[Long-term follow-up of childhood-onset depression - comorbidity, suicidal behavior and prognosis in adulthood].

INTRODUCTION: Several long-term follow-up studies investigate the progression of adolescent onset major depressive disorder but much less explore short and long-term consequences and prognosis into adulthood of childhood- onset depression. The aim of the present study is to follow childhood-onset depression, lifetime comorbid psychiatric disorders and suicidal behavior into adulthood. METHODS: Subjects (N=166) were 25.95+2.42 years old on average, 54.2% were women. Follow-up period lasted for a mean of 14.74+1.31 years. Psychiatric diagnosis was assessed by a DSM-IV based semi-structured interview. Subjects reported on 4 stages of suicidal behavior as one of the symptoms of depressive disorder. RESULTS: The onset of the first depressive episode was at the mean age of 10.17+2.34 years. 40,4% of the sample had only 1 episode while recurrent depressive episode presented in 32.5% above 18 years of age. Lifetime comorbid psychiatric disorders were present in more than 1/3 of the sample. The most frequent lifetime comorbidity was anxiety (42.4%), and specific phobia among anxiety disorders. Lifetime attention deficit-hyperactivity disorder and oppositional/conduct disorder were also frequent (25.9% and 16.9%, respectively). Suicidal behavior was not present life-time in 19.1% of the sample. Thoughts of death and thoughts of suicide were quite frequent (80.8% and 69.5%, respectively), specific plans and suicidal attempt were more frequent in girls (plan:female vs male 53.9% vs 38.4%, attempt: 33.3% vs 9.6%) during follow-up. CONCLUSION: About one-third of childhood-onset depression had recurrence above 18 years of age, which is lower than the recurrence rate for adolescent onset depression. A high rate of lifetime comorbidity was found between depression and anxiety disorders. The assessment of the actual level of suicidal behavior is important in the prevention of selfdestructive behavior.

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.

[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.

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.

Age and sex analyses of somatic complaints and symptom presentation of childhood depression in a Hungarian clinical sample.

OBJECTIVE: To determine whether the symptom presentation of major depressive disorder (MDD) in a large clinical sample of youngsters is influenced by age, sex, and the interaction of age and sex. METHOD: The sample included 559 children (mean age = 11.69 years; range, 7-14 years; 247 girls) with MDD recruited from 23 mental health facilities across Hungary. Psychiatric evaluations were conducted via the semistructured Interview Schedule for Children and Adolescents-Diagnostic Version (ISCA-D). Final DSM-IV diagnoses were rendered via the best-estimate diagnostic procedure. Evaluations were conducted between April 2000 and May 2005. RESULTS: Six depression symptoms increased with age: depressed mood (odds ratio [OR] = 1.10, P < .05), hypersomnia (OR = 1.17, P < .05), psychomotor retardation (OR = 1.11 P < .05), fatigue (OR = 1.13, P < .01), thoughts of death (OR = 1.11, P < .05), and suicidal ideation (OR = 1.18, P < .01), while psychomotor agitation decreased with age (OR = 0.91, P < .05). Boys were less likely to evidence anhedonia (OR = 0.67, P < .05), insomnia (OR = 0.68, P < .05), and hypersomnia (OR = 0.56, P < .05) but more likely to have psychomotor agitation (OR = 1.59, P < .01). There were no age-by-sex interactions. Rates of somatic complaints did not decrease with age (OR = 1.01, P > .05). CONCLUSIONS: The symptom presentation of MDD becomes somewhat more neurovegetative as children get older. However, girls display more affective and atypical symptoms across all age groups. Somatic complaints were common regardless of age and should be considered an associated feature of depression in children and adolescents.

["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.

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.

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.

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.

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.

Stressful life events in a clinical sample of depressed children in Hungary.

BACKGROUND: There is limited information on the characteristics of stressful life events in depressed pediatric clinical populations and the extent to which sex, age, and their interactions may influence the relations of life events and depression. Using a very large clinical sample of children and adolescents with major depressive disorder (MDD), we therefore examined life events in various ways, as well as their relations to age and sex. METHODS: The study included a clinic-based sample of 434 children (ages 7-14) with a DSM-IV diagnosis of MDD and their mothers, and a school-based comparison sample of 724 children and their mothers. Life event information was obtained from the mothers. RESULTS: Children with MDD had twice the number of lifetime stressful events than did the comparison group, with very high levels of stressors by the age of 7-9 that stabilized across adolescence. In contrast, the comparison sample experienced a gradual increase in stressful life events as a function of age up to mid-adolescence. Parental health events, death of close relatives, and intrafamilial events were significantly associated with MDD diagnosis. There were significantly stronger associations between parental health- as well as death-event clusters and MDD diagnosis among younger children than adolescents. LIMITATIONS: Geographical differences between the clinical and comparison samples, as well as possible parental reporting biases may affect the generalizability of these findings. CONCLUSION: The association between some stressful life events and MDD seems to be moderated by age, underscoring the need to examine specific events, as well as clusters of events. Better understanding of such interactions may facilitate early identification of possible risk factors for pediatric MDD.

Association of the neurotrophic tyrosine kinase receptor 3 (NTRK3) gene and childhood-onset mood disorders.

OBJECTIVE: Genome scans have revealed significant evidence for linkage of depression to chromosome 15q25.3-q26.2. The gene for neurotrophic tyrosine kinase receptor 3 (NTRK3), the receptor for neurotrophin-3 (trkC) and a key gene in neurotrophin signaling, is located within this region and, given evidence for synaptic plasticity as a mechanism in mood disorders, was considered a prime candidate. The authors investigated NTRK3 as a susceptibility gene for childhood-onset mood disorders. METHOD: The study sample consisted of 603 families with 723 affected children and adolescents diagnosed with a mood disorder with onset of the first episode by age 15. The authors genotyped 18 polymorphic markers across the NTRK3 gene in this sample and tested for association. RESULTS: Results identified significant evidence for association for five of the markers using the transmission disequilibrium test. Four of the five markers were located in a region of strong linkage disequilibrium and were highly correlated. Haplotype results provided significant evidence for association to haplotypes composed of markers located in two haplotype blocks. CONCLUSIONS: The results for NTRK3 as well as the authors' previous finding for association to brain-derived neurotrophic factor in this sample support synaptic plasticity as a mechanism contributing to mood disorders that begin during childhood and adolescence and specifically implicate the NTRK3 gene as a contributing factor in the 15q-linked region.

GPR50 is not associated with childhood-onset mood disorders in a large sample of Hungarian families.

We investigated the relationship of the gene for the X-linked orphan G protein-coupled receptor (GPR50) to childhood-onset mood disorders in a sample of 384 families with 468 affected children and adolescents collected in Hungary. Our choice of this gene for study was based on a previous report of an association of GPR50 with bipolar disorder and major depressive disorder. A significant association with the deletion allele of an insertion/deletion polymorphism (Delta502-505) located in exon 2 had been reported in a sample of 226 patients with major depressive disorder and 264 patients with bipolar disorder. The association was more significant in females compared with males in those samples. We used for this study a polymorphism in complete linkage disequilibrium with the Delta502-505 polymorphism, Thr532Ala (rs561077), and two additional polymorphisms, Val606Ile (rs13440581) and an intronic polymorphism (rs2072621). We found no evidence for an association for the markers analyzed individually, nor for haplotypes of these markers. Further, we found no evidence of association when the results were analyzed in girls only (n=215). We, therefore, failed to replicate the previous association of this gene with mood disorders.

[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.

Insomnia and hypersomnia associated with depressive phenomenology and comorbidity in childhood depression.

STUDY OBJECTIVES: To examine sleep disturbance (insomnia and hypersomnia) and associated clinical profiles among depressed children and adolescents in terms of illness history, depressive severity, depressive phenomenology, and psychiatric comorbid disorders. DESIGN: Clinical profiles from standardized clinical evaluations were compared. SETTING: Twenty-three mental health facilities in Hungary between April 2000 and December 2004. PATIENTS AND MEASUREMENTS: Five hundred fifty-three children with a current episode of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition major depressive disorder: 55% were boys, mean age was 11.7 years (SD = 2.0, range = 7.3-14.9), and 94% were Caucasian. Sleep and depressive symptoms were assessed with the Interview Schedule for Children and Adolescents-Diagnostic Version. INTERVENTIONS: N/A. RESULTS: Of the total sample, 72.7% had sleep disturbance: 53.5% had insomnia alone, 9.0% had hypersomnia alone, and 10.1% had both disturbances. Depressed girls were more likely to have sleep disturbance than boys (77.0% vs 69.2%, p < .05), but age had no significant effects. Compared with children without sleep disturbance, sleep-disturbed children were more severely depressed and had more depressive symptoms and comorbid anxiety disorders. Across sleep-disturbed children, those with both insomnia and hypersomnia had a longer history of illness, were more severely depressed, and were more likely to have anhedonia, weight loss, psychomotor retardation, and fatigue than were those with either insomnia or hypersomnia. CONCLUSION: Clinical profiles differ between depressed children without and with sleep disturbance, with those presenting insomnia plus hypersomnia being most severely depressed. Differentiating depressed children with different sleep disturbances may have important implications for research efforts on the etiology and therapeutics of child depression.

Early developmental characteristics and features of major depressive disorder among child psychiatric patients in Hungary.

OBJECTIVE: We investigate the relations of early atypical characteristics (perinatal problems, developmental delay, and difficult temperament) and onset-age (as well as severity of) first major depressive disorder (MDD) and first internalizing disorder in a clinical sample of depressed children in Hungary. METHOD: Participants were 371 children (ages 7-14) with MDD, and their biological mothers, recruited through multiple clinical sites. Diagnoses (via DSM-IV criteria) and onset dates of disorders were finalized "best estimate" psychiatrists, and based on multiple information sources. Mothers provided developmental data in a structured interview. RESULTS: Difficult temperament predicted earlier onset of MDD and first internalizing disorder, but its effect was ameliorated if the family was intact during early childhood. Further, the importance of difficult temperament decreased as a function of time. Perinatal problems and developmental delay did not impact onset ages of disorders, and none of the early childhood characteristics associated with MDD episode severity. CONCLUSIONS: Children with MDD may have added disadvantage of earlier onset if they had a difficult temperament in infancy. Because early temperament mirrors physiological reactivity and regulatory capacity, it can affect various areas of functioning related to psychopathology. Early caregiver stability may attenuate some adverse effects of difficult infant temperament.

[Relationship of depressive symptoms and life events in a school-age population]. / Depressziós tünetek és az életesemények összefüggésének vizsgálata általános iskolás populációban.

INTRODUCTION: Few Hungarian studies have been published about the prevalence of depressive symptoms and their risk factors in childhood. In the present study, we examined the prevalence of depressive symptoms and the importance of stressful life events as risk factors of depression in children. METHODS: We collected data in 9 elementary schools in two regions of Hungary. The data of 2652 students were analysed. Depressive symptoms were measured by the shortened version of the Child Depression Inventory (CDI) and life events were collected from the parents through self-report questionnaire. RESULTS: The mean depressive score of the sample by the CDI was 3.61. 14.9% of the students had a score of 7 or higher, which implies an increased risk of clinical depression. Of the 29 life events which were examined, children experienced 2.35 on average. We found significant positive correlation between depressive symptoms and stressful life events. This effect of life events was not diminished significantly by the age and sex of the child. CONCLUSION: Based on our results we can conclude that the risk of depression increases in parallel with the number of stressful life events experienced by the child.

[Quality analysis of life events and their relationship to depressive symptoms in a school age population]. / Eletesemények minoségi elemzése és kapcsolata a depressziós tünetekkel általános iskolás populációban.

INTRODUCTION: Few Hungarian studies have been published about the relationship between individual life events and childhood and adolescent onset depression. In the present study we examined the significance of life events that might be risk factors of childhood depressive symptoms. METHODS: We collected data in 9 elementary schools in two regions of Hungary. 2,652 pupils were examined. Life events were collected from the parents through a self-report questionnaire. Depressive symptoms were measured by the shortened version of the Child Depression Inventory (CDI). RESULTS: Of the 20 life events that were examined, the following showed a significant relationship with the average depressive-symptom scores: illness of family members--especially that of a sibling, divorce, frequent quarrel among family members, teasing, financial problems and moving apartments. In boys, serious illness of the father, frequent quarrel among family members and teasing; in girls, divorce of parents, frequent quarrel among family members, psychiatric illness of a sibling, financial problems, moving apartments and teasing increased the risk of depression. CONCLUSION: The experience of a number of life events can significantly increase the risk of childhood and adolescent depression.