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It is now generally accepted that complex mental disorders are the results of interplay between genetic and environmental factors. This holds out the prospect that by studying G x E interplay we can explain individual variation in vulnerability and resilience to environmental hazards in the development of mental disorders. Furthermore studying G x E findings may give insights in neurobiological mechanisms of psychiatric disorder and so improve individualized treatment and potentially prevention. In this paper, we provide an overview of the state of field with regard to G x E in mental disorders. Strategies for G x E research are introduced. G x E findings from selected mental disorders with onset in childhood or adolescence are reviewed [such as depressive disorders, attention-deficit/hyperactivity disorder (ADHD), obesity, schizophrenia and substance use disorders]. Early seminal studies provided evidence for G x E in the pathogenesis of depression implicating 5-HTTLPR, and conduct problems implicating MAOA. Since then G x E effects have been seen across a wide range of mental disorders (e.g., ADHD, anxiety, schizophrenia, substance abuse disorder) implicating a wide range of measured genes and measured environments (e.g., pre-, peri- and postnatal influences of both a physical and a social nature). To date few of these G x E effects have been sufficiently replicated. Indeed meta-analyses have raised doubts about the robustness of even the most well studied findings. In future we need larger, sufficiently powered studies that include a detailed and sophisticated characterization of both phenotype and the environmental risk. [ABSTRACT FROM AUTHOR]

Stress is known to induce cigarette craving in smokers, but the underlying mechanisms are widely unknown. We investigated how dependence severity, smoking habits and stress-induced cortisol secretion are associated with increased cigarette craving after a standardised laboratory stressor. Hundred and six healthy participants (50 men, age 18-19 years) underwent a standardised public speaking stress task. In all, 35 smoked daily (DS), 13 smoked occasionally (OS), and 58 never smoked (NS). Smoking was unrestricted until 2 h before stress onset. Plasma cortisol was measured before and up to 95 min after the stressor. All current smokers rated intensity of cigarette craving immediately before and immediately after the stressor using the Brief Questionnaire of Smoking Urges (BQSU). Cortisol levels significantly increased in response to stress in all groups. The magnitude of this stress response was significantly lower in DS compared with OS and NS but did not differ between OS and NS. Baseline BQSU scores were significantly higher in DS than OS. BQSU scores increased significantly during the stress period and were positively correlated to the cortisol response in the DS but were unrelated to their nicotine dependence scores. In OS, no change in cigarette craving could be observed. In daily smokers, cigarette craving is increased after compared with before stress exposure and is related to the magnitude of cortisol stress response rather than to severity of nicotine dependence. This result supports, but does not prove, the concept that hypothalamuspituitary-adrenal stimulation is one of the mechanisms how stress can elicit cigarette craving. [ABSTRACT FROM AUTHOR]

Alcohol and nicotine are with us during most of our lifetime. About 4,000 children with fetal alcohol syndrome and another 20,000 children with fetal alcohol effects are born per year in Germany. Alcohol contributes to accidents and suicides especially in young people. It is particularly toxic for the developing brain. Germany is among the countries with a high consumption of alcohol and nicotine. Consequently substance-related diseases are highly prevalent. In the group of people aged 65 and older we expect a doubling of alcohol problems within the next 10 years. This will also lead to a sharp increase in alcohol-related dementias. Overall, treatment is effective especially if one considers the chronic relapsing nature of the disorder. Unfortunately, less than 10% of patients really receive specialist care. This segment needs to be expanded especially by psychiatrists and psychotherapists. Different prevention strategies are being applied but there is a reluctance to use a ban or curtail advertising and to raise taxes for a reduction in overall consumption. [ABSTRACT FROM AUTHOR]

The present study aimed to examine the extent to which the co-occurrence of ADHD and smoking in adolescents could be attributed to common genetic, environmental and psychopathological factors. Data are from an ongoing prospective study of the outcome of early risk factors. At age 15 years, 305 adolescents completed self-report questionnaires measuring tobacco consumption and deviant peer affiliations. Lifetime psychiatric diagnoses were obtained using standardized interviews. DNA was genotyped for the dopamine D4 receptor (DRD4) gene exon III polymorphism. Adolescents with a lifetime diagnosis of ADHD displayed significantly higher smoking activity than non-ADHD controls. A major component of this association could be accounted for by deviant peer affiliations and the comorbidity with oppositional-defiant and conduct disorder, while a minor part was attributable to DRD4 in males but not in females. These findings suggest that the association of ADHD with smoking relies on risk factors shared by the two behaviors. [ABSTRACT FROM AUTHOR]

Objectives: The present study was designed to investigate the association between the DRD4 genotype and auditory P300 amplitudes in a high-risk community sample. Methods: ERPs were elicited in 197 eight-year-olds (98 boys, 99 girls) using a passive and an active oddball task. Auditory stimuli of 60 dB HL were presented binaurally at 1000 (standard stimulus) and 2000 Hz (target stimulus), at a relative frequency ratio of 80:20. Two trial blocks of 250 stimuli each were collected. P300 amplitudes were analyzed from Fz, Cz and Pz. DNA was genotyped for the DRD4 exon III polymorphism. Results: A pattern of significant interactions of the DRD4 genotype with gender and experimental conditions was obtained. In both the active and the passive task, boys with at least one copy of the DRD4 7-repeat allele displayed significantly lower P300 amplitudes during the second trial block than boys carrying other alleles. Conclusions: This finding provides further evidence supporting a role of P300 amplitude reduction as an endophenotype for disinhibited psychopathology. [ABSTRACT FROM AUTHOR]

In recent years, studies focussing on a possible association between the dopamine D4 receptor (DRD4) gene exon III polymorphism and the personality trait of novelty seeking (NS) have yielded inconsistent results. The present study sought to examine the association of the DRD4-7r allele with NS in a sample of 303 15-year-old adolescents (144 males, 159 females) using data from a high-risk community sample. The Junior Temperament and Character Inventory - JTCI/12-18 was administered to assess dimensions of adolescent temperament. Males in the DRD4-7r allele group scored significantly higher on the NS (p?=?.002) and the harm avoidance (p?=?.045) scales than males without this allele. In females no association with temperament was observed. This association could not be explained by the presence of either an attention-deficit/hyperactivity disorder (ADHD) or a DRD4 by ADHD interaction. [ABSTRACT FROM AUTHOR]

Summary. Background: In recent years, a growing number of studies has focused on the dopamine D4 receptor gene (DRD4) as mediating the susceptibility to attention-deficit/hyperactivity disorder (ADHD). While their results are contradictory, the reason for this inconsistency remains as yet unclear. Method: The present study sought to examine the association between ADHD and the DRD4 exon III polymorphism during child development using longitudinal data from a high-risk community sample (n=265, 129 females, 126 males) who have been followed from birth to 11 years of age. Results: Higher rates of ADHD were observed in boys with the 7 repeat allele of exon III than in boys with other alleles at the ages of 4 1/2 (Fisher’s exact test, p=.061), 8 (p=.026), and 11 years (p=.005). Boys with this allele also exhibited higher rates of persistent disorder (p=.024). In girls, a trend towards an association (p=.055) with the 7 repeat allele emerged only at preschool age. Conclusions: These findings provide additional evidence for the role of the dopamine D4 receptor in ADHD during the course of child development. [ABSTRACT FROM AUTHOR]

An atypical EEG pattern of frontal brain activation, which has been related to compromised emotional regulation in children and adults, is hypothesized to be also present in children with externalizing behavior problems. Seventy-eight children at 11 years of age were examined to answer the following questions: 1) do children with externalizing behaviors exhibit an atypical pattern of frontal brain activation which can be linked to the severity of their problem behaviors? and 2) are there gender differences in these frontal activation patterns? Spontaneous EEG activity was subjected to power spectral analysis. In externalizing girls, the well-known pattern of a significantly greater right than left frontal brain activation emerged that has been found previously in emotionally disordered children, whereas healthy girls showed a significantly greater left than right frontal activation. In contrast, healthy boys demonstrated a significantly greater right than left frontal activation, whereas externalizing boys did not display a frontal brain asymmetry. Thus, the pattern of frontal brain activation was gender specific. The atypical activation pattern in externalizing children is hypothesized to be a biological correlate of difficulties in regulating emotion. [ABSTRACT FROM AUTHOR]

Objective: Circadian and stress-response systems mediate environmental changes that affect alcohol drinking. Psychosocial stress is an environmental risk factor for alcohol abuse. Circadian rhythm gene period 1 (Per1) is targeted by stress hormones and is transcriptionally activated in corticotropin releasing factor-expressing cells. The authors hypothesized that Per1 is involved in integrating stress response and circadian rhythmicity and explored its relevance to alcohol drinking.Method: In mice, the effects of stress on ethanol intake in mPer1-mutant and wild-type mice were assessed. In humans, single nucleotide polymorphisms (SNPs) in hPer1 were tested for association with alcohol drinking behavior in 273 adolescents and an adult case-control sample of 1,006 alcohol-dependent patients and 1,178 comparison subjects. In vitro experiments were conducted to measure genotype-specific expression and transcription factor binding to hPer1.Results: The mPer1-mutant mice showed enhanced alcohol consumption in response to social defeat stress relative to their wild-type littermates. An association with the frequency of heavy drinking in adolescents with the hPer1 promoter SNP rs3027172 and with psychosocial adversity was found. There was significant interaction between the rs3027172 genotype and psychosocial adversity on this drinking measure. In a confirmatory analysis, association of hPer1 rs3027172 with alcohol dependence was shown. Cortisol-induced transcriptional activation of hPer1 was reduced in human B-lymphoblastoid cells carrying the risk genotype of rs3027172. Binding affinity of the transcription factor Snail1 to the risk allele of the hPer1 SNP rs3027172 was also reduced.Conclusions: The findings indicate that the hPer1 gene regulates alcohol drinking behavior during stressful conditions and provide evidence for underlying neurobiological mechanisms. [ABSTRACT FROM AUTHOR]

Objective: To examine neurophysiological correlates of attentional processing in children with oppositional-defiant disorder (ODD) independent of ADHD symptoms. Method: Thirteen children with oppositional-defiant disorder without comorbid ADHD symptoms and 13 healthy control children (all 11 years) performed a cued Continuous Performance Test (CPT-AX). Event-related potentials (ERP) to cue and target stimuli were examined for group differences. Results: Children with ODD showed significantly reduced parietal P3a and P3b amplitudes to cues and to targets, compared with healthy controls. ERP amplitudes correlated with oppositional and aggressive behavior scores. Conclusions: Event-related potentials revealed reduced orienting to cues and reduced executive target processing in children with ODD. These findings indicate that ODD children show neurophysiological deviances independent of ADHD comorbidity. [ABSTRACT FROM AUTHOR]

Aim: To examine whether regulatory problems in infancy predict later hyperkinetic symptoms in childhood and pre-adolescence. Methods: In a prospective longitudinal study of 319 children at risk of later developmental problems and psychopathology, hyperkinetic behaviour problems were assessed at the ages of 2, 4.5, 8 and 11 y by means of a standardized parent interview. Infant regulatory problems at the age of 3 mo were determined from multiple sources of information. An observational procedure was used to assess the quality of mother-infant interaction. Results: At the age of 3 mo, 17% of the infants ( n = 55; 27 boys, 28 girls) suffered from multiple regulatory problems. Compared to a control group ( n = 264), these children presented more hyperkinetic symptoms throughout childhood. Negativity in the mother-infant interaction and early family adversity each contributed to later hyperkinetic symptoms. When controlling for family adversity, the association between infant multiple regulatory problems and later hyperkinetic problems was rendered insignificant. Conclusions: These findings suggest that multiple regulatory problems may not be a key variable for later hyperkinetic problems. The impact of early family adversity factors clearly outweighed that of infant psychopathology on later behaviour disorder. [ABSTRACT FROM AUTHOR]

Summary. Objective: To measure neurophysiological correlates of inhibition in children with anxiety disorders. Method: Anxiety-disordered children and healthy control children (11 years of age) performed a cued Continuous Performance Test (CPT-AX). Event-related potentials following NoGo and distractor stimuli as well as performance data were examined for group differences. Results: Anxious children displayed a significantly larger NoGo-related N1 global field power than did control children while no group differences were found for the N2 and P3 potentials. Groups did not differ in CPT performance. Conclusions: Anxious children showed early attentional enhancement (N1) to stimuli indicating need for inhibition but not increased resource allocation to actual response inhibition. [ABSTRACT FROM AUTHOR]

Aim: To determine the significance of young maternal age, family adversity and maternal behaviour during mother-toddler interaction in the prediction of child disruptive behaviour at age eight. Methods: From an ongoing longitudinal study of infants at risk for later psychopathology ( n = 362), 72 young mothers aged between 15 and 24 y (median 22 y) at first birth were compared with 197 primiparous older mothers ranging in age from 25 to 41 y (median 29 y). Family adversity at childbirth was assessed using a modified version of Rutter's Family Adversity Index (FAI) and measures of child disruptive behaviour at age eight were obtained using Achenbach's Teacher Report Form (TRF). An observational procedure was used to assess maternal behaviour during mother-child interaction at the age of 2 y. Results: Young mothers encountered more adverse family characteristics and were more inadequate, restrictive and more negative during interaction with their toddlers. Their school-aged children showed higher scores on all disruptive behaviour scales of the TRF. Hierarchical regression analyses revealed that family adversity and maternal behaviour during toddler interaction could account for most of the association between early motherhood and child disruptive behaviour. Conclusion: The impact of young motherhood on child mental health is not confined to teenage mothers and is mainly attributed to psychosocial and interactional factors. [ABSTRACT FROM AUTHOR]

Abstract Data from a prospective longitudinal study on the development of children born at biological and psychosocial risk were utilised to examine language and learning abilities of 320 children at ages 4.5 and 8 years. Following the research criteria of the ICD-10, specific developmental disorders of speech and language and specific developmental disorders of scholastic skills were diagnosed. Data were also provided for a clinical and general low achievement group according to less stringent criteria. Frequencies in the risk population were low for specific disorders (ICD-10) (0.6%-3.7% depending on age and type of disorder). Higher frequencies were found when a clinical definition (0.6% 13.6%) or overall low achievement score (0.6%-18.6%) was chosen. The impact of well-documented organic and psychosocial risks was analysed. Organic risk affected language abilities at 4.5 years of age but neither language nor learning abilities at 8 years of age. Psychosocial aspects of a child's environment proved to be associated with both specific language and learning abilities. Stability of language disorders, association between language and reading/spelling disorders as well as gender effects were investigated. [ABSTRACT FROM AUTHOR]

The language abilities of 324 children of an at-risk population were investigated at age 2 and 4.5 y. Modified research criteria of the ICD-10 for specific developmental disorders of speech and language were applied. Frequencies between 4% and 7%, depending on age and type of disorder, were diagnosed among children whose performance on the language measure was only 1 instead of ICD-10's 2 SD below group mean, but the discrepancy measure of 1 SD between non-verbal language score and language measure was retained. Psychosocial aspects of a child's environment proved to be better predictors of later language disorders than obstetric complications. Stability of specific language disorders was on the whole fairly low, but children who perform below age level on language measures remained at risk. Gender differences are almost compensated by the age 4.5 y. [ABSTRACT FROM AUTHOR]

Highlights • Prospective study on prenatal stress and nocturnal HPA axis activity. • Assessment of cortisol and cortisone in the first morning urine of 45-month-old children. • Negative association of prenatal stress measures with nocturnal HPA axis activity. • Results point towards lower nocturnal cortisol production in prenatally stressed children. Abstract Prenatal stress (PS) has been related to altered hypothalamic-pituitary-adrenal (HPA) axis activity later in life. So far, studies in children assessing HPA axis functioning have focused on salivary cortisol, reflecting daytime activity. The present work is part of a prospective study and aims to extend knowledge about the association between PS and HPA axis regulation in children. To do so, we investigated cortisol, cortisone, and the ratio cortisone/(cortisone + cortisol) in the first morning urine of 45-month-old children in relation to several measures of maternal stress during pregnancy. Urinary cortisol and cortisone were measured by online turbulent flow chromatography coupled with high performance liquid chromatography-tandem mass spectrometry. PS was defined as: perceived stress for aim 1 (Perceived Stress Scale; n = 280); presence of self-reported (n = 371) and expert-rated psychopathology for aim 2 (Mini International Neuropsychiatric Interview; n = 281); continuous measures of anxiety and depression for exploratory aim 3 (State-Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale; n = 280). Aim 1: Perceived maternal PS showed negative associations with cortisol and cortisone levels. Aim 2: The presence of expert-rated maternal psychopathology was associated with reduced morning cortisone. Aim 3: Continuous measures of anxiety and depression showed negative associations with cortisol and cortisone levels. After correcting for multiple testing, perceived maternal PS (aim 1) and prenatal level of anxiety (aim 3) were significant predictors of children's urinary cortisol and cortisone in the morning (and, in the case of cortisone, also prenatal level of depression). The ratio cortisone/(cortisone + cortisol) as a global marker for the balance between the enzymes metabolizing cortisol to cortisone and vice versa (11β-hydroxysteroid dehydrogenases type 1 and 2; 11β-HSD1 and 2) was not associated with any measure of maternal PS (aims 1–3). The present study provides insight into possible programming effects of PS on nocturnal HPA axis activity and a proxy of 11β-HSD in a large sample. The results suggest that the nocturnal rate of cortisol production is lower in children exposed to PS, but do not support the hypothesis of divergent 11β-HSD activity. [ABSTRACT FROM AUTHOR]

Highlights • A stress test for preschool-aged children was evaluated (n = 339). • It elicited a cortisol response especially 30 and 40 min after the test. • Prenatal stress was associated with a reduced cortisol response. Abstract Prenatal maternal stress is an established risk factor for somatic and psychological health of the offspring. A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in offspring has been suggested as an important mechanism. However, the impact of prenatal stress on stress reactivity in preschool-aged children is not yet well understood. This is partly due to the fact that for this age group there is no stress test as well established as for older children and adults. In the present work a previously published stress test (Kryski et al., 2011) was evaluated in a large sample of 45-month-old children (n = 339). Furthermore, the relation between measures of prenatal maternal stress and cortisol reactivity was investigated. Prenatal stress was defined as psychopathology (self-report available for n = 339; expert-rating available for a subsample of n = 246) and perceived stress (n = 244) during pregnancy. The stress paradigm elicited significant increases in salivary cortisol 30 and 40 min after the test, and 60.8% of the children were classified as responders. Lower cortisol levels after the stress test were observed in the group of children with prenatal stress defined as maternal psychopathology (both self-reported and expert-rated). Maternal perceived stress as a continuous measure was not significantly associated with cortisol levels. However, when comparing children in the highest quartile of maternal perceived stress to all other children, significantly lower cortisol values were observed in the prenatally stressed group. The present study confirms the paradigm by Kryski et al. as an effective stress test for preschool-aged children. Moreover, it provides further evidence that prenatal stress impacts HPA axis reactivity. Future studies should target the timing, nature, and intensity of prenatal stressors and their effect on the stress response in offspring at different developmental stages. [ABSTRACT FROM AUTHOR]

Attention problems affect a substantial number of children and adolescents and are predictive of academic underachievement and lower global adaptive functioning. Considerable variability has been observed with regard to the individual development of attention problems over time. In particular, the period of adolescence is characterized by substantial maturation of executive functioning including attentional processing, with the influence of genetic and environmental factors on individual trajectories not yet well understood. In the present investigation, we evaluated whether the monoamine oxidase A functional promoter polymorphism, MAOA-LPR, plays a role in determining continuity of parent-rated attention problems during adolescence. At the same time, a potential effect of severe life events (SLEs) was taken into account. A multi-group path analysis was used in a sample of 234 adolescents (149 males, 85 females) who took part in an epidemiological cohort study at the ages of 11 and 15 years. Attention problems during early adolescence were found to be a strong predictor of attention problems in middle adolescence. However, in carriers of the MAOA-LPR low-activity variant (MAOA-L) stability was found to be significantly higher than in carriers of the high-activity variant (MAOA-H). Additionally, only in MAOA-L carriers did SLEs during adolescence significantly impact on attention problems at the age of 15 years, implying a possible gene x environment interaction. To conclude, we found evidence that attention problems during adolescence in carriers of the MAOA-L allele are particularly stable and malleable to life stressors. The present results underline the usefulness of applying a more dynamic GxE perspective. [ABSTRACT FROM AUTHOR]

What is already known about this subject? NPY serves as a potent orexigenic signal and plays an important role in body weight regulation. Recently, evidence for the impact of NPY gene variation on body weight regulation and risk of obesity was provided., Research has indicated that genetic influences on some traits such as BMI change with age, with often showing a stronger effect as children mature., What this study adds? We show first evidence from a longitudinal study, demonstrating an association between NPY rs16147 genotype and BMI development from infancy into young adulthood., The NPY effect appears to increase with age, being more pronounced in older age groups than in younger ones., Objective To investigate the association of the neuropeptide Y ( NPY) promoter polymorphism rs16147 with body mass index ( BMI) during the course of development from infancy to adulthood. Design Longitudinal, prospective study of a German community sample. Subjects n = 306 young adults (139 males, 167 females). Measurements Participants' body weight and height were assessed at the ages of 3 months and 2, 4.5, 8, 11, 15 and 19 years. NPY rs16147 was genotyped. Results Controlling for a number of possible confounders, homozygote carriers of the rs16147 C allele exhibited significantly lower BMI scores when compared with individuals carrying the T allele. In addition, a significant genotype by age interaction emerged, indicating that the genotype effect increased during the course of development. Conclusions This is the first longitudinal study to report an association between rs16147 and BMI during childhood and adolescence. The finding that this effect increased during the course of development may either be due to age-dependent alterations in gene expression or to maturation processes within the weight regulation circuits of the central nervous system. [ABSTRACT FROM AUTHOR]

Objective: We investigated in a high-risk sample the differential impact of biological and psychosocial risk factors on antisocial behaviour pathways. Method: One hundred and thirty-eight boys and 155 girls born at differing degrees of obstetric and psychosocial risk were examined from birth until adolescence. Childhood temperament was assessed by a highly-structured parent-interview and standardized behavioural observations, adolescent temperament was measured by self-report. Neurodevelopmental variables were assessed by age-specific developmental tests. Emotional and behaviour problems were measured at the ages of 8 and 15 by the Achenbach scales. Results: In both genders, psychosocial adversity and early self-control temperament were strongly associated with early-onset persistent (EOP) antisocial behaviour. Psychosocial adversity and more severe externalizing problems differentiated the EOP from childhood-limited (CL) pathway. In girls, adolescent-onset (AO) antisocial behaviour was strongly associated with novelty seeking at 15 years. Conclusion: Our findings emphasize the need for early support and intervention in psychosocially disadvantaged families. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the relationship of language competence level and mental distress in teenagers with hearing impairments. Method: 43 pupils were given a battery of linguistic tests and the Strengths and Difficulties Questionnaire (SDQ), which was also completed by 40 parents. Comparisons were made between the group of 33 children in mainstream education and 10 who were in a segregated school for the deaf. Results: The children had impaired language skills relative to published norms, especially marked in segregated schools. Parents rated children as having more distress than published norms. Those with superior level of spoken language had fewer peer relationship problems in mainstream education, but significantly more in segregated schools. The reverse was almost significant for those proficient in signed language. Conclusion: Peer relationship problems are associated with the language competence levels in the way that children at school communicate with one another. [ABSTRACT FROM AUTHOR]

AIMS: Language development was followed from infancy to primary school age in order to examine the predictive significance for later language and scholastic outcome. METHODS: Participants were from a prospective longitudinal study of a birth cohort of initially 362 children. A subsample of 90 children (54 boys, 36 girls) was administered with the Receptive-Expressive Emergent Language Scale (REEL) in order to obtain age-appropriate measures of expressive and receptive language at the age of 10 months. At 11 years, children completed a comprehensive test battery assessing various intellectual skills and language performance. Scholastic measures included a school performance score and a recommendation for type of secondary school. RESULTS: Both expressive and receptive language performance at 10 months were significantly associated with cognitive and educational outcome 10 years later. Infant language performance not only predicted later verbal and nonverbal skills but also school achievement at the end of primary school. Prediction was higher in girls than in boys and slightly better for verbal and academic than for nonverbal performance. CONCLUSIONS: The results demonstrate the importance of early language abilities in predicting cognitive and academic outcome at school age. [ABSTRACT FROM AUTHOR]

The S allele of the 5-HTTLPR has been associated with anxiety-related behavioural traits and harm avoidance. The 5-HTTLPR polymorphism is suggested to modulate the serotonergic response to stress, meaning that individuals carrying the SS genotype who have significant stress histories may tend to develop depressive symptoms. In the Mannheim Study of Risk Children, which followed a cohort of n = 384 from birth to adolescence, the association of 5-HTTLPR with harm avoidance and internalising problems was examined, including gender and early life stress as possible moderators. Child and adolescent characteristics were assessed using the Junior Temperament and Character Inventory, the Child Behaviour Checklist and the Youth Self Report. Early life stress was determined by a risk index measuring the presence of 11 adversity factors. Results did not reveal an association with 5-HTTLPR genotype. There were no moderating effects of early life stress or gender. An explanation for the negative findings is that the S allele may be a necessary but not sufficient component cause in a composite risk factor. [ABSTRACT FROM AUTHOR]

To investigate the role of the corticotropin releasing hormone receptor 1 (CRHR1) in patterns of human alcohol drinking and its potential contribution to alcohol dependence, we analysed two independent samples: a sample of adolescents, which consisted of individuals from the ‘Mannheim Study of Risk Children’ (MARC), who had little previous exposure to alcohol, and a sample of alcohol-dependent adults, who met DSM-IV criteria of alcohol dependence. Following determination of allelic frequencies of 14 polymorphisms of the CRHR1 gene, two haplotype tagging (ht)SNPs discriminating between haplotypes with a frequency of 0.7% were identified. Both samples were genotyped and systematically examined for association with the htSNPs of CRHR1. In the adolescent sample, significant group differences between genotypes were observed in binge drinking, lifetime prevalence of alcohol intake and lifetime prevalence of drunkenness. The sample of adult alcohol-dependent patients showed association of CRHR1 with high amount of drinking. This is the first time that an association of CRHR1 with specific patterns of alcohol consumption has been reported. Our findings support results from animal models, suggesting an importance of CRHR1 in integrating gene–environment effects in alcohol use disorders.Molecular Psychiatry (2006) 11, 594–602. doi:10.1038/sj.mp.4001813; published online 21 March 2006 [ABSTRACT FROM AUTHOR]

An atypical EEG pattern of frontal brain activation, which has been found in children and adults with emotional disorders, also is hypothesized to be present in disruptive behavior disorders. One hundred nineteen children (4 1/2 and 8 years of age) were examined with regard to the following questions: (1) Do children who are diagnosed with oppositional defiant disorder (ODD) exhibit an atypical pattern of frontal brain activation? (2) Can this pattern be demonstrated in preschool children (4 1/2 years of age) as well as in school children (8 years)? (3) Are there gender differences in these patterns similar to those that have been demonstrated in adults? Spontaneous EEG activity was subjected to power spectral analysis. In oppositional preschool and elementary school girls, the well-known pattern of lower left frontal than right frontal activation emerged that has been found previously in emotionally disordered children. Healthy girls showed no frontal brain asymmetry at 4 1/2 years of age, and left frontal activation at 8 years. In contrast, healthy boys demonstrated a greater right than left frontal activation, whereas ODD boys did not display any frontal brain asymmetry. Thus, the pattern of frontal brain activation seems to be gender-specific. The atypical activation pattern in oppositional children is hypothesized to be a biological substrate of negative affective style. [ABSTRACT FROM AUTHOR]