Cognitive functioning in ultra-high risk for psychosis individuals with and without depression: Secondary analysis of findings from the NEURAPRO randomized clinical trial
Introduction
High prevalence of depression, with rates ranging between 40 and 50% is a common characteristic of ultra-high risk (UHR) for psychosis cohorts (Fusar-Poli et al., 2012). Despite this, the primary outcome of interest in most UHR follow-up studies is the transition to psychotic disorder. Thus, prediction of both persistent and incident depression in UHR samples at follow-up has received limited investigation.
Neurocognitive impairments are a well-established feature in UHR cohorts, with performance generally around 0.5 SDs below the average neurocognitive performance of healthy controls in multiple cognitive domains, including verbal learning and processing speed (Hauser et al., 2017). Past studies have differentiated between UHR for psychosis and depression by showing varying neurocognitive impairments across these groups (Schulze et al., 2013). However, to our knowledge, little is known about the relationship between Major Depressive Disorder (MDD) and neurocognitive functioning in those with an at risk mental state for psychosis. According to a recent meta-analysis by Goodall et al. (2018), in studies of young people with MDD, neurocognitive impairments are present in multiple domains including attention, verbal memory, visual memory, IQ and verbal reasoning, with moderate to large effect sizes. Despite broad understanding that neurocognitive abilities are impacted during depression, there remains a lack of agreement regarding the specificity of these impairments (Peters et al., 2017), with no consistent neurocognitive profile having been implicated in MDD (Hammar and Årdal, 2009) and significant shared overlap with the cognitive impairments observed in UHR cohorts.
Lin et al. (2011) in their study of neurocognitive predictors of functional outcomes in UHR, demonstrated that poor functional outcomes at 13-year follow-up were associated with poor performance in verbal learning and memory, processing speed and attention, and verbal fluency at baseline. They further outlined that examining outcomes other than the transition to psychosis would be valuable in terms of understanding clinical outcomes in UHR. Despite the prevalence of MDD in the UHR population, to our knowledge, no studies have yet investigated the association between neurocognition and MDD in UHR populations.
Zammit et al. (2004) investigated the role of premorbid IQ in predicting a range of psychiatric conditions, in male participants. Results demonstrated that lower IQ was associated with an increased risk of developing depression (adjusted OR = 1.19). In keeping with the trait model of neurocognitive impairment, this suggests deficits in neurocognitive ability may be pre-existing vulnerability markers for later development of illness (Allott et al., 2016), giving credence to the idea that low IQ can be considered a risk factor for mental health problems other than psychosis.
Studies conducted in populations of adults with MDD have found that out of several clinical and psychological variables, only depressive symptomatology at baseline could significantly improve the prediction accuracy of the presence of MDD at follow-up (Dinga et al., 2018). Previous UHR studies have generally not taken into account meeting criteria for MDD at baseline in addition to neurocognitive status at baseline, to predict follow-up outcomes.
It is often difficult to identify which UHR individuals will develop MDD based solely on presenting clinical features (Fusar-Poli et al., 2012). This demonstrates a clear need for the identification of other factors, such as neurocognitive variables, to further improve prognostic accuracy (Metzler et al., 2016), with evidence suggesting that combining neurocognitive vulnerability markers with presenting clinical features could improve the accuracy of prediction of psychosis by up to 80% (Koutsouleris et al., 2012). This would also enable identification of risk groups for MDD in UHR through neurocognitive deficits that may be specific for MDD.
Given the lack of research investigating the association between neurocognition and MDD within the at risk mental state, the present study sought to examine neurocognitive functioning in UHR individuals with and without MDD. While controlling for relevant clinical/treatment variables, we also aimed to determine whether neurocognition is an independent predictor of meeting MDD criteria in UHR participants at 12-months and at a mean of 3.4-years follow-up (henceforth referred to as medium-term follow-up). It was hypothesized that: 1) UHR participants meeting criteria for MDD at baseline would have poorer neurocognitive abilities compared to those who do not, and 2) poorer baseline neurocognitive abilities would be significantly associated with meeting criteria for MDD at 12-months and medium-term follow-up, after accounting for clinical characteristics including baseline depression status.
Section snippets
Study design and participants
A secondary analysis of baseline and follow-up data from an international multi-site randomized controlled trial (RCT; ‘NEURAPRO’; trial registration: anzctr.org.au, identifier: 12608000475347) with 304 participants at UHR for psychosis (McGorry et al., 2017), was conducted in the current study. Double-blind randomization was used to assign participants to either the experimental condition in which they were treated with long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs), together with
Participant demographic and clinical information
The sample demographic and clinical information are presented in Table 1. Independent samples t-tests and chi-squared tests were conducted to inspect group differences between individuals with MDD at baseline (N = 119) and those without a history of MDD (N = 88), due to its likely clinical relevance. Those with MDD at baseline had significantly higher levels of negative (p < .001) and positive (p = .04) symptoms compared to those without a history of MDD.
Group differences in baseline neurocognition
The baseline neurocognitive performance
Discussion
The present study examined the neurocognitive functioning of UHR individuals with MDD at baseline compared to those without a history of MDD. It also aimed to determine whether domain-specific neurocognition was significantly associated with MDD outcomes at follow-up, after accounting for MDD status and other relevant clinical variables at baseline. To our knowledge, this is the first study to investigate these questions in the UHR population. After Bonferroni correction no significant
Role of funding source
This work was supported by grant 07TGF-1102 from the Stanley Medical Research Institute, grant 566529 from the NHMRC Australia Program (Drs McGorry, Hickie, and Yung, and Amminger), and a grant from the Colonial Foundation. Dr. Allott was supported by a NHMRC Career Development Fellowship (#1141207); Dr. McGorry was supported by Senior Principal Research Fellowship 1060996 from the National Health and Medical Research Council of Australia (NHMRC); Drs Yung and Amminger were supported by NHMRC
Contributors
S.M. co-designed the study, undertook the literature search, conducted the statistical analyses and wrote the first draft of the manuscript. K.A. co-designed the study, assisted with statistical analysis, and the writing of the first draft of the manuscript. H.P.Y. assisted with the statistical analyses and writing of the first draft of the manuscript. P.G.A, J.F., L.B and B.N. contributed to the study design and assisted with the writing of the first draft of the manuscript. All remaining
Declaration of competing interest
All authors declare no conflict of interest.
Acknowledgements
We thank the young participants, their families and the Orygen Youth Health clinicians for supporting the study.
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