A high risk study of young children of parents with panic disorder and agoraphobia with and without comorbid major depression

Using family study methodology and psychiatric assessments by blind raters, this study tested hypotheses about patterns of familial association between anxiety and depressive disorders among high risk children of clinically referred parents. The study design contrasted five groups of children defined by the presence or absence in a parent of (1) panic disorder and agoraphobia (PDAG) without comorbid major depressive disorder (MDD) (n = 14); (2) comorbid PDAG plus MDD (PDAG + MDD) (n = 25); (3) MDD without comorbid PDAG (n = 12); (4) other psychiatric disorders (n = 23); and (5) normal comparisons (n = 47). While the PDAG and PDAG + MDD groups had similarly elevated rates of anxiety disorders and MDD, offspring of MDD parents had an elevated rate of MDD but not of anxiety disorders. Among children of parents with PDAG + MDD, the presence of an anxiety disorder did not significantly increase the risk for MDD in the same child. Thus, anxiety and MDD did not cosegregate among children of PDAG parents. These findings indicate that parental PDAG, either alone or comorbidly with MDD, increases the risk for both anxiety and depressive disorders in offspring. In the absence of PDAG, however, parental MDD does not appear to place children at risk for anxiety disorders. These findings are most consistent with the hypothesis that PDAG and PDAG + MDD share common familial etiologic factors while MDD alone is an independent disorder. More studies are needed to confirm these preliminary findings as well as to identify mediating factors that influence the transition from childhood to adult anxiety disorders.     

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 controlled study of behavioral inhibition in children of parents with panic disorder and depression

OBJECTIVE: "Behavioral inhibition to the unfamiliar" has been proposed as a precursor to anxiety disorders. Children with behavioral inhibition are cautious, quiet, introverted, and shy in unfamiliar situations. Several lines of evidence suggest that behavioral inhibition is an index of anxiety proneness. The authors sought to replicate prior findings and examine the specificity of the association between behavioral inhibition and anxiety. METHOD: Laboratory-based behavioral observations were used to assess behavioral inhibition in 129 young children of parents with panic disorder and major depression, 22 children of parents with panic disorder without major depression, 49 children of parents with major depression without panic disorder, and 84 children of parents without anxiety disorders or major depression (comparison group). A standard definition of behavioral inhibition based on previous research ("dichotomous behavioral inhibition") was compared with two other definitions. RESULTS: Dichotomous behavioral inhibition was most frequent among the children of parents with panic disorder plus major depression (29% versus 12% in comparison subjects). For all definitions, the univariate effects of parental major depression were significant (conferring a twofold risk for behavioral inhibition), and for most definitions the effects of parental panic disorder conferred a twofold risk as well. CONCLUSIONS: These results suggest that the comorbidity of panic disorder and major depression accounts for much of the observed familial link between parental panic disorder and childhood behavioral inhibition. Further work is needed to elucidate the role of parental major depression in conferring risk for behavioral inhibition in children.     

Behavioral inhibition and disinhibition as hypothesized precursors to psychopathology: implications for pediatric bipolar disorder.

Attention has been devoted over the past two decades to the identification of temperamental risk factors for child psychopathology. These qualities, evident in toddlerhood or earlier, have the advantage of being measurable in standardized laboratory observations well before children reach the age of onset or diagnosis of psychiatric disorders. Our group's programmatic research over the past 15 years, and that of others, has provided evidence linking "behavioral inhibition to the unfamiliar" in toddlerhood or early childhood with later social anxiety disorder. In addition, recent results by our group have suggested that "behavioral disinhibition" in early childhood, measured by the same laboratory methods, may be linked with later disruptive behavior and comorbid mood disorders. In this article, we discuss our approach to the study of temperamental precursors to disorders in high-risk children, summarize the literature linking behavioral inhibition and disinhibition to later psychopathology, and suggest directions to take in applying this methodology to the search for temperamental precursors to pediatric bipolar disorder.     

Major depressive disorder in a family study of obsessive-compulsive disorder with pediatric probands

Objective: This study examined the comorbidity of obsessive–compulsive disorder (OCD) with major depressive disorder (MDD) in a family study of OCD with pediatric probands. Method: This study assessed the lifetime prevalence of MDD in 141 first‐degree relatives (FDR) and 452 second‐degree relatives (SDR) of pediatric probands with OCD and healthy controls, and identified variables associated with MDD in case FDR. All available FDR were directly interviewed blind to proband status; parents were also interviewed to assess the family psychiatric history of FDR and SDR. Best‐estimate diagnoses were made using all sources of information. Data were analyzed with logistic regression and robust Cox regression models. Results: Lifetime MDD prevalence was significantly higher in case than in control FDR (30.4 versus 15.4%). Lifetime MDD prevalence was significantly higher in FDR of case probands with MDD than in FDR of case probands without MDD or control FDR (46.3 versus 19.7 versus 15.4%, respectively). MDD in case FDR was significantly associated with MDD in case probands and with age and OCD in those relatives. Lifetime MDD prevalence was similar in case and control SDR. However, lifetime MDD prevalence was significantly higher in SDR of case probands with MDD than in SDR of case probands without MDD or control SDR (31.9 versus 16.8 versus 15.4%, respectively). Conclusions: MDD prevalence was significantly higher in both FDR and SDR of case probands with MDD than in relatives of case probands without MDD or control relatives, suggesting that pediatric OCD comorbid with MDD is a complex familial syndrome. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.     

Predictors of comorbid personality disorders in patients with panic disorder with agoraphobia

The aim of this study was to ascertain predictors of comorbid personality disorders in patients with panic disorder with agoraphobia (PDAG). Sixty consecutive outpatients with PDAG were administered the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) for the purpose of diagnosing personality disorders. Logistic regressions were used to identify predictors of any comorbid personality disorder, any DSM-IV cluster A, cluster B, and cluster C personality disorder. Independent variables in these regressions were gender, age, duration of panic disorder (PD), severity of PDAG, and scores on self-report instruments that assess the patient's perception of their parents, childhood separation anxiety, and traumatic experiences. High levels of parental protection on the Parental Bonding Instrument (PBI), indicating a perception of the parents as overprotective and controlling, emerged as the only statistically significant predictor of any comorbid personality disorder. This finding was attributed to the association between parental overprotection and cluster B personality disorders, particularly borderline personality disorder. The duration of PD was a significant predictor of any cluster B and any cluster C personality disorder, suggesting that some of the cluster B and cluster C personality disorders may be a consequence of the long-lasting PDAG. Any cluster B personality disorder was also associated with younger age. In conclusion, despite a generally nonspecific nature of the relationship between parental overprotection in childhood and adult psychopathology, the findings of this study suggest some specificity for the association between parental overprotection in childhood and personality disturbance in PDAG patients, particularly cluster B personality disorders.     

Anxiety and major depression comorbidity in a family study of obsessive-compulsive disorder

To understand the familial relationship between obsessive-compulsive disorder (OCD), other anxiety disorders, and major depressive disorder (MDD), we examined the rates of anxiety disorders and MDD in first-degree relatives of OCD probands and controls, the association between age at onset of OCD and the occurrence of other anxiety disorders and major depressive disorder in relatives of probands, and the co-transmission of specific anxiety disorders, MDD, and OCD within families of probands. Recurrence risks were estimated from 466 first-degree relatives of 100 probands with OCD and 113 first-degree relatives of 33 non-psychiatric controls. Rates of non-OCD anxiety disorders and MDD were comparable in relatives of OCD probands and controls. Rates of anxiety disorders and MDD were higher among case relatives with OCD than among case relatives without OCD and control relatives. Fifty percent of case relatives with OCD had at least one comorbid anxiety disorder. Early age at onset (<10 years) in probands was associated with higher rates of anxiety and depression comorbidity among case relatives with OCD but not among case relatives without OCD. The occurrence of specific anxiety disorders and MDD in case relatives was independent of the same comorbid diagnosis in the OCD probands. OCD, panic disorder, generalized anxiety disorder, and MDD occurred together more often than expected by chance among individuals with OCD. Furthermore, age at onset in probands is associated with specific anxiety and affective comorbidity among case relatives. These findings support the hypothesis that early- and late-onset OCD represent different etiologic variants.     

Differences in Axis I and II comorbidity between bipolar I and II disorders and major depressive disorder

OBJECTIVE: To obtain a comprehensive view of differences in current comorbidity between bipolar I and II disorders (BD) and (unipolar) major depressive disorder (MDD), and Axis I and II comorbidity in BD in secondary-care psychiatric settings. METHOD: The psychiatric comorbidity of 90 bipolar I and 101 bipolar II patients from the Jorvi Bipolar Study and 269 MDD patients from the Vantaa Depression Study were compared. We used DSM-IV criteria assessed by semistructured interviews. Patients were inpatients and outpatients from secondary-care psychiatric units. Comparable information was collected on clinical history, index episode, symptom status, and patient characteristics. RESULTS: Bipolar disorder and MDD differed in prevalences of current comorbid disorders, MDD patients having significantly more Axis I comorbidity (69.1% vs. 57.1%), specifically anxiety disorders (56.5% vs. 44.5%) and cluster A (19.0% vs. 9.9%) and C (31.6% vs. 23.0%) personality disorders. In contrast, BD had more single cluster B personality disorders (30.9% vs. 24.6%). Bipolar I and bipolar II were similar in current overall comorbidity, but the prevalence of comorbidity was strongly associated with the current illness phase. CONCLUSIONS: Major depressive disorder and BD have somewhat different patterns in the prevalences of comorbid disorders at the time of an illness episode, with differences particularly in the prevalences of anxiety and personality disorders. Current illness phase explains differences in psychiatric comorbidity of BD patients better than type of disorder.     

Current comorbidity of psychiatric disorders among DSM-IV major depressive disorder patients in psychiatric care in the Vantaa Depression Study

BACKGROUND: While numerous studies have documented the high comorbidity of major depressive disorder (MDD) with individual mental disorders, no published study has reported overall current comorbidity with all Axis I and II disorders among psychiatric patients with MDD, nor systematically investigated variations in current comorbidity by sociodemographic factors, inpatient versus outpatient status, and number of lifetime depressive episodes. METHOD: Psychiatric outpatients and inpatients in Vantaa, Finland, were prospectively screened for an episode of DSM-IV MDD, and 269 patients with a new episode of MDD were enrolled in the Vantaa Depression MDD Cohort Study. Axis I and II comorbidity was assessed via semistructured Schedules for Clinical Assessment in Neuropsychiatry, version 2.0, and Structured Clinical Interview for DSM-II-R personality disorders interviews. RESULTS: The great majority (79%) of patients with MDD suffered from 1 or more current comorbid mental disorders, including anxiety disorder (57%), alcohol use disorder (25%), and personality disorder (44%). Several anxiety disorders were associated with specific Axis II clusters, and panic disorder with agoraphobia was associated with inpatient status. The prevalence of personality disorders varied with inpatient versus outpatient status, number of lifetime depressive episodes, and type of residential area, and the prevalence of substance use disorders varied with gender and inpatient versus outpatient status. CONCLUSION: Most psychiatric patients with MDD have at least 1 current comorbid disorder. Comorbid disorders are associated not only with other comorbid disorders, but also with sociodemographic factors, inpatient versus outpatient status, and lifetime number of depressive episodes. The influence of these variations on current comorbidity patterns among MDD patients needs to be taken account of in treatment facilities.     

Course and outcome of child and adolescent major depressive disorder

Major depressive disorder (MDD) is a familial recurrent illness that significantly interferes with the child's normal development and is associated with increased risk for suicidal behaviors and psychiatric and psychosocial morbidity. Although most children and adolescents recover from their first depressive episode, 30-70%, in particular those with familial history of MDD, comorbid psychiatric disorders, dysthymia, subsyndromal symptoms of depression, anxiety, negative cognitive style, and exposure to negative life events (e.g., family conflicts and abuse) will experience one or more depressive recurrences during their childhood, adolescence, and adulthood. Depressed youth who present with psychosis, psychomotor retardation, pharmacological induced hypomania/mania, and/or family history of bipolar disorder are at high risk to develop bipolar disorder.     

Clinical characteristics of depressive symptoms in children and adolescents with major depressive disorder

OBJECTIVE: Very few studies have compared the symptoms of major depressive disorder (MDD) and rates of comorbid psychiatric disorders between depressed children and adolescents. The aim of this study was to reproduce and extend these findings. METHOD: The Kiddie Schedule for Affective Disorders and Schizophrenia, present version (KSADS-P) was administered to parents (about their children) and in face-to-face interviews with 916 subjects aged 5.6 to 17.9 years with MDD (DSM criteria) (715 adolescents and 201 children; 348 male and 568 female). The subjects were consecutive referrals to an outpatient mood and anxiety disorders clinic. RESULTS: Depressed adolescents had significantly more hopelessness/helplessness, lack of energy/tiredness, hypersomnia, weight loss, and suicidality compared with children (p values < or = .001). In comparison with children, adolescents had significantly more substance abuse and less comorbid separation anxiety disorder and attention-deficit/hyperactivity disorder (p values < or = .001). Depressed female adolescents had significantly more suicidality than depressed male adolescents (p < or = .001). There were no other sex differences between males and females. The symptoms of depressed adolescents grouped into 3 factors (endogenous, negative cognitions/suicidality, and appetite/weight), whereas the symptoms in children grouped into 2 factors (endogenous/negative cognitions/suicidality and appetite/weight). CONCLUSIONS: These results provide further evidence for the continuity of MDD from childhood to adolescence.     

Lack of association between behavioral inhibition and psychosocial adversity factors in children at risk for anxiety disorders

OBJECTIVE: In a previous controlled study of offspring at risk for anxiety disorders, the authors found that parental panic disorder with comorbid major depression was associated with child behavioral inhibition, the temperamental tendency to be quiet and restrained in unfamiliar situations. To explore whether this association was mediated by environmental factors, the authors examined associations between psychosocial adversity variables and behavioral inhibition in this group of children. METHOD: Subjects included 200 offspring of parents with panic disorder and/or major depression and 84 comparison children of parents without mood or anxiety disorders. Behavioral inhibition was assessed through laboratory observations. The associations between behavioral inhibition and the following psychosocial factors were examined: socioeconomic status; an index of adversity factors found in previous studies to be additively associated with child psychopathology; family intactness, conflict, expressiveness, and cohesiveness; exposure to parental psychopathology; sibship size; birth order; and gender. RESULTS: The results showed no associations between behavioral inhibition and any of the psychosocial factors in the study group as a whole, despite adequate power to detect medium effect sizes. Among low-risk comparison children only, some definitions of behavioral inhibition were associated with low socioeconomic status, low family cohesion, and female gender. CONCLUSIONS: The results suggest that the psychosocial adversity factors examined in this study do not explain the previous finding that offspring of parents with panic disorder are at high risk for behavioral inhibition.     

Sleep disturbance and its relation to DSM-IV psychiatric symptoms in preschool-age children with pervasive developmental disorder and community controls

This study describes the relation between sleep problems and psychiatric symptoms in preschool-age children (3 to 5 years old) with pervasive developmental disorder and a community-based sample of children attending early childhood programs. Parents completed the Early Childhood Inventory-4, a Diagnostic and Statistical Manual of Mental Disorders (fourth edition)-referenced rating scale for 2 samples: children with pervasive developmental disorder (n = 112) and nondisabled youngsters (n = 497). Although children with pervasive developmental disorder had a significantly greater number and severity of sleep problems than the community preschoolers did, sleep-disturbed children in both samples exhibited more severe behavioral difficulties-primarily symptoms of attention-deficit hyperactivity disorder and oppositional defiant disorder-than did children without sleep problems. Sleep problems are an indicator of similar comorbid psychiatric symptoms in both children with and without pervasive developmental disorder, which suggests commonalities in their etiology.     

Effect of depression on recovery from PTSD

It has been suggested that the treatment strategy needs to be reviewed and changed if depression occurs in patients with posttraumatic stress disorder (PTSD). We analyzed data extracted from the Marmara Epidemiological Survey (MES) which had examined 683 survivors at 3 years after a devastating earthquake. Fifty three cases (40.5%) out of the 131 cases with PTSD had also been diagnosed with MDD. Comorbid PTSD and MDD group has significantly lower rates of recovery from PTSD in comparison to PTSD without MDD (26.4% vs. 47.4% respectively). Rates of past psychiatric disorder and past traumatic experience were significantly more frequent among the comorbid group. Moreover, comorbidity of PTSD and MDD was clearly associated with greater psychological distress, more severe PTSD, and diminished perceived social support. Past psychiatric disorder, General Health Questionnaire (GHQ-12) and Multidimensional Scale of Perceived Social Scale (MSPSS) total scores succeeded in predicting the comorbidity of PTSD and MDD significantly.     

Defining the problem: psychiatric and behavioral comorbidity in children and adolescents with epilepsy

A variety of comorbid psychiatric conditions are frequently identified in children and adolescents with epilepsy, including depression, anxiety, psychosis, and attention-deficit hyperactivity disorder. Data regarding the epidemiology and precise prevalence of comorbid disorders in childhood epilepsy are incomplete and just now beginning to be compiled. Psychiatric and behavioral comorbidities are believed to affect approximately 40-50% of children and adolescents with epilepsy. Optimal diagnosis, clinical evaluation, and choice of treatment are predicated on the proper identification of coexisting psychiatric and behavioral disorders. Comorbid conditions in children and adolescents with epilepsy should be evaluated and treated as soon as they are recognized.     

Psychiatric correlates of behavioral inhibition in young children of parents with and without psychiatric disorders

Behavioral inhibition is a laboratory-based temperamental category by the tendency to constrict behavior in unfamiliar situations and assumed to reflect low thresholds of limbic arousal. We previously found behavioral inhibition prevalent in the offspring of parents with panic disorder and agoraphobia. In this report, we examined the psychiatric correlates of behavioral inhibition by evaluating the sample of offspring of parents with panic disorder and agoraphobia, previously dichotomized as inhibited and not inhibited, and an existing epidemiologically derived sample of children, followed by Kagan and colleagues and originally identified at 21 months of age as inhibited or uninhibited. A third group of healthy children was added for comparison. Our findings indicate that inhibited children had increased risk for multiple anxiety, overanxious, and phobic disorders. It is suggested that behavioral inhibition may be associated with risk for anxiety disorders in children.     

Comorbid Depressive Disorders in ADHD: The Role of ADHD Severity,Subtypes and Familial Psychiatric Disorders

Objective

To evaluate the presence of Major Depressive Disorder (MDD) and Dysthymic Disorder (DD) in a sample of Italian children with Attention Deficit Hyperactivity Disorder (ADHD) and to explore specific features of comorbid depressive disorders in ADHD.

Methods

Three hundred and sixty-six consecutive, drug-naïve Caucasian Italian outpatients with ADHD were recruited and comorbid disorders were evaluated using DSM-IV-TR criteria. To evaluate ADHD severity, parents of all children filled out the ADHD Rating Scale. Thirty-seven children with comorbid MDD or DD were compared with 118 children with comorbid conduct disorder and 122 without comorbidity for age, sex, IQ level, family psychiatric history, and ADHD subtypes and severity.

Results

42 of the ADHD children displayed comorbid depressive disorders: 16 exhibited MDD, 21 DD, and 5 both MDD and DD. The frequency of hyperactive-impulsive subtypes was significantly lower in ADHD children with depressive disorders, than in those without any comorbidity. ADHD children with depressive disorders showed a higher number of familial psychiatric disorders and higher score in the Inattentive scale of the ADHD Rating Scale, than children without any comorbidity. No differences were found for age, sex and IQ level between the three groups.

Conclusion

Consistent with previous studies in other countries, depressive disorders affect a significant proportion of ADHD children in Italy. Patient assessment and subsequent treatment should take into consideration the possible presence of this comorbidity, which could specifically increase the severity of ADHD attention problems.     

Early Onset Dysthymic Disorder in Children and Adolescents: Clinical Implications and Future Directions

Early onset dysthymic disorder (EODD) is a serious psychiatric disorder that is associated with impaired social and relationship functioning, comorbid psychiatric conditions, a chronic course and increased risk for adult affective disorders. Unlike major depressive disorder (MDD) in childhood, which has been the focus of ongoing research, EODD has been relatively neglected in clinical practice and research. This paper reviews and evaluates EODD research findings and outlines pertinent clinical and research implications.     

Use of health services for major depressive and anxiety disorders in Finland

Factors associated with people suffering from major depressive disorder (MDD) or anxiety disorders seeking or receiving treatment are not well known. In the Health 2000 Study, a representative sample (n=6005) of Finland's general adult (> or =30 years) population was interviewed with the M-CIDI for mental disorders and health service use for mental problems during the last 12 months. Predictors for service use among those with DSM-IV MDD (n=298) or anxiety disorders (n=242) were assessed. Of subjects with MDD, anxiety disorders, or both, 34%, 36%, and 59% used health services, respectively. Greater severity and perceived disability, psychiatric comorbidity, and living alone predicted health care use for MDD subjects, and greater perceived disability, psychiatric comorbidity, younger age, and parent's psychiatric problems for anxiety disorder subjects. The use of specialist-level mental health services was predicted by psychiatric comorbidity, but not characteristics of the disorders per se. Perceived disability and comorbidity are factors influencing the use of mental health services by both anxiety disorder and MDD subjects. However, still only approximately one-half of those suffering from even severe and comorbid disorders use health services for them.     

Depressive disorders in childhood. IV. A longitudinal study of comorbidity with and risk for anxiety disorders

As part of a longitudinal nosologic study of major depressive disorder (MDD), dysthymic disorder (DD), and adjustment disorder with depressed mood (ADDM) in a school-age cohort, we examined the prevalence and clinical consequences of comorbid anxiety disorders. We also estimated the risk of a first anxiety disorder and examined its predictors. Of 104 cases, 41% had anxiety disorders in conjunction with their index depression, which was more likely with MDD and DD than with ADDM. The age-corrected risk of a first anxiety disorder was 0.47 up to age 18 years. Separation-anxiety disorder was the most frequent diagnosis of anxiety, followed by overanxious disorder of childhood. Among the MDD cases with comorbidity, the anxiety disorder preceded the depression about two thirds of the time and often persisted after the depression remitted. The effect of comorbid anxiety disorder on the length of index MDD depended on the presence of other clinical features, but it did not seem to affect the risk of subsequent MDD or the course of DD or ADDM. Concurrent maternal psychopathology and poor physical health increased the risk of anxiety disorder in the children, but a history of prior separation from parental figures did not seem to have an effect.