Predicting schizophrenia: findings from the Edinburgh High-Risk Study

Johnstone, Eve C.; Ebmeier, Klaus P.; Miller, Patrick; Owens, David C.; Lawrie, Stephen M.

doi:10.1192/bjp.186.1.18

Cited by 285 publications

(237 citation statements)

References 30 publications

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“…and those young relatives who had additional high levels of schizotypy had a risk of developing psychosis comparable to the ARMS group (Johnstone et al, 2005). Both the relatives of patients with schizophrenia and individuals with an ARMS show neuropsychological and volumetric MRI abnormalities that are qualitatively similar to those seen in schizophrenia but are quantitatively less severe (Brewer et al, 2005;Woods et al, 2003).…”

Section: Discussionmentioning

confidence: 88%

Abnormal P300 in people with high risk of developing psychosis

et al. 2008

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Background: Individuals with an "At Risk Mental State" (or "prodromal" symptoms) have a 20-40% chance of developing psychosis; however it is difficult to predict which of them will become ill on the basis of their clinical symptoms alone. We examined whether neurophysiological markers could help to identify those who are particularly vulnerable.Method: 35 cases meeting PACE criteria for the At Risk Mental State (ARMS) and 57 controls performed an auditory oddball task whilst their electroencephalogram was recorded. The latency and amplitude of the P300 and N100 waves were compared between groups using linear regression.Results: The P300 amplitude was significantly reduced in the ARMS group [8.6 ±6.4 microvolt] compared to controls [12.7 ±5.8 microvolt] (p<0.01). There were no group differences in P300 latency or in the amplitude and latency of the N100. Of the at-risk subjects that were followed up, seven (21%) developed psychosis. Please find attached a fully revised manuscript titled "Abnormal P300 in people with high risk of developing psychosis". We also enclose a letter with the comments from the reviewers and our detailed answers on how we have done all the changes requested. (t-test; p=0.93). Those making a transition to psychosis were marginally more educated but this was only at trend level with a 3 year average difference in the age at which they completed their studies (t-test; p=0.07).Similarly, logistic regression analyses showed that compared to those who remained at risk, the seven cases who made a transition to psychosis had no significant differences in P300 amplitude/latency or N100 amplitude/latency (p values ranging from 0.30 to 0.63 for all four analyses). We have reported these comparisons very concisely and cautiously because referee #2 said that these analyses with only 7 individual making a transition were preliminary and power is limited. Please see results section paragraph 2. RESPONSE TO REVIEWER #2:Thank you for your suggestions, which have improved the paper. Below are your comments in blue-italics and how we have amended the manuscript accordingly in black with cross-references to the revised manuscript.This paper addresses an important and timely topic, namely, whether auditory P300 is reduced in subjects with at risk mental states and whether the P300 predicts subsequent conversion to psychosis. The study finds a significant deficit in P300 in ARMS subjects, relative to controls, replicating a previously a previously published report. The study had the potential to incrementally * 2. Response to Reviews 2 contribute to the literature by examining the utility of baseline P300 deficits as a predictor of subsequent conversion to psychosis; however, the negative finding coupled with the lack of power for this analysis (only 7 converters) make this aspect of the study inconclusive. More detailed comments are provided below:We have added a paragraph in the discussion to acknowledge the limitation of our small group of converters and how we have low statistical power to compa...

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Section: Discussionmentioning

confidence: 88%

Abnormal P300 in people with high risk of developing psychosis

et al. 2008

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“…[251][252][253] There is remarkable agreement in the literature that deficits in multiple cognitive domains predate the onset of clinical symptoms; [254][255][256][257][258] are not attributable to antipsychotic medications; 259 persist over the course of the illness; are unrelated to its duration; [260][261][262] and behave like a stable trait. 233,263,264 Pervasive cognitive dysfunction has been reported in > 50% of schizophrenia patients in a community-based survey in Scotland, 265 and there…”

Section: Cognitive Dysfunction As An Endophenotypementioning

confidence: 94%

Subtyping schizophrenia: implications for genetic research

2006

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Phenotypic variability and likely extensive genetic heterogeneity have been confounding the search for the causes of schizophrenia since the inception of the diagnostic category. The inconsistent results of genetic linkage and association studies using the diagnostic category as the sole schizophrenia phenotype suggest that the current broad concept of schizophrenia does not demarcate a homogeneous disease entity. Approaches involving subtyping and stratification by covariates to reduce heterogeneity have been successful in the genetic study of other complex disorders, but rarely applied in schizophrenia research. This article reviews past and present attempts at delineating schizophrenia subtypes based on clinical features, statistically derived measures, putative genetic indicators, and intermediate phenotypes, highlighting the potential utility of multidomain neurocognitive endophenotypes.

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“…Schizotypal traits are highly associated with the familial diathesis for schizophrenia (Kendler and Diehl, 1993). Several studies suggest that schizotypy may have a predictive value for later schizophrenia in genetic high risk studies (Johnstone et al, 2005;Miller et al, 2002). The co-occurrence of schizotypy and attentional impairments may therefore represent a subgroup of genetic HR subjects with an increased risk for later emergence of schizophrenia spectrum disorders.…”

Section: Discussionmentioning

confidence: 99%

Psychopathology among offspring of parents with schizophrenia: Relationship to premorbid impairments

Keshavan¹,

Montrose²,

Rajarethinam³

et al. 2008

Schizophrenia Research

104

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Introduction-A broad range of psychopathology, including externalizing disorders is seen in offspring at genetic risk for schizophrenia. However, it is unclear whether such psychopathology may underlie a higher predisposition to the premorbid antecedents of schizophrenia. We examined the prevalence and correlates of psychopathology in an ongoing study of offspring genetically at risk for schizophrenia.Methods-Seventy five consenting high risk offspring (HR: offspring, age 15.68±3.27 years; male/female 34/41) and 82 matched comparison subjects (40 males and 42 females; age 15.92±3.0 years) participated in this study. Diagnoses were ascertained using structured psychiatric interviews and consensus meetings, including all available clinical information.Results-Sixty (60%) of the HR offspring had one or more lifetime diagnosis of axis I psychiatric disorder. HR subjects with axis I psychopathology had significantly more soft neurological signs, poorer premorbid adjustment, and higher schizotypy scores as measured by Chapman psychosis proneness scales. Among those with psychopathology, HR subjects with externalizing disorders showed the most abnormal scores in schizotypy.Discussion-A substantial proportion of HR offspring of parents with schizophrenia manifest a broad range of childhood psychiatric disorders. Psychopathology, especially externalizing disorders such as attention deficit hyperactivity disorder (ADHD) may represent a subgroup with an increased risk for schizophrenia spectrum disorders. This possibility needs to be examined by prospective follow-up studies, and would be of considerable importance to early diagnosis and intervention efforts in schizophrenia.

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Predicting schizophrenia: findings from the Edinburgh High-Risk Study

Abstract: The genetic component of schizophrenia affects many more individuals than will develop the illness, and partial impairment can be found in them. Highly significant predictors of the development of schizophrenia are detectable years before onset.

Cited by 285 publications

References 30 publications

Abnormal P300 in people with high risk of developing psychosis

Abnormal P300 in people with high risk of developing psychosis

Subtyping schizophrenia: implications for genetic research

Psychopathology among offspring of parents with schizophrenia: Relationship to premorbid impairments

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