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.     

Neuropsychological study of IQ scores in offspring of parents with bipolar I disorder

Introduction: Studies comparing IQ in Offspring of Bipolar Parents (OBP) with Offspring of Healthy Controls (OHC) have reported conflicting findings. They have included OBP with mental health/neurodevelopmental disorders and/or pharmacological treatment which could affect results. This UK study aimed to assess IQ in OBP with no mental health/neurodevelopmental disorder and assess the relationship of sociodemographic variables with IQ.

Methods: IQ data using the Wechsler Abbreviated Scale of Intelligence (WASI) from 24 OBP and 34 OHC from the North East of England was analysed using mixed-effects modelling.

Results: All participants had IQ in the average range. OBP differed statistically significantly from OHC on Full Scale IQ (p?=?.001), Performance IQ (PIQ) (p?=?.003) and Verbal IQ (VIQ) (p?=?.001) but not on the PIQ-VIQ split. OBP and OHC groups did not differ on socio-economic status (SES) and gender. SES made a statistically significant contribution to the variance of IQ scores (p?=?.001).

Conclusions: Using a robust statistical model of analysis, the OBP with no current/past history of mental health/neurodevelopmental disorders had lower IQ scores compared to OHC. This finding should be borne in mind when assessing and recommending interventions for OBP.     

Anatomical measurements of the orbitofrontal cortex in child and adolescent patients with bipolar disorder

Imaging studies indicate smaller orbitofrontal cortex (OFC) volume in mood disorder patients compared with healthy subjects. We sought to determine whether child and adolescent patients with bipolar disorder have smaller OFC volumes than healthy controls. Fourteen children and adolescents meeting DSM-IV criteria for bipolar disorder (six males and eight females with a mean age+/-S.D.=15.5+/-3.2 years) and 20 healthy controls (11 males and nine females with mean age+/-S.D.=16.9+/-3.8 years) were studied. Orbitofrontal cortex volume was measured using magnetic resonance imaging. Male bipolar patients had smaller gray matter volumes in medial (p=0.044), right medial (0.037) and right (p=0.032) lateral OFC subdivisions compared to male controls. In contrast, female patients had larger gray matter volumes in left (p=0.03), lateral (p=0.012), left lateral (p=0.007), and trends for larger volumes in right lateral and left medial OFC subdivisions compared with female controls. Male patients exhibit smaller gray matter volumes, while female patients exhibit larger volumes in some OFC sub-regions. Gender differences in OFC abnormalities may be involved in illness pathophysiology among young bipolar patients.     

Attachment and temperament profiles among the offspring of a parent with bipolar disorder

Introduction

Attachment is associated both with the risk of developing a mood disorder and temperamental profile. Relatively little is known about these associations in children of a parent with bipolar disorder (BD). The present study is a preliminary analysis of the association between attachment, temperament and psychopathology among high-risk offspring.

Methods

As part of an ongoing prospective cohort study, offspring from families with one parent with BD (HR) and offspring from families with unaffected parents (C) were clinically assessed using KSADS-PL format interviews annually. Validated self-report measures of perceived attachment and temperament were completed.

Results

Perceived attachment did not differentiate HR from C offspring and did not predict psychopathology or mood disorder in particular. However, high emotionality significantly predicted the risk of psychopathology in HR offspring, where 1 standard deviation increase in emotionality significantly increased the hazard of psychopathology by a factor of 1.36 (p=0.0009) and mood disorder by a factor of 1.24 (p=0.02).

Limitations

Use of retrospective measures and low sample size for some models.

Conclusions

There may be no gross abnormalities in attachment among HR compared to C offspring. It remains unclear if emotionality is a barometer of illness or a true risk factor in this population. More longitudinal research is needed to advance understanding of the influential pathways by which psychosocial risk factors impact the development of BD. This research has implications for targeted early interventions in HR youth.     

Lifetime psychopathology among the offspring of Bipolar I parents

BACKGROUND:

Recent studies have demonstrated high rates of psychopathology in the offspring of parents with bipolar disorder. The aim of this study was to identify psychiatric diagnoses in a sample of children of bipolar parents.

METHOD:

This case series comprised 35 children and adolescents aged 6 to 17 years, with a mean age of 12.5±2.9 years (20 males and 15 females), who had at least one parent with bipolar disorder type I. The subjects were assessed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children – Present and Lifetime version (K-SADS-PL). Family psychiatric history and demographics were also evaluated.

RESULTS:

Of the offspring studied, 71.4% had a lifetime diagnosis of at least one psychiatric disorder (28.6% with a mood disorder, 40% with a disruptive behavior disorder and 20% with an anxiety disorder). Pure mood disorders (11.4%) occurred less frequently than mood disorders comorbid with attention deficit hyperactivity disorder (17.1%). Psychopathology was commonly reported in second-degree relatives of the offspring of parents with bipolar disorder (71.4%).

CONCLUSIONS:

Our results support previous findings of an increased risk for developing psychopathology, predominantly mood and disruptive disorders, in the offspring of bipolar individuals. Prospective studies with larger samples are needed to confirm and expand these results.     

Childhood anxiety: An early predictor of mood disorders in offspring of bipolar parents

Background

Anxiety disorders are common among the offspring of parents with bipolar disorder (BD). This study investigated the nature of the association between anxiety disorders and mood disorders in a prospectively studied high-risk cohort.

Methods

High-risk offspring were identified from families in which one parent had confirmed BD based on SADS-L interviews and best estimate diagnostic procedures. All agreeable offspring aged 8–25 years were enrolled in a longitudinal study involving repeated KSADS-PL format clinical assessments. Control (C) offspring from families in which neither parent met lifetime criteria for a psychiatric disorder were similarly assessed. All DSM-IV diagnoses in the offspring were confirmed on blind consensus review. Cumulative incidence and adjusted Cox Proportional Hazards models were used to calculate the risk of anxiety disorders and the predictive association with mood disorders.

Results

The cumulative incidence of anxiety disorders was higher (23.40% vs. 10.42%; HR=2.136; p=.0382) and occurred earlier (9.79 vs. 14.84 years; p=.0125) in high-risk compared to C offspring. In high-risk offspring generalized anxiety disorders (GAD) followed by social phobia were the most incident anxiety subtypes; while high emotionality (HR 1.111; p=.0096) and shyness (HR 1.144; p=.0053) increased the risk of anxiety disorders. Anxiety disorders increased the adjusted risk of mood disorders (HR 2.166; p=.0004), on average 8.49 years later (SD 5.97).

Limitations

The cumulative incidence of BD is relatively low, as the cohort is still in the period of risk.

Conclusions

Findings highlight the need for longitudinal surveillance of symptomatic high-risk children and suggest anxiety disorders are an important early intervention target.     

Psychopathology in the adolescent offspring of bipolar parents

BACKGROUND: The aim of this study was to determine the prevalence and 14-months incidence of psychopathology in adolescent offspring of a bipolar parent. METHOD: Parent, teacher and self-report rating scales and Kiddie-SADS were used to assess 132 13-23-year-old offspring of bipolar parents. RESULTS: Compared to the general population, there were few differences between rating scale scores for bipolar offspring and problem scores for normative adolescents. Of the sample 49% had a lifetime psychiatric disorder, most commonly (33%) a mood disorder. LIMITATIONS: There was no suitable control group and there are no comparison data for psychiatric diagnoses (DSM-IV), based on semi-structured interviews in the adolescent age group in the Netherlands. CONCLUSIONS: The overall level of psychopathology of bipolar offspring was not particularly elevated, but when there were more problems, they tended to be mood disorders.     

Psychotherapy of bipolar disorder: a review

Background: Bipolar disorder is often only partially treated by medication alone, which has led to recent developments in the adjunctive psychological treatment of bipolar disorder. This paper aims to examine the current evidence for effectiveness of psychological interventions for bipolar disorder and to identify issues for future research in this area. Method: A review of outcome studies of psychological interventions reported since 1990, including psychoeducation, cognitive-behavioural, interpersonal and social rhythm and psychoanalytic therapy. Results: The research to date indicates that a range of psychological approaches appear to benefit people with bipolar disorder. The clearest evidence is for individual CBT which impacts on symptoms, social functioning and risk of relapse. Limitations: Many studies lack appropriate control groups and standardised measures of symptoms and diagnosis. Better designed studies would reduce the risk of over-estimates of effect sizes and subsequent failure to replicate. Further developments of psychotherapy need to be based on clear theoretical models of bipolar disorder. Conclusions: Many current studies are uncontrolled and of poor quality leading to a risk of over-estimating effectiveness of some interventions. Suggestions are made for future research including improving quality of studies, basing treatment developments on clear theoretical models and identifying specific treatment components for particular phases of the bipolar illness course.     

No association of the MCP-1 promoter A-2518G polymorphism with bipolar disorder in the Korean population

It has been suggested that bipolar disorder is associated with altered immune function. Monocyte chemoattractant protien-1 (MCP-1) is a chemokine that influences both neural and immune functions. We thus hypothesized that MCP-1 may be related to the development or pathophysiology of bipolar disorder. In this case–control study, we investigated the association between the A-2518G single nucleotide polymorphism (SNP) of the MCP-1 promoter and bipolar disorder. Patients with bipolar disorder (n = 183; bipolar I = 145, bipolar II = 38) and healthy controls (350) were recruited for the study. No significant allelic or genotypic association was detected between the A-2518G polymorphism and any sample of bipolar disorder patients. When we pooled the healthy controls and the cases of bipolar I disorder from previous Korean studies and this study, we again found no significant association. No significant difference in either allele frequency or genotype distribution was observed between bipolar I and bipolar II disorders. There was no difference in the age at onset of bipolar disorder among the three genotype groups. Our data suggest that the A-2518G polymorphism of MCP-1 is not a major susceptibility factor for bipolar disorder in the Korean population. However, the physiological role of MCP-1 is highly suggestive of its being associated with bipolar disorder, and further analyses of other SNPs of MCP-1 remain to be performed.     

Dysbindin gene variants are associated with bipolar I disorder in a Korean population

The dysbindin gene (DTNBP1) has been associated with schizophrenia in several populations. Because the clinical characteristics of schizophrenia and bipolar disorder overlap in many respects and findings from genetic studies have suggested common genes between them, we conducted a case control association study of bipolar disorder in Korea to investigate the genetic association between DTNBP1 and bipolar disorder. In total, 163 patients with bipolar disorder and 350 controls were evaluated. We genotyped three single nucleotide polymorphisms of DTNBP1 (SNP A, P1763, and P1320) and analyzed the allele, genotype, and haplotype associations with bipolar disorder. We found significant genotypic associations with P1763 and P1320, but no association with SNP A in the bipolar I group. When we included bipolar II and schizoaffective disorder in the affected phenotype, the significance decreased. A positive association was observed between the SNP A-P1763 haplotype and the bipolar I phenotype. This haplotype association was lost when we either broadened our phenotype or included P1320 in a haplotype. The positive results of the present study lost significance after a Bonferroni correction for multiple testing. These findings are consistent with previous findings that showed a positive association of DTNBP1 with bipolar disorders. Moreover, our results suggest that DTNBP1 may contribute more to bipolar I disorder than bipolar II disorder or schizoaffective disorder. Further comprehensive studies will be required to clarify these association, however, it seems likely that DTNBP1 is a susceptibility gene for bipolar disorder.     

Presentation and prevalence of PTSD in a bipolar disorder population: A STEP-BD examination

Background

Co-occurring psychiatric diagnoses have a negative impact on quality of life and change the presentation and prognosis of bipolar disorder (BD). To date, comorbidity research on patients with BD has primarily focused on co-occurring anxiety disorders and trauma history; only recently has there been a specific focus on co-occurring PTSD and BD. Although rates of trauma and PTSD are higher in those with bipolar disorder than in the general population, little is known about differences across bipolar subtypes.

Methods

Using the NIMH STEP-BD dataset (N=3158), this study evaluated whether there were baseline differences in the prevalence of PTSD between participants with bipolar disorder I (BDI) and bipolar disorder II (BDII), using the MINI and the Davidson Trauma Scale. Differences in PTSD symptom clusters between patients with BDI and BDII were also evaluated.

Results

A significantly greater proportion of participants with BDI had co-occurring PTSD at time of study entry (Χ²(1)=12.6; p<.001). BDI and BDII subgroups did not significantly differ in re-experiencing, avoidance, or arousal symptoms.

Limitations

The analysis may suggest a correlational relationship between PTSD and BD, not a causal one. Further, it is possible this population seeks treatment more often than individuals with PTSD alone. Finally, due to the episodic nature of BD and symptom overlap between the two disorders, misdiagnosis is possible.

Conclusions

PTSD may be more prevalent in patients with BDI. However, the symptom presentation of PTSD appears similar across BD subtypes. Individuals should be thoroughly assessed for co-occurring diagnoses in an effort to provide appropriate treatment.     

Association between the so-called “activation syndrome” and bipolar II disorder,a related disorder,and bipolar suggestive features in outpatients with depression

Background

Activation syndrome (AS) is a cluster of symptoms listed by the US Food and Drug Administration as possible suicidality precursors during antidepressant treatment. We aimed to clarify whether AS is associated with bipolar II disorder (BP-II) and its related disorder, i.e., bipolar disorder not otherwise specified (BP-NOS), which are often mistreated as major depressive disorder (MDD), as well as bipolar suggestive features in outpatients with depression.

Methods

The frequency of AS, bipolar suggestive features, and background variables in consecutive outpatients with a major depressive episode (MDE) due to BP-II/BP-NOS or MDD, who were naturalistically treated with antidepressants, were investigated and analyzed retrospectively.

Results

Of 157 evaluable patients (46 BP-II/BP-NOS, 111 MDD), 39 (24.8%) experienced AS. Patients with BP-II/BP-NOS experienced AS significantly more frequently than patients with MDD (52.2% of BP-II/BP-NOS vs. 13.5% of MDD, p<0.01). Univariate analysis revealed that BP-II/BP-NOS diagnosis, cyclothymic temperament, early age at onset of first MDE, psychiatric comorbidities, and depressive mixed state (DMX) were significantly associated with AS development in the entire sample. Multivariate analysis revealed that BP-II/BP-NOS diagnosis and DMX were independent risk factors for AS.

Limitations

This is a retrospective and naturalistic study; therefore, patient selection bias could have occurred.

Conclusions

Cautious monitoring of AS is needed during antidepressant trials in patients with BP-II/BP-NOS. Clinicians should re-evaluate underlying bipolarity when they confront AS. Antidepressants should be avoided for treating a current DMX beyond the unipolar–bipolar dichotomy. Prospective studies are needed to confirm these results.     

Subgenual cingulate volumes in affected and unaffected offspring of bipolar parents

BACKGROUND: Bipolar disorders (BD) have a strong genetic underpinning, yet no biological vulnerability markers for BD have been identified. Decreased volumes of subgenual cingulate (SGC) were replicated in familial bipolar patients. Presence of abnormality in unaffected subjects at genetic risk for an illness needs to be established before SGC volumes can be used as an endophenotype. This is the first study of SGC volumes in affected and unaffected subjects at familial risk for mood disorders. METHOD: High-risk participants were recruited from families multiply affected with BD. The high-risk sample included 13 affected and 13 unaffected offspring of bipolar I parents, who were matched by age and sex with 31 controls without a personal or family history of psychiatric disorders. The expanded sample consisted of 24 unaffected, 19 affected subjects all with a first or second degree relative suffering from BD I or II. The age range for all subjects was 15-30 years. Subgenual cingulate volumes were measured on 1.5 T 3D anatomical MRI images using standard methods. RESULTS: We found comparable SGC volumes among unaffected, affected offspring of BD I parents and controls. Likewise no SGC abnormalities were found in the expanded sample of subjects with BD I or II relatives. Left SGC volumes in all groups were smaller than right SGC volumes without laterality by group interaction. The exclusion of 5 medicated subjects did not change the results. LIMITATIONS: Cross sectional design, inclusion of both bipolar I and bipolar II probands. CONCLUSIONS: Subgenual cingulate volume abnormalities were absent in unaffected or affected relatives of bipolar patients and thus did not meet criteria for endophenotype.     

The clinical significance of creativity in bipolar disorder

Clinical implications of the high rates of creativity within bipolar disorder (BD) have not been explored. The aim of this review is to outline these implications by (i) reviewing evidence for the link between creativity and BD, (ii) developing a provisional model of mechanisms underpinning the creativity–BD link, (iii) describing unique challenges faced by creative-BD populations, and (iv) systematically considering evidence-based psychosocial treatments in the light of this review. While more research into the creativity–BD nexus is urgently required, treatment outcomes will benefit from consideration of this commonly occurring phenotype.     

Investigating the jumping to conclusion bias in bipolar disorder

Introduction: Hemsley and Garety described the “jumping to conclusions bias” in which patients with delusions may reach unreasonable results with insufficient information. In this study patients with bipolar disorder and healthy volunteers were compared in terms of jumping to conclusions bias using the beads in the jar task.

Methods: 37 patients with DSM-5 diagnosis of bipolar disorder and 30 healthy controls were tested with the Beads Task (BT), Tower of London Test (ToL) and Barrat Impulsiveness Scale (BIS).

Results: In the BT, the mean score of DtD (draws to decision) and JTC (jumping to conclusions) scores were not statistically different between the two groups. In the ToL test, the duration of the total execution and the total time were significantly longer in the bipolar group than the control group. BIS scores were significantly higher in the bipolar group. YMRS (Young Mania Rating Scale) scores were not correlated with BT.

Conclusions: This study is the first clinical study to assess the jumping to conclusions bias in patients with bipolar disorder. No JTC bias was detected in bipolar disorder. Further studies may assess JTC in larger samples to determine the effects of clinical state changes, psychotic symptoms, medication and impulsivity.     

Risks associated with gender differences in bipolar I disorder

Background

Previous studies have demonstrated that bipolar patients may differ in several features according to gender, but a number of the differences found remain controversial.

Methods

The demographic, illness course, clinical, comorbidity and temperament characteristics of a total of 1090 consecutive DSM-IV bipolar I manic inpatients were compared according to gender.

Results

Bipolar illness in women was characterised by the predominance of depression, as indicated by a depressive polarity at onset, higher rates of mixed mania, more suicidal behaviour, and a greater number of temperaments with depressive propensities. In contrast, the manic component was found to predominate in men. Men also had an earlier onset of their illness. Women displayed more comorbidities with eating, anxiety, and endocrine/metabolic disorders, whereas men were more comorbid with alcoholism and other forms of substance abuse, neurological, and cancer disorders. The following independent variables were associated with male gender: being single (+), depressive temperament (−), excessive alcohol use (+), cyclothymic temperament (−), excessive other substance use (+), mood congruent psychotic features (+), and manic polarity at onset (+).

Limitations

The retrospective design and the sample being potentially not representative of the bipolar disorder population are limitations.

Conclusions

Findings from this study tend to confirm most of the differences previously observed among bipolar men and women. Furthermore, these results draw attention to the risks that may be specifically linked to gender differences in bipolar I patients.