First episode of depression in children at low and high familial risk for depression

OBJECTIVE: To examine the development of first-onset major depressive disorder (MDD) in children at high and low familial risk for depression in a prospective study. METHOD: High-risk children (n = 76) who were free of any lifetime affective disorder and had at least one first-degree and one second-degree relative with a lifetime history of childhood-onset, recurrent, bipolar, or psychotic depression were included. Low-risk children (n = 63) were included if they were free of any lifetime psychiatric disorder and had no first-degree relatives and fewer than 20% of their second-degree relatives with a lifetime affective disorder. Children and their parents were assessed in a prospective design using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic version (K-SADS-E). The average interval between follow-up interviews was 18 months, and the average follow-up period was 6 years. RESULTS: High-risk children had approximately a threefold increased risk of developing first-onset MDD compared with low-risk children (odds ratio = 3.21). The average age of new-onset MDD was 14.0 +/- 2.9 years (range 9.5-19.5 years). Above and beyond the familial loading for MDD, mother's lifetime anxiety disorder (odds ratio = 2.84) and lifetime behavioral disorder (odds ratio = 3.25) in the child significantly added to the risk of developing a first-onset MDD. CONCLUSIONS: Having high familial loading for affective disorders, a mother with and anxiety disorder, and a behavioral disorder in the child all significantly contributed to the risk of developing depression.     

Schizophrenia and schizophrenia-spectrum personality disorders in the first-degree relatives of children with schizophrenia: the UCLA family study

BACKGROUND: This study tested the hypothesis that childhood-onset schizophrenia (COS) is a variant of adult-onset schizophrenia (AOS) by determining if first-degree relatives of COS probands have an increased risk for schizophrenia and schizotypal and paranoid personality disorders. METHODS: Relatives of COS probands (n = 148) were compared with relatives of attention-deficit/hyperactivity disorder (ADHD) (n = 368) and community control (n = 206) probands. Age-appropriate structured diagnostic interviews were used to assign DSM-III-R diagnoses to probands and their relatives. Family psychiatric history was elicited from multiple informants. Diagnoses of relatives were made blind to information about probands' diagnoses. Final consensus diagnoses, which integrated family history, direct interview information, and medical records, are reported in this article. RESULTS: There was an increased lifetime morbid risk for schizophrenia (4.95% +/- 2.16%) and schizotypal personality disorder (4.20% +/- 2.06%) in the parents of COS probands compared with parents of ADHD (0.45% +/- 0.45%, 0.91% +/- 0.63%) and community control (0%) probands. The parents of COS probands diagnosed as having schizophrenia had an early age of first onset of schizophrenia. Risk for avoidant personality disorder (9.41% +/- 3.17%) was increased in the parents of COS probands compared with parents of community controls (1.67% +/- 1.17%). CONCLUSIONS: The psychiatric disorders that do and do not aggregate in the parents of COS probands are remarkably similar to the disorders that do and do not aggregate in the parents of adults with schizophrenia in modern family studies. These findings provide compelling support for the hypothesis of etiological continuity between COS and AOS.     

A controlled family history study of prepubertal major depressive disorder

First-degree (N = 195) and second-degree (N = 785) adult relatives of prepubertal children with major depression (N = 48), children with nonaffective psychiatric disorders (N = 20), and normal children (N = 27) were assessed by the Family History-Research Diagnostic Criteria method (FH-RDC), except for the adult informant (usually the mother), who was directly interviewed. Compared with normal controls, prepubertal children with major depressive disorder (MDD) had significantly higher familial rates of psychiatric disorders in both first- and second-degree relatives, especially MDD, alcoholism, and "other" (mostly anxiety) diagnoses. Relatives of children in the nonaffective psychiatric control (PC) group had low rates of alcoholism, high rates of other (anxiety) disorder diagnoses, and intermediate rates of MDD (accounted for by those children with separation anxiety). This suggests that prepubertal onset of major depression may be especially likely in families with a high aggregation of affective disorders when these families also have a high prevalence of alcoholism, and that a proportion of children without affective disorder but with separation anxiety disorder in this study were at high risk for the development of affective illness later in life. These results support the validity of prepubertal-onset depressive illness as a diagnostic category, and are consistent with high familial rates of MDD and other psychiatric disorders found in family studies of adolescent and early-onset adult probands with major affective disorders, and with studies of the offspring of parents with major affective disorders. Within the child MDD group substantial heterogeneity was found. Low familial rates of MDD were associated with suicidality and comorbid conduct disorder in the child probands. The highest familial rates of MDD, approximately threefold those in the normal controls, and all the bipolar relatives, were found in the families of prepubertal probands with MDD who never had a concrete suicidal plan or act and who were without comorbid conduct disorder. A useful nosological continuum in which to classify prepubertal MDD may be to place at one end those patients with comorbid conduct disorder and at the other end those patients with manifestations related to bipolarity, including hypomania, mania, and psychotic subtype.     

A family study of major depressive disorder in a community sample of adolescents

BACKGROUND: Family studies provide a useful approach to exploring the continuities and discontinuities between major depressive disorder (MDD) in children and adolescents and MDD in adults. We report a family study of MDD in a large community sample of adolescents. METHODS: Probands included 268 adolescents with a history of MDD, 110 adolescents with a history of nonmood disorders but no history of MDD through age 18 years, and 291 adolescents with no history of psychopathology through age 18 years. Psychopathology in their 2202 first-degree relatives was assessed with semistructured direct and family history interviews, and best-estimate diagnoses were derived with the use of all available data. RESULTS: The relatives of adolescents with MDD exhibited significantly elevated rates of MDD (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.46-2.31), dysthymia (HR, 1.79; 95% CI, 1. 11-2.87), and alcohol abuse or dependence (HR, 1.29; 95% CI, 1.05-1. 53), but not anxiety disorders, drug abuse or dependence, or antisocial and borderline personality disorder. In contrast, anxiety, substance use, and disruptive behavior disorders in adolescents were not associated with elevated rates of MDD in relatives. However, the relatives of probands with anxiety and substance use disorders exhibited elevated rates of anxiety and substance use disorders, respectively. CONCLUSIONS: The results provide evidence of the familial aggregation of adolescent MDD, and also indicate that there is a considerable specificity in the pattern of familial transmission. In addition, we found preliminary evidence of the familial aggregation of adolescent anxiety and substance use disorders.     

Family patterns of psychopathology in psychiatric disorders

ObjectiveFamilial loading and crucial outcomes of family history of psychopathology in psychiatric disorders have long been recognized. There has been ample literature providing convincing evidence for the importance of family psychopathology in development of emotional disturbances in children as well as worse outcomes in the course of psychiatric disorders. More often, maternal psychopathology seems to have been an issue of interest rather than paternal psychopathology while effects of second-degree familiality have received almost no attention. In this study, we addressed the relations between affected first- and second-degree relatives of probands and categories of psychiatric disorders.MethodSubjects were 350 hospitalized psychiatric inpatients, consecutively admitted to psychiatry clinics in Van, Turkey. Mean age was 34.16 (SD ± 12) and 51.4% of the sample consisted of male patients. Assessment of psychopathology in psychiatric probands was conducted based on DSM-IV TR. Familial loading of psychiatric disorders amongst first- and second-degree relatives of patients were initially noted primarily relying on patients' retrospective reports, and confirmed by both phone call and following official health records via the Medical Knowledge System. We analyzed the data using latent class analysis approach.ResultsWe found four patterns of familial psychopathology. Latent homogeneous subsets of patients due to familial characteristics were as paternal kinship psychopathology with schizophrenia, paternal kinship psychopathology with mood disorders, maternal kinship psychopathology and core family psychopathology.ConclusionFamily patterns were critical to exerting variation in psychiatric disorders of probands and affected relatives. Probands with a core family pattern of psychopathology exhibited the most colorful clinical presentations in terms of variation in psychopathology. We observed a specificity of intergenerational transmission of psychiatric disorders when family patterns of psychopathology were taken into consideration, even second-degree relatives of psychiatric probands.     

Phenomenology of children and adolescents with bipolar spectrum disorders

CONTEXT: Children and adolescents who present with manic symptoms frequently do not meet the full DSM-IV criteria for bipolar I disorder (BP-I). OBJECTIVE: To assess the clinical presentation and family history of children and adolescents with BP-I, bipolar II disorder (BP-II), and bipolar disorder not otherwise specified (BP-NOS). DESIGN: Subjects and their primary caretaker were assessed by semistructured interview, and family psychiatric history was obtained from interview of the primary caretaker. SETTING: Outpatient and inpatient units at 3 university centers. PARTICIPANTS: A total of 438 children and adolescents (mean +/- SD age, 12.7 +/- 3.2 years) with BP-I (n = 255), BP-II (n = 30), or BP-NOS (n = 153). MAIN OUTCOME MEASURES: Lifetime psychiatric history and family history of psychiatric disorders. RESULTS: Youth with BP-NOS were not diagnosed as having BP-I primarily because they did not meet the DSM-IV duration criteria for a manic or mixed episode. There were no significant differences among the BP-I and BP-NOS groups in age of onset, duration of illness, lifetime rates of comorbid diagnoses, suicidal ideation and major depression, family history, and the types of manic symptoms that were present during the most serious lifetime episode. Compared with youth with BP-NOS, subjects with BP-I had more severe manic symptoms, greater overall functional impairment, and higher rates of hospitalization, psychosis, and suicide attempts. Elevated mood was present in 81.9% of subjects with BP-NOS and 91.8% of subjects with BP-I. Subjects with BP-II had higher rates of comorbid anxiety disorders compared with the other 2 groups and had less functional impairment and lower rates of psychiatric hospitalization than the subjects with BP-I. CONCLUSIONS: Children and adolescents with BP-II and BP-NOS have a phenotype that is on a continuum with that of youth with BP-I. Elevated mood is a common feature of youth with BP-spectrum illness.     

Clinical presentation and course of depression in youth: does onset in childhood differ from onset in adolescence?

OBJECTIVE: To simultaneously and prospectively compare the clinical presentation, course, and parental psychiatric history between children and adolescents with major depressive disorder. METHOD: A group of prepubertal children (n = 46) and postpubertal adolescents (n = 22) were assessed with structured interviews for psychopathology and parental psychiatric history and followed once every 2 years for approximately 5 years. RESULTS: With the exception of more depressive melancholic symptoms in the adolescents, both groups had similar depressive symptomatology, duration (average 17 months), severity of the index episode, rates of recovery (85%) and recurrence (40%), comorbid disorders, and parental psychiatric history. Female sex, increased guilt, prior episodes of depression, and parental psychopathology were associated with worse longitudinal course. CONCLUSIONS: In general, major depressive disorder is manifested similarly in children and adolescents, and both groups have a protracted clinical course and high family loading for psychiatric disorders.     

The CCC2000 Birth Cohort Study of Register-Based Family History of Mental Disorders and Psychotic Experiences in Offspring

Psychotic experiences (PE) in individuals of the general population are hypothesized to mark the early expression of the pathology underlying psychosis. This notion of PE as an intermediate phenotype is based on the premise that PE share genetic liability with psychosis. We examined whether PE in childhood was predicted by a family history of mental disorder with psychosis rather than a family history of nonpsychotic mental disorder and whether this association differed by severity of PE. The study examined data on 1632 children from a general population birth cohort assessed at age 11–12 years by use of a semistructured interview covering 22 psychotic symptoms. The Danish national registers were linked to describe the complete family history of hospital-based psychiatric diagnoses. Uni- and multivariable logistic regressions were used to test whether a family history of any mental disorder with psychosis, or of nonpsychotic mental disorder, vs no diagnoses was associated with increased risk of PE in offspring (hierarchical exposure variable). The occurrence of PE in offspring was significantly associated with a history of psychosis among the first-degree relatives (adjusted relative risk [RR] = 3.29, 95% CI: 1.82–5.93). The risk increased for combined hallucinations and delusions (adjusted RR = 5.90, 95% CI: 2.64–13.16). A history of nonpsychotic mental disorders in first-degree relatives did not contribute to the risk of PE in offspring nor did any mental disorder among second-degree relatives. Our findings support the notion of PE as a vulnerability marker of transdiagnostic psychosis. The effect of psychosis in first-degree relatives may operate through shared genetic and environmental factors.Key words: psychosis, schizophrenia, epidemiology, family liability, general population, psychiatric family history     

Late Preterm Birth,Maternal Depression,and Risk of Preschool Psychiatric Disorders

ObjectivePreterm children are at greater risk for psychiatric disorders, including anxiety disorders and attention-deficit/hyperactivity disorder (ADHD), than their term-born peers. Prior research has focused primarily on children born at early gestational ages. Less is known about the rate of psychiatric disorders among late preterm or early term children. In addition, whether a history of maternal depression also associated with prematurity has an impact on the risk for psychiatric disorders remains underexplored.MethodPreschoolers between ages 3 and 6 years (N = 306) were recruited for a study examining preschool depression that included healthy and disruptive preschoolers. Preschoolers were placed in the following groups: late preterm (34–36 weeks, n = 39), early term (37–39 weeks, n = 78), and full term (40–41 weeks, n = 154). DSM-IV psychiatric disorders were assessed via the Preschool Age Psychiatric Assessment. Maternal history of psychiatric disorders was assessed using the Family Interview for Genetic Studies.ResultsLate preterm children had higher rates of any Axis I psychiatric diagnosis (odds ratio = 3.18, 95% confidence interval = 1.09–4.76) and of any anxiety disorder (odds ratio = 3.74, 95% confidence interval = 1.59–8.78) than full term children after adjusting for gender, ethnicity, family income, and IQ. There were no differences in rates of psychiatric diagnoses between early term and full term children. A history of maternal depression mediated the relationship between late preterm birth and anxiety disorders in preschoolers.ConclusionsLate preterm children were at increased risk for anxiety disorders at preschool age. A history of maternal depression mediated this association. Findings confirm the extension of the risk of psychiatric disorders associated with prematurity to the late preterm group, and suggest that maternal depression may play a key role in this risk trajectory.     

Clinical characteristics of familial and non-familial bipolar disorder

Objective: To explore the clinical characteristics of familial and non-familial bipolar disorder.

Method: Twenty subjects with bipolar disorder, who also had a family history of bipolar disorder in a first degree relative, were matched for current age, age of first onset of bipolar disorder and gender with 20 subjects with bipolar disorder who had no family history of any psychiatric disorders in first or second degree relatives.

Results: Fourteen subjects in each group were female. The mean age at interview was 45.2 years and the mean age at first admission was 26 years. Although familial and non-familial probands had an equivalent number of illness episodes, familial probands were significantly more likely to experience mixed states as compared to non-familial probands. The latter experienced significantly more depressive episodes and had significantly higher neuroticism (N) scores on the Eysenck Personality Inventory (EPI; Eysenck H, Eysenck S. Manual of the Eysenck Personality Inventory. London: University of London Press, 1964.).

Conclusions: If the results are replicated, they have important implications. For example, such data may aid decisions about the targeting of additional psychosocial interventions in high N score cases. Researchers will wish to investigate whether mixed states show a stronger association with early age of onset or family history of BD.     

Peri-sleep-onset cortisol levels in children and adolescents with affective disorders.

BACKGROUND: Changes in the hypothalamic-pituitary-adrenal (HPA) axis, as evidenced by patterns of cortisol secretion, have been of interest in understanding depression and anxiety disorders across the life span. Previous studies of pediatric depression have pointed to the period around sleep onset as a key time point for observing alterations in cortisol secretion associated with affective disorders. Evidence also indicates that pubertal development may influence the expression of HPA dysregulation. We hypothesized that adolescents with depression and youth with anxiety disorders exhibit elevated peri-sleep-onset cortisol. METHODS: Plasma cortisol was sampled every 20 min around sleep onset from children and adolescents with major depressive disorder (n = 116), anxiety disorders (n = 32), or no history of psychiatric disorder (control; n = 76). Sleep onset was determined by polysomnography. Classification of participants as children or adolescents was based on Tanner staging of pubertal maturation. RESULTS: Children with anxiety disorders had higher peri-sleep-onset cortisol than children with depression or control children. Adolescents with depression had marginally higher peri-sleep-onset cortisol than control adolescents and significantly higher peri-sleep-onset cortisol than children with depression. CONCLUSIONS: Depression and anxiety are associated with altered cortisol secretion around sleep onset, and these changes appear to be influenced by pubertal maturation.     

Clinical characteristics of bipolar I patients according to their family history of affective disorders

BACKGROUND: The familial nature of bipolar disorder has been well described and multiple genes are probably involved in most or all cases. Each gene contributes equally to a bipolar phenotype and it may contribute to clinical characteristics. However, the genetic transmission of bipolar disorder remained undetermined up to now, partly due to clinical and genetically heterogeneity. In Tunisia, genetic study will profit from specific interests and advantages: the high rates of consanguinity, the existence of large families, and the relative geographical stability of the population. OBJECTIVE: The aim of this study was to compare clinical characteristics of familial and nonfamilial bipolar I disorder. METHOD: One hundred and thirty subjects met DSM-IV criteria for a bipolar I disorder; they were recruited and divided into groups according to their family history of affective disorders. Group 1 with a familial history group, comporting bipolar I patients with a family history of affective disorders in first and second degree relatives (n = 76; 52 males and 24 females, mean age = 37.2 +/- 10.7 years) was compared to group 2 (nonfamilial history group), comporting bipolar I patients without a family history of affective disorders (n = 54; 29 males and 25 females, mean age = 38.1 +/- 10.9 years). Available information was obtained from a structured clinical interview, collateral history, and medical records. The family investigation permitted completion of genealogies over three generations. The comparison of the two groups was based on the clinical characteristics (age at onset, numbers of affective episodes, nature and severity of the last affective episode,...). RESULTS: There were no significant differences between the two groups concerning demographic and social features, with the exception of professional activity. Indeed 30.2% of patients with a family history of affective disorders were unemployed versus 12.9% of patients without a family history of affective disorders (p = 0.02). Bipolar I patients with a family history of affective disorders were characterised by an early age at onset of the first episode (before 20 years) (48.7 versus 24.0%; p = 0.004), a high frequency of affective episodes (8.1 +/- 3.6 versus 6.0 +/- 3.5; p = 0.002) and had been more often hospitalised than patients without a family history of affective disorders (5.7 +/- 3.0 versus 4.7 +/- 3.0; p = 0.06). No significant differences were found concerning the nature of the first affective episode in bipolar I patients with or without a family history of affective disorders. Eleven women had developed their first affective episode during the puerperal period; eight of whom had a family history of affective disorders (p = 0.07). The last affective episode was significantly more severe (94.8 versus 77.8%; p = 0.003) and more often associated with psychotic features (55.3 versus 35.2%; p = 0.02) in patients with a family history of affective disorders. After multiple regression, the high frequency of affective episodes and the severity of last episode were more related with a family history of affective disorders. CONCLUSION: The results of our study provide evidence of familiality for some clinical characteristics which can be useful as phenotypic measures in future molecular genetic studies.     

Which factors may play a pivotal role on determining the type of psychiatric disorder in children and adolescents with epilepsy?

Physicians have become aware of the high prevalence of psychiatric disorders (PDs) in children and adolescents with epilepsy; however, there are many controversies as to which factors may have an important role in the different types of PD. This study was designed to assess the main PD; verify the age of onset compared with the age of diagnosis of the PD; and determine which factors may be correlated with the type of PD described. For this purpose, a multidisciplinary team evaluated children and adolescents (4–18 years) with epilepsy and analyzed patient-related factors such as age (grouped according to Piaget’s cognitive scale: <6 years, 7–13 years, >13 years), sex, family history of PDs, and cognitive status. With respect to epilepsy features, we considered age of onset, duration, seizure control at the time of psychiatric evaluation, refractoriness, antiepileptic drugs (mono- vs polytherapy), seizure type (generalized vs focal), and epilepsy type (idiopathic vs symptomatic/probably symptomatic). Depression occurred in 36.4% and attention-deficit hyperactivity disorder (ADHD) in 29.1%, these being the most frequent PDs in this series. Focal epilepsy was significantly more frequent in children and adolescents with PDs. As to the type of PD, age was an important factor, with a predominance of ADHD in children and depression in adolescents (P < 0.0001). Family history was contributory for depression, but not for others PDs (P < 0.0001). Depression remained underdiagnosed and untreated for a longer period. Impact of early diagnosis and treatment remains unknown.     

Relationship between response to methylphenidate treatment in children with ADHD and psychopathology in their families

OBJECTIVE: To compare the pattern of familial aggregation of psychopathology in children who are good responders (GR) to methylphenidate (MPH) versus those who are poor responders (PR). METHOD: A total of 118 clinically referred children ages 6 to 12 years, diagnosed with ADHD participated in a double-blind, placebo-controlled, randomized 2-week crossover trial of MPH from 1999 to 2004. A low dose of 0.5 mg/kg of body weight of MPH divided in two equal doses was used. Family history was obtained by interviewing at least one key historian relative of each subject using Family Interview for Genetic Studies. Information was collected on 342 first-degree and 1,151 second-degree relatives of children with attention-deficit/hyperactivity disorder. RESULTS: Forty-four subjects showed mild or no improvement (PR) and 74 showed moderate or very much improvement (GR) on MPH over placebo. First-degree relatives of GR subjects were at significantly higher risk of attention-deficit/hyperactivity disorder than the relatives of PR subjects (p<.05). Second-degree relatives of the GR were at significantly higher risk of antisocial personality disorder compared to the relatives of PR subjects (p<.05). CONCLUSIONS: The significantly higher presence of attention-deficit/hyperactivity disorder in the first-degree relatives and of antisocial personality disorder in the second-degree relatives of GR children suggests that this group may, at least partially, be distinct from the PR group on the basis of genetic determinants.     

Irritability Without Elation in a Large Bipolar Youth Sample: Frequency and Clinical Description

ObjectiveTo determine whether some children with bipolar disorder (BP) manifest irritability without elation and whether these children differ on sociodemographic, phenotypic, and familial features from those who have elation and no irritability and from those who have both.MethodThree hundred sixty-one youths with BP recruited into the three-site Course and Outcome of Bipolar Illness in Youth study were assessed at baseline and for most severe past symptoms using standardized semistructured interviews. Bipolar disorder subtype was identified, and frequency and severity of manic symptoms were quantified. The subjects were required to have episodic mood disturbance to be diagnosed with BP. The sample was then reclassified and compared based on the most severe lifetime manic episode into three subgroups: elated only, irritable only, and both elated and irritable.ResultsIrritable-only and elated-only subgroups constituted 10% and 15% of the sample, respectively. Except for the irritable-only subjects being significantly younger than the other two subgroups, there were no other between-group sociodemographic differences. There were no significant between-group differences in the BP subtype, rate of psychiatric comorbidities, severity of illness, duration of illness, and family history of mania in first- or second-degree relatives and other psychiatric disorders in first-degree relatives, with the exception of depression and alcohol abuse occurring more frequently in the irritability-only subgroup. The elated-only group had higher scores on most DSM-IV mania criterion B items.ConclusionsThe results of this study support the DSM-IV A criteria for mania in youths. Irritable-only mania exists, particularly in younger children, but similar to elated-only mania, it occurs infrequently. The fact that the irritable-only subgroup has similar clinical characteristics and family histories of BP, as compared with subgroups with predominant elation, provides support for continuing to consider episodic irritability in the diagnosis of pediatric BP.     

Family history of mood disorder and characteristics of major depressive disorder: a STAR*D (sequenced treatment alternatives to relieve depression) study

INTRODUCTION: Clinicians routinely ask patients with major depressive disorder (MDD) about their family history. It is unknown, however, if patients who report a positive family history differ from those who do not. This study compared the demographic and clinical features of a large cohort of treatment-seeking outpatients with non-psychotic MDD who reported that they did or did not have at least one first-degree relative who had either MDD or bipolar disorder. METHODS: Subjects were recruited for the STAR( *)D multicenter trial. Differences in demographic and clinical features for patients with and without a family history of mood disorders were assessed after correcting for age, sex, race, and ethnicity. RESULTS: Patients with a family history of mood disorder (n=2265; 56.5%) were more frequently women and had an earlier age of onset of depression, as compared to those without such a history (n=1740; 43.5%). No meaningful differences were found in depressive symptoms, severity, recurrence, depressive subtype, or daily function. CONCLUSIONS: Women were twice as likely as men to report a positive family history of mood disorder, and a positive family history was associated with younger age of onset of MDD in the proband. Consistent with prior research, early age of onset appears to define a familial and, by extension, genetic subtype of major depressive disorder.     

Family history of suicidal behavior and mood disorders in probands with mood disorders

OBJECTIVE: First-degree relatives of persons with mood disorder who attempt suicide are at greater risk for mood disorders and attempted or completed suicide. This study examined the shared and distinctive factors associated with familial mood disorders and familial suicidal behavior. METHOD: First-degree relatives' history of DSM-IV-defined mood disorder and suicidal behavior was recorded for 457 mood disorder probands, of whom 81% were inpatients and 62% were female. Probands' lifetime severity of aggression and impulsivity were rated, and probands' reports of childhood physical or sexual abuse, suicide attempts, and age at onset of mood disorder were recorded. Univariate and multivariate analyses were carried out to identify predictors of suicidal acts in first-degree relatives. RESULTS: A total of 23.2% of the probands with mood disorder who had attempted suicide had a first-degree relative with a history of suicidal behavior, compared with 13.2% of the probands with mood disorder who had not attempted suicide (odds ratio=1.99, 95% CI=1.21-3.26). Thirty percent (30.8%) of the first-degree relatives with a diagnosis of mood disorder also manifested suicidal behavior, compared with 6.6% of the first-degree relatives with no mood disorder diagnosis (odds ratio=6.25, 95% CI=3.44-11.35). Probands with and without a history of suicide attempts did not differ in the incidence of mood disorder in first-degree relatives (50.6% versus 48.1%). Rates of reported childhood abuse and severity of lifetime aggression were higher in probands with a family history of suicidal behavior. Earlier age at onset of mood disorder in probands was associated with greater lifetime severity of aggression and higher rates of reported childhood abuse, mood disorder in first-degree relatives, and suicidal behavior in first-degree relatives. CONCLUSIONS: Risk for suicidal behavior in families of probands with mood disorders appears related to early onset of mood disorders, aggressive/impulsive traits, and reported childhood abuse in probands. Studies of such clinical features in at-risk relatives are under way to determine the relative transmission of these clinical features.     

Parental schizophrenia spectrum disorders in childhood-onset and adult-onset schizophrenia

OBJECTIVE: Childhood onset of "adult" psychiatric disorders may be caused, in part, by more salient genetic risk. In this study, the rates of schizophrenia spectrum disorders among parents of patients with childhood-onset and adult-onset schizophrenia and parents of community comparison subjects were compared. METHOD: To assess the presence of axis I and axis II disorders associated with schizophrenia, parents of patients with childhood-onset schizophrenia (95 parents), patients with adult-onset schizophrenia (86 parents), and community comparison subjects (123 parents) were interviewed directly by using semistructured instruments. Information on 19 additional parents (parents of childhood-onset patients, N=2; parents of adult-onset patients, N=11; parents of community comparison subjects, N=6) was obtained by using a family history interview with the same instruments. Transcribed interviews were scored by a rater blind to group membership, and the morbid risks for schizophrenia spectrum disorders in the three groups were compared. RESULTS: Parents of patients with childhood-onset schizophrenia had a significantly higher morbid risk of schizophrenia spectrum disorders (24.74%) than parents of patients with adult-onset schizophrenia (11.35%), and parents of both patient groups had a greater risk of schizophrenia spectrum disorders than did parents of comparison subjects (1.55%). CONCLUSIONS: Parents of patients with childhood-onset schizophrenia have a higher rate of schizophrenia spectrum disorders than parents of patients with adult-onset illness. This is consistent with the hypothesis that a childhood onset of schizophrenia is due, at least in part, to a greater familial diathesis for the disorder.     

Anxiety disorders in children and adolescents with bipolar disorder: a neglected comorbidity.

OBJECTIVE: We describe a consecutive clinical sample of children and adolescents with bipolar disorder to define the pattern of comorbid anxiety and externalizing disorders (attention-deficit hyperactivity disorder [ADHD] and conduct disorder [CD]) and to explore the possible influence of such a comorbidity on their cross-sectional and longitudinal clinical characteristics. METHODS: The sample comprised 43 outpatients, 26 boys and 17 girls, (mean age 14.9 years, SD 3.1; range 7 to 18), with bipolar disorder type I or II, according to DSM-IV diagnostic criteria. All patients were screened for psychiatric disorders using historical information and a clinical interview, the Diagnostic Interview for Children and Adolescents-Revised (DICA-R). To shed light on the possible influence of age at onset, we compared clinical features of subjects whose bipolar onset was prepubertal or in childhood (< 12 years) with those having adolescent onset. We also compared different subgroups with and without comorbid externalizing and anxiety disorders. RESULTS: Bipolar disorder type I was slightly more represented than type II (55.8% vs 44.2%). Only 11.6% of patients did not have any other psychiatric disorder; importantly, 10 subjects (23.5%) did not show any comorbid anxiety disorder. Comorbid externalizing disorders were present in 12 (27.9%) patients; such comorbidity was related to the childhood onset of bipolar disorder type II. Compared with other subjects, patients with comorbid anxiety disorders more often reported pharmacologic (hypo)mania.