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For other uses, see Schizophrenia (disambiguation). Schizophrenia_sentence_0


PronunciationSchizophrenia_header_cell_0_1_0 Schizophrenia_cell_0_1_1
SpecialtySchizophrenia_header_cell_0_2_0 PsychiatrySchizophrenia_cell_0_2_1
SymptomsSchizophrenia_header_cell_0_3_0 Hallucinations (usually hearing voices), delusions, confused thinkingSchizophrenia_cell_0_3_1
ComplicationsSchizophrenia_header_cell_0_4_0 Suicide, heart disease, lifestyle diseasesSchizophrenia_cell_0_4_1
Usual onsetSchizophrenia_header_cell_0_5_0 Ages 16 to 30Schizophrenia_cell_0_5_1
DurationSchizophrenia_header_cell_0_6_0 ChronicSchizophrenia_cell_0_6_1
CausesSchizophrenia_header_cell_0_7_0 Environmental and genetic factorsSchizophrenia_cell_0_7_1
Risk factorsSchizophrenia_header_cell_0_8_0 Family history, cannabis use in adolescence, problems during pregnancy, childhood adversity, birth in late winter or early spring, older father, being born or raised in a citySchizophrenia_cell_0_8_1
Diagnostic methodSchizophrenia_header_cell_0_9_0 Based on observed behavior, reported experiences, and reports of others familiar with the personSchizophrenia_cell_0_9_1
Differential diagnosisSchizophrenia_header_cell_0_10_0 Substance abuse, Huntington's disease, mood disorders (bipolar disorder), autism, borderline personality disorderSchizophrenia_cell_0_10_1
ManagementSchizophrenia_header_cell_0_11_0 Counseling, job trainingSchizophrenia_cell_0_11_1
MedicationSchizophrenia_header_cell_0_12_0 AntipsychoticsSchizophrenia_cell_0_12_1
PrognosisSchizophrenia_header_cell_0_13_0 20 years shorter life expectancySchizophrenia_cell_0_13_1
FrequencySchizophrenia_header_cell_0_14_0 ~0.5%Schizophrenia_cell_0_14_1
DeathsSchizophrenia_header_cell_0_15_0 ~17,000 (2015)Schizophrenia_cell_0_15_1

Schizophrenia is a psychiatric disorder characterized by continuous or relapsing episodes of psychosis. Schizophrenia_sentence_1

Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Schizophrenia_sentence_2

Other symptoms include social withdrawal, decreased emotional expression, and apathy. Schizophrenia_sentence_3

Symptoms typically come on gradually, begin in young adulthood, and in many cases never resolve. Schizophrenia_sentence_4

There is no objective diagnostic test; diagnosis is based on observed behavior, a history that includes the person's reported experiences, and reports of others familiar with the person. Schizophrenia_sentence_5

To be diagnosed with schizophrenia, symptoms and functional impairment need to be present for six months (DSM-5) or one month (ICD-11). Schizophrenia_sentence_6

Many people with schizophrenia have other mental disorders that often includes an anxiety disorder such as panic disorder, an obsessive–compulsive disorder, or a substance use disorder. Schizophrenia_sentence_7

About 0.3% to 0.7% of people are affected by schizophrenia during their lifetime. Schizophrenia_sentence_8

In 2017, there were an estimated 1.1 million new cases and in 2019 a total of 20 million cases globally. Schizophrenia_sentence_9

Males are more often affected and on average have an earlier onset. Schizophrenia_sentence_10

The causes of schizophrenia include genetic and environmental factors. Schizophrenia_sentence_11

Genetic factors include a variety of common and rare genetic variants. Schizophrenia_sentence_12

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. Schizophrenia_sentence_13

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. Schizophrenia_sentence_14

The other half will have a lifelong impairment, and severe cases may be repeatedly admitted to hospital. Schizophrenia_sentence_15

Social problems such as long-term unemployment, poverty, homelessness, exploitation, and victimization are common consequences of schizophrenia. Schizophrenia_sentence_16

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 decreased life expectancy of 20 years. Schizophrenia_sentence_17

In 2015, an estimated 17,000 deaths were caused by schizophrenia. Schizophrenia_sentence_18

The mainstay of treatment is antipsychotic medication, along with counselling, job training, and social rehabilitation. Schizophrenia_sentence_19

Up to a third of people do not respond to initial antipsychotics, in which case the antipsychotic clozapine may be used. Schizophrenia_sentence_20

In situations where there is a risk of harm to self or others, a short involuntary hospitalization may be necessary. Schizophrenia_sentence_21

Long-term hospitalization may be needed for a small number of people with severe schizophrenia. Schizophrenia_sentence_22

In countries where supportive services are limited or unavailable, long-term hospital stays are more typical. Schizophrenia_sentence_23

Signs and symptoms Schizophrenia_section_0

Schizophrenia is a mental disorder characterized by significant alterations in perception, thoughts, mood, and behavior. Schizophrenia_sentence_24

Symptoms are described in terms of positive, negative, and cognitive symptoms. Schizophrenia_sentence_25

The positive symptoms of schizophrenia are the same for any psychosis and are sometimes referred to as psychotic symptoms. Schizophrenia_sentence_26

These may be present in any of the different psychoses, and are often transient making early diagnosis of schizophrenia problematic. Schizophrenia_sentence_27

Psychosis noted for the first time in a person who is later diagnosed with schizophrenia is referred to as a first-episode psychosis (FEP). Schizophrenia_sentence_28

Positive symptoms Schizophrenia_section_1

Positive symptoms are those symptoms that are not normally experienced, but are present in people during a psychotic episode in schizophrenia. Schizophrenia_sentence_29

They include delusions, hallucinations, and disorganized thoughts and speech, typically regarded as manifestations of psychosis. Schizophrenia_sentence_30

Hallucinations most commonly involve the sense of hearing as hearing voices but can sometimes involve any of the other senses of taste, sight, smell, and touch. Schizophrenia_sentence_31

They are also typically related to the content of the delusional theme. Schizophrenia_sentence_32

Delusions are bizarre or persecutory in nature. Schizophrenia_sentence_33

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. Schizophrenia_sentence_34

Thought disorders can include thought blocking, and disorganized speech – speech that is not understandable is known as word salad. Schizophrenia_sentence_35

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. Schizophrenia_sentence_36

Negative symptoms Schizophrenia_section_2

Negative symptoms are deficits of normal emotional responses, or of other thought processes. Schizophrenia_sentence_37

The five recognised 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. Schizophrenia_sentence_38

Avolition and anhedonia are seen as motivational deficits resulting from impaired reward processing. Schizophrenia_sentence_39

Reward is the main driver of motivation and this is mostly mediated by dopamine. Schizophrenia_sentence_40

It has been suggested that negative symptoms are multidimensional and they have been categorised into two subdomains of apathy or lack of motivation, and diminished expression. Schizophrenia_sentence_41

Apathy includes avolition, anhedonia, and social withdrawal; diminished expression includes blunt effect, and alogia. Schizophrenia_sentence_42

Sometimes diminished expression is treated as both verbal and non-verbal. Schizophrenia_sentence_43

Apathy accounts for around 50 per cent of the most often found negative symptoms and affects functional outcome and subsequent quality of life. Schizophrenia_sentence_44

Apathy is related to disrupted cognitive processing affecting memory and planning including goal-directed behaviour. Schizophrenia_sentence_45

The two subdomains has suggested a need for separate treatment approaches. Schizophrenia_sentence_46

A lack of distress – relating to a reduced experience of depression and anxiety is another noted negative symptom. Schizophrenia_sentence_47

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 abuse, and social deprivation - termed secondary negative symptoms. Schizophrenia_sentence_48

Negative symptoms are less responsive to medication and the most difficult to treat. Schizophrenia_sentence_49

However if properly assessed, secondary negative symptoms are amenable to treatment. Schizophrenia_sentence_50

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. Schizophrenia_sentence_51

These scales are the Clinical Assessment Interview for Negative Symptoms (CAINS), and the Brief Negative Symptom Scale (BNSS) also known as second-generation scales. Schizophrenia_sentence_52

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. Schizophrenia_sentence_53

The BNSS is designed to assess both the presence and severity and change of negative symptoms of the five recognised domains, and the additional item of reduced normal distress. Schizophrenia_sentence_54

BNSS can register changes in negative symptoms in relation to psychosocial and pharmacological intervention trials. Schizophrenia_sentence_55

BNSS has also been used to study a proposed non-D2 treatment called SEP-363856. Schizophrenia_sentence_56

Findings supported the favouring of five domains over the two-dimensional proposition. Schizophrenia_sentence_57

Cognitive symptoms Schizophrenia_section_3

See also: Visual processing abnormalities in schizophrenia Schizophrenia_sentence_58

Cognitive deficits are the earliest and most constantly found symptoms in schizophrenia. Schizophrenia_sentence_59

They are often evident long before the onset of illness in the prodromal stage, and may be present in early adolescence, or childhood. Schizophrenia_sentence_60

They are a core feature but not considered to be core symptoms, as are positive and negative symptoms. Schizophrenia_sentence_61

However, their presence and degree of dysfunction is taken as a better indicator of functionality than the presentation of core symptoms. Schizophrenia_sentence_62

Cognitive deficits become worse at first episode psychosis but then return to baseline, and remain fairly stable over the course of the illness. Schizophrenia_sentence_63

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. Schizophrenia_sentence_64

Cognitive deficits may be of neurocognition (nonsocial) or of social cognition. Schizophrenia_sentence_65

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. Schizophrenia_sentence_66

Verbal memory and attention are seen to be the most affected. Schizophrenia_sentence_67

Verbal memory impairment is associated with a decreased level of semantic processing (relating meaning to words). Schizophrenia_sentence_68

Another memory impairment is that of episodic memory. Schizophrenia_sentence_69

An impairment in visual perception that is consistently found in schizophrenia is that of visual backward masking. Schizophrenia_sentence_70

Visual processing impairments include an inability to perceive complex visual illusions. Schizophrenia_sentence_71

Social cognition is concerned with the mental operations needed to interpret, and understand the self and others in the social world. Schizophrenia_sentence_72

This is also an associated impairment, and facial emotion perception is often found to be difficult. Schizophrenia_sentence_73

Facial perception is critical for ordinary social interaction. Schizophrenia_sentence_74

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 has been found to be of particular help. Schizophrenia_sentence_75

Onset Schizophrenia_section_4

Further information: Basic symptoms of schizophrenia Schizophrenia_sentence_76

See also: Childhood schizophrenia and Adolescence § Changes in the brain Schizophrenia_sentence_77

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. Schizophrenia_sentence_78

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. Schizophrenia_sentence_79

A later stage of onset can occur between the ages of 40 and 60, known as late-onset schizophrenia. Schizophrenia_sentence_80

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. Schizophrenia_sentence_81

Late onset has shown that a higher rate of females are affected; they have less severe symptoms, and need lower doses of antipsychotics. Schizophrenia_sentence_82

The earlier favouring of onset in males is later seen to be balanced by a post-menopausal increase in the development in females. Schizophrenia_sentence_83

Estrogen produced pre-menopause, has a dampening effect on dopamine receptors but its protection can be overridden by a genetic overload. Schizophrenia_sentence_84

There has been a dramatic increase in the numbers of older adults with schizophrenia. Schizophrenia_sentence_85

An estimated 70% of those with schizophrenia have cognitive deficits, and these are most pronounced in early onset, and late-onset illness. Schizophrenia_sentence_86

Onset may happen suddenly, or may occur after the slow and gradual development of a number of signs and symptoms in a period known as the prodromal stage. Schizophrenia_sentence_87

Up to 75% of those with schizophrenia go through a prodromal stage. Schizophrenia_sentence_88

The negative and cognitive symptoms in the prodrome can precede FEP by many months, and up to five years. Schizophrenia_sentence_89

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. Schizophrenia_sentence_90

The prodromal stage is the high-risk stage for the development of psychosis. Schizophrenia_sentence_91

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 on a young person's ususal cognitive development. Schizophrenia_sentence_92

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. Schizophrenia_sentence_93

It is suggested that the use of anti-inflammatory compounds such as D-serine may prevent the transition to schizophrenia. Schizophrenia_sentence_94

Cognitive symptoms are not secondary to positive symptoms, or to the side effects of antipsychotics. Schizophrenia_sentence_95

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. Schizophrenia_sentence_96

Early treatment with cognitive behavioral therapies are the gold standard. Schizophrenia_sentence_97

Neurological soft signs of clumsiness and loss of fine motor movement are often found in schizophrenia, and these resolve with effective treatment of FEP. Schizophrenia_sentence_98

Causes Schizophrenia_section_5

Main article: Causes of schizophrenia Schizophrenia_sentence_99

See also: Developmental psychobiology Schizophrenia_sentence_100

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. Schizophrenia_sentence_101

The interactions of these risk factors are complex, as numerous and diverse insults from conception to adulthood can be involved. Schizophrenia_sentence_102

A genetic predisposition on its own, without interacting environmental factors, will not give rise to the development of schizophrenia. Schizophrenia_sentence_103

Genetic Schizophrenia_section_6

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. Schizophrenia_sentence_104

These estimates vary because of the difficulty in separating genetic and environmental influences, and their accuracy has been queried. Schizophrenia_sentence_105

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. Schizophrenia_sentence_106

If one parent is affected the risk is about 13% and if both are affected the risk is nearly 50%. Schizophrenia_sentence_107

However, DSM-5 points out that most people with schizophrenia have no family history of psychosis. Schizophrenia_sentence_108

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. Schizophrenia_sentence_109

Many genes are known to be involved in schizophrenia, each with small effect and unknown transmission and expression. Schizophrenia_sentence_110

The summation of these effect sizes into a polygenic risk score can explain at least 7% of the variability in liability for schizophrenia. Schizophrenia_sentence_111

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), duplications at 16p11.2 16p11.2 duplication (most frequently found) and deletions at 15q11.2 (Burnside-Butler syndrome). Schizophrenia_sentence_112

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. Schizophrenia_sentence_113

The genes CRHR1 and CRHBP have been shown to be associated with a severity of suicidal behavior. Schizophrenia_sentence_114

These genes code for stress response proteins needed in the control of the HPA axis, and their interaction can affect this axis. Schizophrenia_sentence_115

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. Schizophrenia_sentence_116

The question of how schizophrenia could be primarily genetically influenced, given that people with schizophrenia have lower fertility rates, is a paradox. Schizophrenia_sentence_117

It is expected that genetic variants that increase the risk of schizophrenia would be selected against due to their negative effects on reproductive fitness. Schizophrenia_sentence_118

A number of potential explanations have been proposed, including that alleles associated with schizophrenia risk confers a fitness advantage in unaffected individuals. Schizophrenia_sentence_119

While some evidence has not supported this idea, others propose that a large number of alleles each contributing a small amount can persist. Schizophrenia_sentence_120

Environment Schizophrenia_section_7

Further information: Prenatal nutrition, Prenatal stress, and Neuroplastic effects of pollution Schizophrenia_sentence_121

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. Schizophrenia_sentence_122

A risk is also associated with maternal obesity, in increasing oxidative stress, and dysregulating the dopamine and serotonin pathways. Schizophrenia_sentence_123

Both maternal stress and infection have been demonstrated to alter fetal neurodevelopment through an increase of pro-inflammatory cytokines. Schizophrenia_sentence_124

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. Schizophrenia_sentence_125

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. Schizophrenia_sentence_126

The increased risk is about five to eight percent. Schizophrenia_sentence_127

Viral infections of the brain during childhood are also linked to a risk of schizophrenia during adulthood. Schizophrenia_sentence_128

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. Schizophrenia_sentence_129

Many adverse childhood experiences can cause toxic stress and increase the risk of psychosis. Schizophrenia_sentence_130

Chronic trauma can promote lasting inflammatory dysregulation throughout the nervous system. Schizophrenia_sentence_131

It is suggested that early stress may contribute to the developmenmt of schizophrenia through these alterations in the immune system. Schizophrenia_sentence_132

Schizophrenia was the last diagnosis to benefit from the link made between ACEs and adult mental health outcomes. Schizophrenia_sentence_133

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. Schizophrenia_sentence_134

A possible link between the urban environment and pollution has been suggested to be the cause of the elevated risk of schizophrenia. Schizophrenia_sentence_135

Other risk factors of importance include social isolation, immigration related to social adversity and racial discrimination, family dysfunction, unemployment, and poor housing conditions. Schizophrenia_sentence_136

Having a father older than 40 years, or parents younger than 20 years are also associated with schizophrenia. Schizophrenia_sentence_137

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. Schizophrenia_sentence_138

Substance use Schizophrenia_section_8

About half of those with schizophrenia use recreational drugs, including cannabis, nicotine, and alcohol excessively. Schizophrenia_sentence_139

Use of stimulants such as amphetamine and cocaine can lead to a temporary stimulant psychosis, which presents very similarly to schizophrenia. Schizophrenia_sentence_140

Rarely, alcohol use can also result in a similar alcohol-related psychosis. Schizophrenia_sentence_141

Drugs may also be used as coping mechanisms by people who have schizophrenia, to deal with depression, anxiety, boredom, and loneliness. Schizophrenia_sentence_142

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. Schizophrenia_sentence_143

However, substance abuse is associated with an increased risk of suicide, and a poor response to treatment. Schizophrenia_sentence_144

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. Schizophrenia_sentence_145

The increased risk may require the presence of certain genes within an individual. Schizophrenia_sentence_146

Its use is associated with doubling the rate. Schizophrenia_sentence_147

The use of more potent strains of cannabis having a high level of its active ingredient tetrahydrocannabinol (THC), increases the risk further. Schizophrenia_sentence_148

One of these strains is well known as skunk. Schizophrenia_sentence_149

Mechanisms Schizophrenia_section_9

Main article: Mechanisms of schizophrenia Schizophrenia_sentence_150

See also: Aberrant salience Schizophrenia_sentence_151

The mechanisms of schizophrenia are unknown, and a number of models have been put forward to explain the link between altered brain function and schizophrenia. Schizophrenia_sentence_152

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. Schizophrenia_sentence_153

Extensive studies support this model. Schizophrenia_sentence_154

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. Schizophrenia_sentence_155

Gene-environment interactions lead to deficits in the neural circuitry that affect sensory and cognitive functions. Schizophrenia_sentence_156

The common dopamine and glutamate models proposed are not mutually exclusive; each is seen to have a role in the neurobiology of schizophrenia. Schizophrenia_sentence_157

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. Schizophrenia_sentence_158

This has been directly related to the symptoms of delusions and hallucinations. Schizophrenia_sentence_159

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. Schizophrenia_sentence_160

A decrease in D1 receptors in the dorsolateral prefrontal cortex may also be responsible for deficits in working memory. Schizophrenia_sentence_161

The glutamate hypothesis of schizophrenia links alterations between glutamatergic neurotransmission and the neural oscillations that affect connections between the thalamus and the cortex. Schizophrenia_sentence_162

Studies have shown that a reduced expression of a glutamate receptorNMDA receptor, and glutamate blocking drugs such as phencyclidine and ketamine can mimic the symptoms and cognitive problems associated with schizophrenia. Schizophrenia_sentence_163

Post-mortem studies consistently find that a subset of these neurons fail to express GAD67 (GAD1), in addition to abnormalities in brain morphometry. Schizophrenia_sentence_164

The subsets of interneurons that are abnormal in schizophrenia are responsible for the synchronizing of neural ensembles needed during working memory tasks. Schizophrenia_sentence_165

These give the neural oscillations produced as gamma waves that have a frequency of between 30 and 80 hertz. Schizophrenia_sentence_166

Both working memory tasks and gamma waves are impaired in schizophrenia, which may reflect abnormal interneuron functionality. Schizophrenia_sentence_167

Deficits in executive functions, such as planning, inhibition, and working memory, are pervasive in schizophrenia. Schizophrenia_sentence_168

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. Schizophrenia_sentence_169

These impairments have been linked to a number of neuroimaging and neuropathological abnormalities. Schizophrenia_sentence_170

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. Schizophrenia_sentence_171

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. Schizophrenia_sentence_172

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. Schizophrenia_sentence_173

Positive symptoms have been linked to cortical thinning in the superior temporal gyrus. Schizophrenia_sentence_174

Severity of negative symptoms has been linked to reduced thickness in the left medial orbitofrontal cortex. Schizophrenia_sentence_175

Anhedonia, traditionally defined as a reduced capacity to experience pleasure, is frequently reported in schizophrenia. Schizophrenia_sentence_176

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. Schizophrenia_sentence_177

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. Schizophrenia_sentence_178

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. Schizophrenia_sentence_179

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. Schizophrenia_sentence_180

Another theory links abnormal brain lateralization to the development of being left-handed which is significantly more common in those with schizophrenia. Schizophrenia_sentence_181

This abnormal development of hemispheric asymmetry is noted in schizophrenia. Schizophrenia_sentence_182

Studies have concluded that the link is a true and verifiable effect that may reflect a genetic link between lateralization and schizophrenia. Schizophrenia_sentence_183

Bayesian models of brain functioning have been utilized to link abnormalities in cellular functioning to symptoms. Schizophrenia_sentence_184

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. Schizophrenia_sentence_185

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. Schizophrenia_sentence_186

Diagnosis Schizophrenia_section_10

Main article: Diagnosis of schizophrenia Schizophrenia_sentence_187

There is no objective test or biomarker to confirm diagnosis. Schizophrenia_sentence_188

Psychoses can occur in several conditions and are often transient making early diagnosis of schizophrenia difficult. Schizophrenia_sentence_189

Psychosis noted for the first time in a person that is later diagnosed with schizophrenia is referred to as a first-episode psychosis (FEP). Schizophrenia_sentence_190

Criteria Schizophrenia_section_11

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. Schizophrenia_sentence_191

These criteria use the self-reported experiences of the person and reported abnormalities in behavior, followed by a psychiatric assessment. Schizophrenia_sentence_192

The mental status examination is an important part of the assessment. Schizophrenia_sentence_193

An established tool for assessing the severity of positive and negative symptoms is the Positive and Negative Syndrome Scale (PANSS). Schizophrenia_sentence_194

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. Schizophrenia_sentence_195

The DSM-5, published in 2013, gives a Scale to Assess the Severity of Symptom Dimensions outlining eight dimensions of symptoms. Schizophrenia_sentence_196

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. Schizophrenia_sentence_197

One of the symptoms needs to be either delusions, hallucinations, or disorganized speech. Schizophrenia_sentence_198

A second symptom could be one of the negative symptoms, or severely disorganized or catatonic behaviour. Schizophrenia_sentence_199

A different diagnosis of schizophreniform disorder can be made before the six months needed for the diagnosis of schizophrenia. Schizophrenia_sentence_200

In Australia the guideline for diagnosis is for six months or more with symptoms severe enough to affect ordinary functioning. Schizophrenia_sentence_201

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. Schizophrenia_sentence_202

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. Schizophrenia_sentence_203

In practice, agreement between the two systems is high. Schizophrenia_sentence_204

The current proposal for the ICD-11 criteria for schizophrenia recommends adding self-disorder as a symptom. Schizophrenia_sentence_205

A major unresolved difference between the two diagnostic systems is that of the requirement in DSM of an impaired functional outcome. Schizophrenia_sentence_206

WHO for ICD argues that not all people with schizophrenia have functional deficits and so these are not specific for the diagnosis. Schizophrenia_sentence_207

Changes made Schizophrenia_section_12

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. Schizophrenia_sentence_208

The definition of schizophrenia remains essentially the same as that specified by the 2000 text revised DSM-IV (DSM-IV-TR). Schizophrenia_sentence_209

However, with the publication of DSM-5, the APA removed all sub-classifications of schizophrenia. Schizophrenia_sentence_210

ICD-11 has also removed subtypes. Schizophrenia_sentence_211

The removed subtype from both, of catatonic has been relisted in ICD-11 as a psychomotor disturbance that may be present in schizophrenia. Schizophrenia_sentence_212

Another major change was to remove the importance previously given to Schneider's first-rank symptoms. Schizophrenia_sentence_213

DSM-5 still uses the listing of schizophreniform disorder but ICD-11 no longer includes it. Schizophrenia_sentence_214

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. Schizophrenia_sentence_215

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. Schizophrenia_sentence_216

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. Schizophrenia_sentence_217

Two of the negative symptoms – avolition and diminished emotional expression, have been given more prominence in both manuals. Schizophrenia_sentence_218

Comorbidities Schizophrenia_section_13

Many people with schizophrenia may have one or more other mental disorders, such as panic disorder, obsessive-compulsive disorder, or substance use disorder. Schizophrenia_sentence_219

These are separate disorders that require treatment. Schizophrenia_sentence_220

When comorbid with schizophrenia, substance use disorder and antisocial personality disorder both increase the risk for violence. Schizophrenia_sentence_221

Comorbid substance abuse also increases risk for suicide. Schizophrenia_sentence_222

Sleep disorders often co-occur with schizophrenia, and may be an early sign of relapse. Schizophrenia_sentence_223

Sleep disorders are linked with positive symptoms such as disorganized thinking and can adversely affect cortical plasticity and cognition. Schizophrenia_sentence_224

The consolidation of memories is disrupted in sleep disorders. Schizophrenia_sentence_225

They are associated with severity of illness, a poor prognosis, and poor quality of life. Schizophrenia_sentence_226

Sleep onset and maintenance insomnia is a common symptom, regardless of whether treatment has been received or not. Schizophrenia_sentence_227

Genetic variations have been found associated with these conditions involving the circadian rhythm, dopamine and histamine metabolism, and signal transduction. Schizophrenia_sentence_228

Limited positive evidence has been found for the use of acupuncture as an add-on. Schizophrenia_sentence_229

Differential diagnosis Schizophrenia_section_14

See also: Dual diagnosis and Comparison of bipolar disorder and schizophrenia Schizophrenia_sentence_230

To make a diagnosis of schizophrenia other possible causes of psychosis need to be excluded. Schizophrenia_sentence_231

Psychotic symptoms lasting less than a month may be diagnosed as brief psychotic disorder, or as schizophreniform disorder. Schizophrenia_sentence_232

Psychosis is noted in Other specified schizophrenia spectrum and other psychotic disorders as a DSM-5 category. Schizophrenia_sentence_233

Schizoaffective disorder is diagnosed if symptoms of mood disorder are substantially present alongside psychotic symptoms. Schizophrenia_sentence_234

Psychosis that results from a general medical condition or substance is termed secondary psychosis. Schizophrenia_sentence_235

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. Schizophrenia_sentence_236

Non-bizarre delusions are also present in delusional disorder, and social withdrawal in social anxiety disorder, avoidant personality disorder and schizotypal personality disorder. Schizophrenia_sentence_237

Schizotypal personality disorder has symptoms that are similar but less severe than those of schizophrenia. Schizophrenia_sentence_238

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. Schizophrenia_sentence_239

There can be considerable overlap with the symptoms of post-traumatic stress disorder. Schizophrenia_sentence_240

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. Schizophrenia_sentence_241

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. Schizophrenia_sentence_242

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. Schizophrenia_sentence_243

Investigations are not generally repeated for relapse unless there is a specific medical indication or possible adverse effects from antipsychotic medication. Schizophrenia_sentence_244

In children hallucinations must be separated from typical childhood fantasies. Schizophrenia_sentence_245

It is difficult to distinguish childhood schizophrenia from autism. Schizophrenia_sentence_246

Prevention Schizophrenia_section_15

Prevention of schizophrenia is difficult as there are no reliable markers for the later development of the disorder. Schizophrenia_sentence_247

There is tentative though inconclusive evidence for the effectiveness of early intervention to prevent schizophrenia in the prodrome phase. Schizophrenia_sentence_248

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. Schizophrenia_sentence_249

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). Schizophrenia_sentence_250

Another preventive measure is to avoid drugs that have been associated with development of the disorder, including cannabis, cocaine, and amphetamines. Schizophrenia_sentence_251

Antipsychotics are prescribed following a first-episode psychosis, and following remission a preventive maintenance use is continued to avoid relapse. Schizophrenia_sentence_252

However, it is recognised 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. Schizophrenia_sentence_253

Management Schizophrenia_section_16

Main article: Management of schizophrenia Schizophrenia_sentence_254

The primary treatment of schizophrenia is the use of antipsychotic medications, often in combination with psychosocial interventions and social supports. Schizophrenia_sentence_255

Community support services including drop-in centers, visits by members of a community mental health team, supported employment, and support groups are common. Schizophrenia_sentence_256

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. Schizophrenia_sentence_257

Voluntary or involuntary admittance to hospital may be needed to treat a severe episode, however, hospital stays are as short as possible. Schizophrenia_sentence_258

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. Schizophrenia_sentence_259

This process was known as deinstitutionalization, and community and supportive services were developed in order to support this change. Schizophrenia_sentence_260

Many other countries followed suit with the US starting in the 60s. Schizophrenia_sentence_261

There will still remain a few people who do not improve enough to be discharged. Schizophrenia_sentence_262

In those countries that lack the necessary supportive and social services long-term hospital stays are more usual. Schizophrenia_sentence_263

Medication Schizophrenia_section_17

The first-line treatment for schizophrenia is an antipsychotic. Schizophrenia_sentence_264

The first-generation antipsychotics, now called typical antipsychotics, are dopamine antagonists that block D2 receptors, and affect the neurotransmission of dopamine. Schizophrenia_sentence_265

Those brought out later, the second-generation antipsychotics known as atypical antipsychotics, can also have effect on another neurotransmitter, serotonin. Schizophrenia_sentence_266

Antipsychotics can reduce the symptoms of anxiety within hours of their use but for other symptoms they may take several days or weeks to reach their full effect. Schizophrenia_sentence_267

They have little effect on negative and cognitive symptoms, which may be helped by additional psychotherapies and medications. Schizophrenia_sentence_268

There is no single antipsychotic suitable for first-line treatment for everyone, as responses and tolerances vary between people. Schizophrenia_sentence_269

Stopping medication may be considered after a single psychotic episode where there has been a full recovery with no symptoms for twelve months. Schizophrenia_sentence_270

Repeated relapses worsen the long-term outlook and the risk of relapse following a second episode is high, and long-term treatment is usually recommended. Schizophrenia_sentence_271

Tobacco smoking increases the metabolism of some antipsychotics, by strongly activitating CYP1A2, the enzyme that breaks them down, and a significant difference is found in these levels between smokers and non-smokers. Schizophrenia_sentence_272

It is recommended that the dosage for those smokers on clozapine be increased by 50%, and for those on olanzapine by 30%. Schizophrenia_sentence_273

The result of stopping smoking can lead to an increased concentration of the antipsychotic that may result in toxicity, so that monitoring of effects would need to take place with a view to decreasing the dosage; many symptoms may be noticeably worsened, and extreme fatigue, and seizures are also possible with a risk of relapse. Schizophrenia_sentence_274

Likewise those who resume smoking may need their dosages adjusted accordingly. Schizophrenia_sentence_275

The altering effects are due to compounds in tobacco smoke and not to nicotine; the use of nicotine replacement therapy therefore has the equivalent effect of stopping smoking and monitoring would still be needed. Schizophrenia_sentence_276

About 30 to 50 percent of people with schizophrenia fail to accept that they have an illness or comply with their recommended treatment. Schizophrenia_sentence_277

For those who are unwilling or unable to take medication regularly, long-acting injections of antipsychotics may be used, which reduce the risk of relapse to a greater degree than oral medications. Schizophrenia_sentence_278

When used in combination with psychosocial interventions, they may improve long-term adherence to treatment. Schizophrenia_sentence_279

Research findings suggested that other neurotransmission systems, including serotonin, glutamate, GABA, and acetycholine, were implicated in the development of schizophrenia, and that a more inclusive medication was needed. Schizophrenia_sentence_280

A new first-in-class antipsychotic that targets multiple neurotransmitter systems called lumateperone (ITI-007), was trialed and approved by the FDA in December 2019 for the treatment of schizophrenia in adults. Schizophrenia_sentence_281

Lumateperone is a small molecule agent that shows improved safety, and tolerance. Schizophrenia_sentence_282

It interacts with dopamine, serotonin, and glutamate in a complex, uniquely selective manner, and is seen to improve negative and positive symptoms, and social functioning. Schizophrenia_sentence_283

Lumateperone was also found to reduce potential metabolic dysfunction, have lower rates of movement disorders, and have lower cardiovascular side effects such as a fast heart rate. Schizophrenia_sentence_284

Side effects Schizophrenia_section_18

Typical antipsychotics are associated with a higher rate of movement disorders including akathisia. Schizophrenia_sentence_285

Some atypicals are associated with considerable weight gain, diabetes and the risk of metabolic syndrome. Schizophrenia_sentence_286

Risperidone (atypical) has a similar rate of extrapyramidal symptoms to haloperidol (typical). Schizophrenia_sentence_287

A rare but potentially lethal condition of neuroleptic malignant syndrome (NMS) has been associated with the use of antipsychotics. Schizophrenia_sentence_288

Through its early recognition, and timely intervention rates have declined. Schizophrenia_sentence_289

However, an awareness of the syndrome is advised to enable intervention. Schizophrenia_sentence_290

Another less rare condition of tardive dyskinesia can occur due to long-term use of antipsychotics, developing after many months or years of use. Schizophrenia_sentence_291

It is more often reported with use of typical antipsychotics. Schizophrenia_sentence_292

Clozapine is associated with side effects that include weight gain, tiredness, and hypersalivation. Schizophrenia_sentence_293

More serious adverse effects include seizures, NMS, neutropenia, and agranulocytosis (lowered white blood cell count) and its use needs careful monitoring. Schizophrenia_sentence_294

Studies have found that antipsychotic treatment following NMS and neutropenia may sometimes be successfully rechallenged (restarted) with clozapine. Schizophrenia_sentence_295

Clozapine is also associated with thromboembolism (including pulmonary embolism), myocarditis, and cardiomyopathy. Schizophrenia_sentence_296

A systematic review of clozapine-associated pulmonary embolism indicates that this adverse effect can often be fatal, and that it has an early onset, and is dose-dependent. Schizophrenia_sentence_297

The findings advised the consideration of using a prevention therapy for venous thromboembolism after starting treatment with clozapine, and continuing this for six months. Schizophrenia_sentence_298

Constipation is three times more likely to occur with the use of clozapine, and severe cases can lead to ileus and bowel ischemia resulting in many fatalities. Schizophrenia_sentence_299

However, the risk of serious adverse effects from clozapine is low, and there are the beneficial effects to be gained of a reduced risk of suicide, and aggression. Schizophrenia_sentence_300

Typical antipsychotics and atypical risperidone can have a side effect of sexual dysfunction. Schizophrenia_sentence_301

Clozapine, olanzapine, and quetiapine are associated with beneficial effects on sexual functioning helped by various psychotherapies. Schizophrenia_sentence_302

Unwanted side effects cause people to stop treatment, resulting in relapses. Schizophrenia_sentence_303

Treatment resistant schizophrenia Schizophrenia_section_19

About half of those with schizophrenia will respond favourably to antipsychotics, and have a good return of functioning. Schizophrenia_sentence_304

However, positive symptoms persist in up to a third of people. Schizophrenia_sentence_305

Following two trials of different antipsychotics over six weeks, that also prove ineffective, they will be classed as having treatment resistant schizophrenia (TRS), and clozapine will be offered. Schizophrenia_sentence_306

Clozapine is of benefit to around half of this group although it has the potentially serious side effect of agranulocytosis (lowered white blood cell count) in less than 4% of people. Schizophrenia_sentence_307

Between 12 and 20 per cent will not respond to clozapine and this group is said to have ultra treatment resistant schizophrenia. Schizophrenia_sentence_308

ECT may be offered to treat TRS as an add-on therapy, and is shown to sometimes be of benefit. Schizophrenia_sentence_309

A review concluded that this use only has an effect on medium-term TRS and that there is not enough evidence to support its use other than for this group. Schizophrenia_sentence_310

TRS is often accompanied by a low quality of life, and greater social dysfunction. Schizophrenia_sentence_311

TRS may be the result of inadequate rather than inefficient treatment; it also may be a false label due to medication not being taken regularly, or at all. Schizophrenia_sentence_312

About 16 per cent of people who had initially been responsive to treatment later develop resistance. Schizophrenia_sentence_313

This could relate to the length of time on APs, with treatment becoming less responsive. Schizophrenia_sentence_314

This finding also supports the involvement of dopamine in the development of schizophrenia. Schizophrenia_sentence_315

Studies suggest that TRS may be a more heritable form. Schizophrenia_sentence_316

TRS may be evident from first episode psychosis, or from a relapse. Schizophrenia_sentence_317

It can vary in its intensity and response to other therapies. Schizophrenia_sentence_318

This variation is seen to possibly indicate an underlying neurobiology such as dopamine supersensitivity (DSS), glutamate or serotonin dysfunction, inflammation and oxidative stress. Schizophrenia_sentence_319

Studies have found that dopamine supersensitivity is found in up to 70% of those with TRS. Schizophrenia_sentence_320

The variation has led to the suggestion that treatment responsive and treatment resistant schizophrenia be considered as two different subtypes. Schizophrenia_sentence_321

It is further suggested that if the subtypes could be distinguished at an early stage significant implications could follow for treatment considerations, and for research. Schizophrenia_sentence_322

Neuroimaging studies have found a significant decrease in the volume of grey matter in those with TRS with no such change seen in those who are treatment responsive. Schizophrenia_sentence_323

In those with ultra treatment resistance the decrease in grey matter volume was larger. Schizophrenia_sentence_324

A link has been made between the gut microbiota and the development of TRS. Schizophrenia_sentence_325

The most prevalent cause put forward for TRS is that of mutation in the genes responsible for drug effectiveness. Schizophrenia_sentence_326

These include liver enzyme genes that control the availability of a drug to brain targets, and genes responsible for the structure and function of these targets. Schizophrenia_sentence_327

In the colon the bacteria encode a hundred times more genes than exist in the human genome. Schizophrenia_sentence_328

Only a fraction of ingested drugs reach the colon, having been already exposed to small intestinal bacteria, and absorbed in the portal circulation. Schizophrenia_sentence_329

This small fraction is then subject to the metabolic action of many communities of bacteria. Schizophrenia_sentence_330

Activation of the drug depends on the composition and enzymes of the bacteria and of the specifics of the drug, and therefore a great deal of individual variation can affect both the usefulness of the drug and its tolerability. Schizophrenia_sentence_331

It is suggested that parenteral administration of antipsychotics would bypass the gut and be more successful in overcoming TRS. Schizophrenia_sentence_332

The composition of gut microbiota is variable between individuals, but they are seen to remain stable. Schizophrenia_sentence_333

However, phyla can change in response to many factors including ageing, diet, substance-use, and medications – especially antibiotics, laxatives, and antipsychotics. Schizophrenia_sentence_334

In FEP, schizophrenia has been linked to significant changes in the gut microbiota that can predict response to treatment. Schizophrenia_sentence_335

Psychosocial interventions Schizophrenia_section_20

Further information: Management of schizophrenia § Psychosocial Schizophrenia_sentence_336

A number of psychosocial interventions that include several types of psychotherapy may be useful in the treatment of schizophrenia such as: family therapy, group therapy, cognitive remediation therapy, cognitive behavioral therapy, and metacognitive training. Schizophrenia_sentence_337

Skills training, and help with substance use, and weight management– often needed as a side effect of an antipsychotic, are also offered. Schizophrenia_sentence_338

In the US, interventions for first episode psychosis have been brought together in an overall approach known as coordinated speciality care (CSC) and also includes support for education. Schizophrenia_sentence_339

In the UK care across all phases is a similar approach that covers many of the treatment guidelines recommended. Schizophrenia_sentence_340

The aim is to reduce the number of relapses and stays in hospital. Schizophrenia_sentence_341

Other support services for education, employment, and housing are usually offered. Schizophrenia_sentence_342

For people suffering from severe schizophrenia, and discharged from a stay in hospital, these services are often brought together in an integrated approach to offer support in the community away from the hospital setting. Schizophrenia_sentence_343

In addition to medicine management, housing, and finances, assistance is given for more routine matters such as help with shopping and using public transport. Schizophrenia_sentence_344

This approach is known as assertive community treatment (ACT) and has been shown to achieve positive results in symptoms, social functioning and quality of life. Schizophrenia_sentence_345

Another more intense approach is known as intensive care management (ICM). Schizophrenia_sentence_346

ICM is a stage further than ACT and emphasises support of high intensity in smaller caseloads, (less than twenty). Schizophrenia_sentence_347

This approach is to provide long-term care in the community. Schizophrenia_sentence_348

Studies show that ICM improves many of the relevant outcomes including social functioning. Schizophrenia_sentence_349

Some studies have shown little evidence for the effectiveness of cognitive behavioral therapy (CBT) in either reducing symptoms or preventing relapse. Schizophrenia_sentence_350

However, other studies have found that CBT does improve overall psychotic symptoms (when in use with medication) and has been recommended in Canada, but it has been seen here to have no effect on social function, relapse, or quality of life. Schizophrenia_sentence_351

In the UK it is recommended as an add-on therapy in the treatment of schizophrenia, but is not supported for use in treatment resistant schizophrenia. Schizophrenia_sentence_352

Arts therapies are seen to improve negative symptoms in some people, and are recommended by NICE in the UK. Schizophrenia_sentence_353

This approach however, is criticised as having not been well-researched, and arts therapies are not recommended in Australian guidelines for example. Schizophrenia_sentence_354

Peer support, in which people with personal experience of schizophrenia, provide help to each other, is of unclear benefit. Schizophrenia_sentence_355

Other Schizophrenia_section_21

Exercise including aerobic exercise has been shown to improve positive and negative symptoms, cognition, working memory, and improve quality of life. Schizophrenia_sentence_356

Exercise has also been shown to increase the volume of the hippocampus in those with schizophrenia. Schizophrenia_sentence_357

A decrease in hippocampal volume is one of the factors linked to the development of the disease. Schizophrenia_sentence_358

However, there still remains the problem of increasing motivation for, and maintaining participation in physical activity. Schizophrenia_sentence_359

Supervised sessions are recommended. Schizophrenia_sentence_360

In the UK healthy eating advice is offered alongside exercise programs. Schizophrenia_sentence_361

An inadequate diet is often found in schizophrenia, and associated vitamin deficiencies including those of folate, and vitamin D are linked to the risk factors for the development of schizophrenia and for early death including heart disease. Schizophrenia_sentence_362

Those with schizophrenia possibly have the worst diet of all the mental disorders. Schizophrenia_sentence_363

Lower levels of folate and vitamin D have been noted as significantly lower in first episode psychosis. Schizophrenia_sentence_364

The use of supplemental folate is recommended. Schizophrenia_sentence_365

A zinc deficiency has also been noted. Schizophrenia_sentence_366

Vitamin B12 is also often deficient and this is linked to worse symptoms. Schizophrenia_sentence_367

Supplementation with B vitamins has been shown to significantly improve symptoms, and to put in reverse some of the cognitive deficits. Schizophrenia_sentence_368

It is also suggested that the noted dysfunction in gut microbiota might benefit from the use of probiotics. Schizophrenia_sentence_369

Violence Schizophrenia_section_22

Most people with schizophrenia are not aggressive, and are more likely to be victims of violence rather than perpetrators. Schizophrenia_sentence_370

However, though the risk of violence in schizophrenia is small the association is consistent, and there are minor subgroups where the risk is high. Schizophrenia_sentence_371

This risk is usually associated with a comorbid disorder such as a substance use disorder - in particular alcohol, or with antisocial personality disorder. Schizophrenia_sentence_372

Substance abuse is strongly linked, and other risk factors are linked to deficits in cognition and social cognition including facial perception and insight that are in part included in theory of mind impairments. Schizophrenia_sentence_373

Poor cognitive functioning, decision-making, and facial perception may contribute to making a wrong judgement of a situation that could result in an inappropriate response such as violence. Schizophrenia_sentence_374

These associated risk factors are also present in antisocial personality disorder which when present as a comorbid disorder greatly increases the risk of violence. Schizophrenia_sentence_375

A review in 2012 showed that schizophrenia was responsible for 6 per cent of homicides in Western countries. Schizophrenia_sentence_376

Another wider review put the homicide figure at between 5 and 20 per cent. Schizophrenia_sentence_377

There was found to be a greater risk of homicide during first episode psychosis that accounted for 38.5 per cent of homicides. Schizophrenia_sentence_378

The association between schizophrenia and violence is complex. Schizophrenia_sentence_379

Homicide is linked with young age, male sex, a history of violence, and a stressful event in the preceding year. Schizophrenia_sentence_380

Clinical risk factors are severe untreated psychotic symptoms - untreated due to either not taking medication or to the condition being treatment resistant. Schizophrenia_sentence_381

A comorbid substance use disorder or an antisocial personality disorder increases the risk for homicidal behaviour by 8-fold, in contrast to the 2-fold risk in those without the comorbid disorders. Schizophrenia_sentence_382

Rates of homicide linked to psychosis are similar to those linked to substance misuse, and parallel the overall rate in a region. Schizophrenia_sentence_383

What role schizophrenia has on violence independent of substance misuse is controversial, but certain aspects of individual histories or mental states may be factors. Schizophrenia_sentence_384

Hostility is anger felt and directed at a person or group and has related dimensions of impulsiveness and aggression. Schizophrenia_sentence_385

When this impulsive-aggression is evident in schizophrenia neuroimaging has suggested the malfunctioning of a neural circuit that modulates hostile thoughts and behaviours that are linked with negative emotions in social interactions. Schizophrenia_sentence_386

This circuit includes the amygdala, striatum, prefrontal cortex, anterior cingulate cortex, insula, and hippocampus. Schizophrenia_sentence_387

Hostility has been reported during acute psychosis, and following hospital discharge. Schizophrenia_sentence_388

There is a known association between low cholesterol levels, and impulsivity, and violence. Schizophrenia_sentence_389

A review finds that people with schizophrenia, and lower cholesterol levels are four times more likely to instigate violent acts. Schizophrenia_sentence_390

This association is also linked to the increased number of suicides in schizophrenia. Schizophrenia_sentence_391

It is suggested that cholesterol levels could serve as a biomarker for violent and suicidal tendencies. Schizophrenia_sentence_392

A review found that just under 10 per cent of those with schizophrenia showed violent behaviour compared to 1.6 per cent of the general population. Schizophrenia_sentence_393

An excessive risk of violence is associated with drugs or alcohol and increases the risk by as much as 4-fold. Schizophrenia_sentence_394

Violence often leads to imprisonment. Schizophrenia_sentence_395

Clozapine is an effective medication that can be used in penal settings such as prisons. Schizophrenia_sentence_396

However, a condition of benign ethnic neutropenia in many African-Americans excludes them from the use of clozapine the most effective medication. Schizophrenia_sentence_397

Cognitive deficits are recognised as playing an important part in the origin and maintenance of aggression, and cognitive remediation therapy may therefore help to prevent the risk of violence in schizophrenia. Schizophrenia_sentence_398

Prognosis Schizophrenia_section_23

Main article: Prognosis of schizophrenia Schizophrenia_sentence_399

See also: Physical health in schizophrenia Schizophrenia_sentence_400

Schizophrenia has great human and economic costs. Schizophrenia_sentence_401

It results in a decreased life expectancy of 20 years. Schizophrenia_sentence_402

This is primarily because of its association with obesity, poor diet, a sedentary lifestyle, and smoking, with an increased rate of suicide playing a lesser role. Schizophrenia_sentence_403

Side effects of antipsychotics may also increase the risk. Schizophrenia_sentence_404

These differences in life expectancy increased between the 1970s and 1990s. Schizophrenia_sentence_405

An Australian study puts the rate of early death at 25 years, and views the main cause to be related to heart disease. Schizophrenia_sentence_406

Several studies indicate that almost 40% of those with schizophrenia die from complications of cardiovascular disease including heart attacks, and sudden cardiac death which is seen to be increasingly associated. Schizophrenia_sentence_407

An underlying factor of sudden cardiac death may be Brugada syndrome (BrS) – BrS mutations that overlap with those linked with schizophrenia are the calcium channel mutations. Schizophrenia_sentence_408

BrS may also be drug-induced from certain antipsychotics and antidepressants. Schizophrenia_sentence_409

Primary polydipsia, or excessive fluid intake, is relatively common in people with chronic schizophrenia. Schizophrenia_sentence_410

This may lead to hyponatremia which can be life-threatening. Schizophrenia_sentence_411

Antipsychotics can lead to a dry mouth, but there are several other factors that may contribute to the disorder. Schizophrenia_sentence_412

It is suggested to lead to a reduction in life expectancy by 13 per cent. Schizophrenia_sentence_413

A study has suggested that real barriers to improving the mortality rate in schizophrenia are poverty, overlooking the symptoms of other illnesses, stress, stigma, and medication side effects, and that these need to be changed. Schizophrenia_sentence_414

Schizophrenia is a major cause of disability. Schizophrenia_sentence_415

In 2016 it was classed as the 12th most disabling condition. Schizophrenia_sentence_416

Approximately 75% of people with schizophrenia have ongoing disability with relapses and 16.7 million people globally are deemed to have moderate or severe disability from the condition. Schizophrenia_sentence_417

Some people do recover completely and others function well in society. Schizophrenia_sentence_418

Most people with schizophrenia live independently with community support. Schizophrenia_sentence_419

About 85% are unemployed. Schizophrenia_sentence_420

In people with a first episode of psychosis in scizophrenia a good long-term outcome occurs in 31%, an intermediate outcome in 42% and a poor outcome in 31%. Schizophrenia_sentence_421

Males are affected more often than females, and have a worse outcome. Schizophrenia_sentence_422

Outcomes for schizophrenia appear better in the developing than the developed world. Schizophrenia_sentence_423

These conclusions have been questioned. Schizophrenia_sentence_424

Social problems, such as long-term unemployment, poverty, homelessness, exploitation, stigmatization and victimization are common consequences, and lead to social exclusion. Schizophrenia_sentence_425

There is a higher than average suicide rate associated with schizophrenia estimated at around 5% to 6%, most often occurring in the period following onset or first hospital admission. Schizophrenia_sentence_426

Several times more (20 to 40%) attempt suicide at least once. Schizophrenia_sentence_427

There are a variety of risk factors, including male gender, depression, a high IQ, heavy smoking, and substance abuse. Schizophrenia_sentence_428

Repeated relapse is linked to an increased risk of suicidal behavior. Schizophrenia_sentence_429

The use of clozapine can reduce the risk of suicide and aggression. Schizophrenia_sentence_430

A strong association between schizophrenia and tobacco smoking has been shown in worldwide studies. Schizophrenia_sentence_431

Smoking is especially high in those diagnosed with schizophrenia, with estimates ranging from 80 to 90% being regular smokers, as compared to 20% of the general population. Schizophrenia_sentence_432

Those who smoke tend to smoke heavily, and additionally smoke cigarettes with high nicotine content. Schizophrenia_sentence_433

Some propose that this is in an effort to improve symptoms. Schizophrenia_sentence_434

Among people with schizophrenia use of cannabis is also common. Schizophrenia_sentence_435

Epidemiology Schizophrenia_section_24

Main article: Epidemiology of schizophrenia Schizophrenia_sentence_436

In 2017, the Global Burden of Disease Study estimated there were 1.1 million new cases, and in 2019 WHO reported a total of 20 million cases globally. Schizophrenia_sentence_437

Schizophrenia affects around 0.3–0.7% of people at some point in their life. Schizophrenia_sentence_438

It occurs 1.4 times more frequently in males than females and typically appears earlier in men – the peak ages of onset are 25 years for males and 27 years for females. Schizophrenia_sentence_439

Onset in childhood, before the age of 13 can sometimes occur. Schizophrenia_sentence_440

A later onset can occur between the ages of 40 and 60, known as late onset, and also after 60 known as very late onset. Schizophrenia_sentence_441

Worldwide, schizophrenia is the most common psychotic disorder. Schizophrenia_sentence_442

The frequency of schizophrenia varies across the world, within countries, and at the local and neighborhood level. Schizophrenia_sentence_443

This variation has been estimated to be fivefold. Schizophrenia_sentence_444

It causes approximately one percent of worldwide disability adjusted life years and resulted in 17,000 deaths in 2015. Schizophrenia_sentence_445

In 2000, the World Health Organization found the percentage of people affected and the number of new cases that develop each year is roughly similar around the world, with age-standardized prevalence per 100,000 ranging from 343 in Africa to 544 in Japan and Oceania for men, and from 378 in Africa to 527 in Southeastern Europe for women. Schizophrenia_sentence_446

About 1.1% of adults have schizophrenia in the United States. Schizophrenia_sentence_447

However, in areas of conflict this figure can rise to between 4.0 and 6.5%. Schizophrenia_sentence_448

History Schizophrenia_section_25

Main article: History of schizophrenia Schizophrenia_sentence_449

Further information: Dementia praecox Schizophrenia_sentence_450

Accounts of a schizophrenia-like syndrome are rare in records before the 19th century. Schizophrenia_sentence_451

The earliest cases detailed were reported in 1797, and 1809. Schizophrenia_sentence_452

Dementia praecox, meaning premature dementia was used by German psychiatrist Heinrich Schüle in 1886, and then in 1891 by Arnold Pick in a case report of hebephrenia. Schizophrenia_sentence_453

In 1893 Emil Kraepelin used the term in making a distinction, known as the Kraepelinian dichotomy, between the two psychoses – dementia praecox, and manic depression (now called bipolar disorder). Schizophrenia_sentence_454

Kraepelin believed that dementia praecox was probably caused by a systemic disease that affected many organs and nerves, affecting the brain after puberty in a final decisive cascade. Schizophrenia_sentence_455

It was thought to be an early form of dementia, a degenerative disease. Schizophrenia_sentence_456

When it became evident that the disorder was not degenerative it was renamed schizophrenia by Eugen Bleuler in 1908. Schizophrenia_sentence_457

The word schizophrenia translates roughly as "splitting of the mind" and is Modern Latin from the Greek roots schizein (σχίζειν, "to split") and phrēn, (φρεν, "mind") Its use was intended to describe the separation of function between personality, thinking, memory, and perception. Schizophrenia_sentence_458

The term schizophrenia used to be associated with split personality by the general population but that usage went into decline when split personality became known as a separate disorder, first as multiple identity disorder , and later as dissociative identity disorder. Schizophrenia_sentence_459

In 2002 in Japan the name was changed to integration disorder, and in 2012 in South Korea, the name was changed to attunement disorder to reduce the stigma, both with good results. Schizophrenia_sentence_460

In the early 20th century, the psychiatrist Kurt Schneider listed the psychotic symptoms of schizophrenia into two groups of hallucinations, and delusions. Schizophrenia_sentence_461

The hallucinations were listed as specific to auditory, and the delusional included thought disorders. Schizophrenia_sentence_462

These were seen as the symptoms of first-rank importance and were termed first-rank symptoms. Schizophrenia_sentence_463

Whilst these were also sometimes seen to be relevant to the psychosis in manic-depression, they were highly suggestive of schizophrenia and typically referred to as first-rank symptoms of schizophrenia. Schizophrenia_sentence_464

The most common first-rank symptom was found to belong to thought disorders. Schizophrenia_sentence_465

In 2013 the first-rank symptoms were excluded from the DSM-5 criteria. Schizophrenia_sentence_466

First-rank symptoms are seen to be of limited use in detecting schizophrenia but may be of help in differential diagnosis. Schizophrenia_sentence_467

The earliest attempts to treat schizophrenia were psychosurgical, involving either the removal of brain tissue from different regions or the severing of pathways. Schizophrenia_sentence_468

These were notably frontal lobotomies and cingulotomies which were carried out from the 1930s. Schizophrenia_sentence_469

In the 1930s a number of shock therapies were introduced which induced seizures (convulsions) or comas. Schizophrenia_sentence_470

Insulin shock therapy involved the injecting of large doses of insulin in order to induce comas, which in turn produced hypoglycemia and convulsions. Schizophrenia_sentence_471

The use of electricity to induce seizures was developed, and in use as electroconvulsive therapy (ECT) by 1938. Schizophrenia_sentence_472

Stereotactic surgeries were developed in the 1940s. Schizophrenia_sentence_473

Treatment was revolutionized in the mid-1950s with the development and introduction of the first typical antipsychotic, chlorpromazine. Schizophrenia_sentence_474

In the 1970s the first atypical antipsychotic clozapine, was introduced followed by the introduction of others. Schizophrenia_sentence_475

In the early 1970s in the US, the diagnostic model used for schizophrenia was broad and clinically-based using DSM II. Schizophrenia_sentence_476

It had been noted that schizophrenia was diagnosed far more in the US than in Europe which had been using the ICD-9 criteria. Schizophrenia_sentence_477

The US model was criticised for failing to demarcate clearly those people with a mental illness, and those without. Schizophrenia_sentence_478

In 1980 DSM III was published and showed a shift in focus from the clinically-based biopsychosocial model to a reason-based medical model. Schizophrenia_sentence_479

DSM IV showed an increased focus to an evidence-based medical model. Schizophrenia_sentence_480

Subtypes of schizophrenia classified as paranoid, disorganized, catatonic, undifferentiated, and residual type were difficult to distinguish between and are no longer recognized as separate conditions by DSM-5 (2013) or ICD-11. Schizophrenia_sentence_481

Society and culture Schizophrenia_section_26

See also: Social construction of schizophrenia, List of people with schizophrenia, and Religion and schizophrenia Schizophrenia_sentence_482

In 2002, the term for schizophrenia in Japan was changed from seishin-bunretsu-byō (精神分裂病, lit. Schizophrenia_sentence_483

"mind-split disease") to tōgō-shitchō-shō (統合失調症, lit. Schizophrenia_sentence_484

"integration-dysregulation syndrome") to reduce stigma. Schizophrenia_sentence_485

The new name also interpreted as "integration disorder" was inspired by the biopsychosocial model; it increased the percentage of people who were informed of the diagnosis from 37 to 70% over three years. Schizophrenia_sentence_486

A similar change was made in South Korea in 2012 to attunement disorder. Schizophrenia_sentence_487

A professor of psychiatry, Jim van Os, has proposed changing the English term to psychosis spectrum syndrome. Schizophrenia_sentence_488

In 2013 with the reviewed DSM-5, the DSM-5 committee was in favor of giving a new name to schizophrenia but they referred this to WHO. Schizophrenia_sentence_489

In the United States, the cost of schizophrenia – including direct costs (outpatient, inpatient, drugs, and long-term care) and non-health care costs (law enforcement, reduced workplace productivity, and unemployment) – was estimated to be $62.7 billion in 2002. Schizophrenia_sentence_490

In the UK the cost in 2016 was put at £11.8 billion per year with a third of that figure directly attributable to the cost of hospital and social care, and treatment. Schizophrenia_sentence_491

The book A Beautiful Mind chronicled the life of John Forbes Nash who had been diagnosed with schizophrenia but who went on to win the Nobel Prize for Economics. Schizophrenia_sentence_492

This was later made into the film with the same name. Schizophrenia_sentence_493

An earlier documentary was made with the title A Brilliant Madness. Schizophrenia_sentence_494

In 1964 a lengthy case study of three males diagnosed with schizophrenia who each had the delusional belief that they were Jesus Christ was published as a book. Schizophrenia_sentence_495

This has the title of The Three Christs of Ypsilanti, and a film with the title Three Christs was released in 2020. Schizophrenia_sentence_496

Such religious delusions are a fairly common feature in psychoses including schizophrenia. Schizophrenia_sentence_497

Media coverage relating to violent acts by people with schizophrenia reinforces public perception of an association between schizophrenia and violence. Schizophrenia_sentence_498

Such sensationalist reporting stigmatizes schizophrenia more than any other mental illness. Schizophrenia_sentence_499

In the UK guidelines are given for the reporting of different conditions. Schizophrenia_sentence_500

Its campaigns have shown a reduction in negative reporting. Schizophrenia_sentence_501

Research directions Schizophrenia_section_27

See also: Animal models of schizophrenia Schizophrenia_sentence_502

Schizophrenia is not believed to occur in other animals but it may be possible to develop a pharmacologically induced non-human primate model of schizophrenia. Schizophrenia_sentence_503

Effects of early intervention is an active area of research. Schizophrenia_sentence_504

One important aspect of this research is early detection of at-risk individuals. Schizophrenia_sentence_505

This includes development of risk calculators and methods for large-scale population screening. Schizophrenia_sentence_506

Various agents have been explored for possible effectiveness in treating negative symptoms, for which antipsychotics have been of little benefit. Schizophrenia_sentence_507

There have been trials on medications with anti-inflammatory activity, based on the premise that inflammation might play a role in the pathology of schizophrenia. Schizophrenia_sentence_508

Various brain stimulation techniques are being studied to treat the positive symptoms of schizophrenia, in particular auditory verbal hallucinations (AVHs). Schizophrenia_sentence_509

A 2015 Cochrane review found unclear evidence of benefit. Schizophrenia_sentence_510

Most studies focus on transcranial direct-current stimulation (tDCM), and repetitive transcranial magnetic stimulation (rTMS). Schizophrenia_sentence_511

Techniques based on focused ultrasound for deep brain stimulation could provide insight for the treatment of AVHs. Schizophrenia_sentence_512

Another active area of research is the study of a variety of potential biomarkers that would be of invaluable help not only in the diagnosis but also in the treatment and prognosis of schizophrenia. Schizophrenia_sentence_513

Possible biomarkers include markers of inflammation, neuroimaging, BDNF, genetics, and speech analysis. Schizophrenia_sentence_514

Some inflammatory markers such as C-reactive protein are useful in detecting levels of inflammation implicated in some psychiatric disorders but they are not disorder-specific. Schizophrenia_sentence_515

However, other inflammatory cytokines are found to be elevated in first episode psychosis and acute relapse that are normalized after treatment with antipsychotics, and these may be considered as state markers. Schizophrenia_sentence_516

Deficits in sleep spindles in schizophrenia may serve as a marker of an impaired thalamocortical circuit, and a mechanism for memory impairment. Schizophrenia_sentence_517

The use of choline as a supplement during pregnancy may have effect in the prevention of the later development of schizophrenia, and is an area of research. Schizophrenia_sentence_518

In 2020 over 3,000 clinical trials into drugs, symptom assessment tools, and treatments related to schizophrenia were listed with some recruiting, and some newly completed. Schizophrenia_sentence_519

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