IL10 polymorphisms associated with Behçet’s disease in Chinese Han

Objective

IL-10 is a potent anti-inflammatory cytokine that plays important roles in the pathogenesis of Behçet’s disease (BD). Two genome-wide association studies have identified IL10 as a potential risk factor for BD. Here, we investigated the association between IL10 polymorphisms and BD in Chinese Han.

Methods

407 BD patients and 679 healthy controls were enrolled, and genotyped by Sequenom MassArray system (Sequenom iPLEX assay, San Diego, CA).

Results

The frequency of risk allele of rs1800871 was notably higher in BD patients than in controls (71.9% vs. 66.2%, OR: 1.30, 95%CI: 1.08–1.58, p_c = 0.024). Similarly, rs1518111, which showed strong linkage disequilibrium (r² = 1) with allele rs1800871, was also associated with BD (p_c = 0.026). Rs3021094 was in association with BD in a dominant model (p_c = 0.035), and the haplotype (GACC) formed by rs1518111, rs3021094, rs3790622, and rs1800871 was associated with BD (p_c = 0.023). Results obtained from meta-analysis combined with our data showed that rs1800871 and rs1518111 were associated with BD.

Conclusion

IL10 may be the susceptibility gene for BD in Chinese Han population.     

No evidence for association between bipolar disorder risk gene variants and brain structural phenotypes

Background

While recent genome-wide association studies have identified several new bipolar disorder (BD) risk variants, structural imaging studies have reported enlarged ventricles and volumetric reductions among the most consistent findings. We investigated whether these genetic risk variants could explain some of the structural brain abnormalities in BD.

Methods

In a sample of 517 individuals (N=121 BD cases, 116 SZ cases, 61 other psychosis cases and 219 healthy controls), we tested the potential association between nine SNPs in the genes CACNA1C, ANK3, ODZ4 and SYNE1 and eight brain structural measures found to be altered in BD, and if these were specifically affecting the BD sample. We also assessed the polygenic effect of all these 9 SNPs on the brain phenotypes.

Results

Our most significant result was an association between the risk allele A in CACNA1C SNP rs4775913 and decreased cerebellar volume (p_nom.=0.0075) in the total sample, which did not remain significant after multiple testing correction (p_threshold<0.0064). There was no evidence for diagnostic specificity for this association in the BD group. Further, no polygenic effect of these 9 SNPs was observed.

Limitations

Low statistical power might increase our type II error rate.

Conclusions

The present findings indicate that these risk SNPs do not explain a large proportion of the structural brain alterations in BD. Thus, these genes which are all related to neuronal functions must be involved in other pathophysiological aspects of BD development.     

In your eyes: Does theory of mind predict impaired life functioning in bipolar disorder?

Background

Deficits in emotion perception and social functioning are strongly implicated in bipolar disorder (BD). Examining theory of mind (ToM) may provide one potential mechanism to explain observed socio-emotional impairments in this disorder. The present study prospectively investigated the relationship between theory of mind performance and life functioning in individuals diagnosed with BD compared to unipolar depression and healthy control groups.

Methods

Theory of mind (ToM) performance was examined in 26 individuals with remitted bipolar I disorder (BD), 29 individuals with remitted unipolar depression (UD), and 28 healthy controls (CTL) using a well-validated advanced theory of mind task. Accuracy and response latency scores were calculated from the task. Life functioning was measured during a 12 month follow-up session.

Results

No group differences for ToM accuracy emerged. However, the BD group exhibited significantly shorter response times than the UD and CTL groups. Importantly, quicker response times in the BD group predicted greater life functioning impairment at a 12-month follow-up, even after controlling for baseline symptoms.

Limitations

The stimuli were static representations of emotional states and do not allow for evaluating the appropriateness of context during emotional communication; due to sample size, neither specific comorbidities nor medication effects were analyzed for the BD and UD groups; preliminary status of theory of mind as a construct.

Conclusions

Results suggest that quickened socio-emotional decision making may represent a risk factor for future functional impairment in BD.     

Attachment,affective temperament,and personality disorders: A study of their relationships in psychiatric outpatients

Background

As the result of extensive translational and cross-disciplinary research, attachment theory is now a construct with significant neuropsychiatric traction. The correlation of attachment with other influential conceptual models (i.e. temperament and personality) is therefore of interest. Consequently, we explored how two attachment dimensions (attachment anxiety and attachment avoidance) correlated with measures of temperament and personality in 357 psychiatric outpatients.

Methods

We performed a retrospective review of four questionnaires (the Experiences in Close Relationship scale (ECR-R), Temperament and Character inventory (TCI), Temperament Evaluation of the Memphis, Pisa, Paris and San Diego questionnaire (TEMPS-A), and Personality Self-Portrait Questionnaire (PSQ)). Frequency measures and correlations were examined, as was the predictive value of attachment security for a personality disorder (PD).

Results

Significant, robust correlations were found between attachment anxiety and (1) several negative affective temperaments (dysthymic and cyclothymic); (2) several indices of personality pathology (low self-directedness (TCI), DSM-IV paranoid, borderline, histrionic, avoidant and dependent personality traits). Attachment avoidance had fewer large correlations. In an exploratory model, the negative predictive value of attachment security for a PD was 86%.

Limitations

Subjects were a relatively homogeneous subset of ambulatory psychiatric outpatients. PD diagnoses were via self-report.

Conclusions

Clinically, these findings highlight the significant overlap between attachment, affective temperament, and personality and support the value of attachment as a screen for PDs. More broadly, given our growing understanding of the neurobiology of attachment (i.e. links with the oxytocin system), these results raise interesting questions about underlying biological systems and psychiatric treatment.     

Verbal episodic memory deficits in remitted bipolar patients: A combined behavioural and fMRI study

Background

Episodic memory deficits affect the majority of patients with bipolar disorder (BD).

Aims

The study investigates episodic memory performance through different approaches, including behavioural measures, physiological parameters, and the underlying functional activation patterns with functional neuroimaging (fMRI).

Methods

26 Remitted BD patients and a matched group of healthy controls underwent a verbal episodic memory test together with monitored autonomic response, psychopathological ratings and functional magnetic resonance imaging (fMRI) during the verbal episodic memory test.

Results

Compared to healthy controls, BD patients performed significantly worse during the episodic memory task. The results further indicate that verbal episodic memory deficits in BD are associated with abnormal functional activity patterns in frontal, occipital and limbic regions, and an increase in stress parameters.

Limitations

We aimed to minimise sample heterogeneity by setting clear criteria for remission, based on the scores of a depression (BDI II) and mania scale (BRMAS) and on the DSM IV criteria. However, our patients were not symptom-free and scored higher on BDI II scores than the control group.

Conclusions

The results are of interest for the treatment of cognitive symptoms in BD patients, as persistent cognitive impairment may hamper full rehabilitation.     

Auditory-prosodic processing in bipolar disorder; from sensory perception to emotion

Objectives

Accurate emotion processing is critical to understanding the social world. Despite growing evidence of facial emotion processing impairments in patients with bipolar disorder (BD), comprehensive investigations of emotional prosodic processing is limited. The existing (albeit sparse) literature is inconsistent at best, and confounded by failures to control for the effects of gender or low level sensory-perceptual impairments. The present study sought to address this paucity of research by utilizing a novel behavioural battery to comprehensively investigate the auditory-prosodic profile of BD.

Methods

Fifty BD patients and 52 healthy controls completed tasks assessing emotional and linguistic prosody, and sensitivity for discriminating tones that deviate in amplitude, duration and pitch.

Results

BD patients were less sensitive than their control counterparts in discriminating amplitude and durational cues but not pitch cues or linguistic prosody. They also demonstrated impaired ability to recognize happy intonations; although this was specific to male's with the disorder. The recognition of happy in the patient group was correlated with pitch and amplitude sensitivity in female patients only.

Limitations

The small sample size of patients after stratification by current mood state prevented us from conducting subgroup comparisons between symptomatic, euthymic and control participants to explicitly examine the effects of mood.

Conclusions

Our findings indicate the existence of a female advantage for the processing of emotional prosody in BD, specifically for the processing of happy. Although male BD patients were impaired in their ability to recognize happy prosody, this was unrelated to reduced tone discrimination sensitivity. This study indicates the importance of examining both gender and low order sensory perceptual capacity when examining emotional prosody.     

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.     

Two-year stability and change of neuroticism and extraversion in treated and untreated persons with depression: Findings from the Netherlands Study of Depression and Anxiety (NESDA)

Background

The personality dimensions neuroticism and extraversion likely represent part of the vulnerability to depression. The stability over longer time periods of these personality dimensions in depressed patients treated with psychological treatment or medication and in untreated persons with depression in the general population remains unclear. Stability of neuroticism and extraversion in treated and untreated depressed persons would suggest that part of the vulnerability to depression remains stable over time. The current study addressed the question whether treatment in depressed patients is related to changes in neuroticism and extraversion.

Methods

Data are from 709 patients with major depressive disorder participating in a cohort study (Netherlands Study of Depression and Anxiety; NESDA). We determined the 2-year stability of extraversion and neuroticism in treated and untreated persons and related change in depression severity to change in personality over time.

Results

Neuroticism decreased from baseline to 2-year follow-up (d=0.73) in both treated and untreated persons. Extraversion did not change significantly after controlling for neuroticism and depression severity at baseline and follow-up. Decreased depressive symptoms over time were related to decreased neuroticism (d=1.91) whereas increased depressive symptoms over time were unrelated to neuroticism (d=0.06).

Limitations

Patients were not randomized to treatment conditions and the groups are therefore not directly comparable.

Conclusions

Treated patients with depression in the general population improve just as much on depression severity and neuroticism as untreated persons with depression. This suggests that changes in neuroticism in the context of treatment likely represent mood-state effects rather than direct effects of treatment.     

Stigma and bipolar disorder: A review of the literature

Background

Psychiatric stigma is pervasive injustice that complicates the course of illness and reduces quality of life for people with mental illnesses. This article reviews the research examining stigma towards bipolar disorder (BD) with a view to guiding the development of stigma reduction initiatives and ongoing research.

Methods

PsychInfo, Medline, and Embase databases were searched for peer-reviewed studies addressing stigma in BD.

Results

Stigma is a serious concern for individuals with BD and their families. Stigma occurs within affected individuals, families, social environments, work and school environments, and the healthcare industry. With stigma often come a loss of social support and occupational success, reduced functioning, higher symptom levels and lower quality of life. BD stigma is comparable to that of other severe mental illnesses, such as schizophrenia. Few interventions are available to specifically target stigma against BD.

Limitations

Most studies have used explicit, attitude-based measures of stigma without controlling for social desirability, which may not translate into real-world stigmatizing behaviors. Furthermore, many studies have not clearly delineated results in a manner consistent with the conceptual framework of stigmatization.

Conclusions

Stigma toward BD is ubiquitous and has insidious consequences for affected individuals and their families. Stigma reduction initiatives should target individuals living with BD, their families, workplaces, and the healthcare industry, taking into account the experiences and impacts of BD stigma to improve social support, course of illness, and quality of life.     

The bipolar disorder prodrome revisited: Is there a symptomatic pattern?

Objectives

To assess the phenomenology and course of pre-(hypo)manic and pre-depressed prodromal symptoms, including mood swings, as precursors of bipolar disorder (BD) in a German multi-center study.

Methods

Semi-structured interviews [Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R); Semi-structured Interview for Mood Swings] were administered to patients within 8 years of BD (BD I, BD II) onset.

Results

Forty two outpatients were included (40.5% male, mean age 35.1±10.0 years, illness onset at 30.5±9.5 years). Feeling extremely energetic (85.7%), racing thoughts (78.6%), physical agitation (76.2%), overtalkativeness (71.4%), and low sleep requirement (71.4%) occurred most frequently prior to the first (hypo)manic episode, whereas depressed mood (83.0%), reduced vitality (81.0%), physical exhaustion (78.6%), tiredness (76.2%), and insomnia (66.7%) preceded pre-depressively. Mood lability (p=.006), odd ideas (p=.003) and the psychosis index score (p=.003) differed significantly in prevalence depending on the episodes’ mood. Extremely energetic (p=.046), overtalkativeness (p<.001), and racing thoughts (p=.013) lasted significantly longer prior to depression. Neither severity nor frequency of prodromal symptoms differed significantly. Most of the symptoms emerged during the proximal prodromal phase. Links between mood swings and subsequent BD were found.

Limitations

Symptoms were evaluated retrospectively with self-reporting tools in bipolar patients from academic treatment settings without comparison to clinical controls.

Conclusions

Not only specific depressive or manic but also general symptoms occurred prior to both affective episodes. The pre-depressive prodrome lasted longer than the pre-manic one, but severity and frequency did not differ significantly. Mood swings and disturbed diurnal rhythm occurred prior to both episodes as early signs of BD.     

Association of genetic variation in CACNA1C with bipolar disorder in Han Chinese

Background

A growing body of evidence highlights the existence of shared genetic susceptibility to both major depressive disorder (MDD) and bipolar disorder (BD), suggesting some potential genetic overlap between the disorders. Genome-wide association studies have identified consistent association of single nucleotide polymorphisms of the α-1 C subunit of the L-type voltage-gated calcium channel gene (CACNA1C) with MDD and BD, suggesting CACNA1C as a promising candidate gene for susceptibility to mood disorders. In the present study, we tested the association of CACNA1C with MDD and BD in Han Chinese.

Methods

We genotyped three potentially functional polymorphisms in 635 MDD patients, 286 BD patients and 730 normal, control patients.

Results

The genotype frequencies of SNP rs1051375 showed statistically significant differences between the BD and control groups (P=0.005). At the allele level, the difference of G allele frequency of rs1051375 between BD patients and control subjects was also significant (P=0.011; OR=1.30, 95% CI: 1.06–1.58). We found that GG genotype of rs1051375 carriers had a lower age at onset than those with the AG or AA genotype, and the mean±standard deviation ages at onset of GG, AG and AA carriers were 24.04±4.22, 25.76±4.75 and 25.78±4.33 years, respectively. Neither genotype nor allele frequencies of the three polymorphisms were found to be significantly different between the MDD patients and control subjects.

Limitations

The relative small sample size in BD group should be considered a limitation of this study.

Conclusions

Our initial findings support a potential association of CACNA1C as a genetic risk factor for BD susceptibility.     

Affective temperaments and ego defense mechanisms associated with somatic symptom severity in a large sample

Background

Several complex mechanisms including biological, psychological and social factors may contribute to the development of bodily symptoms. Affective temperaments may represent heritable subclinical manifestations of mood disorders, and the concept of ego defense mechanisms has also provided a model for the comprehension of psychopathology. The relationship between affective temperaments, defensive functioning and somatic symptom severity remains unknown.

Methods

We obtained data from a subsample of the Brazilian Internet Study on Temperament and Psychopathology (BRAINSTEP). Participants completed the Affective and Emotional Temperament Composite Scale (AFECTS), the Defense Style Questionnaire (DSQ-40) and the Symptom Checklist-90-Revised (SCL-90-R). SCL-90-R Somatization scale was used as outcome variable.

Results

Among 9937 participants (4472 male; 45%), individuals with dysphoric, cyclothymic and depressive temperaments and those who adopted displacement, somatisation and passive aggression as their predominant defense mechanisms presented high somatic symptom severity. Participants with dysphoric temperament and those with higher displacement scores were more likely to endorse numerous bodily symptoms after controlling for age, gender, education and depressive symptoms. Moderator analysis showed that the relationship of dysphoric temperament with somatic symptom severity was much more powerful in people who adopted displacement as their predominant defense.

Limitations

The data was collected from a convenience web-based sample. The study was cross-sectional. There was no information on the presence of established physical illness.

Conclusions

Affective temperaments and defense mechanisms are associated with somatic symptom severity independently of depressive symptoms. These two personality theories provide distinct but interacting views for comprehension of somatic symptom formation.     

Posterior cerebellar vermal deficits in bipolar disorder

Background

Based on growing evidence of the crucial role of the cerebellum in emotional regulation, we sought to identify cerebellar structural deficits in a large sample of patients with bipolar disorder (BD).

Methods

Cerebellar gray matter density was examined in 49 BD patients (24 medication-naive and 25 medication-treated) and 50 carefully matched healthy individuals, using voxel-based morphometry with a high-resolution spatially unbiased atlas template of the human cerebellum. This recently developed methodology is specifically optimized for the assessment of cerebellar structures. We further explored whether antimanic treatment could attenuate cerebellar structural deficits.

Results

BD patients showed a greater reduction in gray matter density of the posterior cerebellar regions, including the bilateral vermi and the right crus relative to healthy individuals (corrected p<.05). A stepwise linear reduction in gray matter density was observed in bilateral vermal regions between healthy individuals, medication-treated, and medication-naive BD patients. Furthermore, positive correlations of longer duration of illness with bilateral vermal gray matter deficits were observed only in medication-naive BD patients, but not in patients with medication history.

Limitations

This study adopted a cross-sectional design. The automatic intensity-normalization method for the measurement of cerebellar gray matter density may have a limitation in providing detailed anatomical information at a cerebellar folia level.

Conclusions

The current findings suggest that BD-related deficits in the posterior cerebellar regions, which appear to progress over the course of illness, could potentially be ameliorated by proper treatment with mood stabilizers.     

Treatment adherence towards prescribed medications in bipolar-II acute depressed patients: Relationship with cyclothymic temperament and “therapeutic sensation seeking” in response towards subjective intolerance to pain

Background

Treatment adherence (TA) is crucial during almost any phase of bipolar disorder (BD), including type-II (BD-II) acute depression. While a number of issues have been traditionally accounted on the matter, additional factors should be likewise involved, including affective temperaments and some clinically suggestive psychopathological traits whose systematic assessment represents the aim of this study.

Methods

Two hundred and twenty BD-II acute depressed outpatients were consecutively evaluated using the Structured Clinical Interviews for Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition Axis-I and II Disorders, Hamilton scales for Depression and Anxiety, Temperament Evaluation of the Memphis Pisa Paris San Diego-Auto-questionnaire-110-item, Visual Analogue Scale (VAS), Zuckerman's Sensation-Seeking Scale-Form-V (SSS-V), Barratt's Impulsivity Scale-11-item, State-Trait Anxiety Inventory modules, Severity module of the Clinical Global Impression Scale for BD, Morisky 8-Item Medication Adherence Scale (MMAS-8) and the Clinician Rating Scale (CRS). Patients were divided into non-adherent vs. treatment-adherent cases depending on MMAS-8+CRS scores.

Results

In the TA⁻ group, higher VAS and cyclothymic temperament scores were highly correlated (r=.699; p≤.001). Those latter scores, along with SSS-V scores and the occurrence of lifetime addiction to painkiller and/or homeopathic medications available over the counter defined a “therapeutic sensation seeking” pattern allowing to correctly classify as much as 93.9% [Exp(B)=3.490; p≤.001] of TA⁻ cases (49/220).

Limits

Lack of objective TA measures and systematic pharmacological record; recall bias on some diagnoses; and relatively small sample size.

Conclusions

Stating the burden of TA in BD, additional studies on this regard are aimed, ideally contributing to enhance the management of BD itself.     

Cognitive performance is impaired in euthymic Chinese patients with Bipolar 1 Disorder

Background

Data from euthymic patients with Bipolar Disorder (BD) has shown cognitive impairment and the notion that sufferers of BD achieve full recovery between illness episodes is questionable. These findings have not been replicated in a Chinese population. The present study examined the cognitive profile of euthymic Chinese patients with Bipolar 1 Disorder (BD-1) and matched healthy control participants.

Methods

Euthymic patients with BD-1 and matched controls (n=104 in total) completed serial measures to assess mood and also completed an IQ test and the Central Nervous System Vital Signs (CNSVS) computerized battery assessing memory (verbal and visual), executive functions, attention, psychomotor and processing speed.

Results

Patients with BD-1 performed worse than controls on all cognitive domains. When using 2 or more scores below the 5th percentile as a cutoff for neurocognitive impairment, 46.2% of the patients with BD-1 and none of the control sample scored in this range (p<.001). Correlational analysis among the illness variables in BD-1 revealed that cognitive performance was inversely correlated with the number of manic episodes and duration of illness.

Limitations

It was not possible to determine the causal relationship between associated illness and performance. The effect of medication on cognitive performance requires further study.

Conclusions

Euthymic Chinese patients with BD-1 demonstrate marked cognitive impairments and these correlated with illness parameters. Cognitive impairment in BD may be independent of language and culture.     

Influence of formalin fixation on tissue dimensions in palatal tonsils

Aim

To investigate the change of tissue dimensions after formalin fixation, and to determine the optimal time of fixation.

Hypothesis

Formalin fixation may lead to shrinkage in tissue dimensions and may thus alter tumor stages.

Background

It is often observed in tumor surgery that the dimensions in vivo seem larger than after resection, and tissue appears to shrink further after formalin fixation. This might alter dimensions and assessment of spread of the tumor and thus lead to a lesser tumor classification and stage. In cases where the decision for adjuvant chemoradiation is based upon the stage, it may thus be of relevance for the patient to evaluate the pathologic and not the in vivo dimensions of the tumor.

Material and methods

In order to obtain comparable tissues, we investigated 100 palatal tonsils after cold steel dissection tonsillectomy for chronic tonsillitis.There were four time points investigated: directly after excision in the operating room and after four, 24 and 72 h of fixation in formaldehyde (4% Formaldehyde in phosphate buffer pH 7.4). The tissue was measured in the following dimensions: volume (ml), weight (g) and length, broadness and width (mm).

Results

The tissue size did not change significantly in dimensions except for an increase in length. The time of fixation did not influence the size.

Discussion

Formalin fixation does not significantly influence the tissue dimensions of palatal tonsils in comparison to direct ex vivo measurements. A minimal time of fixation of 20 h is required in order to stop all degenerative processes; however, longer fixation does not change the dimensions of the specimen.

Conclusion

The null hypothesis has to be withdrawn that tissue dimensions are altered by formalin fixation. Thus, the histopathological measurements do not influence TNM staging.     

Minor hemoglobins HbA2 and HbF associate with disease severity in bipolar disorder with a likely protective role of HbA2 against post-partum episodes

Background

There exist studies indicating that bipolar disorder (BD) associates with changes in brain blood flow. Human brain with its high demand to oxygen constitutes 2% of the total body weight, while it receives 20% of cardiac output. α and β globin chains of hemoglobin were recently found in neural tissues, yet no study has questioned blood hemoglobins in BD.

Methods

A total of 120 euthymic BD patients (40 males and 80 females) were analyzed via high performance liquid chromatography (HPLC) to measure minor hemoglobin levels, which were statistically compared with disease characteristics.

Results

Minor hemoglobins HbA2 and HbF associated positively with episode density as a measure of disease severity in BD. An increased level of HbA2 meant significantly less postpartum episodes in child bearing women. HbF levels were higher in patients with a positive family history of any psychotic disorder. Sum of HbA2 and HbF correlated with episode density with a stronger significance (p<0.001) supporting intermittent hypoxia hypothesis in BD.

Limitations

The study was conducted only on euthymic patients to avoid likely bigger exogenous effects such as electro-convulsive therapy and diverse drug regimes, yet larger comparative studies are needed to support our current findings.

Conclusions

Higher HbA2 and HbF in more severe bipolar disorder may be compensations against intermittent hypoxias in BD. HbA2 increases following myocardial angina and in mountain dwellers, which may indicate protective roles in extreme conditions. HbF increase may act more as a maladaptation or emerge via haplotypal associations of BD genes and gamma-globin locus at 11p15.5.     

A three generations nation-wide population study of family load estimates in bipolar disorder with different age at onset

Objectives

This nation-wide register-based study investigates how often bipolar disorder (BD) occurs in affected families compared to control families by estimating the family load as a random effect; this effect measures the degree of dependence among family members in relation to BD. Furthermore, the study addresses the impact of certain risk factors, namely, sex, age at onset of BD, degree of urbanization, year of birth, month of birth, and maternal and paternal age at birth.

Method

A total of N=1204 children and adolescent psychiatric cases born between 1950 and 1997 and registered in the Danish Central Psychiatric Register (DPCR) developed BD before the age of 58 years. N=3553 controls without any psychiatric diagnosis were matched for age, gender, and region of residence. Psychiatric diagnoses were also obtained on the relatives, e.g. parents, siblings, and offspring as a part of the Danish Three Generation Study (3GS). A family component was obtained by using different regression models.

Results

Familial factors accounted for 20% of the variation in disease outcome when controlling for year and month of birth, sex, and degree of urbanization. Only female sex was associated with an increased hazard ratio of BD. Also having a mother, father or a sibling with the disorder was proven to be a significant risk factor. Furthermore, case relatives did not develop BD earlier than control relatives.

Conclusion

These findings based on a very large and representative dataset provide further and very solid evidence for the high family aggregation of BD.