["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.

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.

[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.

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.

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.

["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.

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).

[Validity and psychometric properties of a quality of life questionnaire in a Hungarian child and adolescent population]. / Eletminoség kérdoív validitása és pszichometriai jellemzoi magyar gyermekpopuláción.

INTRODUCTION: The study of the quality of life in various strata of society is a very important task. No quality of life research has been done on the Hungarian child population until now. In the present study, we assessed the life quality in a sample of elementary school-aged children by asking both the parents and the children themselves. METHODS: Data were collected from 2,620 children and their parents (mean age: 10.45 years, sd: 2.2 years) by administering the Invertar Lebensqualität Kindern und Jugendlichen (ILK) questionnaire. Reliability and validity data of the questionnaire were examined separately for the child, adolescent, and parent versions. RESULTS: Internal consistency was adequate in all three versions, Cronbach alpha was above 0.6. Test-retest reliability (ICC) ranged between 0.67 and 0.75. Discriminant validity was measured in a non-depressed sample versus a population showing symptoms of clinical depression s. Based on the ILK questionnaire, the two samples were clearly different in their quality of life. Satisfaction with school and psychic well-being worsens with increasing age in the average paediatric population. Relations with family members pose problems in 13-15 year-olds, while peer relations cause difficulty to 6-9 year-olds. Most often parents underestimate the troubles of their children. CONCLUSIONS: The ILK questionnaire is well suited for both comprehensive and detailed examinations of quality of life in Hungarian child populations. It shows adequate reliability and validity. Further research is needed to identify factors influencing the quality of life of Hungarian youngsters and to improve therapeutic options.

Childhood adversity predicts reduced physiological flexibility during the processing of negative affect among adolescents with major depression histories.

BACKGROUND: Adversity during early development has been shown to have enduring negative physiological consequences. In turn, atypical physiological functioning has been associated with maladaptive processing of negative affect, including its regulation. The present study therefore explored whether exposure to adverse life events in childhood predicted maladaptive (less flexible) parasympathetic nervous system functioning during the processing of negative affect among adolescents with depression histories. METHODS: An initially clinic-referred, pediatric sample (N=189) was assessed at two time points. At Time 1, when subjects were 10.17years old (SD=1.42), on average, and were depressed, parents reported on adverse life events the offspring experienced up to that point. At Time 2, when subjects were 17.18years old (SD=1.28), and were remitted from depression, parents again reported on adverse life events in their offspring's lives for the interim period. At time 2, subjects' parasympathetic nervous system functioning (quantified as respiratory sinus arrhythmia) also was assessed at rest, during sad mood induction, and during instructed mood repair. RESULTS: Extent of adverse life events experienced by T1 (but not events occurring between T1 and T2) predicted less flexible RSA functioning 7years later during the processing of negative affect. Adolescents with more extensive early life adversities exhibited less vagal withdrawal following negative mood induction and tended to show less physiological recovery following mood repair. CONCLUSIONS: Early adversities appear to be associated with less flexible physiological regulatory control during negative affect experience, when measured later in development. Stress-related autonomic dysfunction in vulnerable youths may contribute to the unfavorable clinical prognosis associated with juvenile-onset depression.

Positive Affectivity is Dampened in Youths with Histories of Major Depression and Their Never-Depressed Adolescent Siblings.

While hedonic capacity is diminished during clinical depression, it is unclear whether that deficit constitutes a risk factor and/or persists after depression episodes remit. To examine these issues, adolescents with current/past major depression (probands; n=218), never depressed biological siblings of probands (n=207), and emotionally-well controls (n=183) were exposed to several positively valenced probes. Across baseline and hedonic probe conditions, controls consistently reported higher levels of positive affect than high-risk siblings, and siblings reported higher levels of positive affect than probands (remitted and depressed probands' reports were similar). Extent of positive affect across the protocol predicted adolescents' self-reports of social support network and parental reports of offspring's use of various adaptive mood repair responses in daily life. Attenuated hedonic responding among youths remitted from depression offers partial support for anhedonia as a trait, while its presence among never depressed high-risk siblings argues for anhedonia as a potential diathesis for clinical depression.

Parasympathetic nervous system activity predicts mood repair use and its effectiveness among adolescents with and without histories of major depression.

Depressive disorders that onset in the juvenile years have been linked to far-reaching adverse consequences, making it imperative to elucidate key mechanisms and contributory factors. Excessive use of regulatory responses that exacerbate sadness (maladaptive mood repair) or insufficient use of regulatory responses that reduce it (adaptive mood repair) may reflect behavioral mechanisms of depression risk. Cardiac vagal control, indexed by patterns of respiratory sinus arrhythmia (RSA), has received attention as a putative physiological risk factor for depression. Although mood repair and RSA are related, the nature of this relationship is not well characterized in the context of depression risk. Therefore, we tested alternative models of the relationships between RSA patterns (at rest and in response to a sad film), trait mood repair, and the effectiveness of a mood repair response in the laboratory (state mood repair) among adolescents with depression histories (n = 210) and emotionally healthy peers (n = 161). In our data, a mediation model best explained the association between the key constructs: Adolescents with normative RSA patterns exhibited lower levels of depression and trait maladaptive mood repair, and benefited more from instructed (state) mood repair in the laboratory. By contrast, adolescents with atypical RSA patterns exhibited higher levels of depression and dispositional maladaptive mood repair, which, in turn, mediated the relations of RSA patterns and depression symptoms. Atypical RSA patterns also predicted reduced benefits from laboratory mood repair.

BDNF Val66Met polymorphism and stressful life events in melancholic childhood-onset depression.

INTRODUCTION: Brain-derived neurotrophic factor (BDNF) polymorphisms have been examined for their contribution toward depression with equivocal results. More homogeneous phenotypes might be used to improve our understanding of genetic liability to depression. The aim of our study was to (a) test for an association between the BDNF Val66Met polymorphism and childhood-onset melancholic depression and (b) to examine the interactive effects of stressful life events (SLE) and the Val66Met polymorphism on the risk of childhood-onset melancholic depression. MATERIALS AND METHODS: A total of 583 depressed probands were involved in this study (162 of the melancholic subtype). Diagnoses were derived through the Interview Schedule for Children and Adolescents - Diagnostic Version and life event data were collected using an Intake General Information Sheet. RESULTS: Overall, 27.8% of the participants fulfilled the criteria for melancholy. In the melancholic group, the proportion of females was higher (53.1%), although there were more males in the overall depressed sample. We detected no significant differences in genotype or allele frequency between the melancholic and the nonmelancholic depressed group. The BDNF Val66Met polymorphism and SLE interaction was not significantly associated with the melancholy outcome. CONCLUSION: In our study, females were more prone to developing the early-onset melancholic phenotype. To our knowledge, this is the first study to investigate the differentiating effect of the genotype and the G×E interaction on the melancholic phenotype in a large sample of depressed young patients. We did not find an association between the melancholic subtype of major depression and the BDNF genotype and SLE interaction in this sample, which is representative of the Hungarian clinic-referred population of depressed youths.

Juvenile onset depression alters cardiac autonomic balance in response to psychological and physical challenges.

Cardiac autonomic balance (CAB) indexes the ratio of parasympathetic to sympathetic activation (Berntson, Norman, Hawkley, & Cacioppo, 2008), and is believed to reflect overall autonomic flexibility in the face of environmental challenges. However, CAB has not been examined in depression. We examined changes in CAB and other physiological variables in 179 youth with a history of juvenile onset depression (JOD) and 161 healthy controls, in response to two psychological (unsolvable puzzle, sad film) and two physical (handgrip, and forehead cold pressor) challenges. In repeated measures analyses, controls showed expected reductions in CAB for both the handgrip and unsolvable puzzle, reflecting a shift to sympathetic relative to parasympathetic activation. By contrast, JOD youth showed increased CAB from baseline for both tasks (p's<.05). No effects were found for the forehead cold pressor or sad film tasks, suggesting that CAB differences may arise under conditions requiring greater attentional control or sustained effort.