People with schizophrenia may show increased rates of unrelated co-occurring conditions. These may include dysfunction of the auditory system or structural abnormalities of the ear canal.

What is the evidence for comorbid auditory dysfunction?

Moderate to low quality evidence is unclear of the prevalence of auditory system dysfunction in people with schizophrenia.

June 2020

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People with schizophrenia may show increased rates of co-occurring conditions. Autoimmune diseases are caused by an overactive immune system. Some of the more common autoimmune diseases include; Celiac disease where the immune system reacts to gluten found in wheat and other grains; lupus, which affects skin, muscles, joints, lungs, heart and kidneys; rheumatoid arthritis, where bone and cartilage are damaged; Graves’ disease, where the thyroid gland is overactive; multiple sclerosis, where the nervous system is affected; type 1 diabetes, where the pancreas does not produce enough insulin to manage blood sugar levels.

What is the evidence for autoimmune disease in people with schizophrenia?

Moderate to high quality evidence finds a small increased risk of non-neurological autoimmune disorders in people with schizophrenia, in particular anemia, celiac disease, Graves’ disease, pemphigoid, and psoriasis. Rates of schizophrenia were also increased in people with celiac disease.

Rheumatoid arthritis and ankylosing spondylitis were reduced in people with schizophrenia, and there were no differences in rates of polymyalgia rheumatic, alopecia areata, Crohn’s disease, systemic lupus erythematosus, type 1 diabetes, or ulcerative colitis.

June 2020

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People with schizophrenia may show increased rates of co-occurring conditions. These can include disorders of the blood, such as leukocytosis (excess leukocytes), hypokalemia (reduced potassium), and neutropenia (low neutrophil levels).

What is the evidence for comorbid blood disorders?

Moderate quality evidence suggests the incidence of mild neutropenia in people taking the antipsychotic clozapine is around 3.8%, and the incidence of severe neutropenia is around 0.9%. Death from neutropenia is rare at around 0.013%.

Moderate to low quality evidence is unclear as to the rates of other blood disorders in people with schizophrenia.

June 2020

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Cancer is a broad group of diseases involving abnormal cell growth, where cells divide and grow forming malignant tumours. Cancer may spread through the lymphatic system or blood stream. Lifestyle, genetic factors and environmental pollutants increase a persons’ risk of developing cancer. People with schizophrenia show increased exposure to risk factors associated with cancer, such as smoking, physical inactivity, poor diet, obesity, substance abuse, diabetes and hepatitis.

What is the evidence for comorbid cancer?

Moderate to high quality evidence finds a small increase in the rate of breast cancer in females with schizophrenia compared to general population rates. Lung cancer may also be increased in females with schizophrenia.

There were small to medium-sized decreases in rates of prostate and colorectal cancers in males with schizophrenia, and a small decrease in malignant melanoma in both males and females with schizophrenia. Decreased incidence of liver cancer was found prior to a diagnosis of schizophrenia in both males and females, and increased incidence of liver cancer was found after a diagnosis of schizophrenia in males only.

There were no differences in rates of brain or stomach cancers.

High quality evidence also finds a small decreased incidence of any cancer in parents and siblings of people with schizophrenia.

Cancer-related mortality in people with schizophrenia was increased by about 40% compared to general population rates.

June 2020

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People with schizophrenia may show increased rates of co-occurring conditions when compared to general population rates. Cerebrovascular disease includes strokes, transient ischemic attacks, aneurysms, and vascular malformations. A stroke happens when blood flow to the brain is interrupted due to a blocked artery (ischaemic stroke) or when an artery bursts (haemorrhagic stroke). A transient ischemic attack is similar to a stroke, but less severe, and an aneurysm involves an enlarged artery caused by weakness in the arterial wall. These can all cause brain damage if cells do not get enough of the oxygen and nutrients that are carried by the blood to the brain.

What is the evidence for comorbid cerebrovascular disease?

Moderate quality evidence suggests a small increase in the rate of cerebrovascular disease, including stroke and death by stroke, in people with schizophrenia, with data adjusted for potential confounding factors that may have accounted for the association.

June 2020

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Symptoms of dementia include memory, language and movement impairment. People with dementia may also be unable to identify objects, people, sound or smell. There is often impaired executive functioning, for example, an inability to think abstractly, plan, initiate or stop actions. Other symptoms include behavioural disturbances, anxiety, apathy, delirium, and mood and sleep disturbances. Schizophrenia is also often associated with cognitive and functional decline; however, people with dementia show greater cognitive impairment.

What is the evidence for comorbid dementia?

Moderate quality evidence finds a medium-sized increased risk of dementia in people with schizophrenia. Studies conducted in non-European countries reported the highest risk. There were no differences in the risk according to differences in study design (prospective or retrospective), study quality, study duration (less than or more than 10 years), participant age (under or over 65 years) or sex. Studies adjusted their results for multiple known risk factors for dementia.

Low quality evidence is unable to determine any benefits of rivastigmine, a cholinergic agent, for people with schizophrenia and dementia.

June 2020

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Oral health is an important part of overall physical health. People with severe mental illness are susceptible to oral disease for a number of reasons which may include poor oral hygiene, concern about dental costs, difficulty in accessing healthcare facilities, and the side-effects of psychiatric drugs such as dry mouth.

What is the evidence for comorbid dental disease?

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People with schizophrenia may show increased rates of unrelated co-occurring illnesses, one example is diabetes. Diabetes is a state of impaired insulin function, either as a result of reduced insulin production (type I diabetes) or reduced insulin responsiveness (type II diabetes). Insulin regulates blood glucose levels, and reduced insulin function effectively increases blood glucose levels (hyperglycaemia). This is a dangerous state in the long term, and can ultimately damage the retina, kidneys, nerves and blood vessels. Consequently, effective management of diabetes is crucial. It is unclear if any increased risk in people with schizophrenia is purely a consequence of biological risk, the metabolic impact of antipsychotic administration, or unhealthy lifestyle choices, but it is likely a combination of many factors.

What is the evidence for comorbid diabetes?

Moderate quality evidence shows people with multi-episode schizophrenia have increased rates of diabetes compared to age and gender-matched population controls, although when only type 1 diabetes was assessed, there were no increases found. People with multi-episode schizophrenia have similar rates of diabetes as people with first-episode psychosis (9.5% vs. 8.7%), while drug naïve patients have slightly lower rates (6.4%).

Moderate quality evidence finds a medium to large effect of increased odds of type 2 diabetes in patients with a family history of type 2 diabetes compared to patients without a family history of type 2 diabetes.

Moderate to high quality evidence finds a large increase in 2-hour oral glucose tolerance test results in unmedicated patients with first-episode psychosis or first-episode mood disorder compared to controls. There were significant, medium-sized increases in insulin levels and insulin resistance in first-episode psychosis patients compared to controls, but no differences between controls and patients with a first-episode mood disorder. There were no significant differences in fasting glucose or haemoglobin A1c.

High quality evidence finds small effects of more impaired global cognition and memory, and a medium-sized effect of more impaired processing speed in people with schizophrenia and diabetes compared to people with schizophrenia without diabetes.

Moderate to high quality evidence finds second generation antipsychotics clozapine, olanzapine, risperidone and quetiapine may be associated with a small increased risk of diabetes mellitus when compared to first generation antipsychotics.

Moderate to high quality evidence suggests a small effect of greater adherence to diabetes medication in people with schizophrenia than in people without schizophrenia (approximately 17 more days per year). Moderate quality evidence shows access to treatments for diabetes was not significantly different.

June 2020

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People with schizophrenia may show increased rates of co-occurring conditions, including appendicitis, gastric ulcers, irritable bowel syndrome, or celiac disease.

What is the evidence for comorbid digestive disorders?

Moderate to high quality evidence finds small increases in rates of anemia and celiac disease in people with schizophrenia or other psychotic disorders compared to people without a psychotic disorder. There were also increased rates of schizophenia in people with celiac disease compared to people without celiac disease. There were no increases in rates of Crohn’s disease or ulcerative colitis.

Moderate to low quality evidence suggests people with schizophrenia show an increased risk of mortality from digestive disease.

June 2020

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People with schizophrenia may show increased rates of co-occurring conditions. These include epilepsy, which is a neurological disorder characterised by recurrent seizures. There are several types of seizures; focal or partial seizures are subtle and may go unnoticed as mild activity starts in one area of the brain and can spread to other areas. Generalised seizures are more severe, involve both hemispheres simultaneously and result in loss of consciousness. There are also ‘epileptic spasms’ that are of unknown origin.

What is the evidence for epilepsy?

Moderate quality evidence suggests the prevalence rate of schizophrenia or interictal psychosis in people with epilepsy is around 5.4%, which is higher than general population rates (around 1%). Interictal psychosis is a schizophrenia-like psychosis that would fulfil diagnostic criteria for schizophrenia if epilepsy was not present.

June 2020

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