Rickard L. Sjöberg

Development of depression: sex and the interaction between environment and a promoter polymorphism of the serotonin transporter gene

Previous research has demonstrated that a polymorphism in the serotonin transporter gene (5-HTTLPR) and adverse psychosocial circumstances interact to predict depression. The purpose of the present study was to explore the extent to which sex modulates these effects. Eighty-one boys and 119 girls (16-19 years old) were interviewed about psychosocial background variables and genotyped for the 5-HTT promoter polymorphism. There were two main results. First, boys and girls carrying the short 5-HTTLPR allele react to different kinds of environmental factors. Whereas males were affected by living in public housing rather than in own owned homes and by living with separated parents, females were affected by traumatic conflicts within the family. Second, the responses of males and females carrying the short 5-HTTLPR allele to environmental stress factors go in opposite directions. Thus, whereas females tend to develop depressive symptoms, males seem to be protected from depression. The results suggest that both the molecular and the psychosocial mechanisms underlying depression may differ between boys and girls.

Obesity, Shame, and Depression in School-Aged Children: A Population-Based Study

Objectives. To investigate whether there is an association between adolescent obesity and depression in a nonclinical population and whether psychosocial and economic status and subjective experiences of shame (defined as experiences of being degraded or ridiculed by others) may account for such an association. Method.We examined associations between self-reported body mass index (BMI) and depression, controlling for gender, shame, parental employment, parental separation, and economy. The study was performed on a sample of 4703 adolescents (71% of the target population of 15- and 17-year-old students in 1 Swedish County) who answered the Survey of Adolescent Life in Vestmanland 2004. Results.Obesity was significantly related to depression and depressive symptoms among 15- and 17-year-olds. Obesity was also significantly related to experiences of shame. All significant association between BMI grouping and depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition disappeared when shaming experiences, parental employment, and parental separation were controlled for. Adolescents who reported many experiences of shame had an increased risk (odds ratio: 11.3; confidence interval: 8.3–14.9) for being depressed. Conclusions.There is a significant statistical association between adolescent obesity and depression. Effects of experiences of shame, parental separation, and parental employment explain this association. These results suggest that clinical treatment of obesity may sometimes not just be a matter of diet and exercise but also of dealing with issues of shame and social isolation.

Role of monoamine oxidase A genotype and psychosocial factors in male adolescent criminal activity

BACKGROUND A number of important sociological, psychological, and biological predictors of adolescent criminal behavior have been identified during the most recent decades. The aim of this study was to replicate recent findings that interactions between a polymorphism in the monoamine oxidase A (MAO-A) gene promoter region and psychosocial factors might predict male adolescent criminal activity. METHODS A cross-sectional study with a randomized sample from the total population of 16- and 19-year-olds from the county of Västmanland, Sweden. Eighty-one male adolescents, who volunteered to participate, were randomly selected from groups representing different degrees of deviant risk behavior. RESULTS The present study strongly supports the notion that carrying the 3-repeat allele of the MAO-A-gene promoter increases the risk of male adolescent criminal behavior, when interacting with psychosocial factors. No effects at all of the MAO-A genotype on adolescent criminal activity were found when MAO-A genotype was considered alone (i.e., without its psychosocial context). The explained variance of the bio-psychosocial model (controlling for MAO-A) in this study exceeded the psychosocial model by 12%. CONCLUSIONS The findings support the notion that genotype and psychosocial factors interact to precipitate male adolescent criminal behavior.

Adolescent girls and criminal activity : role of MAOA-LPR genotype and psychosocial factors.

Recent findings among boys show that interactions between a polymorphism in the monoamine oxidase A gene promoter region (MAOA‐LPR) and psychosocial factors predict criminal activity. The objective of this study was to investigate whether this finding could be extended to adolescent girls. One hundred nineteen female adolescents were recruited among respondents to a cross‐sectional study of the total population of 16‐ and 19‐year old girls. These girls constituted a randomly selected sub‐sample from groups representing different degrees of risk behavior. The subjects filled in a questionnaire and were interviewed and genotyped with regard to MAOA‐LPR. The results indicate that the long, (4‐repeat) allele confer an increased risk for criminal behavior in the presence of psychosocial risk. Among girls without social risk, MAOA‐LPR genotype was of no importance for criminal behavior. The present results suggest that previous observations on adolescent males, which demonstrate that the short MAOA‐LPR genotype and psychosocial adversity interact to predict criminal activity, may not be applicable to females.

A Non-Additive Interaction of a Functional MAO-A VNTR and Testosterone Predicts Antisocial Behavior

A functional VNTR polymorphism in the promoter of the monoamine oxidase A gene (MAOA-LPR) has previously been shown to be an important predictor of antisocial behavior in men. Testosterone analogues are known to interact with the MAOA promoter in vitro to influence gene transcription as well as in vivo to influence CSF levels of the MAO metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in human males. We examined the possible joint effects of testosterone (measured in CSF) and MAOA-LPR genotype on antisocial personality disorder and scores on the Brown–Goodwin Aggression scale in 95 unrelated male criminal alcoholics and 45 controls. The results confirm that MAOA genotype and CSF testosterone interact to predict antisocial behaviors. The MAOA/testosterone interaction also predicted low levels of CSF MHPG, which tentatively suggests the possibility that the interaction may be mediated by a direct effect on gene transcription. If replicated these findings offer plausible explanations for previous inconsistencies in studies of the relationship between testosterone and male human aggression, as well as for how MAOA genotype may influence aggressive behavior in human males.

Gene–Environment Interactions and Response to Social Intrusion in Male and Female Rhesus Macaques

BACKGROUND Genetic factors interact with environmental stressors to moderate risk for human psychopathology, but sex may also be an important mediating factor. Different strategies for coping with environmental stressors have evolved in males and females, and these differences may underlie the differential prevalence of certain types of psychopathology in the two sexes. In this study, we investigated the possibility of sex-specific gene-environment interactions in a nonhuman primate model of response to social threat. METHODS Rhesus macaques (77 males and 106 females) were exposed to an unfamiliar conspecific. Using factor analysis, we identified three behavioral factors characterizing the response to social threat. Monkeys were genotyped for the serotonin transporter-linked polymorphism (5-HTTLPR), and the effects of genotype, early life stress, and sex on behavioral responses were evaluated. RESULTS Factor analysis produced five factors: High-Risk Aggression, Impulsivity/Novelty-Seeking, Gregariousness/Boldness, Harm Avoidance, and Redirected Aggression. Overall, males displayed higher levels of High-Risk Aggression and Gregariousness/Boldness than females. Levels of High-Risk Aggression in males carrying the s allele were significantly higher if they were also exposed to early adversity in the form of peer rearing. CONCLUSIONS Our findings support those from studies in humans suggesting that males are more vulnerable to externalizing or aggression-related disorders. The results highlight the importance of interactions that exist among behavior, genes, and the environment and suggest that sex differences in vulnerability to psychopathology may be grounded in our evolutionary history.

Effects of MAOA-genotype, alcohol consumption, and aging on violent behavior.

BACKGROUND Environmental factors appear to interact with a functional polymorphism (MAOA-LPR) in the promoter region of the monoamine oxidase A gene (MAOA) in determining some forms of antisocial behavior. However, how MAOA-LPR modulates the effects of other factors such as alcohol consumption related to antisocial behavior is not completely understood. METHODS This study examines the conjunct effect of MAOA-LPR, alcohol consumption, and aging on the risk for violent behavior. Recidivism in severe impulsive violent behavior was assessed after 7 to 15 years in a sample of 174 Finnish alcoholic offenders, the majority of whom exhibited antisocial or borderline personality disorder or both, and featured impulsive temperament traits. RESULTS The risk for committing new acts of violence increased by 2.3% for each kilogram of increase in yearly mean alcohol consumption (p = 0.004) and decreased by 7.3% for every year among offenders carrying the high activity MAOA genotype. In contrast, alcohol consumption and aging failed to affect violent behavior in the low activity MAOA genotyped offenders. MAOA-LPR showed no main effect on the risk for recidivistic violence. CONCLUSIONS Violent offenders carrying the high activity MAOA genotype differ in several ways from carriers with the low activity MAOA risk allele previously associated with antisocial behavior. Finnish high activity MAOA genotyped risk alcoholics exhibiting antisocial behavior, high alcohol consumption, and abnormal alcohol-related impulsive and uncontrolled violence might represent an etiologically distinct alcohol dependence subtype.

Shaming experiences and the association between adolescent depression and psychosocial risk factors.

ObjectiveTo investigate whether psychosocial risk factors such as parental separation, parental unemployment and experiences of sexual abuse are associated with adolescent depression, and whether shaming experiences (defined as experiences of being degraded, or ridiculed by others) may account for such an association.MethodA total of 5048 Swedish adolescents answered the Survey of Adolescent Life in Vestmanland 2004 (SALVe—2004) during classhours. The survey included questions about depressive symptoms, parental separation, parental unemployment and experiences of sexual abuse.ResultsThe psychosocial risk factors studied were all associated with depression, but several of these associations became non-significant when a factor for shaming experiences was entered into the models. The explained variance for depression furthermore increased from approximately 4–7% to 17–20% when shame was included.ConclusionShaming experiences may mediate part of the association between psychosocial risk factors and depression. These findings may have important implications for the understanding of psychotherapeutic treatment of the effects of risk factors in depressed patients.

Psychopathy, PCL-R, and MAOA genotype as predictors of violent reconvictions.

The Revised Psychopathy Checklist (PCL-R) has shown a moderate association with violence. The efficacy of PCL-R in varying monoamine oxidase A (MAOA) genotypes is, however, unexamined. The aim of this study was to investigate the effect of PCL-R and psychopathy on the risk for violent reconvictions among 167 MAOA genotyped alcoholic offenders. Violent reconvictions and PCL-R scores among violent offenders were assessed after a 7-year non-incarcerated follow-up. Regression analysis was used to evaluate the alcohol exposure and age-adjusted effect of PCL-R score and psychopathy on the risk for reconvictions among differing MAOA genotypes. Results suggest that the PCL-R total score predicts impulsive reconvictions among high-activity MAOA offenders (6.8% risk increase for every one-point increase in PCL-R total score, P = 0.015), but not among low-activity MAOA offenders, whereas antisocial behavior and attitudes predicted reconvictions in both genotypes (17% risk increase among high-activity MAOA offenders and 12.8% increase among low-activity MAOA offenders for every one-point increase in factor 2 score). Both narcissistic self-image with related interpersonal style (factor 1 score) and psychopathy (PCL-R ≥ 30) failed to predict future violence. Results suggest that the efficacy of PCL-R is altered by MAOA genotype, alcohol exposure, and age, which seems important to note when PCL-R is used for risk assessments that will have legal or costly preventive work consequences.

Transcription factor AP-2β genotype and psychosocial adversity in relation to adolescent depressive symptomatology

The aim of this study was to investigate possible interactions between the gene coding for activating protein-2β (AP-2β) and psychosocial factors to predict depressive symptoms in adolescents. Two-hundred 16- and 19-year-old adolescents from the county of Västmanland, Sweden, were asked to complete a questionnaire, interviewed about psychosocial risk factors, and genotyped with regard to the transcription factor AP-2β intron 2 polymorphism. AP-2β genotype interacted significantly both with type of housing and parental separation to predict depressive symptoms. Individuals who were homozygous for the short AP-2β allele displayed higher depression scores when psychosocial adversity was taken into account. Amongst carriers of one or two copies of the long allele, there was no difference in depressive symptoms despite differences in psychosocial environments.