Cognitive deficits have been reported in people with schizophrenia. Deficits in memory, attention and executive functioning are most commonly reported, with lesser degree of dysfunction in perceptual and language processes. Cognitive deficits are present early in the course of the disorder and are stable over time, and may be heritable. First-degree relatives of people with schizophrenia may show attenuated signs of cognitive deficits. If cognitive deficits found in people with schizophrenia are also found in their relatives, this may be suggestive of the underlying genetic basis. This is particularly informative in disorders that display complex inheritance patterns such as schizophrenia.

What is the evidence for cognition in first-degree relatives?

High quality evidence shows small to medium-sized effects of poor executive functioning (including tasks of attention and language), poor visual memory, verbal memory, short-term and long-term episodic memory, and social cognition (Theory of Mind and negative facial expression recognition) in relatives of people with schizophrenia compared to people without schizophrenia. Moderate to high quality evidence suggests small to medium-sized effects of lower IQ, poorer working and prospective memory, and slower processing speed, and moderate quality evidence suggests poorer psychomotor and visuospatial ability in relatives compared to people without schizophrenia.

Compared to relatives of people with bipolar disorder, moderate to high quality evidence suggests relatives of people with schizophrenia show small to medium-sized effects of poorer performance on IQ, verbal memory, working memory, processing speed, verbal fluency, and accuracy on executive functioning tasks.

March 2022

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The collection of information relating to a person’s family history of mental illness can be a valuable tool for diagnosing and understanding their current mental state, in both clinical and research settings, where it may not be feasible to interview the family members themselves.

What is the evidence for the family history method?

The only evidence regarding family history method is moderate quality and suggests that a patient can usually correctly identify a particular family member with schizophrenia, if one exists.

March 2022

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Familial coaggregation is the rate of related disorders found in a family. Many studies have suggested a fundamental association between schizophrenia and bipolar disorder. Many family studies have investigated the possibility of this association by assessing whether schizophrenia and bipolar disorder diagnoses may cluster within the same extended family.

What is the evidence for familial coaggregation of schizophrenia and bipolar disorder?

Moderate to low quality evidence suggests high familial coaggregation of schizophrenia and bipolar disorder, with first-degree relatives of patients with schizophrenia or bipolar showing an increased risk of developing either disorder.

March 2022

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Several familial traits have been associated with increased risk for schizophrenia. These include; familial high expressed emotion (hostility, emotional over-involvement, and critical comments); negative parental affective style (guilt induction, over-intrusiveness, and personal criticism); and communication deviance (lack of clarity in communication).

What is the evidence for family relationships?

Moderate quality evidence finds people with schizophrenia may have had poor relationships with parents during childhood, with increased family instability, high communication deviance, negative emotions, and poor self-concept.

Moderate to high quality evidence suggests increased familial expressed emotion is related to more relapses in patients.

March 2022

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A diagnosis of schizophrenia can have a large impact not only on the affected individuals, but also on the people closest to them. This topic considers the impact of schizophrenia on family members, and on the family as a unit.

Sometimes the family of a person with schizophrenia may experience different types of burden, particularly during acute phases of the illness. Burden is considered in terms of objective effects, such as illness severity or financial output, but also in terms of subjective effects, such as the emotional impact of the illness on family members.

What is the evidence for the impact of schizophrenia on families?

Moderate to low quality evidence suggests caregiving can have both negative and positive impacts. Coping, appraisal/attribution, and interpersonal response styles account for most of the variation in caregiver distress, with a strong association between emotional over-involvement and caregiver distress. High expressed emotion is common in families with around 50% of families reporting this trait. Emotional over-involvement, critical comments, hostility, and distress are reported in around 30% of families.

Siblings experience increased subjective burden, including feelings of guilt, shame, hurt and anxiety. Burden is highest in younger, female or more educated siblings, and the levels of burden is associated with patients’ symptom severity. Siblings have expressed a need for more information regarding the illness and its treatment, and would generally like to be involved in family support groups.

Family members often have difficulty recognising that an illness is developing in their relative and that the person is in need of help, resulting in delays in timing and type of help sought. Predominant barriers to seeking help by relatives are the perceived stigma of having a family member with a mental illness and reluctance of the ill relative to participate in the help-seeking process. The ill individuals’ wider social context and informal networks may inhibit help-seeking. Crises, or overt psychotic symptoms, are the main promoters of active help-seeking and facilitators to accessing services. Relatives’ informal networks often serve to assist in this process.

Moderate to high quality evidence finds carer psychoeducation improves carers’ perceived burden and depression, their knowledge of psychosis, negative caregiving experiences, and overall morbidities. Moderate quality evidence also shows family psychoeducation has a medium-sized benefit for reducing familial expressed emotion. Family intervention, which can include psychoeducation or mutual support, improves long-term family functioning, while also reducing long-term carer support service use. Home-based crisis intervention reduces family disruption and burden, and increases patients’ and relatives’ overall satisfaction levels.

Moderate quality evidence finds babies of mothers with schizophrenia in the peri-natal and post-natal periods show a two- to three-fold increase in the risk of mortality or congenital malformation. Lower quality evidence is unclear about the risk of mortality in older children. Moderate to high quality evidence suggests a two-fold increased risk of foetal mortality among pregnant mothers with a psychotic disorder, though the absolute risk of stillbirth in offspring of mothers with schizophrenia is <2%. This evidence does not take into account any effects of other contributing factors such as medical conditions, medications or substance use.

March 2022

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Relatives of people with schizophrenia may show attenuated signs of the illness, such as physical features that are commonly identified with the disorder. Identifying these signs can help determine how genetics may contribute to the risk of schizophrenia.

What is the evidence for physical abnormalities in family members?

Moderate to high quality evidence found increases in pituitary and left thalamus volume of relatives compared to controls. There were decreases in total grey matter volume, and decreases in the hippocampus, third ventricle, bilateral anterior cingulate gyrus, right insula, left amygdala, left subcallosal gyrus, left inferior frontal gyrus, left middle temporal gyrus, and right cerebellum of relatives.

There was also abnormal brain activation in relatives compared to controls during cognitive tasks. Relatives show abnormalities in closed loop gain during smooth pursuit eye movement tasks. There was increased intrusive anticipatory saccades, impairment in fixational stability, and increased error rate in visual and memory guided saccades. EEG studies also show abnormalities, with large effects of increased P50 ratio and reduced P50 suppression, a medium-sized effect of reduced P300 amplitude, a small to medium-sized effect of longer latency, and a small trend effect of reduced mismatch negativity amplitude in relatives.

Moderate quality evidence found biochemical alterations in relatives compared to controls. There were small effects of increased thalamic glutamate + glutamine concentrations and reduced variability of striatal D2/D3 receptor availability. There was reduced glutamate/glutamine ratio in the dorsolateral prefrontal cortex, and reduced N-Acetylaspartate/creatine ratio in the anterior cingulate cortex and hippocampus of relatives.

There were large increases in rates of neurological soft signs (mild motor or sensory anomalies), and small increases in rates of movement disorders (dyskinesia or parkinsonism) in relatives compared to controls.

March 2022

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Due to the significant genetic loading of schizophrenia, first-degree relatives may also show signs of psychopathology. This could include schizophrenia, bipolar disorder or other mental disorders.

What is the evidence regarding psychopathology in relatives?

Moderate to high quality evidence finds no significant increases in anxiety disorders in offspring of people with schizophrenia.

Moderate to low quality evidence also finds no significant increases in disruptive behavioural disorders in offspring of people with schizophrenia.

No systematic reviews were identified that assessed psychopathology in other family members.

April 2022

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Sibship is a medical term meaning a group of individuals born of the same parents. Factors associated with sibship include birth order, number of siblings or number of births in the family, and inter-birth interval periods. It is not known how these factors may be associated with risk for schizophrenia.

What is the evidence for sibship?

Moderate quality evidence suggests a small to medium-sized increased risk of schizophrenia in people who had one, four or five births in their family, or in children born less than 18 months before or after their closest sibling. First birth order may be associated with a reduced risk for schizophrenia.

March 2022

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