Negative Symptoms and Functioning in Youth at Risk of Psychosis: A Systematic Review and Meta-analysis

Devoe, Daniel J.; Braun, Amy; Seredynski, Thomas; Addington, Jean

doi:10.1097/hrp.0000000000000273

Cited by 30 publications

(17 citation statements)

References 103 publications

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“…Such results suggest that the abnormal myelination found in our study could underlie poorer functioning and faster functional drop, as well as more severe negative symptoms prior to the onset of psychosis. Largely in line with previous studies, it is recognised that negative symptoms are commonly presented at the premorbid phase of psychosis and are frequently associated with poorer functioning, more cognitive impairments, and worse long-term outcome, especially in youth at CHR of psychosis 32. Since negative symptoms have been conceptualised as the insufficient communication between brain regions, the disrupted myelin found in our CHR sample could underlie the insufficiency of information communication and integration between hemispheres, which subsequently gives rise to negative symptoms.…”

Section: Discussionsupporting

confidence: 77%

Different patterns of association between white matter microstructure and plasma unsaturated fatty acids in those with high risk for psychosis and healthy participants

et al. 2022

Gen Psych

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BackgroundDisrupted white matter (WM) microstructure has been commonly identified in youth at clinical high risk (CHR) for psychosis. Several lines of evidence suggest that fatty acids, especially unsaturated fatty acids (UFAs), might play a crucial role in the WM pathology of early onset psychosis. However, evidence linking UFA and WM microstructure in CHR is quite sparse.AimsWe investigated the relationship between the plasma UFA level and WM microstructure in CHR participants and healthy controls (HC).MethodsPlasma fatty acids were assessed and diffusion tensor imaging (DTI) data were performed with tract-based spatial statistics (TBSS) analysis for 66 individuals at CHR for psychosis and 70 HC.ResultsBoth the global and regional diffusion measures showed significant between-group differences, with decreased fractional anisotropy (FA) but increased mean diffusivity (MD) and radial diffusivity (RD) found in the CHR group compared with the HC group. On top of that, we found that in the HC group, plasma arachidic acid showed obvious trend-level associations with higher global FA, lower global MD and lower global RD, which regionally spread over the corpus callosum, right anterior and superior corona radiata, bilateral anterior and posterior limb of the internal capsule, and bilateral superior longitudinal fasciculus. However, there were no associations between global WM measures and any UFA in the CHR group. Conversely, we even found negative associations between arachidic acid levels and regional FA values in the right superior longitudinal fasciculus and right retrolenticular part of the internal capsule in the CHR group.ConclusionsCompared with the HC group, CHR subjects exhibited a different pattern of association between WM microstructure and plasma UFA, with a neuroprotective effect found in the HC group but not in the CHR group. Such discrepancy could be due to the excessively upregulated UFAs accumulated in the plasma of the CHR group, highlighting the role of balanced plasma-membrane fatty acids homeostasis in WM development.

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Section: Discussionsupporting

confidence: 77%

Different patterns of association between white matter microstructure and plasma unsaturated fatty acids in those with high risk for psychosis and healthy participants

et al. 2022

Gen Psych

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“…Negative symptoms are often the first symptoms that CHR-P individuals develop (Metzak et al ., 2020 ). There is a strong negative relationship between negative symptoms and functioning in CHR-P individuals (Devoe et al ., 2020 ; Metzak et al ., 2020 ), a finding also confirmed in individuals with schizophrenia (Ventura et al ., 2009 ). Therefore, the observed clinical improvements in the severity of core CHR-P symptoms were paralleled by functional improvements at follow-up.…”

Section: Discussionmentioning

confidence: 99%

Clinical outcomes in individuals at clinical high risk of psychosis who do not transition to psychosis: a meta-analysis

Pablo

Soardo

Cabras

et al. 2022

Epidemiol Psychiatr Sci

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Aims The clinical outcomes of individuals at clinical high risk of psychosis (CHR-P) who do not transition to psychosis are heterogeneous and inconsistently reported. We aimed to comprehensively evaluate longitudinally a wide range of outcomes in CHR-P individuals not developing psychosis. Methods “Preferred Reporting Items for Systematic reviews and Meta-Analyses” and “Meta-analysis Of Observational Studies in Epidemiology”-compliant meta-analysis (PROSPERO: CRD42021229212) searching original CHR-P longitudinal studies in PubMed and Web of Science databases up to 01/11/2021. As primary analysis, we evaluated the following outcomes within CHR-P non-transitioning individuals: (a) change in the severity of attenuated psychotic symptoms (Hedge's g); (b) change in the severity of negative psychotic symptoms (Hedge's g); (c) change in the severity of depressive symptoms (Hedge's g); (d) change in the level of functioning (Hedge's g); (e) frequency of remission (at follow-up). As a secondary analysis, we compared these outcomes in those CHR-P individuals who did not transition vs. those who did transition to psychosis at follow-up. We conducted random-effects model meta-analyses, sensitivity analyses, heterogeneity analyses, meta-regressions and publication bias assessment. The risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale (NOS). Results Twenty-eight studies were included (2756 CHR-P individuals, mean age = 20.4, 45.5% females). The mean duration of follow-up of the included studies was of 30.7 months. Primary analysis: attenuated psychotic symptoms [Hedges’ g = 1.410, 95% confidence interval (CI) 1.002–1.818]; negative psychotic symptoms (Hedges’ g = 0.683, 95% CI 0.371–0.995); depressive symptoms (Hedges’ g = 0.844, 95% CI 0.371–1.317); and functioning (Hedges’ g = 0.776, 95% CI 0.463–1.089) improved in CHR-P non-transitioning individuals; 48.7% remitted at follow-up (95% CI 39.3–58.2%). Secondary analysis: attenuated psychotic symptoms (Hedges’ g = 0.706, 95% CI 0.091–1.322) and functioning (Hedges’ g = 0.623, 95% CI 0.375–0.871) improved in CHR-P individuals not-transitioning compared to those transitioning to psychosis, but there were no differences in negative or depressive symptoms or frequency of remission (p > 0.05). Older age was associated with higher improvements of attenuated psychotic symptoms (β = 0.225, p = 0.012); publication years were associated with a higher improvement of functioning (β = −0.124, p = 0.0026); a lower proportion of Brief Limited Intermittent Psychotic Symptoms was associated with higher frequencies of remission (β = −0.054, p = 0.0085). There was no metaregression impact for study continent, the psychometric instrument used, the quality of the study or proportion of females. The NOS scores were 4.4 ± 0.9, ranging from 3 to 6, revealing the moderate quality of the included studies. Conclusions Clinical outcomes improve in CHR-P individuals not transitioning to psychosis but only less than half remit over time. Sustained clinical attention should be provided in the longer term to monitor these outcomes.

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“…This is an important finding as both negative symptoms and social functioning are considered the hardest to treat. Although some recent meta-analytic evidence showed small effects of cognitive behaviorally informed interventions on negative symptoms 38,39 and functioning 38 in individuals with psychosis, two meta-analyses specifically focusing on youth at clinical high risk for psychosis concluded that, currently, no effective treatments are available for either improving functioning 40 or ameliorating negative symptoms 41 in the early stages of psychosis. Yet, negative symptoms are considered the most disabling symptoms 42,43 , being closely associated with lower levels of functioning and higher risk for a more disabling course of illness.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Acceptance and Commitment Therapy in Daily Life (ACT-DL) in early psychosis: Results from the multi-center INTERACT randomized controlled trial

Myin-Germeys

Aubel

Vaessen

et al. 2021

Preprint

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Importance Treatment in the early stages of psychosis is crucial to prevent poor clinical and social outcomes. Currently, no preventive interventions are available that reduce psychotic distress, or affective and negative symptoms as well as functioning, calling for more and dedicated treatments for these. Objective To investigate the efficacy of Acceptance and Commitment Therapy in Daily Life (ACT-DL), combining face-to-face therapy with an Ecological Momentary Intervention (EMI), in addition to treatment as usual for psychotic distress, in comparison to treatment as usual only. Design This single-blinded randomized clinical INTERACT trial investigated participants post-intervention and at 6 and 12-month follow-up. Participants were recruited between June 1, 2015 and December 31, 2018. Assessors were blinded to treatment allocation. Setting INTERACT is a multi-center trial recruiting participants from secondary mental health services in 5 regions in Belgium and The Netherlands. Participants The sample was a referral sample of individuals aged 15-65 years with a clinically established UHR or FEP status. Interventions Individuals were randomly assigned (1:1) to ACT-DL, consisting of 8 ACT sessions augmented with an EMI app in addition to treatment as usual, or to treatment as usual only. Main outcomes and measures The primary outcome was a reduction in psychotic distress as assessed with CAARMS at post-intervention, 6- and 12-month follow-up. Secondary outcomes included symptom severity (measured with BPRS and BNNS), functioning (measured with SOFAS and SFS) and momentary psychotic distress (measured with the Experience Sampling Method, a structured diary technique). All analyses were described in the trial protocol and in a postregistration on the open-science framework, prior to accessing the data. Results Of the 196 individuals assessed for eligibility, 148 were randomized to ACT-DL+TAU (n=71) or TAU (n=77) (72 female (49%), average age 25 (SD = 6), 71 FEP (48%)). 115 (78%) provided primary outcome data at least at one follow-up assessment. There was no evidence of a greater reduction in CAARMS distress in ACT-DL+TAU compared to TAU (χ2(3)=2.38; p=.50). However, general psychopathology (χ2(3)=14.44; p=.002); affective (χ2(3)=8.55; p=.04) and negative symptom severity (χ2(3)=19.96; p<.001) as measured with the BPRS was reduced, as well as negative symptoms as assessed with BNNS (χ2(3)=15.96; p=.001) in. Furthermore, global functioning improved (χ2(3)=8.72; p=.033) in ACT-DL+TAU compared to TAU, whereas social functioning failed to reach significance (χ2(3)=7.41; p=.060). Finally, a clear and significant reduction was found in momentary psychotic distress (χ2(3)=21.56; p<0.001), whereas no effects were found for momentary psychotic experiences (χ2(3)=1.02; p=.599), momentary positive (χ2(3)=4.17; p=.124) or negative (χ2(3)=2.78; p=.249) affect. No serious adverse events directly related to the therapy occurred. Conclusions and relevance INTERACT did not support a significant effect on psychotic distress as assessed with the CAARMS. However, significant improvements were found for momentary psychotic distress, global functioning and negative symptomatology. These results are promising given that these latter problems are among the hardest to treat.

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Negative Symptoms and Functioning in Youth at Risk of Psychosis: A Systematic Review and Meta-analysis

Cited by 30 publications

References 103 publications

Different patterns of association between white matter microstructure and plasma unsaturated fatty acids in those with high risk for psychosis and healthy participants

Different patterns of association between white matter microstructure and plasma unsaturated fatty acids in those with high risk for psychosis and healthy participants

Clinical outcomes in individuals at clinical high risk of psychosis who do not transition to psychosis: a meta-analysis

Efficacy of Acceptance and Commitment Therapy in Daily Life (ACT-DL) in early psychosis: Results from the multi-center INTERACT randomized controlled trial

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