Duration of untreated psychosis and neurocognitive functioning in first-episode psychosis: a systematic review and meta-analysis

Allott, Kelly; Fraguas, David; Bartholomeusz, Cali F.; Díaz‐Caneja, Covadonga M.; Wannan, Cassandra; Parrish, Emma M.; Amminger, G. Paul; Pantelis, Christos; Arango, Celso; McGorry, Patrick D.; Rapado-Castro, Marta

doi:10.1017/s0033291717003002

Cited by 31 publications

(30 citation statements)

References 92 publications

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“…Moreover, we dichotomized DUP into short (<12 months) and long (>12 months) based on a number of studies that used this cutoff to define long and short DUP (refs. 4,[38][39][40][41] ), including those predicting treatment outcomes in early psychosis 42 and poorer outcomes after the first hospitalization 43 .…”

Section: Duration Of Untreated Psychosismentioning

confidence: 99%

Hippocampal glutamate and hippocampus subfield volumes in antipsychotic-naive first episode psychosis subjects and relationships to duration of untreated psychosis

et al. 2020

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Evidence points toward a relationship between longer duration of untreated psychosis (DUP) and worse long-term outcomes in patients with first episode psychosis (FEP), but the underlying neurobiology remains poorly understood. Proton magnetic resonance spectroscopy studies have reported altered hippocampus glutamatergic neurotransmission, and structural MRI as reported hippocampal atrophy that may be associated with memory impairment in schizophrenia. Here, we quantify left hippocampus glutamate (Glx) and left hippocampus subfield volumes in 54 antipsychotic-naive FEP and 41 healthy controls (HC), matched on age, sex, and parental occupation. While there were no significant group difference in Glx levels, hippocampal Glx levels were significantly higher in those who underwent a long DUP (>12 months) compared to those with a short DUP, and compared to HC. Compared to HC, FEP had significantly reduced whole hippocampus volume, as well as of CA1, CA4, granule cell layer, subiculum, and presubiculum subfields. Smaller whole hippocampal volume, as well as CA1, molecular layer, subiculum, presubiculum, and hippocampal tail volumes were significantly associated with longer DUP. However, we found no significant association between hippocampal Glx levels and hippocampal volume or subfields, suggesting that these alterations are not related, or their relationship does not follow a linear pattern. However, our results strongly suggest that one or several pathophysiological processes underlie the DUP. Importantly, our data highlight the critical need for reducing the DUP and for early pharmacological intervention with the hope to prevent structural deficits and, hopefully, improve clinical outcomes.

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Section: Duration Of Untreated Psychosismentioning

confidence: 99%

Hippocampal glutamate and hippocampus subfield volumes in antipsychotic-naive first episode psychosis subjects and relationships to duration of untreated psychosis

et al. 2020

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“…Many mental health services devote significant resources to early intervention in psychosis based, at least partly, on the premise that reducing DUP improves outcomes [10][11][12][13][14][15] . This notion has been investigated in over a hundred studies examining a number of different outcomes, summarized in several meta-analyses [16][17][18][19][20][21][22][23] . However, due to the inclusion of overlapping samples in different meta-analyses, and differences in inclusion criteria, definition of outcomes, reporting standards and analysis techniques, it is difficult to generate a clear hierarchy of evidence.…”

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confidence: 99%

The clinical significance of duration of untreated psychosis: an umbrella review and random‐effects meta‐analysis

et al. 2021

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The idea that a longer duration of untreated psychosis (DUP) leads to poorer outcomes has contributed to extensive changes in mental health services worldwide and has attracted considerable research interest over the past 30 years. However, the strength of the evidence underlying this notion is unclear. To address this issue, we conducted an umbrella review of available meta‐analyses and performed a random‐effects meta‐analysis of primary studies. MEDLINE, Web of Science, PsycINFO and EMBASE were searched from inception to September 3, 2020 to identify relevant meta‐analyses of studies including patients with schizophrenia spectrum disorders, first‐episode psychosis, or affective and non‐affective psychosis. Thirteen meta‐analyses were included, corresponding to 129 individual studies with a total sample size of 25,657 patients. We detected potential violations of statistical assumptions in some of these meta‐analyses. We therefore conducted a new random‐effects meta‐analysis of primary studies. The association between DUP and each outcome was graded according to a standardized classification into convincing, highly suggestive, suggestive, weak, or non‐significant. At first presentation, there was suggestive evidence for a relationship between longer DUP and more severe negative symptoms (beta=–0.07, p=3.6×10–5) and higher chance of previous self‐harm (odds ratio, OR=1.89, p=1.1×10–5). At follow‐up, there was highly suggestive evidence for a relationship between longer DUP and more severe positive symptoms (beta=–0.16, p=4.5×10–8), more severe negative symptoms (beta=–0.11, p=3.5×10–10) and lower chance of remission (OR=2.16, p=3.0×10–10), and suggestive evidence for a relationship between longer DUP and poorer overall functioning (beta=–0.11, p=2.2×10–6) and more severe global psychopathology (beta=–0.16, p=4.7×10–6). Results were unchanged when analysis was restricted to prospective studies. These effect sizes are clinically meaningful, with a DUP of four weeks predicting >20% more severe symptoms at follow‐up relative to a DUP of one week. We conclude that DUP is an important prognostic factor at first presentation and predicts clinically relevant outcomes over the course of illness. We discuss conceptual issues in DUP research and methodological limitations of current evidence, and provide recommendations for future research.

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“…They were also younger and had a longer DUP. While longer DUP is associated with poorer outcomes in general (Marshall et al ., 2005; Perkins et al ., 2005), a recent meta-analysis found that the relationship between DUP and most cognitive domains is not significant, particularly for studies with DUP longer than 1 year (Allott et al ., 2017), as was the case for this study.…”

Section: Discussionmentioning

confidence: 52%

Cognitive functioning following discontinuation of antipsychotic medication. A naturalistic sub-group analysis from the OPUS II trial

et al. 2018

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Duration of untreated psychosis and neurocognitive functioning in first-episode psychosis: a systematic review and meta-analysis

Abstract: There may not be a generalised association between DUP and neurocognition, however, specific cognitive functions may be associated with longer DUP or delayed help-seeking.

Cited by 31 publications

References 92 publications

Hippocampal glutamate and hippocampus subfield volumes in antipsychotic-naive first episode psychosis subjects and relationships to duration of untreated psychosis

Hippocampal glutamate and hippocampus subfield volumes in antipsychotic-naive first episode psychosis subjects and relationships to duration of untreated psychosis

The clinical significance of duration of untreated psychosis: an umbrella review and random‐effects meta‐analysis

Cognitive functioning following discontinuation of antipsychotic medication. A naturalistic sub-group analysis from the OPUS II trial

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