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- Madrid-Gambin, Francisco, et al.
(author)
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Integrated Lipidomics and Proteomics Point to Early Blood-Based Changes in Childhood Preceding Later Development of Psychotic Experiences : Evidence From the Avon Longitudinal Study of Parents and Children
- 2019
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In: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 86:1, s. 25-34
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Journal article (peer-reviewed)abstract
- BACKGROUND: The identification of early biomarkers of psychotic experiences (PEs) is of interest because early diagnosis and treatment of those at risk of future disorder is associated with improved outcomes. The current study investigated early lipidomic and coagulation pathway protein signatures of later PEs in subjects from the Avon Longitudinal Study of Parents and Children cohort.METHODS: Plasma of 115 children (12 years of age) who were first identified as experiencing PEs at 18 years of age (48 cases and 67 controls) were assessed through integrated and targeted lipidomics and semitargeted proteomics approaches. We assessed the lipids, lysophosphatidylcholines (n = 11) and phosphatidylcholines (n = 61), and the protein members of the coagulation pathway (n = 22) and integrated these data with complement pathway protein data already available on these subjects.RESULTS: Twelve phosphatidylcholines, four lysophosphatidylcholines, and the coagulation protein plasminogen were altered between the control and PEs groups after correction for multiple comparisons. Lipidomic and proteomic datasets were integrated into a multivariate network displaying a strong relationship between most lipids that were significantly associated with PEs and plasminogen. Finally, an unsupervised clustering approach identified four different clusters, with one of the clusters presenting the highest case-control ratio (p < .01) and associated with a higher concentration of smaller low-density lipoprotein cholesterol particles.CONCLUSIONS: Our findings indicate that the lipidome and proteome of subjects who report PEs at 18 years of age are already altered at 12 years of age, indicating that metabolic dysregulation may contribute to an early vulnerability to PEs and suggesting crosstalk between these lysophosphatidylcholines, phosphatidylcholines, and coagulation and complement proteins.
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| 2. |
- Yin, Xiaofei, et al.
(author)
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Plasma lipid alterations in young adults with psychotic experiences : A study from the Avon Longitudinal Study of Parents and Children cohort
- 2022
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In: Schizophrenia Research. - : Elsevier. - 0920-9964 .- 1573-2509. ; 243, s. 78-85
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Journal article (peer-reviewed)abstract
- BACKGROUND: Psychotic experiences (PEs) are associated with an increased risk of future psychotic and non-psychotic mental disorders. The identification of biomarkers of PEs may provide insights regarding the underlying pathophysiology.METHODS: The current study applied targeted lipidomic approaches to compare plasma lipid profiles in participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort who did (n = 206) or did not (n = 206) have PEs when aged approximately 24 years.RESULTS: In total, 202 lipids including 8 lipid classes were measured by using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). Eight lipid clusters were generated. Thirteen individual lipids were nominally significantly higher in the PEs group compared to the control group. After correction for multiple comparisons, 9 lipids comprising 3 lysophosphatidylcholines (LPCs), 2 phosphatidylcholines (PCs) and 4 triacylglycerols (TGs) remained significant. In addition, PEs cases had increased levels of TGs and LPCs with a low double bond count.CONCLUSIONS: These findings indicate plasma lipidomic abnormalities in individuals experiencing PEs. The lipidomic profile measures could aid our understanding of the underlying pathophysiological mechanisms.
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| 4. |
- Zammit, Stanley, et al.
(author)
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Individuals, Schools, and Neighborhood. A Multilevel Longitudinal Study of Variation in Incidence of Psychotic Disorders
- 2010
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In: Archives of General Psychiatry. ; 67:9, s. 914-922
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Journal article (peer-reviewed)abstract
- Context Incidence of schizophrenia and other nonaffective psychoses is greater in urban than rural areas, but the reason is unclear. Few studies have examined whether both individual and neighborhood characteristics can explain this association. Furthermore, as has been shown for ethnicity, the effect of individual characteristics may depend on neighborhood context. Objectives To examine (1) whether individual, school, or area characteristics are associated with psychosis and can explain the association with urbanicity and (2) whether effects of individual characteristics on risk of psychosis vary according to school context (reflecting both peer group and neighborhood effects). Design Multilevel longitudinal study of all individuals born in Sweden in 1972 and 1977. Diagnoses were identified through linkage with the Swedish National Patient Register until December 31, 2003. Setting Population-based. Participants A total of 203 829 individuals with data at individual, school, municipality, and county levels. Main Outcome Measures Any nonaffective psychosis, including schizophrenia (881 subjects; 0.43% cumulative incidence). For the study of interactions, the outcome was any psychosis (1944 subjects; 0.95% cumulative incidence). Results Almost all the variance in risk of nonaffective psychosis was explained by individual-level rather than higher-level variation. An association between urbanicity and nonaffective psychosis was explained by higher-level characteristics, primarily school-level social fragmentation. We observed cross-level interactions between individual- and school-level markers of ethnicity, social fragmentation, and deprivation on risk of developing any psychotic disorder, all with qualitative patterns of interaction. Conclusions The association between urbanicity and psychosis appears to be a reflection of increased social fragmentation present within cities. The qualitative interactions observed are consistent with a hypothesis that certain characteristics that define individuals as being different from most other people in their local environment may increase risk of psychosis. These findings have potentially important implications for understanding the etiology of psychotic disorders and for informing social policy.
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