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Whether Mild or Extreme, Psychotic Experiences Share Risk Factors

August 8, 2014. Mild to severe psychotic experiences share similar genetic and environmental risk factors, reports a twin study published online July 30 in JAMA Psychiatry. The study, led by Angelica Ronald at Birkbeck College in London, United Kingdom, polled 5,059 adolescent twin pairs to dissect the genetic and environmental contributors to these psychotic experiences, which fall below the threshold of the frank psychosis seen in schizophrenia. The study found that the most severe psychotic experiences stemmed from a profile of genetic and environmental influences similar to that observed for milder experiences, which suggests the same causal factors are at work.

In schizophrenia, psychosis onset is preceded by brief experiences of hallucinations, delusions, or disorganized thinking. Such psychotic experiences also appear in the general population, including children (see SRF related news report). Though most people with these low-grade psychotic experiences do not go on to develop full-blown psychosis, researchers have been examining these experiences to understand their causes and how different they are from psychosis itself. For example, are the more severe and frequent kinds of psychotic experiences somehow distinct from the milder kind, and do they portend more risk for a psychotic disorder?

The new twin study—the largest of its kind—suggests that, in terms of etiology, there is no difference between mild and extreme. Whether the far side of this continuum includes outright psychosis remains unclear, as the study did not examine people with psychotic disorders. So far, previous genetic studies of people with psychotic experiences do not find that they are enriched for risk variants associated with schizophrenia (Zammit et al., 2013, and Sieradzka et al., 2014).

“More work is required to examine to what degree the apparent continuity in psychosis below the threshold of psychotic disorder is mediated by continuous liability to affective illness and to what degree other etiologic factors may “kick in,” causing individuals to pass the threshold for clinical psychotic disorder,” wrote Jim van Os of Maastricht University Medical Centre in the Netherlands in an accompanying editorial.

Parsing psychosis
First author Helena Zavos and colleagues had monozygotic and dizygotic teenage twin pairs (mean age 16 years old) drawn from the Longitudinal Experiences and Perceptions (LEAP) study answer the Specific Psychotic Experiences Questionnaire (SPEQ), which is designed to quantitatively assess different components of psychotic experiences: paranoia, hallucinations, cognitive disorganization, grandiosity, and anhedonia. Parents answered questions about the twins’ negative symptoms. The researchers then examined the extent to which these scores were shared within twin pairs to get at the extent to which each component arose from genetic or environmental factors.

Genetics were definitely at work, because for each component, correlations were higher in monozygotic twins, who are genetically identical and share much the same environment, than dizygotic twins, who share about 50 percent of their DNA and much the same environment. Paranoia and negative symptoms scores were especially genetic (heritability of 50 percent and 59 percent, respectively), and hallucination scores less so (32 percent in girls, 15 percent in boys).

But the environment also was influential. For example, the dizygotic twin correlations for negative symptoms were more than half of those found in monozygotic twins, which suggests shared environmental influences. Significant shared environmental influences were also detected for hallucinations, explaining 20 percent of variation in boys and 17 percent in girls.

Non-shared environmental influences—a category that includes anything that could happen to one twin but not the other, such as childhood trauma, stress, or cannabis use—were also implicated, given that different scores arose between monozygotic twins. This sector explained 49-64 percent of the variance in self-rated scores.

The researchers also found that scores for some components tended to co-vary more than expected by chance: paranoia and hallucinations, paranoia and cognitive disorganization, hallucinations and cognitive disorganization, and cognitive disorganization and negative symptoms. Genetics seemed to drive this co-variation, with heritability ranging from 54 percent to 71 percent.

Extreme focus
The researchers then used three different analytical methods to see if the profile of genetic and environmental factors obtained for those reporting the most severe or frequent psychotic experiences was any different from that obtained for those with milder experiences. One method singled out twins scoring in the top 5 percent, 10 percent, or 15 percent for psychotic experiences (the 5 percent cutoff captured people with a prevalence similar to that of the “at-risk mental state”), and found that heritability estimates for the six components of psychosis in these extreme groups were not significantly different from those found in the entire sample. Similarly, the estimates for shared and non-shared environmental factors in the extreme groups resembled those for the entire sample.

Two other ways of looking at the data also found causal similarities across the range of psychotic experiences. One found that the correlations between twins did not vary substantially across the spectrum of psychotic experiences, including those in the extreme subgroups. The other looked for linear changes in genetic and shared environmental influences in each component of psychotic experience and found none, save for one in negative symptoms.

Together, the analyses reiterate the idea that the psychotic experiences assessed in this study, whether mild or severe, stem from the same titration of genetic and environmental factors. The results may ultimately help recognize people at risk for developing full-blown psychosis and guide development of early interventions.—Michele Solis.

Zavos HM, Freeman D, Haworth CM, McGuire P, Plomin R, Cardno AG, Ronald A. Consistent Etiology of Severe, Frequent Psychotic Experiences and Milder, Less Frequent Manifestations: A Twin Study of Specific Psychotic Experiences in Adolescence. JAMA Psychiatry. 2014 Jul 30. Abstract

van Os J. The Many Continua of Psychosis. JAMA Psychiatry. 2014 Jul 30. Abstract

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