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.     

Early detection of bipolar disorder: a pilot familial high-risk study of parents with bipolar disorder and their adolescent children

OBJECTIVES: Disturbances in cognition, affect, sleep and activity have been identified in bipolar disorder (BD) but little is known about the possible role of these factors in the development of the condition. We studied these variables in a familial high-risk sample. METHODS: Twenty-five children (13-19 years) of bipolar parents were compared with 22 similar aged children of age- and sex-matched healthy controls. Participants were assessed using Schedule for Affective Disorders and Schizophrenia-Lifetime version (SADS-L) and completed self-report measures of dysfunctional attitudes, behavioural inhibition/activation, social rhythms, coping styles and subjective experience of sleep. Children completed a 7-day recording of actigraphy (sleep and activity) and a 7-day diary measuring self-esteem, positive and negative affect and reactions to positive and negative events. RESULTS: Fifty-six per cent of children of bipolar parents (CBP) reported mood symptoms compared to 9% of children of control parents (CC). The CBP group had coping styles and instability of self-esteem consistent with abnormal strategies for regulating affect. Both groups also differed on sleep measures. The majority of differences observed were between CBP with a current or past mood diagnosis and CC. BD parents reported dysfunctional coping styles and (to a lesser extent) disrupted activity patterns. CONCLUSIONS: A familial high-risk strategy for studying the role of psychological factors in BD is feasible and informative. This pilot study indicates that abnormal coping styles, instability of self-esteem and dysregulation of sleep may be early markers of bipolar illness. However, current findings need to be explored further in longitudinal studies to clarify which potential markers are truly predictive of BD.     

High levels of cortisol among adolescent offspring of parents with bipolar disorder: a pilot study

The hypothalamic-pituitary-adrenal (HPA) axis is compromised at several levels in major depressive and bipolar disorder (BD). However, it is not known whether HPA abnormalities predate the onset of these disorders. We conducted a pilot study comparing salivary cortisol levels of 10 adolescent offspring of parents with BD and 10 offspring of parents with no mental disorder (NMD). For two days, samples were collected at awakening and during the day in the adolescents' natural environment. The offspring of parents with BD had higher mean cortisol levels in the mornings and afternoons than the offspring of parents with NMD. When controlling for age, group differences in cortisol persisted in the afternoon, but not morning samples. None of the adolescents met diagnostic criteria for anxiety, affective, attention-deficit, or conduct disorders. Although preliminary, the results suggest that there is an early abnormality in the HPA system of the offspring of parents with BD.     

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

BACKGROUND: To examine the risk for psychopathology in offspring at risk for bipolar disorder and the course of psychiatric disorders in these youth. METHODS: Using structured diagnostic interviews (Structured Clinical Interview for DSM-IV [SCID] and Kiddie Schedule for Affective Disorders and Schizophrenia [K-SADS]), psychiatric diagnoses of 117 nonreferred offspring of parents with diagnosed bipolar disorder were compared with those of 171 age- and gender-matched offspring of parents without bipolar disorder or major depression. RESULTS: Compared with offspring of parents without mood disorders, high-risk youth had elevated rates of major depression and bipolar disorder, anxiety, and disruptive behavior disorders. High-risk offspring also had significantly more impaired Global Assessment of Functioning (GAF) scores, higher rates of psychiatric treatment, and higher rates of placement in special education classes. Disruptive behavior disorders, separation anxiety disorder, generalized anxiety disorder (GAD), social phobia, and depression tended to have their onset in early or middle childhood, whereas bipolar disorder, obsessive-compulsive disorder (OCD), panic disorder, and substance use disorder had onset most frequently in adolescence. CONCLUSIONS: These findings support the hypothesis that offspring of parents with bipolar disorder are at significantly increased risk for developing a wide range of severe psychiatric disorders and accompanying dysfunction. Early disruptive behavior and anxiety disorders, as well as early-onset depression, may be useful markers of risk for subsequent bipolar disorder in high-risk samples.     

Cognitive behavioral therapy for rapid-cycling bipolar disorder: a pilot study

Bipolar disorder is characterized by depressive and/or manic episodes that interfere with daily functioning. Between 10%-24% of bipolar patients experience a rapid-cycling course, with 4 or more mood episodes occurring per year. Characterized by nonresponse to standard mood stabilizing medications, patients with rapid-cycling bipolar disorder are particularly in need of effective, adjunctive treatments. Adjunctive cognitive-behavioral therapy (CBT) has been shown to improve adherence to medication and reduce relapse rates in patients with bipolar disorder. However, no published trials to date have examined the application of CBT to the treatment of patients with a rapid-cycling course of illness, with only a single case study published in the literature. We recently developed a CBT protocol that addresses the specific needs of bipolar patients with rapid cycling. The present study was designed to investigate outcomes with this CBT protocol. Study participants were 10 patients with rapid-cycling bipolar disorder, 6 of whom completed the study. Completers showed significant decreases in depressive mood, and improvements remained stable during the 2-month follow-up. This suggests that CBT for rapid cycling may have beneficial effects.     

The early manifestations of bipolar disorder: a longitudinal prospective study of the offspring of bipolar parents

OBJECTIVE: A major aim of this longitudinal high-risk study is to identify reliable early indicators of emerging bipolar disorder (BD) among offspring from well-characterized parents. METHODS: High-risk offspring were recruited from families in which one parent had BD diagnosed on the basis of the Schedule for Affective Disorders and Schizophrenia - Lifetime version (SADS-L) interviews and DSM-IV diagnostic criteria and the other parent was well. Bipolar parents were further subdivided on the basis of response or non-response to long-term lithium. A comparison group of offspring was recruited from well parents diagnosed on the basis of either SADS-L interviews or the family history method. All consenting offspring from high-risk and control families were assessed longitudinally with the Schedule for Affective Disorders and Schizophrenia for School-aged Children - Present and Lifetime version (KSADS-PL) interviews and DSM-IV diagnoses were made on a blind consensus review. The offspring were reassessed on average annually, as well as at any time symptoms developed. RESULTS: Antecedent conditions to BD in both high-risk groups included sleep and anxiety disorders, while attention-deficit hyperactivity disorder and pre-psychotic conditions were antecedents among the offspring of lithium non-responders only. Among those offspring developing BD, the index mood episode was almost always depressive. CONCLUSIONS: Despite a specific genetic risk, BD began with non-specific psychopathology and/or depressive disorders in a majority of offspring. Therefore, diagnosis based only on cross-sectional assessment of symptoms appears to be insufficient for the accurate early detection of emerging BD. Other parameters such as family history and associated antecedents should be taken into account.     

A pilot study of visual backward masking performance among affected versus unaffected offspring of parents with bipolar disorder

BACKGROUND: Cognitive dysfunction is evident in some euthymic patients with established bipolar disorder (BD), including deficits in visual backward masking (VBM) tasks which map to a specific neural pathway. A high-risk paradigm would clarify the temporal relation of cognitive dysfunction to clinical course. METHOD: We compared euthymic offspring (age range: 18-32 years) of lithium-responsive bipolar parents with and without a previous lifetime history of psychiatric illness to healthy comparison subjects with a negative family history, on a VBM task that requires target location. RESULTS: High-risk offspring with no lifetime psychiatric history performed the VBM task at levels of healthy controls. High-risk offspring with a previous history of a mood disorder, in complete remission, made significantly more errors at short target-mask intervals than control or never ill offspring. These higher error rates were not a consequence of faster response times. CONCLUSIONS: There is preliminary evidence of specific cognitive dysfunction early in the course of illness in affected offspring of parents with lithium responsive BD. VBM is ideal for future longitudinal studies addressing whether cognitive dysfunction in BD is a trait marker or a consequence of illness manifestation.     

N-acetylaspartate levels in bipolar offspring with and at high-risk for bipolar disorder

OBJECTIVES: Studies have reported decreased N-acetylaspartate (NAA) in dorsolateral prefrontal cortex (DLPFC) of adults and children with bipolar disorder (BD), suggesting decreased neuronal density in this area. However, it is unclear if this finding represents neurodegeneration after or a trait marker present before BD onset. To address this question, we used proton magnetic resonance spectroscopy ((1)H-MRS) to compare DLPFC levels of NAA among bipolar offspring with early-onset BD, bipolar offspring with subsyndromal symptoms of BD and healthy children. METHODS: Participants were 9-18 years old, and included 60 offspring of parents with bipolar I or II disorder (32 with BD and 28 with subsyndromal symptoms of BD), and 26 healthy controls. (1)H-MRS at 3 T was used to study 8-cm(3) voxels placed in left and right DLPFC. RESULTS: There were no significant group differences in mean right or left DLPFC NAA/Cr ratios. Exploratory analyses of additional metabolites (myoinositol, choline) also yielded no significant group differences. NAA/Cr ratios were not correlated with age, duration of illness, or exposure to lithium or valproate. CONCLUSIONS: Our findings suggest that DLPFC NAA/Cr ratios cannot be used as a trait marker for BD. Although we did not find decreased DLPFC NAA/Cr ratios in children and adolescents with BD, it is still possible that such levels begin to decrease after longer durations of illness into adulthood. Longitudinal neuroimaging studies of patients with BD accounting for developmental and treatment factors are needed to further clarify the neurodegenerative aspects of BD.     

Clinical staging model in offspring of parents with bipolar disorder: a systematic review

Objective

We sought to systematically review the literature on the psychiatric risk of offspring of parents with bipolar disorder (OPBD) using a developmental psychopathology framework. The review also sought to establish the utility of clinical stage modelling as a framework for identifying precursor disorders to later onset of bipolar disorder (BD) in OPBD.

Methods

A systematic search was performed using EMBASE, PsychINFO and Medline. Reference lists of included studies and previous reviews were also searched. Studies were included if they reported diagnostic outcomes for child, adolescent and young adult offspring of parents diagnosed with BD.

Results

Twenty‐six studies were identified representing 21 individual cohorts. The review identified that OBPD present as a high‐risk group for a range of mood and non‐mood disorders in childhood, adolescence and young adulthood. The trajectory of risk was from non‐mood disorders in childhood via non‐bipolar mood disorders in early adolescence towards mania/hypomania in late adolescence and early adulthood. From a clinical staging perspective, childhood anxiety disorders were associated with later onset of BD. Recurrent substance use disorder was identified as a risk in OPBD during late adolescence and early adulthood. Quality ratings indicated that studies were methodologically robust.

Conclusions

Our review provides evidence for a developmental psychopathology trajectory of precursor risks to BD in OPBD. There is support for clinical stage modelling as a conceptual framework for understanding developmental risk in OPBD and as a tool for developing early and individualized intervention strategies.     

A follow-up investigation of offspring of parents with bipolar disorder

Seven male children who each had a manic-depressive parent (five alos had a parent with unipolar depression) and 12 control children were studied. The proband children had shown a range of adjustment problems as infants and toddlers. Four years later, they continued to have substantial behavior problems, including ones that could be classified as DSM-III psychiatric diagnoses. On the basis of psychiatric interviews and psychological assessments, the proband children received more DSM-III diagnoses than the control children. Proband children reported internalizing symptoms; this pattern was corroborated by their mothers, who also characterized these children as showing antisocial behavior patterns.     

Daytime cortisol and stress reactivity in the offspring of parents with bipolar disorder

The hypothalamic-pituitary-adrenal (HPA) axis is compromised in major depression and bipolar disorder (BD). It is not known however whether HPA abnormalities predate the onset of these disorders. Preliminary data indicated that the adolescent offspring of parents with BD (high-risk), as compared to adolescents of parents with no mental disorder (low-risk), had higher levels of daytime salivary cortisol. The present study re-examined the cortisol increase after awakening and basal cortisol levels in a larger sample, and tested the hypothesis that high-risk offspring are more reactive to psychosocial stress than low-risk offspring. Saliva samples were collected from 58 adolescents, 29 high-risk (14 male/15 female, 16.8 years) and 29 (14 male/15 female, 16.6 years) low-risk, in their natural environment during at least two days. Twenty-five high-risk (13 male/12 female) and 25 low-risk (13 male/12 female) youth completed a child adaptation (15 years) or the standard version of the “Trier Social Stress Test”. Consistent with our previous finding, high-risk offspring had higher daytime levels of cortisol in their natural environment than low-risk offspring, and the difference was unrelated to clinical symptoms or other known confounds. Irrespective of risk status, female participants had higher daytime levels of cortisol than male participants. In contrast, there were no group differences in the cortisol response to the laboratory psychosocial stressor. The offspring of parents with BD show evidence of increased daytime basal HPA functioning with normal reactivity to psychosocial stress.     

Neurochemical deficits in the cerebellar vermis in child offspring of parents with bipolar disorder

Singh MK, Spielman D, Libby A, Adams E, Acquaye T, Howe M, Kelley R, Reiss A, Chang KD. Neurochemical deficits in the cerebellar vermis in child offspring of parents with bipolar disorder.
Bipolar Disord 2011: 13: 189–197. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objectives: We aimed to compare concentrations of N‐acetyl aspartate, myo‐inositol, and other neurometabolites in the cerebellar vermis of offspring at risk for bipolar disorder (BD) and healthy controls to examine whether changes in these neuronal metabolite concentrations occur in at‐risk offspring prior to the onset of mania. Methods: A total of 22 children and adolescents aged 9–17 years with a familial risk for bipolar I or II disorder [at‐risk offspring with non‐bipolar I disorder mood symptoms (AR)], and 25 healthy controls (HC) were examined using proton magnetic resonance spectroscopy at 3T to study metabolite concentrations in an 8‐cc voxel in the cerebellar vermis. Results: Decreased myo‐inositol and choline concentrations in the vermis were seen in the AR group compared to HC (p < 0.01). Conclusions: Decreased cellular metabolism and interference with second messenger pathways may be present in the cerebellar vermis in youth at risk for BD as evident by decreased myo‐inositol and choline concentrations in this region. These results may be limited by a cross‐sectional design, co‐occurring diagnoses, and medication exposure. Longitudinal studies are necessary to determine whether early neurochemical changes can predict the development of mania. Improved methods for identifying children with certain neurochemical vulnerabilities may inform preventive and early intervention strategies prior to the onset of mania.     

Affective lability in offspring of parents with major depressive disorder,bipolar disorder and schizophrenia

European Child & Adolescent Psychiatry - Affective lability, defined as the propensity to experience excessive and unpredictable changes in mood, has been proposed as a potential...     

Lifetime psychopathology in child and adolescent offspring of parents diagnosed with schizophrenia or bipolar disorder: a 2-year follow-up study

Having one parent diagnosed with a severe mental disorder is considered one of the main risk factors for developing that disorder in adulthood, and it also increases the risk of a wide range of mental disorders in the offspring. The aim of this study is to compare the prevalence of several psychopathological diagnoses, the presence of prodromal symptoms, and global functioning in offspring of parents with schizophrenia or bipolar disorder and in offspring of controls at baseline and 2-year follow-up. This study included 41 offspring of parents with schizophrenia, 90 offspring of parents with bipolar disorder, and 107 offspring of controls (mean age 11.7 ± 3.2 at baseline and 13.9 ± 3.2 at follow-up). The prevalence of psychopathology and comorbidity was higher in offspring of parents with schizophrenia and offspring of parents with bipolar disorder than in offspring of controls at baseline and at 2-year follow-up. Interestingly, mood disorders were more prevalent in offspring of parents with bipolar disorder and disruptive disorders were more prevalent in offspring of parents with schizophrenia. Prodromal symptoms were more frequent in offspring of parents with schizophrenia than in offspring of controls, while the offspring of parents with bipolar disorder showed an intermediate pattern. Finally, global functioning was lower in the offspring of parents with schizophrenia than the offspring of parents with bipolar disorder and the offspring of controls. Screening patients’ children is clinically relevant, since, as a group, they have an elevated risk of developing a psychiatric disorder and of experiencing their first symptoms during childhood and adolescence.