The emergence of psychotic experiences in the early adolescence of 22q11.2 Deletion Syndrome

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Abstract

Individuals with 22q11.2 Deletion Syndrome (22q11.2DS) are at substantial increased risk of psychosis spectrum outcomes including schizophrenia. We conducted a prospective, longitudinal study of the psychopathological and neurocognitive correlates of early psychotic phenomena in young people with 22q11.2DS (n = 75, mean age time 1 (T1) 9.9 years, time 2 (T2) 12.5 years). We also assessed unaffected control siblings (n = 33, mean age T1 10.6 years, T2 13.4 years). The prevalence of psychotic experiences, defined as subthreshold psychotic phenomena, substantially increased in children with 22q11.2DS from 4% (n = 3) in childhood (T1) to 21% (n = 16) in early adolescence (T2) (p = 0.001), and at T2 prevalence was significantly elevated (p = 0.020) relative to control siblings (3%). The emergence of psychotic experiences was associated with levels of childhood anxiety symptoms at T1 and differential development of the attention-executive domain. IQ ability and IQ change, however, were not associated with the emergence of psychotic experiences, indicating that initial changes in attention-executive functioning may precede the decline in global cognition that has been reported to be associated with later stages of psychosis development. Our study highlights that psychotic phenomena emerge early in 22q11.2DS and we implicate attention-executive functioning and anxiety as key domains associated with the development of these psychotic experiences.

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Schizophrenia is a cognitive illness: time for a change in focus.

René S Kahn, Richard Keefe (2013)

Schizophrenia is currently classified as a psychotic disorder. This article posits that this emphasis on psychosis is a conceptual fallacy that has greatly contributed to the lack of progress in our understanding of this illness and hence has hampered the development of adequate treatments. Not only have cognitive and intellectual underperformance consistently been shown to be risk factors for schizophrenia, several studies have found that a decline in cognitive functioning precedes the onset of psychosis by almost a decade. Although the question of whether cognitive function continues to decline after psychosis onset is still debated, it is clear that cognitive function in schizophrenia is related to outcome and little influenced by antipsychotic treatment. Thus, our focus on defining (and preventing) the disorder on the basis of psychotic symptoms may be too narrow. Not only should cognition be recognized as the core component of the disorder, our diagnostic efforts should emphasize the changes in cognitive function that occur earlier in development. Putting the focus back on cognition may facilitate finding treatments for the illness before psychosis ever emerges.

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High rates of schizophrenia in adults with velo-cardio-facial syndrome.

K Murphy, L A Jones, M. Owen (1999)

Velo-cardio-facial syndrome (VCFS), a syndrome characterized by an increased frequency of schizophrenia and bipolar disorder, is associated with small interstitial deletions of chromosome 22q11. We evaluated 50 adults with VCFS using a structured clinical interview (Schedules for Clinical Assessment in Neuropsychiatry or Psychiatric Assessment Schedule for Adults With Developmental Disability if IQ <50) to establish a DSM-IV diagnosis. The schizophrenia phenotype in individuals with VCFS and schizophrenia was compared with a matched series of individuals with schizophrenia and without VCFS (n = 12). The King's Schizotypy Questionnaire was administered to individuals with VCFS (n = 41), their first-degree relatives (n = 68), and a series of unrelated normal controls (n = 316). All individuals with VCFS deleted for the N25 probe (n = 48) were genotyped for a genetic polymorphism in the COMT gene that results in variations in enzymatic activity. Fifteen individuals with VCFS (30%) had a psychotic disorder, with 24% (n = 12) fulfilling DSM-IV criteria for schizophrenia. In addition, 6 (12%) had major depression without psychotic features. The individuals with schizophrenia had fewer negative symptoms and a relatively later age of onset compared with those with schizophrenia and without VCFS. We found no evidence that possession of the low-activity COMT allele was associated with schizophrenia in our sample of individuals with VCFS. The high prevalence of schizophrenia in this group suggests that chromosome 22q11 might harbor a gene or genes relevant to the etiology of schizophrenia in the wider population.

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Strauss (1969) revisited: a psychosis continuum in the general population?

Jim J. van Os, Manon Hanssen, Rob V Bijl … (2000)

Although dichotomously defined for clinical purposes, psychosis may exist as a continuous phenotype in nature. A random sample of 7076 men and women aged 18-64years were interviewed by trained lay interviewers with the Composite International Diagnostic Interview (CIDI). Those with evidence of psychosis according to the CIDI were additionally interviewed by psychiatrists. For the 17 CIDI core psychosis items, we compared a psychiatrist's rating of hallucinations and/or delusions (Clinical Psychosis; sample prevalence 4.2%) with three other possible positive CIDI ratings of the same items: (i) symptom present, but not clinically relevant (NCR Symptom; sample prevalence 12.9%); (ii) symptom present, but the result of drugs or somatic disorder (Secondary Symptom; sample prevalence 0.6%); (iii) symptom appears present, but there is a plausible explanation (Plausible Symptom; sample prevalence 4.0%). Of the 1237 individuals with any type of positive psychosis rating (sample prevalence 17.5%), only 26 (2.1%) had a DSM-III-R diagnosis of non-affective psychosis. All the different types of psychosis ratings were strongly associated with the presence of psychiatrist-rated Clinical Psychosis (NCR Symptom: OR=3.4; 95% CI: 2.9-3.9; Secondary Symptom: OR=4.5; 95% CI: 2.7-7.7; Plausible Symptom: OR=5.8; 95% CI: 4.7-7.1). Associations with lower age, single marital status, urban dwelling, lower level of education, lower quality of life, depressive symptoms and blunting of affect did not differ qualitatively as a function of type of rating of the psychotic symptom, were similar in individuals with and without any CIDI lifetime diagnosis, and closely resembled those previously reported for schizophrenia. Presence of any rating of hallucinations was strongly associated with any rating of delusions (OR=6.7; 95% CI: 5.6-8.1), regardless of presence of any CIDI lifetime diagnosis. The observation by Strauss (1969. Hallucinations and delusions as points on continua function. Arch. Gen. Psychiatry 21, 581-586) that dichotomously diagnosed psychotic symptoms in clinical samples are, in fact, part of a continuum of experiences, may also apply to the general population. The boundaries of the psychosis phenotype may extend beyond the clinical concept of schizophrenia.