Evidence that complement and coagulation proteins are mediating the clinical response to omega-3 fatty acids: A mass spectrometry-based investigation in subjects at clinical high-risk for psychosis

Preliminary evidence indicates beneficial effects of omega-3 polyunsaturated fatty acids (PUFAs) in early psychosis. The present study investigates the molecular mechanism of omega-3 PUFA-associated therapeutic effects in clinical high-risk (CHR) participants. Plasma samples of 126 CHR psychosis participants at baseline and 6-months follow-up were included. Plasma protein levels were quantified using mass spectrometry and erythrocyte omega-3 PUFA levels were quantified using gas chromatography. We examined the relationship between change in polyunsaturated PUFAs (between baseline and 6-month follow-up) and follow-up plasma proteins. Using mediation analysis, we investigated whether plasma proteins mediated the relationship between change in omega-3 PUFAs and clinical outcomes. A 6-months change in omega-3 PUFAs was associated with 24 plasma proteins at follow-up. Pathway analysis revealed the complement and coagulation pathway as the main biological pathway to be associated with change in omega-3 PUFAs. Moreover, complement and coagulation pathway proteins significantly mediated the relationship between change in omega-3 PUFAs and clinical outcome at follow-up. The inflammatory protein complement C5 and protein S100A9 negatively mediated the relationship between change in omega-3 PUFAs and positive symptom severity, while C5 positively mediated the relationship between change in omega-3 and functional outcome. The relationship between change in omega-3 PUFAs and cognition was positively mediated through coagulation factor V and complement protein C1QB. Our findings provide evidence for a longitudinal association of omega-3 PUFAs with complement and coagulation protein changes in the blood. Further, the results suggest that an increase in omega-3 PUFAs decreases symptom severity and improves cognition in the CHR state through modulating effects of complement and coagulation proteins

Plasma polyunsaturated fatty acids and mental disorders in adolescence and early adulthood: cross-sectional and longitudinal associations in a general population cohort

Polyunsaturated fatty acids (PUFAs) may be pertinent to the development of mental disorders, for example via modulation of inflammation and synaptogenesis. We wished to examine cross-sectional and longitudinal associations between PUFAs and mental disorders in a large cohort of young people. Participants in the Avon Longitudinal Study of Parents and Children were interviewed and provided blood samples at two sampling periods when approximately 17 and 24 years old. Plasma PUFA measures (total omega-6 [n-6], total omega-3 [n-3], n-6:n-3 ratio and docosahexaenoic acid [DHA] percentage of total fatty acids) were assessed using nuclear magnetic resonance spectroscopy. Cross-sectional and longitudinal associations between standardised PUFA measures and three mental disorders (psychotic disorder, moderate/severe depressive disorder and generalised anxiety disorder [GAD]) were measured by logistic regression, adjusting for age, sex, body mass index and cigarette smoking. There was little evidence of cross-sectional associations between PUFA measures and mental disorders at age 17. At age 24, the n-6:n-3 ratio was positively associated with psychotic disorder, depressive disorder and GAD, while DHA was inversely associated with psychotic disorder. In longitudinal analyses, there was evidence of an inverse association between DHA at age 17 and incident psychotic disorder at age 24 (adjusted odds ratio 0.44, 95% confidence interval 0.22–0.87) with little such evidence for depressive disorder or GAD. There was little evidence for associations between change in PUFA measures from 17 to 24 years and incident mental disorders at 24 years. These findings provide support for associations between PUFAs and mental disorders in early adulthood, and in particular, for DHA in adolescence in relation to prevention of psychosis

Towards a new paradigm of care: the International Declaration on Youth Mental Health.

A recent and growing body of evidence on young people\u27s mental health has pointed to the need for an international response to the increasing and concerning rates of mental ill-health among young people.[1, 2] The periods of adolescence and emerging adulthood[3] are considered the peak periods for the onset of mental ill-health[4] with 75% of all adult diagnoses of mental ill-health having had an onset before the age of 25 years.[5] In an era when the physical health of young people has never been better,[6] their psychological and mental health has never been worse.[7] This leaves young people vulnerable to developing potentially intractable and enduring mental health difficulties with the inevitable personal, familial, social and vocational consequences that accompany the experience of mental ill-health.[4, 8] In spite of growing concerns about young people\u27s mental health, service provision for young people remains largely inadequate and unsuited to their needs. A number of systemic factors can be implicated in insufficient and unsuitable mental health service provision for young people. Internationally, there has been an endemic failure to invest in mental health across the lifespan with an average global spend on mental health of less than $US3 per capita per year.[9] This global underinvestment brings with it particular challenges in relation to the level of priority afforded to youth mental health and the concurrent commitment needed to respond to the scale of young people\u27s mental health needs. Even in developed countries where mental health services exist, there are widespread problems with services targeting young people. Primary care and other front line community agencies can struggle to respond to high levels of need, often with little support from specialist mental health services. Specialist mental health services have traditionally followed a paediatric-adult split, with child and adolescent services offering intervention until the largely arbitrary ages of 16 or 18 years and adult services taking all young people 18 years and older.[1] In many instances, there have been gaps in service provision between the ages of 16 and 18 years.[10] This has resulted in many young people being unable to access specialist mental health support during these critical years along with high rates of attrition and dissatisfaction by young people during this transitional period.[11, 12] With a recognition that, in many sociocultural contexts, the transition from adolescence to adulthood is a variable one that spans a period from the mid-teens to the mid- to late-20s,[13] both young people and youth mental health advocates have called for a reorganization of mental health services to mirror this extended developmental period for young people.[2] Not surprisingly, there has been a trend of poor help seeking and engagement by young people in mental health services.[14, 15] A key challenge remains in supporting young people to reach out for help when they need it and early evidence suggests that factors such as ease of access, the physical environment, location, atmosphere, branding and peer influence can promote help seeking among young people.[12] It must be noted, however, that even when services are youth friendly and appropriate to their needs, individual and psychological factors strongly influence help-seeking behaviour among young people experiencing emotional or psychological distress.[16, 17] From both an economic[18] and a human impact perspective, there is a strong rationale to invest in efforts to tackle the reality of mental ill-health among the youth population.[2] Efforts to establish a new youth mental health paradigm have already begun and are gaining momentum internationally, reflected most recently in the establishment of a new International Association for Youth Mental Health (http://www.iaymh.org). The first International Youth Mental Health Conference was held in Melbourne, Australia, in 2010 and the second is being held in 2013 in Brighton, the UK (http://www.iaymh2013.com). Those involved in the youth mental health movement recognize that positively impacting on young people\u27s mental health trajectories requires transformative change. Along with a need for early promotion, detection and intervention, stemming the tide of mental ill-health among young people requires a fundamental change in how we think about young people and their mental health. It demands that we challenge traditional approaches to service development and delivery and replace them with approaches that are inclusive and empowering for young people and their families. Young people and their families need to be involved in designing and implementing more creative, responsive, accessible and youth-friendly mental health services that have the capacity to meet their needs

Functional Outcomes Among Young People With Trajectories of Persistent Childhood Psychopathology

IMPORTANCE Understanding which children in the general population are at greatest risk of poor functional outcomes could improve early screening and intervention strategies. OBJECTIVE To investigate the odds of poor outcomes in emerging adulthood (ages 17 to 20 years) for children with different mental health trajectories at ages 9 to 13 years. DESIGN, SETTING, AND PARTICIPANTS Growing Up in Ireland is a longitudinal, nationally representative population-based cohort study. Data collection began in August 2007 and was repeated most recently in September 2018. All results were weighted to account for sampling bias and attrition and were adjusted for socioeconomic factors. Data analysis took place from October 2022 to April 2023. EXPOSURE Four latent classes captured variation in mental health in children aged 9 and 13 years, based on the parent-completed Strengths and Difficulties Questionnaire. Classes included no psychopathology, internalizing, externalizing, and high (comorbid) psychopathology. Those who remained in the same class from ages 9 to 13 years were included. MAIN OUTCOMES AND MEASURES Poor functional outcomes in emerging adulthood were measured at approximate ages 17 years (range, 16 to 18 years) and 20 years (range, 19 to 21 years). Outcomes included poor mental health, poor physical health, social isolation, heavy substance use, frequent health service use, poor subjective well-being, and adverse educational/economic outcomes. RESULTS Of 5141 included participants, 2618 (50.9%) were male. A total of 3726 (72.5%) were classed as having no childhood psychopathology, 1025 (19.9%) as having persistent externalizing psychopathology, 243 (4.7%) as having persistent internalizing psychopathology, and 147 (2.9%) as having persistent high psychopathology. Having any childhood psychopathology was associated with poorer functional outcomes in emerging adulthood. The internalizing group had elevated odds of most outcomes except for heavy substance use (range of odds ratios [ORs]: 1.38 [95% CI, 1.05-1.81] for frequent health service use to 3.08 [95% CI, 2.33-4.08] for poor mental health). The externalizing group had significantly elevated odds of all outcomes, albeit with relatively small effect sizes (range of ORs: 1.38 [95% CI, 1.19-1.60] for frequent health service use to 1.98 [95% CI, 1.67-2.35] for adverse educational/economic outcomes). The high psychopathology group had elevated odds of all outcomes (nonsignificantly for frequent health service use), though with wide confidence intervals (range of ORs: 1.53 [95% CI, 1.06-2.21] for poor physical health to 2.91 [95% CI, 2.05-4.12] for poor mental health). Female participants with any psychopathology had significantly higher odds of poor physical health and frequent health service use compared with male participants with any psychopathology

ApoE elevation is associated with the persistence of psychotic experiences from age 12 to age 18: Evidence from the ALSPAC birth cohort

Apolipoproteins, which play important roles in lipid metabolism, innate immunity and synaptic signalling, have been implicated in first episode psychosis and schizophrenia. This is the first study to investigate plasma apolipoprotein expression in children with psychotic experiences that persist into adulthood. Here, using semi-targeted proteomic analysis we compared plasma apolipoprotein expression levels in age 12 subjects who reported psychotic experiences at both age 12 and age 18 (n = 37) with age-matched subjects who only experienced psychotic experiences (PEs) at age 12 (n = 38). Participants were recruited from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) cohort who participated in psychiatric assessment interviews at ages 12 and 18. We identified apoE, a protein with significant regulatory activity on cholesterol metabolism in the brain, to be significantly up regulated (p < 0.003) in those with persistent psychotic experiences. We confirmed this finding in these samples using ELISA. Our findings indicate elevated plasma apoE in age 12 children who experience PEs is associated with persistence psychotic experiences