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  • Comasco, Erika, et al. (författare)
  • Genetic and Functional Study of L-Type Amino Acid Transporter 1 in Schizophrenia
  • 2017
  • Ingår i: Neuropsychobiology. - Basel : S. Karger. - 0302-282X .- 1423-0224. ; 74:2, s. 96-103
  • Tidskriftsartikel (refereegranskat)abstract
    • Schizophrenia involves neural catecholaminergic dysregulation. Tyrosine is the precursor of catecholamines, and its major transporter, according to studies on fibroblasts, in the brain is the L-type amino acid transporter 1 (LAT1). The present study assessed haplotype tag single-nucleotide polymorphisms (SNPs) of the SLC7A5/LAT1 gene in 315 patients with psychosis within the schizophrenia spectrum and 233 healthy controls to investigate genetic vulnerability to the disorder as well as genetic relationships to homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major catecholamine metabolites in the cerebrospinal fluid (CSF). Moreover, the involvement of the different isoforms of the system L in tyrosine uptake and LAT1 tyrosine kinetics were studied in fibroblast cell lines of 10 patients with schizophrenia and 10 healthy controls. The results provide suggestive evidence of individual vulnerability to schizophrenia related to the LAT1 SNP rs9936204 genotype. A number of SNPs were nominally associated with CSF HVA and MHPG concentrations but did not survive correction for multiple testing. The LAT1 isoform was confirmed as the major tyrosine transporter in patients with schizophrenia. However, the kinetic parameters (maximal transport capacity, affinity of the binding sites, and diffusion constant of tyrosine transport through the LAT1 isoform) did not differ between patients with schizophrenia and controls. The present genetic findings call for independent replication in larger samples, while the functional study seems to exclude a role of LAT1 in the aberrant transport of tyrosine in fibroblasts of patients with schizophrenia.
  • Oreland, Sadia, et al. (författare)
  • Does the transcription factor AP-2beta have an impact on the genetic and early environmental influence on ethanol consumption?
  • 2010
  • Ingår i: Journal of neural transmission. - 0300-9564 .- 1435-1463. ; 117:9, s. 1077-1081
  • Tidskriftsartikel (refereegranskat)abstract
    • Genes involved in alcoholism have consensus sites for the transcription factor activator protein (TFAP) 2beta. In the present study, we investigated TFAP-2beta protein levels in the ethanol-preferring alko, alcohol (AA) and the ethanol-avoiding alko, non-alcohol (ANA) rat lines. Furthermore, basal and ethanol-induced TFAP-2beta levels were examined in Wistar rats exposed to different early postnatal environments that are known to affect later ethanol consumption. Taken together, we found differences in brainstem TFAP-2beta protein between the AA and ANA rats.
  • Oreland, Sadia, et al. (författare)
  • Ethanol-induced effects on the dopamine and serotonin systems in adult Wistar rats are dependent on early-life experiences
  • 2011
  • Ingår i: Brain Research. - 0006-8993 .- 1872-6240. ; 1405, s. 57-68
  • Tidskriftsartikel (refereegranskat)abstract
    • Some individuals control their ethanol consumption throughout life, but others escalate their intake to levels that increase the risk for addiction. The early environment influences the individual response to ethanol and affects the underlying physiological processes that lead to a transition from a voluntary to a compulsive use of ethanol. However, the neurobiological substrates for these processes are not understood. The present study aimed to test the hypothesis that early environmental experiences affect the neurobiological effects that are induced by voluntary ethanol consumption. Rat pups were subjected to three different rearing environments: conventional animal facility rearing or separation from dam and littermates for either 15 or 360 min. In adulthood, the rats were exposed to a two-bottle free choice between ethanol and water for seven weeks. Tissue levels of dopamine, 5-hydroxytryptamine (5-HT) and their metabolites were measured in brain areas that have been implicated in reward and addiction processes. Differences in ethanol-induced effects were noted in 5-HT-related measurements in the nucleus accumbens and ventral tegmental area and in dopamine-related measurements in the dorsal raphe nucleus (DRN). These results provided evidence of an early environmental impact on interactive neuronal circuits between the DRN and reward pathways. The amygdala, a key area in addiction processes, was particularly sensitive to early-life conditions. The animals that experienced the longest separation differed from the others; they had low basal 5-HT levels and responded with an increase in 5-HT after ethanol. These altered responses to initial ethanol consumption as a result of early environmental factors may affect the transition from habitual to compulsive drinking and contribute to individual vulnerability or resilience to addiction.
  • Oreland, Sadia, et al. (författare)
  • Two repeated maternal separation procedures differentially affect brain 5-hydroxytryptamine transporter and receptors in young and adult male and female rats
  • 2009
  • Ingår i: Brain Research. - : Elsevier. - 0006-8993 .- 1872-6240. ; 1305:Suppl. 1, s. S37-S49
  • Tidskriftsartikel (refereegranskat)abstract
    • Early environment is a known determinant for individual differences in vulnerability for adult psychopathology, e.g. ethanol addiction. One underlying mechanism could be dysfunction in serotonergic neurotransmission. This study focused on the methodological considerations regarding an animal model for studying effects of early environment, maternal separation (MS), using two different paradigms. Age- and sex-specific effects on brain stem 5-hydroxytryptamine (5-HT) transporter and receptors were examined. Male and female rat pups were assigned to either litter-wise MS for 15 or 360 minutes (MS15l or MS360l) or individual MS for 15 or 360 minutes (MS15i or MS360i) daily during postnatal days 1-21. Normal animal facility reared rats were used as controls. Analyses were performed in young and adult rats. As compared to the other males, MS15l males had lower 5-HT1A and 5-HT2C receptor mRNA expression at both ages, lower 5-HT2A receptor mRNA when young and lower 5-HTT mRNA expression when adult. In contrast, adult MS15l females had higher 5-HT2C receptor mRNA expression than the other females. The strong impact of MS15l on 5-HT-related genes was either transient or persistent depending on sex and fewer effects on gene expression were observed in females than in males. This study shows the importance of tactile contact for the consequences of short, but not long MS, as evidenced by major differences between MS15l and MS15i. The results suggest that MS15i is less suitable than MS15l to simulate a protective environment in studies of for instance ethanol addiction processes. 
  • Ruchkin, Vladislav V, et al. (författare)
  • Platelet MAO-B, personality, and psychopathology
  • 2005
  • Ingår i: Journal of Abnormal Psychology. - 0021-843X .- 1939-1846. ; 114:3, s. 477-482
  • Tidskriftsartikel (refereegranskat)abstract
    • The article investigates the relationships between platelet monoamine oxidase-B (MAO-B) activity, personality, and psychopathology (Diagnostic and Statistical Manual of Mental Disorders [4th ed.; American Psychiatric Association, 1994] diagnoses. These relationships were assessed in 178 incarcerated male juvenile delinquents. Even after controlling for smoking, the authors found that both Internalizing and Externalizing Psychopathology were negatively related to MAO-B activity. In the final reduced model, novelty seeking fully mediated the relationships between MAO-B and Externalizing Psychopathology but not between MAO-B and Internalizing Psychopathology. It was hypothesized that low platelet MAO-B activity does not directly predispose individuals to psychopathology but is related to specific personality traits, which in turn represent a vulnerability factor for psychopathology. Future studies should help clarify the nature of the relationships between personality, biological markers, and psychopathology.
  • af Klinteberg, Britt, et al. (författare)
  • On the psychobiology of impulsivity
  • 2004
  • Ingår i: On the psychobiology of personality. - : Elsevier B.V., Amsterdam. - 0080442099 ; , s. 455-478
  • Bokkapitel (refereegranskat)
  • af Klinteberg, Britt, et al. (författare)
  • Smoking habits – Associations with personality/behavior, platelet monoamine oxidase activity and plasma thyroid hormone levels
  • 2017
  • Ingår i: Personality and Individual Differences. - : Elsevier. - 0191-8869 .- 1873-3549. ; 118, s. 71-76
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective was to outline results from our scientific studies on the associations among childhood behavior, adult personality, and biochemical factors in smoking habits. The studies consisted of: (1) follow-up of young criminals and controls, subdivided into risk for antisocial behavior groups, based on childhood rating levels of a projective test; and adult smoking habit groups; and (2) a large group of young adults examined on the same inventories. Personality in terms of KSP and EPQ-I scale scores, controlled for intelligence, indicated that the high and very high risk groups displayed significantly higher self-rated impulsiveness, anxiety, and nonconformity, as compared to the low risk group. Further, the very high risk group subjects, found to be overrepresented among subjects with heavy smoking habits, displayed lower mean platelet MAO-B activity and higher thyroid hormone levels than the low risk group. Thus, the higher the childhood risk for antisocial behavior, the clearer the adult personality pattern making subjects more disposed for smoking appeared; and the higher smoking habits, the stronger the relationships with biochemical measures. Results are discussed in terms of possible underlying mechanisms influencing personality and smoking habits.
  • Comasco, Erika, et al. (författare)
  • Adolescent alcohol consumption : Biomarkers PEth and FAEE in relation to interview and questionnaire data
  • 2009
  • Ingår i: Journal of Studies on Alcohol and Drugs. - : Alcohol Research Documentation, Inc.. - 1937-1888 .- 1938-4114. ; 70:5, s. 797-804
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE  The aim of this study was to investigate the congruence of biomarkers, questionnaires, and interviews as instruments to assess adolescent alcohol consumption. METHOD  The methodology used was a cross-sectional study with a randomized sample. Four different methods were used to estimate high adolescent alcohol consumption. The concordance of the results was investigated. Surveys were performed, and biological specimens were collected at all schools in the county of Västmanland, Sweden, in 2001. Eighty-one boys and 119 girls from a population of 16- and 19-year-old adolescents were randomly selected from quartiles of volunteers representing various degrees of psychosocial risk behaviors. Using a questionnaire (for a 1-hour session) and in-depth interviews, subjects were assessed regarding their alcohol-use habits. Blood and hair samples were analyzed for phosphatidylethanol (PEth) and fatty acid ethyl esters (FAEEs), respectively. RESULTS  High alcohol consumption was underreported in the questionnaire compared with the interviews. PEth and FAEE analyses weakly confirmed the self-reports, and the results of the two biochemical tests did not overlap. The PEth blood test was the most specific but the least sensitive, whereas the FAEE hair test revealed low specificity and an overrepresentation of positive results in girls. CONCLUSIONS The expected higher self-report of high alcohol consumption by interview rather than by questionnaire was confirmed partly because of the influence of a bogus pipeline procedure. The absence of overlap between PEth and FAEE results and their poor agreement with self-reports suggested that biomarkers are unsuitable as screening tools for alcohol consumption in adolescents.
  • Comasco, Erika, et al. (författare)
  • Alcohol Consumption Among Pregnant Women in a Swedish Sample and Its Effects on the Newborn Outcomes
  • 2012
  • Ingår i: Alcoholism. - 0145-6008 .- 1530-0277. ; 36:10, s. 1779-1786
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Little is known about the effects of low levels of maternal alcohol intake on the neuropsychological development of the child. This study is part of an ongoing investigation on maternal drinking and presents data on demographic variables, maternal alcohol use, and birth outcomes from that study. Methods The sample comprised 2,264 women from a Swedish antenatal clinic. Retrospective self-report data were collected on alcohol consumption before and during pregnancy, using the Alcohol Use Disorders Identification Test (AUDIT), and on nicotine use. Specific alcohol biomarkers for excessive drinking, carbohydrate-deficient transferrin (CDT) in serum and phosphatidylethanol (PEth) in whole blood, were determined during mid-pregnancy in a subsample of the women. Data on labor and early characteristics of the child were also assessed. Results Before pregnancy, 89% of the women regularly consumed alcohol and 49% reported occasional or frequent binge drinking. Nicotine was used by 15% before and by 5% during pregnancy. During pregnancy, 12% continued using alcohol and 5% also admitted binge drinking. However, all alcohol biomarker values were below the reporting limits (CDT = 1.7% disialotransferrin; total PEth < 0.1 mu mol/L). Self-reported drinking during pregnancy was associated with a higher AUDIT score before pregnancy, nicotine use at the time of the first prenatal visit, older age, and previous legal abortions. Conclusions The AUDIT questionnaire and 2 specific alcohol biomarkers were used in routine maternity care to collect information about drinking during pregnancy and thereby to identify children at risk for alcohol-related complications. While the AUDIT results suggested that a significant number of women continued using alcohol during pregnancy, implying a risk for fetal disorders, the biomarkers showed negative test values thus indicating only modest drinking levels.
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