Personality of parents with bipolar disorder and interpersonal functioning among their offspring: a prospective 10-year study

A comparison of offspring of parents with bipolar disorder (OBD) and offspring of parents with no mental disorder (ONMD) showed that parents' neuroticism was associated with internalizing and externalizing problems among their children. The present study examined whether parents' neuroticism predicted poor interpersonal functioning among offspring 10 years later and whether the problems observed in middle childhood mediated the association between parents' neuroticism and offspring functioning. When offspring were in middle childhood, parents completed the revised NEO Personality Inventory and rated the child's behavior on the Child Behavior Checklist. Ten years later, 65 OBD and 59 ONMD completed interviews assessing mental disorders and interpersonal and noninterpersonal functioning. High neuroticism and low agreeableness in parents predicted poor interpersonal functioning in their offspring in late adolescence-early adulthood. The offspring's externalizing and internalizing problems in middle childhood partially mediated the association between parents' personality and offspring interpersonal functioning. Moreover, the association between parents' neuroticism and offspring internalizing problems was stronger among the OBD than the ONMD. Overall, the results suggested an intergenerational transmission of risk whereby high neuroticism and low agreeableness in parents were associated with behavioral problems among offspring in middle childhood that, in turn, predicted poor interpersonal functioning 10 years later.     

Psychopathology in children of bipolar parents

BACKGROUND: Few studies have examined the psychopathological profiles of child offspring of bipolar parents. Such investigations are useful as a first step to identifying potential prodromal manifestations of bipolar disorder. METHODS: The presence of psychopathology in 37 children with at least one parent with bipolar I disorder and 29 demographically matched children with parents free of any DSM-IV Axis I psychopathology was evaluated using the Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U KSADS). RESULTS: Twenty-nine (78%) of 37 high-risk children were diagnosed with at least one DSM-IV Axis I diagnosis as compared to seven (24%) of 29 children of healthy control parents (Fisher's exact test, p < 0.0001, odds ratio=11, 95% CI=3.33, 33). Sixteen percent (N=6) of high-risk offspring met DSM-IV criteria for bipolar I disorder as compared to none of the healthy control offspring (Fisher's exact test, p < 0.03). High-risk offspring also had statistically significant elevations in rates of other affective and disruptive behavior disorders as well as subsyndromal manifestations of psychopathology. CONCLUSIONS: Children of bipolar parents had an elevated risk for developing bipolar and other psychiatric disorders. The study of children of bipolar parents who are at high risk for developing bipolar disorder themselves is essential to identify potential prodromal manifestations of the disorder and to eventually establish targeted early intervention strategies. Longitudinal studies to confirm the prodromal manifestations of bipolar disorder and risk factors associated with the development of specific diagnoses in children are needed.     

Assortative mating for major affective disorder

The families of 26 married bipolar manic depressives were examined in detail. The rate of affective disorder in their spouses, and the parents and siblings of their spouses, was ascertained. The prevalence of affective disorder among the parents and siblings and of the spouses of age- and social class-matched schizophrenics and well controls was also ascertained. Finally, the prevalence of affective and other psychiatric disorders in the adult offspring of the bipolar probands was ascertained and related to the presence or absence of affective disorder in the spouse. We did not find clear evidence of assortative mating for major affective disorder, although dual mating for affective disorder had the expected result of increasing the risk for affective disorder in the adult offspring.     

A controlled longitudinal 5-year follow-up study of children at high and low risk for panic disorder and major depression

BACKGROUND: To evaluate the longitudinal course of psychiatric disorders in children of parents with panic disorder (PD) and major depression (MD) as they transition through the period of risk from childhood into adolescence. METHOD: Over a 5-year follow-up, we compared psychiatric disorders in four groups of children: (1) offspring of parents with PD plus MD (n=136); (2) offspring of parents with PD without MD (n=27); (3) offspring of parents with MD but without PD (n=53); and (4) offspring of non-PD non-MD parents (n=103). RESULTS: Parental PD was significantly associated with increased risk for anxiety disorders, irrespective of parental MD. Parental MD was associated with increased risk for MD, disruptive behavior disorders, and deficits in psychosocial functioning, irrespective of parental PD. CONCLUSIONS: These longitudinal findings confirm and extend previous cross-sectional results documenting significant associations between PD and MD in parents and patterns of psychopathology and dysfunction in their offspring.     

Parental concordance for affective disorders: psychopathology in offspring

This paper examines the effects of parental concordance for affective disorders and psychopathology among the 219 offspring of probands with major depression and normal controls. The lifetime prevalence of psychiatric disorders was significantly higher among the spouses of depressed probands as compared to those of normal controls. The spouses of 37% of the normals and 69% of the depressed probands met criteria for a diagnosis of major depression, an anxiety disorder, or alcoholism. Parental concordance for diagnoses, particularly for anxiety disorders, substantially increased the risk of major depression and anxiety disorders in their children. Moreover, the marital relationship, some aspects of family adjustment and severity of current symptoms were significantly worse among the couples who exhibited diagnostic concordance for anxiety, alcoholism and/or depression. The major implication of these findings is that the diagnostic status of both parents should be considered in the design and analysis of studies of children. The findings of the present study also underscore the importance of assessment of comorbid disorders in parents and offspring. Although the original study design focused on the risk of depression in children of parents in treatment for major depression, stronger transmissibility was found for anxiety disorders plus depression than for major depression alone. However, the exclusion criteria of a lifetime history of mania or hypomania led to an extremely low proportion of probands with pure major depression without concomitant anxiety disorders. These findings confirm the results of previous studies which have demonstrated a strong degree of overlap between affective and anxiety syndromes. The increased risk of anxiety disorders in the offspring of parents who had sought treatment for non-bipolar major depression suggests that anxiety may constitute an early form of expression of affective disorders. Confirmation of the finding of age-dependent expression of anxiety and depression in prospective longitudinal studies of children is indicated.     

Family environment patterns in families with bipolar children

BACKGROUND: We studied the characteristics of family functioning in bipolar children and healthy comparison children. We hypothesized that the family environment of bipolar children would show greater levels of dysfunction as measured by the Family Environment Scale (FES). METHODS: We compared the family functioning of 36 families that included a child with DSM-IV bipolar disorder versus 29 comparison families that included only healthy children. All subjects and their parents were assessed with the K-SADS-PL interview. The parents completed the FES to assess their current family functioning. Multivariate analysis of variance was used to compare the family environment of families with and without offspring with bipolar disorder. RESULTS: Parents of bipolar children reported lower levels of family cohesion (p<0.001), expressiveness (p=0.005), active-recreational orientation (p<0.001), intellectual-cultural orientation (p=0.04) and higher levels of conflict (p<0.001) compared to parents with no bipolar children. Secondary analyses within the bipolar group revealed lower levels of organization (p=0.031) and cohesion (p=0.014) in families where a parent had a history of mood disorders compared to families where parents had no history of mood disorders. Length of illness in the affected child was inversely associated with family cohesion (r=-0.47, p=0.004). LIMITATIONS: Due to the case-control design of the study, we cannot comment on the development of these family problems or attribute their cause specifically to child bipolar disorder. CONCLUSION: Families with bipolar children show dysfunctional patterns related to interpersonal interactions and personal growth. A distressed family environment should be addressed when treating children with bipolar disorder.     

School-aged children of depressed parents: a blind and controlled study

This study examines the prevalence of psychiatric dysfunction in the children of parents diagnosed with affective disorders. Sixty children from 37 proband families were compared to 43 children from 26 families obtained from matched controls as well as 20 children from 13 medically ill families. Group differences in diagnosable childhood disorders and familial characteristics are investigated. Significantly more disorders and symptoms were noted in the children with psychiatrically ill parents as compared to children from matched controls and medically ill parents. Using logistic and Cox survival analyses, correlates for the risk of affective disorder, attention deficit and conduct disorder in the children were examined. Maternal depression and paternal alcoholism were related to the risk for depression in the child. The child's sex and the presence of affective disorders in the father were significantly related to the risk for attention deficit disorder. Maternal alcoholism, parental divorce and the type of subject (proband or control family) were significantly related to the risk for conduct disorder. The findings are discussed relative to results from earlier studies on rates of disorder in the offspring of depressed parents.     

The psychosocial context of bipolar disorder: environmental, cognitive, and developmental risk factors

In this article, we review empirical research on the role of individuals' current environmental contexts, cognitive styles, and developmental histories as risk factors for the onset, course, and expression of bipolar spectrum disorders. Our review is focused on the following over arching question: Do psychosocial factors truly contribute risk to the onset, course, or expression of bipolar disorders? As a secondary issue, we also address whether the psychosocial risks for bipolar disorders are similar to those for unipolar depression. We begin by discussing the methodological requirements for demonstrating a psychosocial risk factor and the challenges posed by bipolar spectrum disorders for psychosocial risk research. Next, we review the extant studies on the role of recent life events and supportive and non-supportive social interactions (current environment) in bipolar disorders, as well as psychosocial treatments designed to remediate these current environmental factors. We then review the role of cognitive styles featured as vulnerabilities in theories of unipolar depression as risk factors for bipolar disorder alone and in combination with life events, including studies of cognitive-behavioral therapies for bipolar disorder. Finally, we review studies of parenting and maltreatment histories in bipolar disorders. We conclude with an assessment of the state of the psychosocial risk factors literature in bipolar disorder with regard to our guiding questions.     

Multiple dimensions of familial psychopathology affect risk of mood disorder in children of bipolar parents.

The aim of our study was to determine whether familial loading of unipolar disorder, bipolar disorder, and substance use disorder are associated with DSM-IV mood disorders in adolescents at risk for bipolar disorder. One hundred and forty adolescents aged 12-21 years of 86 bipolar parents participated in the study. Lifetime DSM-IV diagnoses of the bipolar offspring were assessed with the Schedule for Affective Disorders and Schizophrenia for School Age Children Kiddie-SADS-Present and Lifetime Version (SADS-PL). Parents were interviewed using the Family History Research Diagnostic Criteria (FH-RDC) which were used to calculate a continuous familial loading score (FL) for unipolar disorder, bipolar disorder, and for substance use disorder in first- and second-degree relatives of the adolescents. FL for unipolar disorder and substance use disorder were strong and independent predictors for lifetime mood disorders in the adolescents. The gender adjusted hazard ratios for mood disorders in the children were 1.5 (95% confidence interval (CI) = 1.2-2.0) for FL of unipolar disorder and 1.8 (95% CI = 1.3-2.4) for FL of substance use disorder. Expression of mood disorders in children of bipolar parents varies with the degree of additional FL of unipolar disorder and substance use disorder in the extended family.     

A review of potential cognitive and environmental risk markers in children of bipolar parents

Although there is clear evidence that bipolar disorder runs in families, the mechanisms by which this illness is transmitted across generations are poorly understood. In particular, there has been limited consideration of nature of the psychosocial risk factors that might be present in offspring of bipolar parents and of how these factors might increase the likelihood of transition to illness. Recent research has begun to explore psychosocial factors in both healthy and diagnosed children of bipolar parents. This review explores the findings that have been obtained to date in terms of personality, cognitive functioning, life events and family factors. Three potential theoretical frameworks are then considered which might prove fruitful for facilitating theoretically driven empirical studies in this important area. Implications for future research and therapy are noted.     

Effects of parental anxiety disorders in children at high risk for panic disorder: a controlled study

BACKGROUND: To examine the association between anxiety disorders in parents and offspring in a sample of children at risk for panic disorder. We hypothesized that individual anxiety disorders will breed true in offspring. METHODS: Comparisons were made between offspring of parents with PD+MD (N=136), PD (N=27), MD (N=27), and Controls (N=103). All subjects were assessed with structured diagnostic interviews. Individual anxiety disorders in the offspring were used as dependent variables in logistic regression models where parental PD status, parental MD, and the same parental anxiety diagnosis were used as independent binary variables. RESULTS: Social phobia and separation anxiety disorder in the offspring were accounted for by the same disorders in the parent, whereas agoraphobia and OCD in the offspring were accounted for by parental panic disorder. CONCLUSIONS: These findings suggest that differing risk factors underlie the expression of individual anxiety disorders in children at risk for panic disorder.     

Parental attitudes towards early intervention in children at high risk for affective disorders

BACKGROUND: Parents volunteered to complete surveys on attitudes toward treatment intervention in children at a theoretically high (20-30%) or very high (70%) risk for affective disorders because of an assumed uni-lineal or bi-lineal family history of bipolar illness. METHODS: Questions focused on examining at what ages and stage of symptom and syndrome evolution parents would wish their child to begin treatment with different types of therapeutic approaches and clinical trial designs. Sixty percent of the respondents had a personal history of unipolar or bipolar affective disorders. RESULTS: In 156 completed surveys, 83% of parents favored acute medication intervention and 67% favored long-term medication treatment for those children at very high risk at or before the development of severe symptoms (i.e. even prior to meeting full diagnostic thresholds). On the average, parents indicated that they would enter their child in a trial of: two types of psychotherapy at a point in illness evolution between moderate and severe symptoms, two types of open medications between severe symptoms and a definite diagnosis, two blind medications at a definite diagnosis, and a blind trial of placebo and medication after a definite diagnosis but before multiple recurrences of the illness. Parents, primarily on the basis of perceived safety, would allow their children to use medications that have been found to be effective in adults. LIMITATIONS: In addition to a number of methodological limitations, responders to the survey were self-selected. CONCLUSIONS: The results indicate a willingness on the part of most parents to treat a child at high risk for affective illness early in the course of symptom evolution, even prior to a full syndromic illness or diagnosis. This and other parental views of the risk-benefit and ethical dimensions of early intervention may be helpful in the initiation and design of studies aimed at assessing the efficacy of early interventions in childhood-onset bipolar illness and its prodromes.     

Stress, personality and depressive symptoms in a 6.5 year follow-up of subjects at familial risk for affective disorders and controls

BACKGROUND: The aim of the study was to identify risk factors in subjects at risk for depressive disorders and controls. METHODS: In a 6.5 year follow-up study we examined the effects of personality (neuroticism, frustration intolerance, rigidity, melancholic type), adverse life events and chronic difficulties on depressive symptoms in 89 high-risk subjects (HRS, siblings and children of patients suffering from an affective disorder), without any mental illness at wave 1 (T1), and 49 controls without any personal and family history of psychiatric disorder at T1. To this end, regression analysis and path analysis using a structural equation model (only for HRS) were performed. RESULTS: Risk factors for depressive symptoms at wave 2 (T2) in HRS comprised acute adverse life events, frustration intolerance (T1) and depressive symptoms (T1). Risk factors for depressive symptoms in controls included chronic difficulties, neuroticism and rigidity. HRS had less stressful life events and the same risk for chronic difficulties, but perceived adverse events as more stressful. LIMITATION: The sample size of the control group is too small for identifying slight effects. CONCLUSION: Our results indicate that the impact on the emergence of depressive symptoms of various risk factors is different in high-risk subjects and controls. High-risk subjects are more sensitive to the depressogenic effects of acute stress and thus avoid potential stressful changes in their life to a higher extent. On the other hand, the influence of persistent factors such as personality traits (neuroticism, rigidity) and chronic difficulties on subsequent depressive symptoms was less pronounced in HRS as compared to controls.     

Measures of attention and hyperactivity symptoms in a high-risk sample of children of bipolar parents

BACKGROUND: To determine whether significant symptoms of inattention were present among the offspring of well-characterized bipolar parents. METHODS: We included 53 offspring of 30 parents meeting DSM-IV criteria for bipolar disorder diagnosed by consensus on the basis of a SADS-L interview and a wealth of longitudinal clinical data. The unaffected parent had no lifetime history of a major psychiatric illness. Offspring, prospectively followed for up to 5 years, completed psychometric measures of attention and mood when judged to be at a good level of functioning (well, remitted or treated). RESULTS: Those offspring with any lifetime psychiatric diagnosis endorsed more subjective problems with attention. However, there was no measurable difference on tasks of sustained attention between those with and those without a lifetime psychiatric illness including affective disorder. There was a significant association between self-reported symptoms of depression and inattention, but no association between either self-report measure and an objective measure of sustained attention. LIMITATIONS: This study was not intended to be a comprehensive neuropsychological investigation of at risk offspring. CONCLUSIONS: In this high-risk population, subjective difficulty with attention appeared to be state-dependent, associated with the degree of subjective distress related to an underlying psychiatric illness.     

Towards a multifactorial approach for prediction of bipolar disorder in at risk populations

BackgroundThe high prevalence, recurrence rate, chronicity, and illness burden in bipolar disorder (BD) are well documented. Moreover, insufficient response with conventional pharmacological and manual-based psychosocial interventions, as well as evidence of illness progression and acceleration, invite the need for early detection and primary prevention.MethodsHerein we comprehensively review extant studies reporting on a bipolar prodrome. The overarching aim is to propose a predictive algorithm (i.e. prediction of BD in at-risk populations) integrating genetic (i.e. family history), environmental (e.g. childhood maltreatment) and biological markers (i.e. BDNF, inflammatory and oxidative stress markers). Computerized databases i.e. Pubmed, PsychInfo, Cochrane Library and Scielo were searched using the followed terms: bipolar disorder cross-referenced with prodromal, preclinical, at risk mental states, clinical high risk, ultra high risk, biomarkers, brain-derived neurotrophic factor, inflammation, cytokines, oxidative stress, prediction and predictive model.ResultsAvailable evidence indicates that a prodrome to bipolar disorder exists. Commonly encountered features preceding the onset of a manic episode are affective lability, irritability, anger, depression, anxiety, substance use disorders, sleep disorders, as well as disturbances in attention and cognition. Non-specificity and insufficient sensitivity have hampered the development of an adequate prediction algorithm.LimitationsLimitations include biases associated with retrospective studies, poor characterization of clinical high risk, inadequacy of prospective studies regarding sample selection and absence of specificity of risk states.ConclusionWe propose a hypothetical prediction algorithm that is combinatorial in approach that attempts to integrate family history, early adversity, and selected biomarkers.     

Association study of the tryptophan hydroxylase gene and bipolar affective disorder using family-based internal controls

The tryptophan hydroxylase (TPH) gene encodes for the rate-limiting enzyme of the serotonin metabolism and, therefore, has to be considered a major candidate for association studies in affective disorders. Recently, an association between this gene and bipolar affective disorder has been reported in a French population. We sought to replicate this finding in a German sample. Allele frequencies of a biallelic polymorphism (A218C) of the TPH gene were determined in 95 bipolar I patients and their parents. Preferential transmission of alleles from heterozygous parents to bipolar offspring was tested with the "transmission disequilibrium test" (TDT), which eliminates the contribution of population stratification to an association finding. Our sample yielded a power >90% to detect the originally reported effect. Neither allele 218A nor allele 218C were preferentially transmitted from heterozygous parents to bipolar offspring. Our results, therefore, do not support the hypothesis that the TPH gene is involved in the etiology of bipolar disorder.     

Cardiovascular risk factors in affective disorder

100 patients with affective disorder (unipolar affective disorder and bipolar affective disorder) were evaluated for evidence of increased risk for the major cardiovascular risk factors including hypertension, hypercholesterolemia, obesity, and cigarette use. Unipolar affective disorder patients showed no evidence of increased cardiovascular risk compared to population controls. Bipolar affective disorder patients displayed increased systolic blood pressure, definite hypertension, and use of cigarettes. These findings are consistent with a link between affective disorders and excess cardiovascular mortality.     

The use of the GBI as predictor of bipolar disorder in a population of adolescent offspring of parents with a bipolar disorder

OBJECTIVE: To assess the usefulness of the General Behavior Inventory (GBI) to predict the development of mood disorders in the offspring of parents with bipolar disorder. METHOD: The GBI and the K-SADS (first measurement) and the SCID (last measurement) were used to assess psychopathology among 129 adolescent and young adult offspring of a bipolar parent with an interval of 5 years. Based on the SCID results at the last measurement, the offspring were assigned to one of four groups: with bipolar mood disorder, with unipolar mood disorders, with non-mood disorders and without disorders and GBI-scores at the first measurement were compared across the four groups. RESULTS: The scores on the Depression scale of the GBI for the offspring who later developed a bipolar or any mood disorder were significantly higher than for the offspring who did not develop a mood disorder across a 5-year interval. For the offspring with a unipolar mood disorder at the first measurement, the scores on the Depression scale were significantly higher for those who switched to bipolar disorder versus those who remained unipolar. CONCLUSIONS: The GBI can be used in a high-risk sample of offspring of parents with bipolar disorder as a self-report measure as an aid to detect those who will develop bipolar disorder across a 5-year interval.     

Characteristics and psychosocial problems of patients with bipolar disorder at high risk for suicide attempt.

BACKGROUND: Bipolar disorder with a history of substance abuse or suicide attempt is a strong predictor of suicide. A high comorbidity of substance use disorders may obscure the specificity of findings about suicide behaviors in Western patients with bipolar disorder. METHODS: The clinical data of Chinese bipolar patients (DSM-III-R) in Taiwan who had been naturalistically followed up for at least 15 years were obtained by a combination of chart reviews and interviews with patients and family members. The national identity numbers were used to search for deceased subjects. RESULTS: There were 158 patients originally included for chart review; 4 of them died from suicide. A 9.9% lifetime prevalence of alcohol use disorders was found in 101 final subjects who accepting interview. Multiple logistic regression showed that subjects with a history of suicide attempt (n = 53, 52.5%) were more likely to have interpersonal problems with spouse or romantic partner (adjusted odds ratio = 2.85, 95% C.I. = 0.69-11.51), occupational problems mainly maladjustment and frequently changing job (adjusted odds ratio = 3.08, 95% C.I. = 1.12-10.49), and an earlier age (< or = 22 years) of onset (adjusted odds ratio = 0.96, 95% C.I. = 0.90-1.02). LIMITATION: To use an interview schedule for assessing the psychosocial problems of clinical population limits the interpretation and generalisability of the data. CONCLUSION: Despite low comorbidity of alcohol/drug use disorders in Chinese bipolar patients, a consistently high rate of suicide attempts reinforces that bipolar disorder is a high-risk group of suicide. An earlier age of onset, interpersonal problems with spouse or romantic partner, and occupational maladjustment rather than demographic characteristics may collectively identify those at high risk of suicide attempt in bipolar disorder.