Anne Margrethe Myhre

The impact of ADHD and conduct disorder in childhood on adult delinquency: A 30 years follow-up study using official crime records

BackgroundFew longitudinal studies have explored lifetime criminality in adults with a childhood history of severe mental disorders. In the present study, we wanted to explore the association between adult delinquency and several different childhood diagnoses in an in-patient population. Of special interest was the impact of disturbance of activity and attention (ADHD) and mixed disorder of conduct and emotions on later delinquency, as these disorders have been variously associated with delinquent development.MethodsFormer Norwegian child psychiatric in-patients (n = 541) were followed up 19-41 years after hospitalization by record linkage to the National Register of Criminality. On the basis of the hospital records, the patients were re-diagnosed according to ICD-10. The association between diagnoses and other baseline factors and later delinquency were investigated using univariate and multivariate Cox regression analyses.ResultsAt follow-up, 24% of the participants had been convicted of criminal activity.In the multivariate Cox regression analysis, conduct disorder (RR = 2.0, 95%CI = 1.2-3.4) and hyperkinetic conduct disorder (RR = 2.7, 95% CI = 1.6-4.4) significantly increased the risk of future criminal behaviour. Pervasive developmental disorder (RR = 0.4, 95%CI = 0.2-0.9) and mental retardation (RR = 0.4, 95%CI = 0.3-0.8) reduced the risk for a criminal act. Male gender (RR = 3.6, 95%CI = 2.1-6.1) and chronic family difficulties (RR = 1.3, 95% CI = 1.1-1.5) both predicted future criminality.ConclusionsConduct disorder in childhood was highly associated with later delinquency both alone or in combination with hyperactivity, but less associated when combined with an emotional disorder. ADHD in childhood was no more associated with later delinquency than the rest of the disorders in the study population. Our finding strengthens the assumption that there is no direct association between ADHD and criminality.

Patients with familial hypercholesterolaemia show enhanced spontaneous chemokine release from peripheral blood mononuclear cells ex vivo. Dependency of xanthomas/xanthelasms, smoking and gender.

AIMS Familial hypercholesterolaemia (FH) is associated with increased risk of premature atherosclerosis and coronary artery disease (CAD). However, onset of clinically manifested CAD varies widely among patients with heterozygous FH, and we hypothesized that inflammatory mediators such as chemokines could contribute to atherogenesis in these patients. METHODS AND RESULTS We compared peripheral blood mononuclear cells (PBMCs) from FH patients with an identical mutation with PBMCs from sex- and age-matched healthy controls with respect to spontaneous and oxidized low density lipoprotein (oxLDL)-stimulated release of chemokines. Our main findings were: (1) PBMCs from FH patients spontaneously released significantly higher levels of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and interleukin (IL)-8, and had a significantly lower oxLDL-stimulatory ratio for MIP-1alpha and MIP-1beta than cells from healthy controls. (2) Spontaneous release of these chemokines correlated positively and stimulatory ratio correlated negatively with plasma concentrations of total and LDL cholesterol. (3) Among FH patients, release of MIP-1alpha, MIP-1beta and IL-8 from PBMCs varied with the presence of xanthomas/xanthelasms, smoking and gender. (4) In vitro studies showed that FH serum but not control serum was able to induce enhanced spontaneous release of chemokines in PBMCs from both FH patients and control subjects. CONCLUSIONS Our data may suggest that a pathophysiological consequence of FH is enhanced chemokine responses, which in turn may promote recruitment and activation of leukocytes within the vessel wall, contributing to atherosclerosis as well as to the different phenotypes in these patients with an identical FH mutation.

The impact of ADHD symptoms and global impairment in childhood on working disability in mid-adulthood: a 28-year follow-up study using official disability pension records in a high-risk in-patient population

BackgroundIndividuals with ADHD have been associated with more employment difficulties in early adulthood than healthy community controls. To examine whether this association is attributable specifically to disturbance of activity and attention (ADHD) or to psychopathology in general, we wanted to extend existing research by comparing the rate of mid-adulthood working disabilities for individuals diagnosed with ADHD as children with the rate for clinical controls diagnosed with either conduct disorder, emotional disorder or mixed disorder of conduct and emotions.MethodsFormer Norwegian child-psychiatric in-patients (n = 257) were followed up 17–39 years after hospitalization by record linkage to the Norwegian national registry of disability pension (DP) awards. Based on the hospital records, the patients were re-diagnosed according to ICD-10. Associations between the diagnoses, other baseline factors and subsequent DP were investigated using Kaplan–Meier survival analyses and logrank testing.ResultsAt follow-up, 19% of the participants had received a DP award. In the logrank testing, ADHD was the only disorder associated with a subsequent DP, with 30% being disabled at follow-up (p = 0.01). Low psychosocial functioning (assessed by the Children’s Global Assessment Scale) at admission uniquely predicted future DP (p = 0.04).ConclusionsADHD in childhood was highly associated with later receiving a DP. Our finding of worse prognosis in ADHD compared with other internalizing and externalizing disorders in mid-adulthood supports the assumption of ADHD being specifically linked to working disability. Assessment of psychosocial functioning in addition to diagnostic features could enhance prediction of children who are most at risk of future disability.

Uptake of vitamin A in macrophages from physiologic transport proteins: Role of retinol-binding protein and chylomicron remnants

Vitamin A plays an important role in reducing infectious disease morbidity and mortality by enhancing immunity, an effect that is partly mediated by macrophages. Thus, knowing how these cells take up vitamin A is important. The results in the present study demonstrate that J774 macrophages efficiently take up chylomicron remnant retinyl esters and retinol-binding protein (retinol-RBP) bound retinol by specific and saturable mechanisms. The binding of (125)I-RBP to plasma membrane vesicles demonstrated that the macrophage receptor had a similar binding affinity, as was discovered previously for other cells. The B(max) for the macrophages was smaller than the values reported for placenta, bone marrow, and kidney, but larger than that reported for liver. The J774 cells also bound and took up [(3)H]retinol-RBP. Approximately 50 to 60% of the uptake may compete with excess unlabeled retinol-RBP and approximately 30 to 40% with excess transtyrethin. Following the uptake of [(3)H]retinol-RBP, an extensive esterification occurred: After 5 hours of incubation, 77.8 +/- 3.9% (SD; n = 3) of the cellular radioactivity was recovered as retinyl esters. The J774 cells also demonstrated saturable binding of chylomicron remnant [(3)H]retinyl esters, and a continuous uptake at 37 degrees C followed by an extensive hydrolysis of the retinyl esters. Binding could be inhibited by approximately 50% by excess unlabeled low density lipoprotein (LDL). In addition, lipoprotein lipase increased the binding of chylomicron remnant [(3)H]retinyl esters by approximately 30% and the uptake of chylomicron remnant [(3)H]retinyl ester by more than 300%. Furthermore, because sodium chlorate reduced binding with 40% and uptake with 55%, the results suggest that proteoglycans are involved in the uptake. Thus, the results suggest that both LDL receptor and LDL-related protein are involved in the uptake of chylomicron remnant [(3)H]retinyl ester in macrophages.

Exploring the agreement between questionnaire information and DSM-IV diagnoses of comorbid psychopathology in children with autism spectrum disorders:

Autism spectrum disorders are often comorbid with other psychiatric symptoms and disorders. However, identifying psychiatric comorbidity in children with autism spectrum disorders is challenging. We explored how a questionnaire, the Child Behavior Check List, agreed with a Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition (DSM-IV)-based semi-structured interview, the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children (Kiddie-SADS). The sample comprised 55 children and adolescents (age 6 to 18 years) with autism spectrum disorders, including the main autism spectrum disorder subgroups and the broad range of cognitive and language functioning. High rate of psychopathology was found both through questionnaire and interview assessment. Using predefined Child Behavior Check List cutoffs, we found good agreement between the Child Behavior Check List and the Kiddie-SADS for identifying attention deficit/hyperactivity disorder, depressive disorders, and oppositional defiant disorder. However, overall the specificity of the Child Behavior Check List was low. The Child Behavior Check List was not useful for identifying anxiety disorders. The Child Behavior Check List may capture core symptoms of autism spectrum disorders as well as comorbid psychopathology, and clinicians should be aware that the Child Behavior Check List may be unspecific when used in children and adolescents with autism spectrum disorders.

Co-Occurrence of ODD and CD in Preschool Children With Symptoms of ADHD:

Objective: Patterns of co-occurrence between ADHD, Oppositional Defiant Disorder (ODD), and Conduct Disorder (CD) were examined in a sample of non-referred preschool children. ADHD subtypes and sex differences were also explored. Method: Children aged 3.5 years (n = 1,048) with high scores on ADHD characteristics were recruited from the Norwegian Mother and Child Cohort Study and clinically assessed, including a semi-structured psychiatric interview. Results: In children with ADHD, concurrent ODD was present more often than CD (31% vs. 10%), but having ADHD gave higher increase in the odds of CD than of ODD (ODD: odds ratio [OR] = 6.7, 95% confidence interval [CI] = [4.2, 10.8]; CD: OR = 17.6, 95% CI = [5.9, 52.9]). We found a greater proportion of children having the combined ADHD subtype as well as more severe inattentiveness among children with co-occurring CD compared with ODD. Sex differences were minor. Conclusion: There are important differences in co-occurring patterns of ODD and CD in preschool children with ADHD.

Retinoylation of proteins in a macrophage tumor cell line J774, following uptake of chylomicron remnant retinyl ester

Abstract Following uptake of chylomicron remnant retinyl esters by the macrophage cell line J774, the retinyl esters are hydrolyzed to retinol before retinol is further metabolized to retinal and the various retinoic acid isoforms. One hour after the addition of chylomicron remnant [ 3 H]retinyl esters to the cells, the percentage of cell-associated radioactivity in the retinyl ester fraction had decreased from approximately 90% to approximately 40%, whereas the radioactivity in the retinol fraction increased correspondingly. After 4 hours of incubation, more than 79% of the radioactive retinyl esters had been hydrolyzed to retinol. When we measured incorporation of radioactivity in the protein fraction, we observed that the level of [ 3 H]retinoylated proteins increased rapidly the first 4 hours, and then continued to increase at a lower rate up to 24 hours, when approximately 0.6% of the cell-associated radioactivity was covalently bound to protein. These data suggest that approximately 0.18% of all the cellular proteins might be retinoylated under such conditions. In summary, in the present study we have demonstrated that retinoids taken up by a macrophage cell line as chylomicron remnant retinyl esters, a physiologic plasma transport molecule for vitamin A, might be covalently linked to proteins. Such retinoylation might be relevant both for normal function, as well as for the toxic and teratogenic effects of vitamin A.

The Association between Hair Cortisol and Self-Reported Symptoms of Depression in Pregnant Women

Depression has been linked to an imbalance in cortisol. Until recently, cortisol has been studied by measuring concentrations at single time points in blood or saliva samples. Cortisol concentrations vary with circadian rhythm and experiences, from time point to time point. The measurement of hair cortisol concentration (HCC) is a new method of accessing mean, long-term cortisol concentrations. Recent studies show positive associations between depression and HCC, and prenatal maternal cortisol is thought to influence the developing fetus. We therefore examined the association between HCC and self-reported symptoms of depression in second trimester pregnant women. Participants were 181 women, recruited between September 2011 and October 2013 to the Little-in-Norway (LiN)-study. These women answered the Edinburgh Postnatal Depression Rating Scale (EPDS) on self-reported symptoms of depression, and one cm maternal scalp hair was collected and analyzed for cortisol concentrations. Multiple regression analyses did not show depressive symptoms as a predictor for HCC in our selection of pregnant women, while gestational age was significantly related. In conclusion, our study indicated that symptoms of depression during pregnancy did not predict HCC, but further studies of clinically depressed, pregnant women using gestational age as an adjustment variable are warranted.

Retinoylation of proteins in rat hepatocytes following uptake of chylomicron remnant retinyl ester.

Several proteins may covalently bind retinoic acid, a process called retinoylation. Recently, we have demonstrated that proteins were retinoylated in vivo in liver, kidney and lung. In order to gain further knowledge about the mechanism of this process, we studied retinoylation in rat hepatocytes administered vitamin A as [3H]retinyl esters in chylomicron remnants. This resembles the normal physiological uptake of vitamin A. After 24 h incubation, about 0.0017 mol [3H]retinoid was covalently bound per mol protein. Citral, an inhibitor of the oxidation of retinol to retinoic acid, reduced retinoylation about 40%, indicating that oxidation of retinol to retinoic acid is necessary for a large fraction of the observed covalent modification of proteins. When cells were incubated with physiological concentrations of [3H]retinol or [3H]retinoic acid dissolved in ethanol, much less retinoid was covalently bound per mol protein compared with cells incubated with chylomicron remnant. Saturation of the retinoylation was apparent with retinoic acid around the physiological concentration. Retinoylated proteins were also analysed by SDS-PAGE. In general, the same protein bands were labelled with both [3H]retinol and [3H]retinoic acid, although the intensity of the bands varied. Major bands had an apparent molecular weight of about 16, 35, 50 and 120 kDa. In a parallel experiment in which liver stellate cells were incubated with [3H]retinol, major retinoylated protein bands were about 35, 60 and 65 kDa. Thus, different proteins appear to be retinoylated in hepatocytes and liver stellate cells, suggesting that protein retinoylation is a cell specific phenomenon. These results demonstrate that retinoids presented to hepatocytes as chylomicron remnant retinyl esters are covalently linked to proteins. We therefore suggest that retinoylation of proteins represents a minor but significant pathway whereby cells metabolize vitamin A.

Healthy Adolescent Performance With Standardized Scoring Tables for the MATRICS Consensus Cognitive Battery: A Multisite Study

Abstract Objective The aim of this study was to develop standardized scores and scoring tables for test performance in healthy adolescents for the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) for each year from 11 to 19 years of age, by sex, with T scores and percentile ranks. Methods A total of 502 healthy participants (aged 11–19 years) from 7 cohorts from Ireland, Norway, Sweden, and United States, were included in this multisite study. Regression-predicted means for the MCCB tests, except the social cognition subtest, were calculated using the MCCB test scores as outcome variables and age, age2, sex, age × sex as predictors. The regression-predicted means for each combination of age and sex were added with the residuals from the entire cohort to yield the expected distribution of that group. Age effects were examined using regression models with age and age2 as predictors. Sex differences were examined using Student’s t-tests. Results Significant positive age effects were found for all tests, except for the Brief Visuospatial Memory Test, revised (BVMT-R; measure of visual learning). Females performed significantly better than males on BACS Symbol coding (measure of speed of processing) and BVMT-R, while males performed significantly better than females on NAB Mazes (measure of reasoning and problem solving). Based on the regression-predicted distributions of scores, 19 standardized scoring tables for each test and domain were created. Conclusions With the results from this study, we have developed an accessible standardized data set of healthy adolescent test performance for the MCCB.