Search

Background: Psychoses, especially schizophrenia, are often preceded by cognitive deficits and psychosis risk states. Altered metabolic profiles have been found in schizophrenia. However, the associations between metabolic profiles and poorer cognitive performance and psychosis risk in the population remain to be determined. Methods: Detailed molecular profiles were measured for up to 8976 individuals from two general population-based prospective birth cohorts: the Northern Finland Birth Cohort 1986 (NFBC 1986) and the Avon Longitudinal Study of Parents and Children (ALSPAC). A high-throughput nuclear magnetic resonance spectroscopy platform was used to quantify 70 metabolic measures at age 15–16 years in the NFBC 1986 and at ages 15 and 17 years in ALSPAC. Psychosis risk was assessed using the PROD-screen questionnaire at age 15–16 years in the NFBC 1986 or the psychotic-like symptoms assessment at age 17 years in ALSPAC. Cognitive measures included academic performance at age 16 years in both cohorts and general intelligence and executive function in ALSPAC. Logistic regression measured cross-sectional and longitudinal associations between metabolic measures and psychosis risk and cognitive performance, controlling for important covariates. Results: Seven metabolic measures, primarily fatty acid (FA) measures, showed cross-sectional associations with general cognitive performance, four across both cohorts (low density lipoprotein diameter, monounsaturated FA ratio, omega-3 ratio and docosahexaenoic acid ratio), even after controlling for important mental and physical health covariates. Psychosis risk showed minimal metabolic associations. Conclusions: FA ratios may be important in marking risk for cognitive deficits in adolescence. Further research is needed to clarify whether these biomarkers could be causal and thereby possible targets for intervention.

Psychotic disorders usually become evident during adolescence and early adulthood and are commonly preceded by psychosis risk states. Young people at risk for developing psychosis may already have cognitive deficits. This research examined factors associated with psychosis risk and adverse cognitive performance, particularly in those at risk for developing psychosis. We aimed to characterise genetic risk factors for psychosis risk and adverse cognitive performance. Additionally, early and later biological risk markers for adverse cognitive performance and psychosis risk were explored. Two longitudinal birth cohorts, the Northern Finland Birth Cohort 1986 (NFBC 1986, n=6,985 at 16 years) and Avon Longitudinal Study of Parents and Children (ALSPAC, n=5,217 at 17 years), two NFBC 1986 sub-studies, the Oulu Brain and Mind 1 (n=182 for these analyses) and Oulu Brain and Mind 2 (n=471 for these analyses) studies, and two Irish case control studies, the Adolescent Brain Development (n=212) and Challenging Times (n=211) studies, were utilised. Predictors of interest were selected Single Nucleotide Polymorphisms (SNPs at COMT, BDNF and DRD2), prenatal exposure to maternal cigarette smoking (PEMCS) and adolescent metabolic measures. Though not directly associated with psychotic experiences, the COMT-Val158Met Val-Val genotype interacted with experience of childhood trauma to predict more psychotic experiences. Two DRD2 SNPs were associated with poorer cognitive performance, though only in those with risk for psychotic disorders. PEMCS was associated with adult vocabulary and matrix reasoning performance in males, though not in males with adolescent psychotic experiences. Adolescent academic performance, but not psychotic experiences, were associated with metabolic measures, especially with ratios of omega-3 to total fatty acids. These findings impact on prevention strategies for long-term adverse outcomes. Some risk factors differ for those with psychotic experiences compared to the general population, while others do not. SNPs at COMT and DRD2 may be more relevant in those with psychotic experiences. Interventions targeting these groups may be particularly beneficial. Smoking in pregnancy, however, is harmful to male cognitive performance across the population, suggesting elimination of this risk is more broadly relevant. Fatty acid-related metabolic measures may mark risk for cognitive deficits or may represent a developmental feature that is potentially open to intervention. Tiivistelmä Psykoottiset häiriöt puhkeavat tavallisesti nuoruusiässä tai varhaisessa aikuisiässä. Varsinaista psykoosijaksoa edeltää usein psykoosialttiusvaihe. Nuoruusiän psykoosialttiusvaiheeseen liittyy kognitiivisia puutoksia. Tässä tutkimuksessa selvitettiin tekijöitä, jotka liittyvät psykoosialttiuteen ja heikkoon kognitiiviseen suoriutumiseen, etenkin nuorilla, jotka olivat psykoosiriskissä. Tutkimuksessa tarkasteltiin psykoosialttiuteen ja heikkoon kognitiiviseen suoriutumiseen liittyviä geneettisiä tekijöitä. Lisäksi tutkittiin biologisia varhaisia ja myöhempiä psykoosialttiutta ja heikkoa kognitiivista suoriutumista ennustavia tekijöitä. Tutkimusaineisto käsitti kaksi pitkittäistä syntymäkohorttia: Pohjois-Suomen syntymäkohortti 1986 (n=6,985 16-vuotiaana) ja englantilainen Avon Longitudinal Study of Parents and Children (ALSPAC, n=5,217 17-vuotiaana) -tutkimukset. Pohjois-Suomen syntymäkohortti 1986:sta analysoitiin kahta ala-otosta eli Aivot ja Mieli I (n=182) ja Aivot ja Mieli II (n=471) tutkimusta. Lisäksi tutkimusaineistoon kuului kaksi irlantilaista tapaus-verrokki tutkimusta: Adolescent Brain Development (n=212) ja Challenging Times (n=211) tutkimukset. Ennustavina tekijöinä tarkasteltiin yhden nukleotidin polymorfismia (Single Nucleotide Polymorphisms, SNP; COMT, BDNF ja DRD2 -geeneissä), äidin raskaudenaikaista tupakointia, lapsuuden traumaattisia kokemuksia ja nuoruusiän metabolisia arvoja. COMT-Val158Met geenin Val-Val genotyyppi ei ollut suoraan yhteydessä psykoottisiin kokemuksiin, mutta yhdessä lapsuuden traumaattisten kokemusten kanssa ennusti suurempaa psykoosioireiden määrää. Kaksi DRD2 SNP-varianttia assosioituivat heikompaan kognitiiviseen suoriutumiseen, vaikkakin vain tutkittavilla jotka olivat psykoosialttiita. Äidin raskaudenaikainen tupakointi ennusti huonompaa kognitiivista suoriutumista pojilla, tosin ei pojilla joilla oli nuoruusiässä psykoosioireita. Metaboliset tekijät, erityisesti omega-3 rasvahapon suhde kokonaisrasvahapon määrään oli yhteydessä koulumenestykseen. Tutkimuksen tulosten perusteella voidaan mahdollisesti suunnitella ennaltaehkäiseviä toimia myöhempien haittojen ehkäisemiseksi. Jotkut tutkituista riskitekijöistä assosioituivat eri tavalla kognitioon psykoosialttiilla kuin yleisväestössä. COMT ja DRD2 geenien variantit psykoosialttiilla saattavat olla keskeisiä. Interventiot nuorille, joilla on nämä variantit ja psykoosioireita, voisivat olla erityisesti hyödyllisiä. Äidin raskauden aikaisen tupakointi ennusti poikien kognitiivista suoriutumista. Äidin raskaudenaikaisen tupakoinnin vähentämisellä olisi suotuinen vaikutus tässäkin suhteessa. Rasvahappoihin liittyvät metaboliset suureet voivat olla riski kognitiivisille puutoksille tai ne voivat merkitä kehityksellistä piirrettä, joka voisi mahdollistaa varhaisen ennaltaehkäisyn.

Plausible diagnostics for the top of the tropical cyclone boundary layer include (i) the top of the layer of strong frictional inflow and (ii) the top of the “well-mixed” layer; that is, the layer over which potential temperature θ is approximately constant. Observations show that these two candidate definitions give markedly different results in practice, with the inflow layer being roughly twice the depth of the layer of nearly constant θ. Here, we will present an analysis of the thermodynamics of the tropical cyclone boundary layer derived from an axisymmetric model. We show that the marked dry static stability in the upper part of the inflow layer is due largely to diabatic effects. The radial wind varies strongly with height, and therefore so does radial advection of θ. This process also stabilizes the boundary layer, but to a lesser degree than diabatic effects. We also show that this differential vertical advection contributes to the observed superadiabatic layer adjacent to the ocean surface, where the vertical gradient of the radial wind is reversed, but that the main cause of this unstable layer is heating from turbulent dissipation. The top of the “well-mixed” layer is thus distinct from the top of the boundary layer in tropical cyclones. The top of the inflow layer is a better proxy for the top of the boundary layer, but is not without limitations. These results may have implications for boundary-layer parameterisations that diagnose the boundary layer depth from thermodynamic, or partly thermodynamic, criteria.