Right frontal cingulate cortex mediates the effect of prenatal complications on youth internalizing behaviors.

Prenatal and perinatal complications represent well-known risk factors for the future development of psychiatric disorders. Such influence might become manifested during childhood and adolescence, as key periods for brain and behavioral changes. Internalizing and externalizing behaviors in adolescence have been associated with the risk of psychiatric onset later in life. Both brain morphology and behavior seem to be affected by obstetric complications, but a clear link among these three aspects is missing. Here, we aimed at analyzing the association between prenatal and perinatal complications, behavioral issues, and brain volumes in a group of children and adolescents. Eighty-two children and adolescents with emotional-behavioral problems underwent clinical and 3 T brain magnetic resonance imaging (MRI) assessments. The former included information on behavior, through the Child Behavior Checklist/6-18 (CBCL/6-18), and on the occurrence of obstetric complications. The relationships between clinical and gray matter volume (GMV) measures were investigated through multiple generalized linear models and mediation models. We found a mutual link between prenatal complications, GMV alterations in the frontal gyrus, and withdrawn problems. Specifically, complications during pregnancy were associated with higher CBCL/6-18 withdrawn scores and GMV reductions in the right superior frontal gyrus and anterior cingulate cortex. Finally, a mediation effect of these GMV measures on the association between prenatal complications and the withdrawn dimension was identified. Our findings suggest a key role of obstetric complications in affecting brain structure and behavior. For the first time, a mediator role of frontal GMV in the relationship between prenatal complications and internalizing symptoms was suggested. Once replicated on independent cohorts, this evidence will have relevant implications for planning preventive interventions.

Cultural contributions to adults' self-rated mental health problems and strengths: 7 culture clusters, 28 societies, 16 906 adults.

BACKGROUND: It is unknown how much variation in adult mental health problems is associated with differences between societal/cultural groups, over and above differences between individuals. METHODS: To test these relative contributions, a consortium of indigenous researchers collected Adult Self-Report (ASR) ratings from 16 906 18- to 59-year-olds in 28 societies that represented seven culture clusters identified in the Global Leadership and Organizational Behavioral Effectiveness study (e.g. Confucian, Anglo). The ASR is scored on 17 problem scales, plus a personal strengths scale. Hierarchical linear modeling estimated variance accounted for by individual differences (including measurement error), society, and culture cluster. Multi-level analyses of covariance tested age and gender effects. RESULTS: Across the 17 problem scales, the variance accounted for by individual differences ranged from 80.3% for DSM-oriented anxiety problems to 95.2% for DSM-oriented avoidant personality (mean = 90.7%); by society: 3.2% for DSM-oriented somatic problems to 8.0% for DSM-oriented anxiety problems (mean = 6.3%); and by culture cluster: 0.0% for DSM-oriented avoidant personality to 11.6% for DSM-oriented anxiety problems (mean = 3.0%). For strengths, individual differences accounted for 80.8% of variance, societal differences 10.5%, and cultural differences 8.7%. Age and gender had very small effects. CONCLUSIONS: Overall, adults' self-ratings of mental health problems and strengths were associated much more with individual differences than societal/cultural differences, although this varied across scales. These findings support cross-cultural use of standardized measures to assess mental health problems, but urge caution in assessment of personal strengths.

Relationship between parenting measures and parents and child psychopathological symptoms: a cross-sectional study.

BACKGROUND: Increasing evidence suggests a complex role of family influences, such as the exposure to parent psychopathology through parenting behavior, in parent-to-child psychopathology transmission. Parenting behaviour could represent a relevant target of psychoeducative intervention. Given these premises, we aimed to evaluate homotypic and heterotypic relationships between parent and child psychopathology, mediated by parenting behaviours, taking into account the constructs of parent and offspring internalizing and externalizing psychopathology. METHODS: Internalizing and externalizing symptoms in 272 clinically-referred subjects (mean age = 14.5 ± 2.3; F = 23.5%) and their parents (mothers n = 272, fathers n = 242) were assessed through the Child Behavior Checklist and the Adult Self Report; four areas of parenting behaviours were investigated through the Family Life Questionnaire. Multiple mediation models were built, considering mother and father psychopathology scales as independent variables, parenting measures and family functioning as mediators (Affirmation, Rules, Discipline and Special Allowances), child psychopathology scales as dependent variables and demographic variables as covariates. RESULTS: Regression models showed a significant effect of maternal internalizing symptomatology on child externalizing behavioral problems; high levels of maternal pathology predicted high levels of children's psychopathology. A total mediating effect of parenting measures was found: high levels of internalizing symptoms in mothers predicted low levels of affirmation, which in turn predicted high levels of externalizing psychopathology in children. CONCLUSIONS: Our study results confirmed the existence of interdependent links between mothers' psychiatric symptomatology, parenting behaviour and offspring outcomes, specifically in an Italian context. On a clinical and rehabilitation basis, this work offers suggestions about parenting practices, specifically maternal, involved in the maintenance of child psychopathology.

The mental simulation of state/psychological verbs in the adolescent brain: An fMRI study.

This fMRI study investigated mental simulation of state/psychological and action verbs during adolescence. Sixteen healthy subjects silently read verbs describing a motor scene or not (STIMULUS: motor, state/psychological verbs) and they were explicitly asked to imagine the situation or they performed letter detection preventing them from using simulation (TASK: imagery vs. letter detection). A significant task by stimuli interaction showed that imagery of state/psychological verbs, as compared to action stimuli (controlled by the letter detection) selectively increased activation in the right supramarginal gyrus/rolandic operculum and in the right insula, and decreased activation in the right intraparietal sulcus. We compared these data to those from a group of older participants (Tomasino et al. 2014a). Activation in the left supramarginal gyrus decreased for the latter group (as compared to the present group) for imagery of state/psychological verbs. By contrast, activation in the right superior frontal gyrus decreased for the former group (as compared to the older group) for imagery of state/psychological verbs.

Light up ADHD: I. Cortical hemodynamic responses measured by functional Near Infrared Spectroscopy (fNIRS): Special Section on "Translational and Neuroscience Studies in Affective Disorders" Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summarise relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by deficits in cognitive and emotional self-control. Optical technique acquisitions, such as near infrared spectroscopy (NIRS), seem to be very promising during developmental ages, as they are non- invasive techniques and less influenced by body movements than other neuroimaging methods. Recently, these new techniques are being widely used to measure neural correlates underlying neuropsychological deficits in children with ADHD. METHODS: In a short series of articles, we will review the results of functional NIRS (fNIRS) studies in children with ADHD. The present brief review will focus on the results of the fNIRS studies that investigate cortical activity during neuropsychological and/or emotional tasks. RESULTS: According to the reviewed studies, children and adolescents with ADHD show peculiar cortical activation both during neurological and emotional tasks, and the majority of the reviewed studies revealed lower prefrontal cortex activation in patients compared to typically developmental controls. LIMITATIONS: a consistent interpretation of these results is limited by the substantial methodological heterogeneity including patients' medication status and washout period, explored cerebral regions, neuropsychological tasks, number of channels and sampling temporal resolutions. CONCLUSIONS: fNIRS seems to be a promising tool for investigating neural substrates of emotional dysregulation and executive function deficits in individuals with ADHD during developmental ages.

Latent classes of emotional and behavioural problems in epidemiological and referred samples and their relations to DSM-IV diagnoses.

Researchers' interest have recently moved toward the identification of recurrent psychopathological profiles characterized by concurrent elevations on different behavioural and emotional traits. This new strategy turned to be useful in terms of diagnosis and outcome prediction. We used a person-centred statistical approach to examine whether different groups could be identified in a referred sample and in a general-population sample of children and adolescents, and we investigated their relation to DSM-IV diagnoses. A latent class analysis (LCA) was performed on the Child Behaviour Checklist (CBCL) syndrome scales of the referred sample (N = 1225), of the general-population sample (N = 3418), and of the total sample. Models estimating 1-class through 5-class solutions were compared and agreement in the classification of subjects was evaluated. Chi square analyses, a logistic regression, and a multinomial logistic regression analysis were used to investigate the relations between classes and diagnoses. In the two samples and in the total sample, the best-fitting models were 4-class solutions. The identified classes were Internalizing Problems (15.68%), Severe Dysregulated (7.82%), Attention/Hyperactivity (10.19%), and Low Problems (66.32%). Subsequent analyses indicated a significant relationship between diagnoses and classes as well as a main association between the severe dysregulated class and comorbidity. Our data suggested the presence of four different psychopathological profiles related to different outcomes in terms of psychopathological diagnoses. In particular, our results underline the presence of a profile characterized by severe emotional and behavioural dysregulation that is mostly associated with the presence of multiple diagnosis.

Effect of family structure and TPH2 G-703T on the stability of dysregulation profile throughout adolescence.

BACKGROUND: Two different polymorphisms (TPH2 G-703T and 5-HTTLPR) involved in the serotonergic pathway have been reported to play a role, both alone and in interaction with the environment, in early and adult emotion regulation. As most of these studies are cross-sectional, we know little about the impact of these polymorphisms over time, particularly during adolescence. METHODS: Because we were interested in the effects of these polymorphisms and environment (i.e., family structure) at different time-points on the emotional dysregulation profile, we performed a path analysis model in a general adolescent population sample of a five-year follow-up study. RESULTS: We found a high stability of Dysregulation Profile problems independently from the examined allelic variants. We also found that early family structure directly influences the levels of dysregulation problems in early adolescence, both alone and in interaction with TPH2, suggesting the presence of a gene-environment interaction effect. Furthermore, we found that in adolescents homozygous for the TPH2 G allele, the effect of the early family structure remains active during late adolescence, albeit mediated by earlier emotional problems. LIMITATIONS: The high attrition rate, the use of only one source on behavioral problems of adolescents, and the focus on a single polymorphism in the investigated genes could limit the generalizability of the present results. CONCLUSIONS: These results suggest that early family structure could play a significant role in the development and maintenance of emotional and behavioral problems not only in early adolescence but also in late-adolescence, although this effect was mediated and moderated by behavioral and genetic variables.

Syndromes of Self-Reported Psychopathology for Ages 18-59 in 29 Societies.

This study tested the multi-society generalizability of an eight-syndrome assessment model derived from factor analyses of American adults' self-ratings of 120 behavioral, emotional, and social problems. The Adult Self-Report (ASR; Achenbach and Rescorla 2003) was completed by 17,152 18-59-year-olds in 29 societies. Confirmatory factor analyses tested the fit of self-ratings in each sample to the eight-syndrome model. The primary model fit index (Root Mean Square Error of Approximation) showed good model fit for all samples, while secondary indices showed acceptable to good fit. Only 5 (0.06%) of the 8,598 estimated parameters were outside the admissible parameter space. Confidence intervals indicated that sampling fluctuations could account for the deviant parameters. Results thus supported the tested model in societies differing widely in social, political, and economic systems, languages, ethnicities, religions, and geographical regions. Although other items, societies, and analytic methods might yield different results, the findings indicate that adults in very diverse societies were willing and able to rate themselves on the same standardized set of 120 problem items. Moreover, their self-ratings fit an eight-syndrome model previously derived from self-ratings by American adults. The support for the statistically derived syndrome model is consistent with previous findings for parent, teacher, and self-ratings of 1½-18-year-olds in many societies. The ASR and its parallel collateral-report instrument, the Adult Behavior Checklist (ABCL), may offer mental health professionals practical tools for the multi-informant assessment of clinical constructs of adult psychopathology that appear to be meaningful across diverse societies.

The ability of CBCL DSM-oriented scales to predict DSM-IV diagnoses in a referred sample of children and adolescents.

The majority of studies examining associations between clinical-diagnostic and empirical-quantitative approaches have concentrated only on the target diagnosis without taking into account any possible co-variation of psychopathological traits, which is intrinsic to child psychopathology. The ability of child behaviour checklist (CBCL) DSM-oriented scales (DOSs) to predict target and other DSM diagnoses, taking into consideration the covariation of psychopathological traits, was analysed by logistic regression analysis. Corresponding odds ratio (OR) was used as indicator of the strength of the relationship between the clinical score in DOSs and the presence of DSM-IV diagnoses. Logistic regression allowed us to consider multiple scales simultaneously, thus addressing the problem of co-occurrence of psychopathological traits, and to include gender and age as covariates. The sample consisted of 360 children and adolescents aged 6-16 years, consecutively referred for behavioural and emotional problems. As a whole, the CBCL DOSs seem to be more specific but with a weaker association with DSM-IV diagnoses than syndrome scales, and with some distinctive features: clinical scores in the anxiety DOS suggest a diagnosis of both anxiety and mood disorder; clinical scores in the somatic problems DOS are very strong and specific predictors for diagnosis of separation anxiety disorder; clinical scores in the oppositional defiant problems DOS are not only predictors of the oppositional defiant disorder but are also strong predictors of generalized anxiety disorder; clinical scores in the conduct problems DOS are a specific and strong predictor for oppositional defiant disorder. Results confirm the clinical usefulness of CBCL and suggest using both syndrome and DOS scales for a complete and accurate assessment of children and adolescents.

Further evidence of complex motor dysfunction in drug naive children with autism using automatic motion analysis of gait.

In order to increase the knowledge of locomotor disturbances in children with autism, and of the mechanism underlying them, the objective of this exploratory study was to reliably and quantitatively evaluate linear gait parameters (spatio-temporal and kinematic parameters), upper body kinematic parameters, walk orientation and smoothness using an automatic motion analyser (ELITE systems) in drug naïve children with Autistic Disorder (AD) and healthy controls. The children with AD showed a stiffer gait in which the usual fluidity of walking was lost, trunk postural abnormalities, highly significant difficulties to maintain a straight line and a marked loss of smoothness (increase of jerk index), compared to the healthy controls. As a whole, these data suggest a complex motor dysfunction involving both the cortical and the subcortical area or, maybe, a possible deficit in the integration of sensory-motor information within motor networks (i.e., anomalous connections within the fronto-cerebello-thalamo-frontal network). Although the underlying neural structures involved remain to be better defined, these data may contribute to highlighting the central role of motor impairment in autism and suggest the usefulness of taking into account motor difficulties when developing new diagnostic and rehabilitation programs.

COMT Val158Met polymorphism and socioeconomic status interact to predict attention deficit/hyperactivity problems in children aged 10-14.

The functional Val158Met COMT polymorphism appears to affect a host of behaviours mediated by the pre-frontal cortex, and has been found associated to the risk for disruptive behaviours including ADHD. Parental socioeconomic status (SES) has also been reported as a predictor for the same childhood disorders. In a general population sample of 575 Italian pre-adolescents aged 10-14, we examined the association of the functional Val158Met COMT polymorphism and SES-both as linear and interactive effects-with oppositional defiant problems, conduct problems, and attention deficit/hyperactivity problems, as defined by the newly established Child Behaviour Check-List/6-18 DSM oriented scales. Multivariate- and subsequent univariate-analysis of covariance showed a significant association of COMT x SES interaction with CBCL 6/18 DOS attention deficit/hyperactivity problems (p = 0.004), and revealed higher scores among those children with Val/Val COMT genotype who belonged to low-SES families. We also found a significant association of SES with attention deficit/hyperactivity problems and conduct problems DOS (p = 0.04 and 0.01, respectively). Our data are consistent with a bulk of recent literature suggesting a role of environmental factors in moderating the contribution of specific genetic polymorphisms to human variability in ADHD. While future investigations will refine and better clarify which specific environmental and genetic mechanisms are at work in influencing the individual risk to ADHD in pre-adolescence, these data may contribute to identify/prevent the risk for ADHD problems in childhood.

The influence of family structure, the TPH2 G-703T and the 5-HTTLPR serotonergic genes upon affective problems in children aged 10-14 years.

BACKGROUND: Both genetic and psychosocial risk factors influence the risk for depression in development. While the impacts of family structure and of serotonergic polymorphisms upon individual differences for affective problems have been investigated separately, they have never been considered together in a gene-environment interplay perspective. METHODS: We examined the effects of family structure and two serotonergic polymorphisms (the TPH2 G-703T and the 5-HTTLPR) upon depressive symptoms assessed by the new CBCL/6-18 DSM-oriented Affective Problems scale in a general population sample of 607 Italian children aged 10-14 years. RESULTS: Belonging to 'one-parent' families, the TPH2 G-703T 'G variant', and the 5-HTTLPR 'short' alleles were associated - both alone and in apparent gene-by-environment interaction - with higher Affective Problems scores. As predicted by quantitative genetics theory, both polymorphisms contributed with a small effect size, while 'family structure' had a moderate effect size. CONCLUSIONS: A putative hazard factor impinging on individual risk at the family-wide level, namely family structure, appears to act interactively with two pivotal serotonergic genes in heightening risk for Affective Problems. Although it remains to be demonstrated that belonging to a one- rather than a two-parent family has true environmental causal effects on Affective Problems, these data may contribute to identify/prevent risk for depression in childhood.

Socioeconomic status mediates the genetic contribution of the dopamine receptor D4 and serotonin transporter linked promoter region repeat polymorphisms to externalization in preadolescence.

The impact of socioeconomic status (SES) and genetic polymorphisms on individual differences for externalized behaviors have often been investigated separately in studies of children and adults. In a general population sample of 607 Italian preadolescents, we examined the independent and joint effects of SES and the dopamine receptor D4 (DRD4) and serotonin transporter linked promoter region (5-HTTLPR) polymorphisms upon rule-breaking and aggressive behaviors measured with the Child Behavior CheckList/6-18. We found evidence, which was based on both one locus and two-loci genotype analyses, that low SES and DRD4 long and 5-HTTLPR long alleles, both alone and in interaction, are associated with higher aggressive behavior scores. The effects were similar but more modest and limited to one locus genotype analyses for rule-breaking behavior. Consistent with studies that showed the effects of societal moderators on the heritability of externalized behaviors across different segments of the population, we suggest that diminished social constraints associated with low parental SES may act as enhancers of the genetic influence of specific DRD4 and 5-HTTLPR alleles over aggressive behaviors in preadolescence.

A case-control and family-based association study of the 5-HTTLPR in pediatric-onset depressive disorders.

BACKGROUND: Pediatric depression can be particularly informative for clarification of the causes of mood disorders. The aim of this work was to explore the possible association between childhood- and early-adolescent-onset DSM-IV depressive disorders (DD; including major depression and dysthymia) and the serotonin transporter-linked promoter polymorphism (5-HTTLPR) locus. METHODS: The case-control sample consisted of 68 unrelated patients with DD, and 68 unrelated age- and gender-matched healthy control subjects. The same patients were included in the family-based study, which consisted of 41 triads and 11 dyads. RESULTS: An excess of the SS-genotype (p =.025) and of the S-allele (p =.021) was found among DD children (odds ratio = 1.81; 95% confidence interval = 1.12-2.94). The family-based results suggested that the S-allele was preferentially transmitted to depressed children (haplotype-based haplotype relative risk: chi(2) = 7.231 df = 1, p =.007; transmission disequilibrium test: chi(2) = 5.233, df = 1, p =.022). CONCLUSIONS: A role for the 5-HTTLPR locus that needs replication in larger samples is suggested in childhood DD.