["Risk factors of childhood depression" research grant - past, present, future].

The authors summarize the last 10 years of an ongoing collaborative study between the Universities of Szeged and Pittsburgh on early onset major depression. First, the "Risk factors of childhood depression" grant is presented briefly as an initial research study in which the subjects of the current studies were recruited. This is a prominently large clinical sample in the field of child psychiatry even on an international level. In addition to the follow-up of the prognosis of the disorder, recent studies continue to explore the early onset depression in two directions. On the one hand, two studies investigate the role of biobehavioral inflexibility markers in the development of major depression ("Biobehavioral inflexibility and risk for juvenile-onset depression" and "Biobehavioral inflexibility and risk for juvenile-onset depression - renewal grant"). On the other hand, the authors would like to have a better understanding of the possible relationship between the major depression and cardiovascular diseases ("Pediatric depression and subsequent cardiac risk factors: a longitudinal study"). The most significant aims of the three studies will be demonstrated, as well as how the studies were prepared and organized along with the already existing experience concerning research management and involvement of new collaborating partners and experts.

The Development of Mood Repair Response Repertories: I. Age-Related Changes Among 7- to 14-Year-Old Depressed and Control Children and Adolescents.

The purpose of this study was to test developmentally informed hypotheses about regulatory responses to sadness that attenuate versus exacerbate it (adaptive versus maladaptive mood repair responses, respectively) across late childhood, early adolescence, and mid-adolescence. In a multi-site study in Hungary, clinic-based, 7- to 14-year-olds with Diagnostic and Statistical Manual of Mental Disorders' (4th ed., text rev.) depressive disorders (N = 697; 55% male) and age/sex matched (at 1:2) nondepressed, school-based controls (N = 1,394) reported on their usual responses to sadness/dysphoria; parental reports were obtained separately. Adaptive and maladaptive response repertoire scores were compared across ages within and across subject groups, and by informant, controlling for confounds. Contrary to Hypothesis 1, older (vs. younger) youths in both groups reported fewer adaptive regulatory responses. Maladaptive response repertoires were unrelated to age among controls but significantly increased with age among depressed youths, particularly the girls. Partially supporting Hypothesis 2, subject groups differed in age-related trajectories of mood repair repertories, but not as expected (e.g., younger depressed children reported larger adaptive response repertoires than did controls). Parental reports revealed no developmental changes in offspring's mood repair repertories. Parent-offspring reports were most discordant for younger (vs. older) offspring, tended to converge around age 11, and were consistently and significantly larger in the depressed sample. Self-reported adaptive mood repair repertories appear to have been laid down by late childhood and then undergo "trimming" across ages 7-14 years. The extensive maladaptive mood repair response repertoires of depressed youths, which increased with age, distinguish them primarily from controls. Therefore, reducing maladaptive regulatory responses to sadness should be a priority when treating depressed youths.

Positive autobiographical memory deficits in youth with depression histories and their never-depressed siblings.

OBJECTIVES: Impaired positive autobiographical memory (AM) is closely linked to emotional disorders. AM impairments are often found in depressed adults and may be related to the difficulties such persons have in regulating their dysphoric mood. By contrast, less is known about AM disturbances among adolescents, or about the functional relationship of AM disturbances to early-onset depression. DESIGN: A high-risk family design served to compare four groups of youth who differed in depression histories and familial depression risk. METHODS: Thirty-one currently depressed probands, 185 remitted probands, 204 never-depressed siblings of probands, and 180 healthy control youth were induced into a negative mood prior to recalling positive AMs via a novel memory elicitation procedure. Several positive AM characteristics were assessed. RESULTS: Relative to control youth, unaffected siblings and probands exhibited consistently impaired positive AMs. Moreover, we also found some evidence that probands were more impaired than siblings, who were in turn more impaired than controls, consistent with a gradient effect. CONCLUSIONS: Positive AM disturbances may not only precede the onset of depression in vulnerable youth, but also continue to persist after remission of a depressive episode. Clinical and basic research implications of the findings are discussed. PRACTITIONER POINTS: Positive AM impairments may be trait-like, persist in the euthymic phase of depression, and may serve as a risk marker for early-onset depression among vulnerable adolescents. Disturbances in positive AM may negatively impact the mood-regulatory functions of positive memory recall and contribute to persistent sadness and anhedonia, which are core features of depression. Our sample of currently depressed youth was relatively small, tempering our conclusions. Although we collected data on some important covariates (e.g., socioeconomic status), we lacked information on other relevant variables such as youths' executive functioning or IQ.

Mood repair via attention refocusing or recall of positive autobiographical memories by adolescents with pediatric-onset major depression.

BACKGROUND: Impaired emotion regulation is increasingly recognized as a core feature of depressive disorders. Indeed, currently and previously depressed adults both report greater problems in attenuating sadness (mood repair) in daily life than healthy controls. In contrast, studies of various strategies to attenuate sad affect have mostly found that currently or previously depressed adults and controls were similarly successful at mood repair in the laboratory. But few studies have examined mood repair among depression-prone youths or the effects of trait characteristics on mood repair outcomes in the laboratory. METHODS: Adolescents, whose first episode of major depressive disorder (MDD) had onset at age 9, on average (probands), and were either in remission or depressed, and control peers, watched a sad film clip. Then, they were instructed to engage in refocusing attention (distraction) or recalling happy memories. Using affect ratings provided by the youths, we tested two developmentally informed hypotheses about whether the subject groups would be similarly able to attenuate sadness via the two mood repair strategies. We also explored if self-reported habitual (trait) mood repair influenced laboratory performance. RESULTS: Contrary to expectations, attention refocusing and recall of happy memories led to comparable mood benefits across subjects. Control adolescents reported significantly greater reductions in sadness than did depressed (Cohen's d = .48) or remitted (Cohen's d = .32) probands, regardless of mood repair strategy, while currently depressed probands remained the saddest after mood repair. Habitual mood repair styles moderated the effects of instructed (state) mood repair in the laboratory. CONCLUSIONS: Whether depressed or in remission, adolescents with MDD histories are not as efficient at mood repair in the laboratory as controls. But proband-control group differences in mood repair outcomes were modest in scope, suggesting that the abilities that subserve affect regulation have been preserved in probands to some degree. Further information about the nature of mood repair problems among youths with depression histories would help to better understand the clinical course of MDD and to design personalized interventions for depression.

[The possibility of prenatal diagnosis of autism spectrum disorder]. / Az autizmusspektrum-zavarok prenatális diagnózisának lehetoségei.

Autism spectrum disorder (ASD) is an idiopathic multifactorial disease. Chromosomal abnormalities could be found only in a few percent (0.3-0.6) of cases. The estimated prevalence is 0.6 in Europe and the prevalence of the disease has been increased in last few decades. ASD have an impact on the quality of life of the patient and his family. The early diagnosis of ASD is most important. There are limited data regarding the measure of biparietal diameter (BPD) of the fetus in the first trimester of pregnancy. These data suggested the BPD is an important screening marker for ASD, but the complex prenatal screening is unresolved. There is a need for further investigations of the genetic background of ASD and to identify potentially first trimester ultrasound markers for ASD.

The association between major depressive disorder in childhood and risk factors for cardiovascular disease in adolescence.

OBJECTIVE: Depression in adults is associated with risk factors for cardiovascular disease (CVD). It is unclear, however, when the association between clinical depression and cardiac risk factors develops or how early in life this association can be detected. METHODS: In an ongoing study of pediatric depression, we compared CVD risk factors including smoking, obesity, physical activity level, sedentary behavior, and parental history of CVD across three samples of adolescents: probands with established histories of childhood-onset major depressive disorder (n = 210), never-depressed siblings of probands (n = 195), and controls with no history of any major psychiatric disorder (n = 161). RESULTS: When assessed during adolescence, 85% of the probands were not in a major depressive episode. Nevertheless, at that assessment, probands had a higher prevalence of regular smoking (odds ratio [OR] = 12.54, 95% confidence interval [CI] = 4.36-36.12) and were less physically active than controls (OR = 0.59, CI = 0.43-0.81) and siblings (OR = 0.70, CI = 0.52-0.94) and had a higher rate of obesity than did controls (OR = 3.67, CI = 1.42-9.52). Parents of probands reported high rates of CVD (significantly higher than did parents of controls), including myocardial infarction and CVD-related hospitalization (ORs = 1.62-4.36, CIs = 1.03-15.40). Differences in CVD risk factors between probands and controls were independent of parental CVD. CONCLUSIONS: Major depression in childhood is associated with an unfavorable CVD risk profile in adolescence, and risks for pediatric depression and CVD may coincide in families. Effective prevention and treatment of childhood depression may be a means to reduce the incidence of adult CVD.

Blood lipid peroxidation, antioxidant enzyme activities and hemorheological changes in autistic children.

OBJECTIVES: Early infantile autism is a severe form of childhood psychiatric disease with characteristic symptoms. Hyperserotoninaemia in 43.5%, lactic acidosis 43% and hyperpyruvataemia in 30% were biochemically demonstrated in autistic children. Our earlier results led to the postulation that a dissequilibrium in the blood redox is involved in infantile autism; the oxidative loading and the antioxidant defending enzyme system were investigated together with the hemorheological parameters in infantile autism. METHODS: Malonyl-dialdehyde (MDA) endproduct of lipid peroxidation and activities of the antioxidant enzymes: superoxide dismutase (SOD), catalase (C-ase), glutathione peroxidase (GP-ase) and reduced glutathione (GSH) were biochemically determined from plasma and red blood cells. PATIENTS: The antioxidant specificities were investigated in plasma and red blood cell haemolysate from 25 infantile autistic children. RESULTS: Significantly increased superoxide dismutase (SOD) (2.89 vs. 1.32 U/mg protein, p < 0.01) and decreased glutathione peroxidase (0.620 vs. 0.910 U/mg protein, p < 0.01) levels as well as catalase (0.463 vs. 4.948 BU/mg protein, p < 0.001) activities were detected; while the plasma and erythrocyte lipid peroxidation and the reduced glutathione (GSH) levels did not change. The results of the investigated prooxidant and the antioxidant status provide evidence that there exists an oxidative stress in children with infantile autism. While investigating the hemorheological parameters of 25 infantile autistic patients, some characteristic pathological parameters were detected: the initial filtration rate (Fi) (0.72 vs. 0.75 p < 0.01) and the clogging rate (CR) (1.926 vs. 2.912, p < 0.01) values of red blood cells (RBC) decreased while the mean transit time (Tc) (8.93 vs. 7.39, p < 0.001) increased suggesting reduced RBC deformability.

[Symptoms of depression in children and adolescents in relation to psychiatric comorbidities]. / A gyermek- és serdulokori depresszio tuneteinek összefuggése a pszichiatriai komorbiditásokkal.

INTRODUCTION: The lifetime prevalence of MDD before adolescence is 4-5%, while the symptoms concern 13-20% of the adolescents. In the development of suicidal behaviour the most important risk factors are the use of psychoactive drugs and smoking. Psychiatric comorbidities are aggravating significantly the major depression. The comorbidities are high among major depression, anxiety and disruptive disorders. SAMPLE AND METHOD: We examined 649 children being in a depressive episode diagnosed by ISCA-D semi-structured interview, 45,9% of them were girls, and 54,1% were boys, the mean age was 11,7 years ( SD=2,00). The participants were enrolled into three groups according to their comorbidities: group with only depression without comorbidities, group with anxiety comorbidity, and group with disruptive comorbidity. We compared the three groups according to the frequency of their depressive symptoms. RESULTS: Anxiety comorbidities increase the incidence of depressive symptoms. Among the criteria symptoms irritability where the most frequent symptom independently from the comorbidities, the depressed mood is the most frequent within the anxiety group, while anhedonia occurred with a moderate frequency in each groups. In the anxiety group the vegetative symptoms, while in the disruptive group the psychomotor agitation and the feeling of worthlessness are the most frequent symptoms. Comorbidities are increasing the incidence of the suicide symptoms. The incidence of impaired decision making was high in each group, the comorbidities didn't influence it's frequency. Among depressed boys irritability and feelings of worthlessness (low self-esteem) increase the presence of externalisation comorbidity. Among depressed girls guilt was significantly more frequent in the anxiety comorbidity group, and concentration problems are the most typical symptoms in the clear MDD group, without comorbidities.

The methylome in females with adolescent Conduct Disorder: Neural pathomechanisms and environmental risk factors.

Conduct Disorder (CD) is an impairing psychiatric disorder of childhood and adolescence characterized by aggressive and dissocial behavior. Environmental factors such as maternal smoking during pregnancy, socio-economic status, trauma, or early life stress are associated with CD. Although the number of females with CD is rising in Western societies, CD is under-researched in female cohorts. We aimed at exploring the epigenetic signature of females with CD and its relation to psychosocial and environmental risk factors. We performed HpaII sensitive genome-wide methylation sequencing of 49 CD girls and 50 matched typically developing controls and linear regression models to identify differentially methylated CpG loci (tags) and regions. Significant tags and regions were mapped to the respective genes and tested for enrichment in pathways and brain developmental processes. Finally, epigenetic signatures were tested as mediators for CD-associated risk factors. We identified a 12% increased methylation 5' of the neurite modulator SLITRK5 (FDR = 0.0046) in cases within a glucocorticoid receptor binding site. Functionally, methylation positively correlated with gene expression in lymphoblastoid cell lines. At systems-level, genes (uncorr. P < 0.01) were associated with development of neurons, neurite outgrowth or neuronal developmental processes. At gene expression level, the associated gene-networks are activated perinatally and during early childhood in neocortical regions, thalamus and striatum, and expressed in amygdala and hippocampus. Specifically, the epigenetic signatures of the gene network activated in the thalamus during early childhood correlated with the effect of parental education on CD status possibly mediating its protective effect. The differential methylation patterns identified in females with CD are likely to affect genes that are expressed in brain regions previously indicated in CD. We provide suggestive evidence that protective effects are likely mediated by epigenetic mechanisms impairing specific brain developmental networks and therefore exerting a long-term effect on neural functions in CD. Our results are exploratory and thus, further replication is needed.

No evidence of an association between two genes, EDN1 and ACE, and childhood-onset mood disorders.

Recent evidence supports a pathological link between heart disease and depressive symptoms, suggesting that depression is both etiologic and prognostic to heart disease. Thus, biological molecules which are at the interface between heart and mind are plausible candidate genes for depressive disorders. To investigate this line of enquiry we have investigated two genes, Endothelin 1 (EDN1) and Angiotensin-converting enzyme (ACE) in a family-based sample with childhood-onset mood disorders (COMDs). EDN1 is highly expressed in endothelium where it acts as a potent vasoconstrictor, and is also expressed in the brain where it exhibits neurotransmitter characteristics. ACE acts as a potent vasopressor, and interacts with the hypothalamic-pituitary-adrenocortical (HPA) system, which is often dysregulated in mood disorders. Furthermore, ACE has recently been found to be associated with major depression. Polymorphisms were selected to best capture the genetic variation at the two loci, and to replicate previous associations. The markers were genotyped across EDN1 and ACE in a sample comprised of 382 Hungarian nuclear families ascertained through affected probands diagnosed with a mood disorders before the age of 15. We found no evidence of association between either of these genes and COMD. Consequently, we were unable to support our hypothesis that these two genes, which are involved in both vascular and brain functions are contributing to the susceptibility to mood disorders of children/adolescents.

Neuropsychological Subgroups of Emotion Processing in Youths With Conduct Disorder.

Background: At the group level, youths with conduct disorder (CD) show deficient emotion processing across various tasks compared to typically developing controls (TDC). But little is known about neuropsychological subgroups within the CD population, the clinical correlates of emotion processing deficits [for instance, with regard to the presence or absence of the DSM-5 Limited Prosocial Emotions (LPE) specifier], and associated risk factors. Methods: 542 children and adolescents with CD (317 girls) and 710 TDCs (479 girls), aged 9-18 years, were included from the FemNAT-CD multisite study. All participants completed three neuropsychological tasks assessing emotion recognition, emotion learning, and emotion regulation. We used a self-report measure of callous-unemotional traits to create a proxy for the LPE specifier. Results: Relative to TDCs, youths with CD as a group performed worse in all three emotion domains. But using clinically based cut-off scores, we found poor emotion recognition skills in only 23% of the participants with CD, followed by emotion regulation deficits in 18%, and emotion learning deficits in 13% of the CD group. Critically, the majority of youths with CD (~56%) did not demonstrate any meaningful neuropsychological deficit, and only a very small proportion showed pervasive deficits across all three domains (~1%). Further analyses indicate that established DSM-5 subtypes of CD are not tightly linked to neurocognitive deficits in one particular emotion domain over another (i.e., emotion recognition deficits in CD+LPE vs. emotion regulation deficits in CD-LPE). Conclusions: Findings from this large-scale data set suggest substantial neuropsychological diversity in emotion processing in the CD population and, consequently, only a subgroup of youths with CD are likely to benefit from additional behavioral interventions specifically targeting emotion processing mechanisms.

Further genetic evidence implicates the vasopressin system in childhood-onset mood disorders.

Studies in both animals and humans advocate a role for the vasopressin (AVP) system in the aetiology of depressive symptoms. Attention has particularly focused on the role of AVP in the overactivation of the hypothalamic-pituitary-adrenal (HPA)-axis in mood disorders. Elevated AVP plasma levels have been found in mood disorder patients, which are often positively correlated with the severity of symptoms. We recently reported an association between childhood-onset mood disorders (COMD) and polymorphisms in the receptor responsible for the AVP-mediated activation of the HPA-axis (AVPR1B). As genetic variation in the vasopressinergic system could provide a mechanism to explain the endocrine alterations observed in mood disorders, we investigated other genes in this system. The gene encoding AVP is the strongest candidate, particularly as genetic variation in this gene in rodents is associated with anxiety-related behaviours. Six single-nucleotide polymorphisms (SNPs) were genotyped across the AVP gene in a sample comprised of 586 Hungarian nuclear families ascertained through affected probands with a diagnosis of COMD. In addition, AVP coding and putative regulatory regions were screened for mutations using denaturing high-performance liquid chromatography. One SNP, 3' to the AVP, gene reached significance (P = 0.03), as did the overtransmission of a five-marker haplotype with a frequency of 22% (P = 0.0001). The subsequent mutation screen failed to identify any putative functional polymorphisms. The outcome of this study, combined with our previous association between COMD and AVPR1B, implicates genetic variation in vasopressinergic genes in mediating vulnerability to COMD.

Assessing quality of life: mother-child agreement in depressed and non-depressed Hungarian.

PURPOSE: An important question in child psychiatry is the agreement between parents and children. We studied mother-child concordance about the quality of life of children (QoL). We hypothesized that mothers of depressed children rate lower QoL than children for themselves while mothers of non-depressed children rate better QoL; that inter-informant agreement is higher in the non-depressed sample; and finally that agreement increases with age of the child. METHODS: QoL of depressed children (N = 248, mean age 11.45 years, SD 2.02) were compared to that of non-depressed children (N = 1695, mean age 10.34 years, SD 2.19). QoL was examined by a 7 item questionnaire (ILK). RESULTS: Mothers of depressed children rated lower QoL than their children while mothers of nondepressed children rated higher QoL than their children. Agreement was low in both samples but higher in the controls. Inter-informant agreement was only influenced by depression. CONCLUSIONS: Our results show that mothers relate more serious negative effects to childhood depression than their children and rate less problems for their non-depressed children compared to self-reports. Mother-child agreement is negatively influenced by depression which further stresses the importance of obtaining reports from the child and at least one parent in order to understand the subjective experiences caused by the illness.

Tagging SNP association study of the IL-1beta gene (IL1B) and childhood-onset mood disorders.

Given substantial evidence for IL-1beta involvement in the etiology of depression, the IL1B gene is a strong candidate for involvement in susceptibility to depressive disorders. However, association studies investigating this, to date, have been limited to just two polymorphisms (rs1143627[-31T/C] and rs16944[-511C/T]) that constitute only a fraction of the genetic variation that is actually present across this gene in the population. Here, in a family-based association study of childhood-onset mood disorders (COMD), characterized by onset of depression before the age of 15, we have used a gene-wide approach, employing a panel of five tagging SNPs spanning the entire gene. Based on TDT analyses of both individual alleles and haplotypes, in a study sample of 646 families (with 782 affected children), none of the SNPs, including those implicated in transcriptional regulation of the gene, showed evidence for association with COMD. This is the largest and most comprehensive study of IL1B in relation to mood disorders that has been carried out, to date. The results do not support the involvement of IL1B as a major factor in genetic risk for early-onset mood disorders.

G72/G30 (DAOA) and juvenile-onset mood disorders.

The chromosome 13q region has been linked to bipolar disorder in a number of genome scans as well as focused linkage studies. Previously we identified linkage to the 13q32 region in a genome scan of 146 affected sibling pair families from Hungary with juvenile-onset mood disorders. Within this region are the overlapping genes G72/G30, with G72 now officially named as D-amino-acid oxidase activator (DAOA). This locus has been associated with panic disorder, schizophrenia, and bipolar disorder. In this study, we tested for association to 11 markers in these genes and mood disorders in a sample of 646 nuclear families identified with a proband with onset of a mood disorder before 14.9 years of age. We identified evidence for association to three markers within the gene (rs2391191, rs3918341, rs1935062), two of which had been associated with bipolar disorder in previous studies. When corrected for the number of markers tested, the results were no longer significant, however the prior evidence for association of this gene in multiple studies points to this gene as a potential contributor to juvenile-onset mood disorders.

Genome scan in sibling pairs with juvenile-onset mood disorders: Evidence for linkage to 13q and Xq.

Mood disorders (bipolar and depressive disorders) in children and adolescents are associated with significant morbidity and mortality. Twin and family studies, for the most part, indicate higher familiality and heritability for mood disorders that onset in childhood/adolescence than those that onset in adulthood. To identify the genetic contribution to mood disorders that onset in childhood/adolescence, we performed a genome scan on 146 nuclear families from Hungary containing an affected proband and affected siblings. In total, the pedigrees contained 303 affected children: 146 probands, 137 siblings with a first episode of mood disorder before 14.9 years of age, and 20 siblings with onset of their first episode after 14.9 years of age but before the age of 18. The results of the genome scan using 405 microsatellite markers did not provide evidence for linkage at the recommended genome wide significance level for any novel loci. However, markers on two chromosomes, 13q and Xq, provided evidence for linkage in regions previously identified as linked to bipolar disorder in multiple studies. For the marker on chromosome 13q the peak non-parametric multipoint LOD score was at the marker D13S779 (LOD = 1.5, P = 0.004). On chromosome Xq, evidence for linkage was observed across a large region spanning two regions previously linked to bipolar disorder; Xq24 to Xq28, with a peak at marker TTTA062 (LOD 2.10, P = 0.0009) in Xq28. Results for these regions exceed the recommended P-value for a replication study of P < 0.01 and thus provide evidence for these two loci as contributing to mood disorders with juvenile onset.

["Risk factors for childhood depression"--research design, implementation, proceedings: history of 13 years: experience in grant preparation, writing, organization in connection with an American NIMH Grant]. / A gyermekkori depresszió rizikótényezio kutatás megtervezése, megvalósítása, lefolyása.

The authors summarize their experiences in research organization accumulated during 13 years. At first they outline preliminary studies which are prerequisites of high prestige international grants. Then they describe the huge administrative apparatus dedicated - besides skilled professionals - for the construction and organization of the research, the management, continuous checking and evaluation of data in such a multisite study. Finally, they report on the scientific results obtained after 13 years of hard work.

Emotion Regulation Among Adolescents With Pediatric Depression As a Function of Anxiety Comorbidity.

Background: Both depression and anxiety (two of the most common internalizing psychopathologies among youths) are associated with difficulties in emotion regulation (ER). Little is known about whether anxiety as a comorbid condition has an effect on the habitual use of different ER strategies in youngsters with depression histories. We aimed 1) to compare ER in adolescents with histories of childhood onset major depressive disorder (MDD) with and without comorbid anxiety and 2) to examine whether certain ER response clusters (Cognitive, Social, and Behavioral/Physical) characterize comorbid children and adolescents. Methods: We analyzed data on 217 youth (11-18 years old) with depression history: 85 subjects with lifetime anxiety comorbidity (comorbid group) and 132 without lifetime anxiety (non-comorbid group). Psychiatric diagnosis was established by a comprehensive Diagnostic and Statistical Manual of Mental Disorders (DSM) IV-based diagnostic procedure. ER strategies were examined via the self-rated "Feelings and Me" Child version questionnaire (FAM-C). Results: The comorbid group used maladaptive ER strategies significantly more frequently than the non-comorbid youngsters. The Behavioral/Physical and Social ER skills, especially those reflecting social withdrawal and self-harm, were responsible for the higher maladaptive scores. Limitations: Because our study is a cross-sectional analysis, we have no information about the development or the onset of maladaptive ER strategies. Therefore, we were unable to examine whether maladaptive ER was a risk factor or a consequence of the internalizing psychopathology and comorbidity. Conclusions: Comorbid anxiety worsens the impaired use of ER strategies in depression-prone youths. Further longitudinal research is needed to explore the causal role of dysfunctional ER in the development of internalizing psychopathology.

Dysregulated behavioral responses to hedonic probes among youth with depression histories and their high-risk siblings.

Affect dysregulation in response to rewarding stimuli has been proposed as a vulnerability factor for major depressive disorder (MDD). However, it remains unclear how affective behavioral dynamics may be altered among individuals who are at high risk for depression but not currently depressed. We examined the dynamics of affective facial behavior during hedonic probes among 3 groups of adolescents: remitted probands who had histories of childhood-onset MDD (n = 187), never-depressed siblings of probands (high familial risk; n = 207), and healthy controls (n = 166). Participants' happy and sad facial expressions were coded during 3 hedonic laboratory tasks: receiving a preferred prize, describing a positive autobiographical memory, and watching a humorous film. Happy and sad behavioral dynamics were indexed by mean level- and time-dependent reactivity, variability (mean of the squared successive differences), and inertia (autocorrelation). Relative to controls, probands and siblings exhibited a more rapid decrease in happy behaviors, and probands exhibited higher inertia of sad behaviors during hedonic probes. Both probands and siblings exhibited lower inertia of sad behaviors while receiving a desired prize, which highlights the importance of context variation in testing hypotheses. Overall, our study provides new evidence that hedonic behavioral dysregulation, as reflected in dynamic facial behavior, may highlight depression vulnerability. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Evidence of an association between the vasopressin V1b receptor gene (AVPR1B) and childhood-onset mood disorders.

CONTEXT: Disturbances in stress hormones have been implicated in mood disorders, in particular in the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Arginine vasopressin (AVP) plays a crucial role in modulating the HPA axis under stress and does so through a G protein-coupled receptor, vasopressin V1b receptor (AVPR1b). OBJECTIVE: To determine if genetic variation in AVPR1B could be contributing to vulnerability to mood disorders. DESIGN: We genotyped single nucleotide polymorphisms (SNPs) across the AVPR1B gene in a family-based sample with childhood-onset mood disorders. Six SNPs were genotyped; 2 were novel nonsynonymous polymorphisms, and the other 4 were constituents of a haplotype that was previously shown to be protective against depression. SETTING: Twenty-three mental health facilities in Hungary. PARTICIPANTS: The sample was composed of 382 Hungarian nuclear families ascertained through affected probands with a diagnosis of childhood-onset mood disorder. MAIN OUTCOME MEASURES: Association with childhood-onset mood disorders was tested using the transmission disequilibrium test, which measures the transmission frequency of alleles, or haplotypes, from parents to affected offspring. RESULTS: Two of the AVPR1B SNPs showed association individually (Lys65Asn: chi(2) = 7.81, P = .005; S4: chi(2) = 4.58, P = .03); of particular interest is Lys65Asn, which causes an amino acid change in an intracellular protein domain. Haplotype analysis demonstrated significant overtransmission of the most frequent haplotype (chi(2)(3) = 22.42, P <.001). Furthermore, stratifying the sample by sex established that the association was predominantly in affected females, which is consistent with previous observations. CONCLUSIONS: We have found evidence to implicate the AVPR1B gene in the etiology of mood disorders, particularly in females. Antagonists of AVPR1b exhibit antidepressant qualities; hence, genetic variation in AVPR1B may have implications in HPA axis dysregulation in mood disorders.