom, regardless of whether treatment has been received or not. Genetic variations have been found associated with these conditions involving the circadian rhythm, dopamine and histamine metabolism, and signal transduction. Limited positive evidence has been found for the use of acupuncture as an add-on.

Differential diagnosis

To make a diagnosis of schizophrenia other possible causes of psychosis need to be excluded. Psychotic symptoms lasting less than a month may be diagnosed as brief psychotic disorder, or as schizophreniform disorder. Psychosis is noted in Other specified schizophrenia spectrum and other psychotic disorders as a DSM-5 category. Schizoaffective disorder is diagnosed if symptoms of mood disorder are substantially present alongside psychotic symptoms. Psychosis that results from a general medical condition or substance is termed secondary psychosis.

Psychotic symptoms may be present in several other conditions, including bipolar disorder, borderline personality disorder, substance intoxication, substance-induced psychosis, and a number of drug withdrawal syndromes. Non-bizarre delusions are also present in delusional disorder, and social withdrawal in social anxiety disorder, avoidant personality disorder and schizotypal personality disorder. Schizotypal personality disorder has symptoms that are similar but less severe than those of schizophrenia. Schizophrenia occurs along with obsessive–compulsive disorder (OCD) considerably more often than could be explained by chance, although it can be difficult to distinguish obsessions that occur in OCD from the delusions of schizophrenia. There can be considerable overlap with the symptoms of post-traumatic stress disorder.

A more general medical and neurological examination may be needed to rule out medical illnesses which may rarely produce psychotic schizophrenia-like symptoms, such as metabolic disturbance, systemic infection, syphilis, HIV-associated neurocognitive disorder, epilepsy, limbic encephalitis, and brain lesions. Stroke, multiple sclerosis, hyperthyroidism, hypothyroidism, and dementias such as Alzheimer's disease, Huntington's disease, frontotemporal dementia, and the Lewy body dementias may also be associated with schizophrenia-like psychotic symptoms. It may be necessary to rule out a delirium, which can be distinguished by visual hallucinations, acute onset and fluctuating level of consciousness, and indicates an underlying medical illness. Investigations are not generally repeated for relapse unless there is a specific medical indication or possible adverse effects from antipsychotic medication. In children hallucinations must be separated from typical childhood fantasies. It is difficult to distinguish childhood schizophrenia from autism.

Prevention

Prevention of schizophrenia is difficult as there are no reliable markers for the later development of the disorder. There is tentative though inconclusive evidence for the effectiveness of early intervention to prevent schizophrenia in the prodrome phase. There is some evidence that early intervention in those with first-episode psychosis may improve short-term outcomes, but there is little benefit from these measures after five years. Cognitive behavioral therapy may reduce the risk of psychosis in those at high risk after a year and is recommended in this group, by the National Institute for Health and Care Excellence (NICE). Another preventive measure is to avoid drugs that have been associated with development of the disorder, including cannabis, cocaine, and amphetamines.

Antipsychotics are prescribed following a first-episode psychosis, and following remission a preventive maintenance use is continued to avoid relapse. However, it is recognized that some people do recover following a single episode and that long-term use of antipsychotics will not be needed but there is no way of identifying this group.

Management

The primary treatment of schizophrenia is the use of antipsychotic medications, often in combination with psychosocial interventions and social supports. Community support services including drop-in centers, visits by members of a community mental health team, supported employment, and support groups are common. The time between the onset of psychotic symptoms to being given treatment – the duration of untreated psychosis (DUP) – is associated with a poorer outcome in both the short term and the long term.

Voluntary or involuntary admittance to hospital may be imposed by doctors and courts who deem a person to be having a severe episode. In the UK, large mental hospitals termed asylums began to be closed down in the 1950s with the advent of antipsychotics, and with an awareness of the negative impact of long-term hospital stays on recovery. This process was known as deinstitutionalization, and community and supportive services were developed in order to support this change. Many other countries followed suit with the US starting in the 60s. There still remain a smaller group of people who doctors and courts do not agree to discharge. In some countries that lack the necessary supportive and social services, long-term hospital stays are more usual.