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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]

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]

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]

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]

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]

Evidence suggests that maternal care constitutes a protective factor for psychopathology which may be conditional on the level of family adversity. Given that psychopathology is frequently linked with social deficits and the amygdala with social functioning, we investigated the impact of early maternal care on amygdala function under high vs low familial risk for psychopathology. Amygdala activity and habituation during an emotional face-matching paradigm was analyzed in participants of an epidemiological cohort study followed since birth (n = 172, 25 years). Early mother-infant interaction was assessed during a standardized nursing and play setting at the age of 3 months. Information on familial risk during the offspring's childhood and on the participants' lifetime psychopathology was obtained with diagnostic interviews. An interaction between maternal stimulation and familial risk was found on amygdala habituation but not on activation, with higher maternal stimulation predicting stronger amygdala habituation in the familial risk group only. Furthermore, amygdala habituation correlated inversely with Attention Deficit Hyperactivity Disorder (ADHD) diagnoses. The findings underline the long-term importance of early maternal care on the offspring's socioemotional neurodevelopment and of interventions targeting maternal sensitivity early in life, particularly by increasing maternal interactive behavior in those with familial risk., (© The Author(s) 2021. Published by Oxford University Press.)

Early adversity has been related to brain structure alterations and to an increased risk of psychiatric disorders. The orbitofrontal cortex (OFC) is a key region for emotional processing, with structural alterations being described in several mental disorders. However, little is known about how its cortical thickness (CT) is affected by the long-term impact of life stress (LS) at different developmental stages. The present study aimed to investigate the effect of LS during infancy, childhood, and adolescence on CT alterations in the OFC and on psychopathology in 190 adults of an ongoing prospective cohort study. Chronic stressful life events were assessed in regular intervals. Participants rated depressive symptoms at the ages of 22 and 23 years. Morphometric data were collected at the participants' age of 25 years. Chronic LS during infancy was associated with reduced CT in the right OFC and increased depressive symptoms. Moreover, the impact of chronic LS during infancy on OFC thickness was partially mediated by depressive symptoms in adulthood, suggesting an interplay of early LS, psychopathology, and CT alterations. Our findings highlight the long-term impact of early LS on an affective core brain structure and psychopathology later in life., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)