Parental predictors of pediatric panic disorder/agoraphobia: a controlled study in high-risk offspring

Our objective was to evaluate parental risk factors for pediatric-onset panic disorder/agoraphobia (PD/AG) in offspring at high risk for PD/AG. Comparisons were made between parents with PD who had a child with PD or AG (N = 27) and parents with PD without children with PD or AG (N = 79). Comparisons were also made between the spouses of these parents with PD. Separation anxiety disorder, social phobia, obsessive-compulsive disorder, and bipolar disorder in the parents with PD and their spouses accounted for the risk for childhood onset PD/AG in the offspring. This risk was particularly high if both parents were affected with social phobia. These findings suggest that psychiatric comorbidity with other anxiety disorders and with bipolar disorder in parents with PD and their spouses confer a particularly high risk in their offspring to develop PD/AG in childhood.     

Memory deficits in children with and at risk for anxiety disorders

There are limited data on the neurocognitive correlates of childhood anxiety disorders. The objective of this study was to examine whether visual and verbal memory deficits of nonemotional stimuli are (1) a shared feature of three common childhood anxiety disorders (social phobia, separation anxiety disorder, and generalized anxiety disorder) or whether these deficits are restricted to specific anxiety disorders, and (2) present in offspring who possess at least one of the following established risk factors for anxiety disorders, parental history of panic disorder (PD), or major depressive disorder (MDD). One hundred and sixty offspring, ages 9-20 years, were recruited from parents with lifetime diagnoses of PD, MDD, PD plus MDD, or neither illness. Different clinicians blindly administered semistructured diagnostic interviews to offspring and parents. Verbal and visual memory subtests of the Wide Range Assessment of Memory and Learning were administered to offspring. The results showed that offspring with ongoing social phobia demonstrated reduced visual but not verbal memory scores compared to those without social phobia when controlling for offspring IQ, separation anxiety disorder, and generalized anxiety disorder. No other offspring anxiety disorder predicted memory performance. Neither parental PD nor parental MDD was associated with offspring memory performance. These findings are relevant to understanding the phenomenology of childhood anxiety disorders and may provide insights into the neural circuits underlying these disorders.     

Response to 5% carbon dioxide in children and adolescents: relationship to panic disorder in parents and anxiety disorders in subjects

BACKGROUND: Carbon dioxide (CO(2)) sensitivity is postulated to be a familial risk marker of panic disorder (PD). Exaggerated responses to CO(2) inhalation have been reported in adults with PD and their unaffected adult relatives, as well as in clinic-referred children with anxiety disorders. OBJECTIVE: To test in a family-based design whether CO(2) hypersensitivity is a familial risk marker for PD and associated with current anxiety disorders in children and adolescents. SETTING AND PARTICIPANTS: One hundred forty-two offspring (aged 9-19 years) of parents with PD, major depressive disorder, or no disorder. Forty-five (32%) had a current anxiety disorder, excluding specific phobia. DESIGN AND MAIN OUTCOME MEASURES: Parents and offspring received diagnostic assessments. Offspring underwent 5% CO(2) inhalation at home. Panic symptoms and panic attacks were rated with the Acute Panic Inventory at baseline, while anticipating CO(2) delivery ("threat"), and during CO(2) inhalation. Respiratory rate and volume were measured with spirometry. RESULTS: No group differences were found in Acute Panic Inventory ratings at baseline or in respiratory measures during threat. Risk for PD was not associated with CO(2) sensitivity (panic symptoms and respiratory physiologic response). During CO(2) inhalation, offspring with anxiety disorders, relative to offspring without anxiety disorders, experienced significantly more panic symptoms and panic attacks, as well as elevated respiratory rates. During threat, panic symptoms were significantly and independently associated with both parental PD and offspring anxiety disorders. CONCLUSIONS: No support was obtained for CO(2) hypersensitivity as a familial risk marker for PD in children and adolescents. Links between childhood anxiety disorders and CO(2) sensitivity were replicated. Familial risk for PD in children and adolescents may be associated with vulnerability to anticipatory anxiety.     

Psychopathology in the young offspring of parents with bipolar disorder: a controlled pilot study

Studies have suggested that the offspring of parents with bipolar disorder are at risk for a spectrum of psychopathology, but few have focused on children in the youngest age ranges or examined the impact of comorbid parental disorders. We utilized a pre-existing sample of young (mean age: 6.8 years) offspring of parents with bipolar disorder (n=34), of parents with panic or major depression (n=179), and of parents with neither mood or anxiety disorder (n=95). Children were assessed blindly to parental diagnoses using the Schedule for Affective Disorders and Schizophrenia-Epidemiologic version (K-SADS-E). Offspring of bipolar parents had significantly higher rates of disruptive behavior and anxiety disorders than offspring from both of the comparison groups, accounted for by elevated rates of ADHD and overanxious disorder. These comparisons were significant even when lifetime histories of the corresponding categories of comorbid disorders in the parents (disruptive behavior disorders and anxiety disorders) were covaried. In addition, offspring of bipolar parents had increased rates of bipolar I disorder, compared with psychiatric controls. Results support the hypotheses of elevated behavior, anxiety, and mood disorders among offspring at risk for bipolar disorder, and suggest that this psychopathology is already evident in early childhood.     

Patterns of psychopathology and dysfunction in high-risk children of parents with panic disorder and major depression

OBJECTIVE: The purpose of the study was to evaluate 1) whether an underlying familial predisposition is shared by all anxiety disorders or whether specific risks are associated with specific disorders, and 2) whether panic disorder and major depression have a familial link. METHOD: The study compared four groups of children: 1) offspring of parents with panic disorder and comorbid major depression (N=179), 2) offspring of parents with panic disorder without comorbid major depression (N=29), 3) offspring of parents with major depression without comorbid panic disorder (N=59), and 4) offspring of parents with neither panic disorder nor major depression (N=113). RESULTS: Parental panic disorder, regardless of comorbidity with major depression, was associated with an increased risk for panic disorder and agoraphobia in offspring. Parental major depression, regardless of comorbidity with panic disorder, was associated with increased risks for social phobia, major depression, disruptive behavior disorders, and poorer social functioning in offspring. Both parental panic disorder and parental major depression, individually or comorbidly, were associated with increased risk for separation anxiety disorder and multiple (two or more) anxiety disorders in offspring. CONCLUSIONS: These findings confirm and extend previous results documenting significant associations between the presence of panic disorder and major depression in parents and patterns of psychopathology and dysfunction in their offspring.     

Relationship between separation anxiety disorder,parental panic disorder,and atopic disorders in children: a controlled high-risk study

OBJECTIVE: To test the hypotheses that rates of atopic disorders are elevated in offspring of parents with panic disorder (PD) and in children with separation anxiety disorder (SAD). METHOD: Rates of atopic disorders were assessed in 343 offspring (aged 6-17 years) of parents with PD, nonpanic psychiatric disorders, and no psychiatric disorder. Lifetime history of atopic disorders was determined by parental responses to a clinician-administered questionnaire assessing medical treatment for asthma and allergies. Logistic regression analyses assessed the association between atopic disorders and parental PD, and between atopic disorders and probable or definite childhood SAD. Analyses controlled for age, sex, socioeconomic status, and treatment for other medical illnesses. RESULTS: Increased rates of atopic disorders were found in offspring of parents with PD (odds ratio [OR] = 2.56, 95% confidence interval [CI] = 1.27-5.16, p = .009) and in children with SAD (OR = 2.71, 95% Cl = 1.22-6.03, p = .015). Associations remained significant when both parental PD and SAD were included in the model, suggesting that each contributed independently to increased rates of atopy. The interaction of parental PD and child SAD was not significant. CONCLUSIONS: Atopic disorders in children are associated with parental PD and with childhood SAD. Results do not appear to support that having both childhood SAD and a parent with PD confers increased risk for atopic disorders above and beyond either condition alone.     

Children of parents with obsessive-compulsive disorder -- a 2-year follow-up study

OBJECTIVE: To examine the association between parental obsessive-compulsive disorder (OCD) and emotional and behavioural disorders in offspring. METHOD: Demographic, clinical, and diagnostic data were collected from parents with OCD, control subjects, and their respective offspring. Offspring were reassessed at a 2-year follow-up. RESULTS: Probands with OCD and controls were relatively well matched for age, gender, race, educational rating, and marital status. Offspring of OCD probands were at greater risk than offspring of controls for dimensionally measured anxiety, depression, somatization, and social problems. OCD offspring were significantly more likely than control offspring to have lifetime overanxious disorder, separation anxiety disorder, OCD, or 'any anxiety disorder'. Female gender in the parent with OCD, evidence of family dysfunction, and high symptom levels in offspring were predictive of broadly defined OCD at follow-up. CONCLUSION: Children having a parent with OCD are more likely than control offspring to have social, emotional, and behavioural disorders.     

Executive functioning in offspring at risk for depression and anxiety

Background: Executive functioning deficits (EFDs) have been found in adults with major depression and some anxiety disorders, yet it is unknown whether these deficits predate onset of disorder, or whether they reflect acute symptoms. Studies of at‐risk offspring can shed light on this question by examining whether EFDs characterize children at high risk for depression and anxiety who are not yet symptomatic. Methods: This study examined neuropsychological functioning in a sample of 147 children, ages 6–17 years (M age=9.16, SD=1.82), of parents with major depression (MDD) and/or panic disorder (PD) and of controls with neither disorder. Children were assessed via structured diagnostic interviews and neuropsychological measures. Results: Although parental MDD and PD were not associated with neuropsychological impairments, presence of current offspring MDD was associated with poorer performance on several executive functioning and processing speed measures. Children with current generalized anxiety showed poorer verbal memory, whereas children with social phobia had more omissions on a continuous performance task. Conclusions: Findings suggest that EFDs do not serve as trait markers for developing anxiety or depression but appear to be symptomatic of current disorder. Depression and Anxiety, 2009. © 2009 Wiley‐Liss, Inc.     

Family discord, parental depression, and psychopathology in offspring: ten-year follow-up

OBJECTIVE: To determine the independent effects of parental depression and family discord on psychopathology in offspring at high and low risk for major depression. METHOD: One hundred eighty-two offspring of depressed or nondepressed parents were followed over 10 years. In direct interviews, parents' and offspring's psychopathology was evaluated by raters blind to parents' clinical status. Five dimensions of family discord-poor marital adjustment, parent-child discord, low family cohesion, affectionless control, and parental divorce-were assessed. RESULTS: Offspring exposed to either parental depression or family discord had higher rates of psychopathology than their counterparts. High-risk offspring had few family discord measures associated with their psychopathology; in low-risk offspring, family discord was associated with all offspring diagnoses. Between the two risk factors, parental depression proved a more important predictor for offspring major depressive disorder (MDD) and anxiety disorder, whereas family discord was a more important predictor for substance use disorder. CONCLUSIONS: Parental depression is a strong and consistent risk factor for offspring MDD and anxiety disorder. Without parental depression, offspring have less exposure to family discord and lower rates of psychopathology. In the presence of family discord, rates of MDD, anxiety disorder and substance use disorder increased. When offspring matured into young adulthood, effects of parental depression and family discord persisted.     

Anxiety symptoms distinguishing social phobia from panic and generalized anxiety disorders

Social phobic (N = 14), generalized anxiety disorder (N = 18), and panic disorder patients (N = 48) were compared on four categories of anxiety symptoms: autonomic hyperactivity, muscular tension, vigilance, and apprehensive expectation. Six specific symptoms (palpitations, chest pains, tinnitus, blurred vision, headaches, fear of dying, and dry mouth) distinguished social phobia from panic disorder, while four (headaches, fear of dying, sweating, and dyspnea) distinguished social phobia from generalized anxiety disorder. Most symptom differences were in the autonomic hyperactivity category of symptoms. These findings further confirm the validity of social phobia as a distinct disorder and may help provide specific target symptoms for the treatment of related but different anxiety disorders.     

Electroencephalographic measures of regional hemispheric activity in offspring at risk for depressive disorders.

BACKGROUND: Electroencephalographic (EEG) studies have found abnormal regional hemispheric asymmetries in depressive disorders, which have been hypothesized to be vulnerability markers for depression. In a longitudinal high-risk study, resting EEG was measured in primarily adult offspring of depressed or nondepressed probands. METHODS: Electroencephalograms from12 homologous sites over each hemisphere (digitally linked-ears reference) were analyzed in right-handed offspring for whom both parents (n = 18), one parent (n = 40), or neither parent (n = 29) had a major depressive disorder (MDD). RESULTS: Offspring with both parents having MDD showed greater alpha asymmetry at medial sites, with relatively less activity (more alpha) over right central and parietal regions, compared with offspring having one or no parent with MDD. Relatively less left frontal activity at lateral sites was associated with lifetime MDD in offspring but not with parental MDD. Offspring with both parents having a MDD also showed markedly greater anterior-to- posterior increase in alpha with eyes closed compared with those with one or no parent with a MDD. CONCLUSIONS: Alpha asymmetry indicative of right parietotemporal hypoactivity, previously reported for depressed adolescents and adults, and heightened anterior-to-posterior gradient of alpha are present in high-risk offspring having parents concordant for MDD.     

Laboratory-observed behavioral disinhibition in the young offspring of parents with bipolar disorder: a high-risk pilot study

OBJECTIVE: This study tested whether behavioral disinhibition is more prevalent among offspring of parents with bipolar disorder than among offspring of parents without bipolar disorder. METHOD: The authors conducted a secondary analysis of data from a preexisting high-risk study of offspring at risk for panic disorder and depression (N=278) that had included some children with parents who had bipolar disorder (N=34). Children (ages 2-6) had been classified as behaviorally inhibited, disinhibited, or neither in laboratory assessments. RESULTS: Offspring of bipolar parents had significantly higher rates of behavioral disinhibition than offspring of parents without bipolar disorder. Behavioral inhibition did not differ between groups. Differences were not accounted for by parental panic disorder or major depression or by parental history of attention deficit hyperactivity disorder, conduct disorder, antisocial personality, or substance use disorders. CONCLUSIONS: Results suggest a familial link between bipolar disorder in parents and behavioral disinhibition in their offspring. Behavioral disinhibition may be a familially transmitted predisposing factor for dysregulatory distress later in life.     

Further evidence of association between behavioral inhibition and social anxiety in children

OBJECTIVE: The authors sought to examine psychopathological correlates of behavioral inhibition in young offspring of parents with panic disorder and/or major depression. METHOD: Behavioral inhibition, determined by using standard laboratory observations, was assessed in four groups of children (age 2-6 years): 129 children of parents with both panic disorder and major depression, 22 children of parents with panic disorder alone, 49 children of parents with major depression alone, and 84 comparison children of parents with neither panic disorder nor major depression. Psychopathology in children > or =5 years was compared between children with behavioral inhibition (N=64) and without (N=152). RESULTS: Social anxiety disorder (social phobia or avoidant disorder) was significantly more likely to be found in the children with behavioral inhibition (17%) than in those without (5%). Noninhibited children were significantly more likely than inhibited children to have disruptive behavior disorders (20% versus 6%, respectively) and had higher scores on the attention problems scale of the Child Behavior Checklist (mean=52.1 versus 50.8). CONCLUSIONS: This study adds to the growing literature suggesting an association between behavioral inhibition and social anxiety disorder and an inverse relationship between inhibition and disruptive behavior disorders.     

Clinical distinctions between selective mutism and social phobia: an investigation of childhood psychopathology

OBJECTIVE: To investigate the hypothesis that children with selective mutism are more socially anxious than children with social anxiety disorder but who are not selectively mute. METHOD: Twenty-three children with comorbid selective mutism and social phobia and 23 age-matched controls with social phobia alone and their parents participated in a comprehensive assessment of social anxiety and related aspects of psychopathology. RESULTS: The results do not uniformly support previous suggestions that children with selective mutism refuse speech because they are "frozen with fear." Although clinician and observer ratings for children with selective mutism revealed higher ratings of social distress than for children with social phobia alone, self-report data do not support this conclusion. Furthermore, although there were no group differences on measures of trait anxiety, general fears, or scores on the Child Behavior Checklist broadband Internalizing or Externalizing scales, children with selective mutism scored higher than children with social phobia alone on the Child Behavior Checklist Delinquency subscale, suggesting the presence of a broader clinical syndrome. CONCLUSION: It remains unclear whether children with selective mutism have extreme levels of social anxiety. Potential areas that might shed further light on this interesting disorder are discussed.     

The role of parental psychopathology and family environment for social phobia in the first three decades of life

Background: To examine the role of parental psychopathology and family environment for the risk of social phobia (SP) in offspring from childhood to early adulthood, encompassing the high risk period for SP. Methods: A community sample of 1,395 adolescents was prospectively followed‐up over 10 years. Offspring and parental psychopathology were assessed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV) using the Munich Composite International Diagnostic Interview (M‐CIDI), and direct diagnostic interviews in parents were supplemented by family history reports. Parental rearing was assessed by the Questionnaire of Recalled Rearing Behavior administered to offspring. Family functioning was assessed by the McMaster Family Assessment Device administered to parents. Results: Parental SP was associated with offspring's risk to develop SP (OR=3.3, 95%CI:1.4–8.0). Other parental anxiety disorders (OR=2.9, 95%CI:1.4–6.1), depression (OR=2.6, 95%CI:1.2–5.4), and alcohol use disorders (OR=2.8, 95%CI:1.3–6.1) were also associated with offspring SP. Parental rearing styles of overprotection, rejection, and lack of emotional warmth were associated with offspring SP. Family functioning measures were not associated with offspring SP. Analyses of interaction of parental psychopathology and parental rearing indicated combined effects on the risk for offspring SP. Conclusions: Parental psychopathology and rearing were associated with offspring SP, independently as well as in their interaction. Further delineation of these associations is warranted as malleable components of these risk factors may provide potential targets for prevention programs. In addition, parent‐to‐offspring transmission of other internalizing disorders should be considered to examine the degree of diagnostic specificity. Depression and Anxiety, 2009. © 2008 Wiley‐Liss, Inc.     

Low birth weight and risk of affective disorders and selected medical illness in offspring at high and low risk for depression

Numerous studies have demonstrated that low birth weight (LBW) is associated with the development of medical conditions, such as hypertension and diabetes, and psychiatric disorders, such as depression. One possible mechanism through which LBW might increase risk for both medical and psychiatric disorders is by altering the biologic systems (such as the hypothalamic-pituitary-adrenal [HPA] axis function) that govern emotion regulation and physical reactivity. In this study, we conducted secondary data analyses in a longitudinal study originally designed to understand the intergenerational transmission of major depressive disorder (MDD). We examined the risk for both medical and psychiatric illnesses known to be influenced by HPA axis dysregulation in the context of parental depression. The study had 2 primary objectives: (1) to examine whether LBW increases the risk of selected adult illness that may be influenced by the HPA axis and (2) to examine whether the increased risk of illness varies by parental depression status. We conducted longitudinal assessments of 244 offspring of depressed and nondepressed parents for more than 20 years. Psychopathology and medical illness were assessed by direct interview conducted by clinicians blind to risk status and previous diagnosis. We examined the effect of BW in 3 categories: less than 2.5 kg (LBW), 2.5-3.5 kg, and more than 3.5 kg (reference group). Offspring with LBW had a significantly increased risk of MDD, anxiety disorders, phobia, suicidal ideation, impaired functioning, allergies, and hypertension compared to those with BW exceeding 3.5 kg. The association between LBW and depression was stronger among children of depressed parents than among children of nondepressed parents, with an interaction term (BW and parental depression status) significant for MDD (P = .05), suggesting that parental depression may augment the impact of LBW on offspring depression:     

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.     

Temperament among offspring at high and low risk for depression

The purpose of this study was to examine relationships between parental depression, offspring temperament, and offspring major depressive disorder (MDD), and to determine whether difficult temperament, as measured by the Dimensions of Temperament Survey (DOTS), mediates the relation between parental MDD and offspring MDD. Offspring (n=169) of depressed or never depressed parents were followed over approximately 20 years and were blindly assessed up to 4 times (Waves 1 to 4) using semi-structured interviews. Offspring completed the DOTS at the time of first or second assessment. The results showed: (1) high-risk offspring with one or more depressed parent were significantly more likely than offspring with neither parent depressed to have a difficult temperament; (2) offspring with a difficult temperament were more than twice as likely as those with an easy temperament to develop a MDD; and (3) difficult temperament explained more than 10% of the association between parental depression and new onsets of MDD in offspring. The findings suggest that offspring temperament is associated with development of MDD and that difficult temperament at least partially mediates the relationship between parental depression and offspring depression. When identifying those at greatest risk for MDD, measures of temperament could serve as a useful supplement to family psychiatric history of MDD.     

Anxiety disorders in mothers and their children: prospective longitudinal community study

The relationship between DSM-IV anxiety disorders and their clinical characteristics in mothers and anxiety in offspring was examined in 933 mother-child pairs from a longitudinal community study. Offspring of mothers with an anxiety disorder had an elevated risk of developing any anxiety disorder, compared with offspring of mothers with no anxiety disorder. Increased risk of anxiety in the offspring was especially associated with maternal social phobia and generalised anxiety disorder, and with maternal diagnoses of early onset, greater number and more severe impairment. These results suggest that the type of maternal anxiety disorder and its severity of manifestation contribute to mother-offspring aggregation of anxiety.     

Family discord, parental depression, and psychopathology in offspring: 20-year follow-up

OBJECTIVE: To determine the independent effects of parental depression and family discord on offspring psychopathology among children at high and low risk of depression. METHOD: Family discord factors were assessed when subjects were approximately 17 years old, and offspring diagnoses were assessed about 20 years later. Parental and offspring psychopathology was assessed by interviewers blind to parents' clinical status. The following dimensions of family discord were assessed: poor marital adjustment, parent child discord, low family cohesion, affectionless control, and parental divorce. RESULTS: Most family discord factors were associated with parental depression. Among children of depressed parents, none of the measures of family discord had a statistically significant association with offspring major depressive disorder or anxiety disorders. Among children of nondepressed parents, parental affectionless control was associated with an almost fivefold increased risk of major depressive disorder (odds ratio [OR] = 4.8; p < or = .05) and with more than a 14-fold increased risk of substance use disorders (OR = 14.3; p < or = .01). CONCLUSIONS: Parental depression is associated with family discord and is a consistent risk factor for offspring major depressive disorder and anxiety disorders, as shown over a 20-year follow-up of offspring of depressed and nondepressed parents. Family discord factors may be a risk factor for major depressive disorder and substance use disorders in offspring of nondepressed parents.