Michael Lucht

Mental and physical distress is modulated by a polymorphism in the 5-HT transporter gene interacting with social stressors and chronic disease burden

Previous studies have yielded conflicting results as to the putative role of the functional polymorphism of the promoter region of the serotonin transporter gene (SLC6A4) in the etiology of anxiety-related traits and depressive disorders. Recently, a significant gene–environment interaction was found between life stressors, the short allele of the SLC6A4 polymorphism and depression. The aim of the present study was to investigate if such a gene–environment interaction could be replicated within a different population with a different risk structure. A total of 1005 subjects from a general population sample (Study of Health in Pomerania) were genotyped. Mental and physical distress were assessed on 38 items of the modified complaint scale (BL-38). The interaction between the SLC6A4 genotype, social stressors and chronic diseases with regard to the BL-38 score was evaluated by ANOVA. There was no independent association of genotype with mental and physical distress. However, significant interactions between genotype, unemployment and chronic diseases (F=6.6; df=3, 671; P<0.001) were found in females but not in males. The genotype explained 2% of the total variance of the BL-38 score and 9.1% of the explained variance. The results partly confirm previous findings of a significant gene–environment interaction of the short allele, indicating a higher mental vulnerability to social stressors and chronic diseases. The relevance of this finding is sustained by the fact that the sample characteristics and the risk structure were highly different from previous studies.

The Stigma of Alcohol Dependence Compared with Other Mental Disorders: A Review of Population Studies

AIMS Stigma is likely to aggravate the severe medical and social consequences of alcohol dependence. We aim to explore the characteristics of the alcohol dependence stigma by comparing it with the stigma of other conditions. METHODS On the basis of a systematic literature search, we identified 17 representative population studies published before July 2010 that examine aspects of the stigma of alcoholism and simultaneously of other mental, medical or social conditions. Seven surveys were located in Europe, five in North America, three in New Zealand and one each in Brazil and Ethiopia, respectively. RESULTS Compared with people suffering from other, substance-unrelated mental disorders, alcohol-dependent persons are less frequently regarded as mentally ill, are held much more responsible for their condition, provoke more social rejection and more negative emotions, and they are at particular risk for structural discrimination. Only with regard to being a danger, they are perceived to be at a similarly negative level to that of people suffering from schizophrenia. CONCLUSION Alcoholism is a particularly severely stigmatized mental disorder. Cultural differences are likely, but under-researched. We discuss possible reasons for the differences between the stigma of alcoholism and of other mental diseases and the consequences for targeted anti-stigma initiatives.

Associations between the oxytocin receptor gene (OXTR) and affect, loneliness and intelligence in normal subjects

Associations of oxytocin receptor gene (OXTR) variants and autism spectrum disorders (ASD) have been reported in earlier studies; in one of the studies associations with IQ and daily living skills were found additionally. Variations of the oxytocin receptor gene might also regulate affect, attachment and separation beyond the diagnostic borders of autism. We tested hypotheses of associations between positive and negative affects and social and emotional loneliness (285 adults), IQ (117 adolescents) and polymorphisms of the oxytocin receptor gene (OXTR rs53576, rs2254298 and rs2228485) in normal subjects. Individuals with the oxytocin OXTR rs53576 A/A genotype showed lower positive affect scores (F=5.532, df=1; p=0.019). This effect was restricted to males (F=13.098, df=1; p=0.00047). Haplotypes constructed with the three markers were associated with positive affect (p=0.0012), negative affect (p<0.0001) and emotional loneliness (p<0.0001). Non-verbal intelligence was significantly reduced in rs53576 A/A adolescents (T=2.247, p=0.027). Our findings support a role for the oxytocin receptor haplotypes in the generation of affectivity, emotional loneliness and IQ.

Serotonin transporter gene (SLC6A4) promoter polymorphisms and the susceptibility to posttraumatic stress disorder in the general population.

OBJECTIVE There has been debate whether polymorphisms within the serotonin transporter-linked polymorphic region (5-HTTLPR) moderate susceptibility to posttraumatic stress disorder (PTSD). The authors investigated 5-HTTLPR genotypes and their interaction with the number of traumatic events in the prediction of PTSD in a general population sample. METHOD Analyses were based on data from 3,045 subjects who participated in the Study of Health in Pomerania. All participants were assessed with the PTSD module of the Structured Clinical Interview for DSM-IV. The short (S)/long (L) polymorphism of 5-HTTLPR (rs4795541) and the A-G polymorphism (rs25531) were genotyped. RESULTS Among the participants, 1,663 had been exposed to at least one traumatic event, and 67 (4.0%) developed PTSD. Among those who had experienced less than three traumatic events, the lifetime prevalence of PTSD was 2.6%, 3.5%, and 4.3% for those with zero, one, and two L(A) alleles, respectively, but the lifetime prevalence was 0%, 7.3%, and 19.6%, respectively, among those with three or more traumatic experiences. This finding suggests that there is an additive excess risk for frequent trauma in the L(A)/L(A) genotype, which was confirmed by the relative excess risk due to interaction (RERI). In allelic analysis, RERI was 3.3. Thus, the odds ratio for PTSD in L(A) allele carriers exposed to three or more traumas was 3.3 times higher as a result of the interaction between PTSD and the L(A) allele. CONCLUSIONS An additive gene-environment interaction with the high expression L(A) allele of 5-HTTLPR and frequent trauma in PTSD was found. The attributable proportion indicated that more than 60% of all L(A) allele carriers who were exposed to three or more traumas developed PTSD as a result of an interaction between genotype and exposure.

Childhood maltreatment, the corticotropin-releasing hormone receptor gene and adult depression in the general population†‡

Dysregulations of the hypothalamic‐pituitary‐adrenal (HPA) axis have been implicated in the pathogenesis of depressive disorders and the corticotropin‐releasing hormone (CRH) was found to modulate emotional memory consolidation. Recently, two studies have reported an interaction between childhood abuse and the TAT–haplotype of the CRH‐Receptor Gene (CRHR1) connecting childhood adversities and genetic susceptibility to adult depression. We tested the hypothesis of an interaction of childhood maltreatment with single nucleotide polymorphisms (SNPs) and haplotypes of the CRHR1 gene not previously investigated. Caucasian subjects (n = 1,638) from the German general population (Study of Health in Pomerania, SHIP) were analyzed. As in the previous studies, childhood abuse and neglect were assessed with the Childhood Trauma Questionnaire (CTQ) and depression with the Beck Depression Inventory (BDI‐2). The CRHR1‐SNPs were genotyped on the Affymetrix Genome‐Wide Human SNP Array 6.0 platform. We identified an interaction between the TAT–haplotype and childhood physical neglect. The interaction with physical neglect showed significant (P < 0.05) results in 23 of the 28 SNPs, with rs17689882 (P = 0.0013) reaching “gene‐wide” significance. Although we did not replicate the specific interaction of abuse and the TAT–haplotype of the CRHR1 gene we confirmed the relevance of an interplay between variants within the CRHR1 gene and childhood adversities in the modulation of depression in adults. The largest effect was found for rs17689882, a SNP previously not analyzed. Relevant sample differences between this and prior studies like lower BDI‐2 scores, less childhood maltreatment and higher psychosocial functioning may account for the differences in gene–environment interaction findings.

Self-stigma in alcohol dependence: consequences for drinking-refusal self-efficacy.

BACKGROUND Public stigma and self-stigma are two facets of mental illness stigma. Self-stigma denotes the internalization of negative public perceptions by persons with mental illness and has been shown to decrease general self-efficacy. To date, self-stigma has not been examined in people suffering from alcohol dependence, a particularly severely stigmatized mental disorder. METHODS By adopting the Self-Stigma in Mental Illness Scale (SSMI), we developed the Self-Stigma in Alcohol Dependence Scale (SSAD). The scale is based on a focus-group derived list of 16 negative stereotypes about alcohol dependent persons. It consists of four 16-item subscales measuring four hypothetical stages of self-stigma, stereotype awareness (aware), stereotype agreement (agree), self-concurrence (apply), and self-esteem decrement (harm). We employed the SSAD in a cross-sectional study of 153 patients hospitalized for alcohol detoxification to examine its reliability and validity. RESULTS The four stages of self-stigma could be reliably measured with the SSAD (Cronbachs alpha, 0.86-0.93). Each step in the process of self-stigmatization was most closely associated with its preceding step. Other significantly related independent variables in multiple regression analyses included desire for social distance (associated with agree), duration of drinking problems (associated with apply) and depressive symptoms (associated with apply and harm). Both apply and harm were significantly related to reduced drinking-refusal self-efficacy in analyses controlling for depressive symptoms and variables related to duration and severity of the drinking problem. DISCUSSION The SSAD showed good validity and reliability measuring the stages of self-stigma in this group. Self-stigma appears to be associated with lower drinking-refusal self-efficacy.

Influence of Punishment, Emotional Rejection, Child Abuse, and Broken Home on Aggression in Adolescence: An Examination of Aggressive Adolescents in Germany

The results of this study provide evidence for the importance of psychosocial risks in childhood for aggressive behavior in adolescence. This study demonstrated that aggressive adolescents differed from a nonaggressive control group in an increased exposure to prior psychotraumatic events, such as sexual abuse (tendency), physical abuse, and broken homes. However, in predicting later aggressive behavior, long-term and chronically effective negative living conditions seem of greater importance. Parenting behavior which includes harsh punishment and emotional rejection as well as separation of the parents early in life are particularly important factors. Whereas aggressive girls do not differ from the nonaggressive control group in terms of self-reported mental health, the aggressive boys reported more attention deficits, depression, anxiety, delinquency, and social problems.

Gender Differences in Dissociation

Considering that epidemiological research on dissociative disorders has suggested a 9 to 1 predominance of female cases, this study investigated the relationship between gender and dissociation using a dimensional approach. A total of 2,153 participants from different diagnostic groups completed the Dissociative Experience Scale. In order to control for the confounding effect of current psychopathology a subgroup 790 subjects additionally completed the SCL-90. We did not find any differences in the general or pathological dissociation scores. Hypothetical gender differences in dissociative psychopathology were not a function of diagnostic categories. There were no significant sex differences in the distribution of high dissociators. Our findings suggest that men and women do not generally differ in dissociative psychopathology. The implications for future investigations on the epidemiology, etiology, and psychobiology of dissociative symptoms are discussed.

Gender differences in unipolar depression: a general population survey of adults between age 18 to 64 of German nationality

BACKGROUND Several studies from different epidemiological backgrounds have shown that unipolar depression is more prevalent in females than in males. This study examines gender differences in depression in a sample of 4075 probands recruited representatively from the general population in the northern German epidemiological catchment area of Lübeck. METHODS Probands were interviewed with M-CIDI by lay interviewers. RESULTS Being married only seems to increase the female depression risk when having children, while higher education reduced female excess; both male and female risk for depression raised sharply in separated, divorced and widowed probands. Not being employed was associated with an increased risk in male depression whereas in females risk was nearly unchanged. The gender ratio increased with the minimum number of depressive symptoms. Female excess was not reduced by a higher degree of subjective impairment or melancholic features. Females also predominated in longer episode durations. Female excess in the total group emerged beginning from adolescence with a tendency for a male excess in the prepubescent ages. No birth cohort effect was observed. LIMITATIONS The cross-sectional design of this study precluded causal analysis of reported associations and some retrospective assessments are error-prone because of recall bias. CONCLUSIONS We support previous findings of variations in gender differences in depression, however observed social parameter influences underline the need for a more detailed analysis of subgroups and underlying psychological mechanisms.

Associations between the oxytocin receptor gene (OXTR) and "mind-reading" in humans--an exploratory study.

Abstract Background/aims: The application of intranasal oxytocin enhances facial emotion recognition in normal subjects and in subjects with autism spectrum disorders (ASD). In addition, various features of social cognition have been associated with variants of the oxytocin receptor gene (OXTR). Therefore, we tested for associations between mind-reading, a measure for social recognition and OXTR polymorphisms. Methods: 76 healthy adolescents and young adults were tested for associations between OXTR rs53576, rs2254298, rs2228485 and mind-reading using the “Reading the Mind in the Eyes Test” (RMET). Results: After Bonferroni correction for multiple comparisons, rs2228485 was associated with the number of incorrect answers when subjects evaluated male faces (P =0.000639). There were also associations between OXTR rs53576, rs2254298 and rs2228485 and other RMET dimensions according to P <0.05 (uncorrected). Conclusion: This study adds further evidence to the hypothesis that genetic variations in the OXTR modulate mind-reading and social behaviour.