High Risk For Bipolar Disorder Research Articles

Reduced Inferior Frontal Gyrus Activation During Response Inhibition to Emotional Stimuli in Youth at High Risk of Bipolar Disorder

Functional brain imaging of young people at increased genetic risk for bipolar disorder provides a means of identifying potential endophenotypes for this condition. Dysfunctional neural mechanisms for the cognitive control of emotion are implicated in the genetic predisposition to bipolar disorder, with aberrant activity in frontocortical, striatal, and limbic brain regions previously reported in subjects with established bipolar disorder during inhibitory and emotion processing tasks. Functional brain activity during inhibition of emotional material in young people at increased genetic risk for bipolar disorder was investigated using a facial-emotion go/no-go task during functional magnetic resonance imaging. Data from 47 genetically high-risk individuals aged 18 to 30 years with at least one first-degree relative with bipolar disorder were compared with 49 control subjects (within the same age range but without a family history of bipolar disorder or other severe mental illness). Whole-brain corrected analyses revealed a highly specific and significant lack of recruitment of the inferior frontal gyrus when inhibiting responses to fearful faces in the high-risk participants compared with control subjects (p = .011, family-wise error, peak voxel). Impaired inhibitory function of the inferior frontal cortex may represent a trait marker of vulnerability to bipolar disorder. That this finding was revealed during inhibition of emotional material further implicates dysregulated frontolimbic brain networks as a potential neurocognitive endophenotype for bipolar disorder and provides evidence for pre-existing functional disturbances in those at high genetic risk for bipolar disorder.

Affective disorders among patients with borderline personality disorder.

BackgroundThe high co-occurrence between borderline personality disorder and affective disorders has led many to believe that borderline personality disorder should be considered as part of an affective spectrum. The aim of the present study was to examine whether the prevalence of affective disorders are higher for patients with borderline personality disorder than for patients with other personality disorders.MethodsIn a national cross-sectional study of patients receiving mental health treatment in Norway (N = 36 773), we determined whether psychiatric outpatients with borderline personality disorder (N = 1 043) had a higher prevalence of affective disorder in general, and whether they had an increased prevalence of depression, bipolar disorder or dysthymia specifically. They were compared to patients with paranoid, schizoid, dissocial, histrionic, obsessive-compulsive, avoidant, dependent, or unspecified personality disorder, as well as an aggregated group of patients with personality disorders other than the borderline type (N = 2 636). Odds ratios were computed for the borderline personality disorder group comparing it to the mixed sample of other personality disorders. Diagnostic assessments were conducted in routine clinical practice.ResultsMore subjects with borderline personality disorder suffered from unipolar than bipolar disorders. Nevertheless, borderline personality disorder had a lower rate of depression and dysthymia than several other personality disorder groups, whereas the rate of bipolar disorder tended to be higher. Odds ratios showed 34% lower risk for unipolar depression, 70% lower risk for dysthymia and 66% higher risk for bipolar disorder in patients with borderline personality disorder compared to the aggregated group of other personality disorders.ConclusionsThe results suggest that borderline personality disorder has a stronger association with affective disorders in the bipolar spectrum than disorders in the unipolar spectrum. This association may reflect an etiological relationship or diagnostic overlapping criteria.

White matter integrity as an intermediate phenotype: Exploratory genome-wide association analysis in individuals at high risk of bipolar disorder

White matter integrity, as measured using diffusion tensor imaging (DTI), is reduced in individuals with bipolar disorder (BD), their unaffected relatives and carriers of specific risk-alleles. Fractional anisotropy (FA), an index of white matter integrity, is highly heritable but the genetic architecture of this trait has received little investigation. In this study we performed a genome-wide association study with FA as quantitative phenotype, in unaffected relatives of patients with BD (N=70) and a matched control group (N=80). Amongst our top results were SNPs located in genes involved in cell adhesion, white matter development and neuronal plasticity. Pathway analysis of the top associated polymorphisms and genes confirmed the enrichment of processes relevant to BD and white matter development, including axon guidance, ErbB-signalling neurotrophin signalling, phosphatidylinositol signalling, and cell adhesion. The majority of genes implicated in these pathways were differentially associated with FA in individuals at high familial risk, suggesting interactions with genetic background or environmental factors secondary to familial risk for BD. Although the present findings require independent replication, the results encourage the use of global FA as a quantitative phenotype in future large-scale studies which may help to identify the biological processes underlying reduced FA in BD and other psychiatric disorders.

Socio-emotional processing and functioning of youth at high risk for bipolar disorder

BackgroundThe goal of this study was to investigate differences in socio-emotional processing and functioning in children and adolescents at high risk for bipolar disorder (BD) and healthy control participants. MethodsChildren and adolescents with a parent with bipolar disorder, who had mood dysregulation but not fully syndromal BD (high risk, HR, n=24), were compared to participants with no personal or family history of psychopathology (healthy control, HC, n=27) across several neuropsychological domains. Social reciprocity was measured by the Social Responsiveness Scale, theory of mind was measured by use of the NEPSY, and affect recognition was measured by the NEPSY and the Diagnostic Test of Nonverbal Accuracy 2 (DANVA). ResultsThe HR group demonstrated significant impairment in social reciprocity, including impairments in social awareness, social cognition, social communication, social motivation, and autistic mannerisms. There were no significant group differences in performance on theory of mind or affect recognition tasks. LimitationsLack of impairment in tasks associated with theory of mind or affect recognition indicate that social functioning difficulties are not likely due to impairments in these areas, or that the measures employed were not sufficiently sensitive to detect group differences. ConclusionsYouth at high risk for BD demonstrated impairments in numerous social domains, which may be due to innate differences in brain development governing socio-emotional functioning or may be due to disruptions in normal development caused by mood regulation difficulties.

Interventions for Youth at High Risk for Bipolar Disorder and Schizophrenia

Increasing evidence from retrospective and prospective studies is beginning to validate criteria to identify individuals at high risk for developing bipolar disorder or schizophrenia. In parallel, intervention trials are evaluating the efficacy and tolerability of pharmacologic and nonpharmacologic approaches for the treatment of subthreshold and possibly prodromal presentations in these high-risk populations with the ultimate objective of mitigating illness progression. This article reviews current evidence for candidate interventions for high-risk individuals to guide future research in this rapidly emerging field. A clinical vignette describing antidepressant-induced manic symptoms in an adolescent with a family history of bipolar disorder is provided.

Using Electronic Health Record-Based Tools To Screen for Bipolar Disorder in Primary Care Patients With Depression

National guidelines recommend screening all persons with depression for bipolar disorder (BPD); one way to facilitate screening is through the use of electronic health records (EHRs). This study examined the impact of an EHR-based screening and decision support tool on diagnosis and treatment of BPD among patients diagnosed with depression in primary care offices. This nonrandomized, controlled trial was conducted in a national network of offices using EHRs. The intervention included a screening instrument and other tools for diagnosis and management of BPD, which were embedded into the EHR. This instrument automatically activated when a patient with a diagnosis of depression but no diagnosis of BPD was seen in the office. The primary outcomes were the rates of new diagnoses of BPD and prescription of new BPD medications during the 6-month study period (April to October 2009). Twenty-one offices with 75 clinicians and 8355 adult patients with depression composed the intervention group, whereas 17 offices with 81 clinicians and 8799 adult patients with depression served as the comparison group. The screening tool was used with 47.5% of intervention patients, of whom 2.5% scored at high or very high risk for BPD. Intervention patients were more likely than comparison patients to be newly diagnosed with BPD (1.11% vs. 0.36%; P < .01) and be prescribed new BPD medications (1.85% vs. 1.19%; P < .01). The study suggests that EHR-based tools can be useful for screening and management of BPD for patients with depression in primary care offices.

Effects of a mis‐sense DISC1 variant on brain activation in two cohorts at high risk of bipolar disorder or schizophrenia

Bipolar disorder and schizophrenia share a number of clinical features and genetic risk variants of small effect, suggesting overlapping pathogenic mechanisms. The effect of single genetic risk variants on brain function is likely to differ in people at high familial risk versus controls as these individuals have a higher overall genetic loading and are therefore closer to crossing a threshold of disease liability. Therefore, whilst the effects of genetic risk variants on brain function may be similar across individuals at risk of both disorders, they are hypothesized to differ compared to that seen in control subjects. We sought to examine the effects of the DISC1 Leu(607) Phe polymorphism on brain activation in young healthy individuals at familial risk of bipolar disorder (n = 84), in a group of controls (n = 78), and in a group at familial risk of schizophrenia (n = 47), performing a language task. We assessed whether genotype effects on brain activation differed according to risk status. There was a significant genotype × group interaction in a cluster centered on the left pre/postcentral gyrus, extending to the inferior frontal gyrus. The origin of this genotype × group effect originated from a significant effect of the presumed risk variant (Phe) on brain activation in the control group, which was absent in both high-risk groups. Differential effects of this polymorphism in controls compared to the two familial groups suggests a commonality of effect across individuals at high-risk of the disorders, which is likely to be dependant upon existing genetic background.

Behavioural Risk of Bipolar Disorder in an Analogue Population: The Role of Cognitive, Developmental and Interpersonal Factors

Research to date has identified the contribution of a number of cognitive, developmental and interpersonal risk factors in the development of bipolar affective disorder. However, further work is needed to understand the mechanisms and interactions between these risk factors in relation to bipolar mood instability. The aim of this study is to explore the possibility of identifying high risk of bipolar disorder through cognitive and interpersonal factors and to further expand our knowledge regarding the relationship between such factors. The findings from this work demonstrate that when both cognitive and interpersonal variables are entered into one model to predict bipolar high risk, direct effects are observed for the interpersonal factors, which then have a fully mediational effect on the cognitive factors. This work proposes that interpersonal factors develop and maintain cognitive risk factors and that future formulations and treatment of bipolar disorder need to focus on addressing such interpersonal issues.

The Neural Basis of Familial Risk and Temperamental Variation in Individuals at High Risk of Bipolar Disorder

Bipolar disorder is a highly heritable psychiatric disorder characterized by episodic elevation or depression of mood. Bipolar disorder is associated with structural and functional brain abnormalities but it is unclear whether these are present in relatives of affected individuals and if they are associated with subclinical symptoms or traits associated with the disorder. Functional magnetic resonance imaging scans were conducted on 93 unrelated relatives of bipolar disorder patients and 70 healthy comparison subjects performing the Hayling sentence completion paradigm. Examination of comparison subjects versus high-risk individuals was followed by assessments of associations with depression scores and measures of cyclothymic temperament. Examination of comparison subjects versus high-risk subjects revealed increased activation in the high-risk group in the left amygdala. No interaction effects were observed between the groups for scores of depression or cyclothymia and activation in any region. Significant associations were found across the groups with depression ratings and activation in the ventral striatum and with cyclothymia and activation in ventral prefrontal regions, however no interaction effects were observed between the groups. Differences in activation in the left amygdala in those at familial risk may represent a heritable endophenotype of bipolar disorder. Activation in striatal and ventral prefrontal regions may, in contrast, represent a distinct biological basis of subclinical features of the illness regardless of the presence of familial risk.

Depression across mood disorders: review and analysis in a clinical sample

ObjectivesIn this article we aimed to: (1) review literature concerning the clinical and psychopathologic characteristics of Bipolar (BP) depression; (2) analyze an independent sample of depressed patients to identify any demographic and/or clinical feature that may help in differentiating mood disorder subtypes, with special attention to potential markers of bipolarity. MethodsA sample of 291 depressed subjects, including BP -I (n = 104), BP -II (n = 64), and unipolar (UP) subjects with (n = 53) and without (n = 70) BP family history (BPFH), was examined to evidence potential differences in clinical presentation and to validate literature-derived markers of bipolarity. Demographic and clinical variables and, also, single items from the Hamilton Depression Rating Scale (HDRS), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Young Mania Rating Scale (YMRS) were compared among groups. ResultsUP subjects had an older age at onset of mood symptoms. A higher number of major depressive episodes and a higher incidence of lifetime psychotic features were found in BP subjects. Items expressing depressed mood, depressive anhedonia, pessimistic thoughts, and neurovegetative symptoms of depression scored higher in UP, whereas depersonalization and paranoid symptoms' scores were higher in BP. When compared with UP, BP I had a significantly higher incidence of intradepressive hypomanic symptoms. Bipolar family history was found to be the strongest predictor of bipolarity in depression. ConclusionsOverall, our findings confirm most of the classical signs of bipolarity in depression and support the view that some features, such as BPFH, together with some specific symptoms may help in detecting depressed subjects at higher risk for BP disorder.

Early psychosocial intervention for youth at risk for bipolar I or II disorder: a one-year treatment development trial

Previous studies have identified behavioral phenotypes that predispose genetically vulnerable youth to a later onset of bipolar I or II disorder, but few studies have examined whether early psychosocial intervention can reduce risk of syndromal conversion. In a one-year open trial, we tested a version of family-focused treatment adapted for youth at high risk for bipolar disorder (FFT-HR). A referred sample of 13 children (mean 13.4±2.69 years; 4 boys, 9 girls) who had a parent with bipolar I or II disorder participated at one of two outpatient specialty clinics. Youth met DSM-IV criteria for major depressive disorder (n=8), cyclothymic disorder (n=1), or bipolar disorder not otherwise specified (n=4), with active mood symptoms in the past month. Participants were offered FFT-HR (12 sessions in four months) with their parents, plus psychotropic medications as needed. Independent evaluators assessed depressive symptoms, hypomanic symptoms, and global functioning at baseline and then every four months for one year, with retrospective severity and impairment ratings made for each week of the follow-up interval. Families were mostly adherent to the treatment protocol (85% retention), and therapists administered the FFT-HR manual with high levels of fidelity. Youth showed significant improvements in depression, hypomania, and psychosocial functioning scores on the Adolescent Longitudinal Interval Follow-up Evaluation. They also showed significant improvements in Young Mania Rating Scale and Children's Depression Rating Scale scores. FFT-HR is a promising intervention for youth at high risk for BD. Larger-scale randomized trials that follow youth into young adulthood will be necessary to determine whether early psychosocial intervention can reduce the probability of developing bipolar I or II disorder among genetically vulnerable youth.

Correlates of Medication Adherence Among Patients With Bipolar Disorder

To identify and describe correlates of medication adherence in a large, national sample of outpatients with bipolar disorder. Data were collected via a self-report, Web-based survey in January and February of 2008 from US patients aged 18-65 years who reported a diagnosis of bipolar disorder and current use of psychotropic medication. Patients with a Composite International Diagnostic Interview-bipolar disorder (CIDI-bipolar disorder) score ≥ 7, indicating a high risk of bipolar disorder, were included in the analyses. Medication adherence was assessed via the Morisky Medication Adherence Scale, with scores ≥ 2 being considered nonadherent. The primary analysis was a multivariate binomial logistic regression with adherence as the dependent variable. Covariates included patient demographics, physical health measures including Medical Outcomes Study 8-item Short-Form Health Survey physical summary score, number of manic and depressive episodes, 24-item Behavior and Symptom Identification Scale (BASIS-24), Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS), Satisfaction With Antipsychotic Medication scale (SWAM), and current psychiatric medication use. Nearly half (49.5%) of the 1,052 bipolar patients in the analysis were classified as being nonadherent. Adherence was positively associated with college degree, higher SWAM total score, and monotherapy treatment. Adherence was negatively associated with female sex, alcohol use, BASIS-24 total score, and LUNSERS total score. Nonadherence is common among patients with bipolar disorder. By addressing tolerability issues and treatment satisfaction, which are both significant correlates of adherence, health care providers may be able to improve adherence and, ultimately, treatment outcomes.

Effect of divalproex on brain morphometry, chemistry, and function in youth at high-risk for bipolar disorder: a pilot study.

Divalproex has been found efficacious in treating adolescents with and at high risk for bipolar disorder (BD), but little is known about the effects of mood stabilizers on the brain itself. We sought to examine the effects of divalproex on the structure, chemistry, and function of specific brain regions in children at high-risk for BD. A total of 24 children with mood dysregulation but not full BD, all offspring of a parent with BD, were treated with divalproex monotherapy for 12 weeks. A subset of 11 subjects and 6 healthy controls were scanned with magnetic resonance imaging (MRI, magnetic resonance spectroscopy [MRS], and functional MRI [fMRI]) at baseline and after 12 weeks. There were no significant changes in amygdalar or cortical volume found over 12 weeks. Furthermore, no changes in neurometabolite ratios were found. However, we found the degree of decrease in prefrontal brain activation to correlate with degree of decrease in depressive symptom severity. Bipolar offspring at high risk for BD did not show gross morphometric, neurometabolite, or functional changes after 12 weeks of treatment with divalproex. Potential reasons include small sample size, short exposure to medications, or lack of significant neurobiological impact of divalproex in this particular population.

Regulatory factor X4 variant 3: A transcription factor involved in brain development and disease

Regulatory factor X4 variant 3 (RFX4_v3) is a recently identified transcription factor specifically expressed in the brain. Gene disruption in mice demonstrated that interruption of a single allele (heterozygous, +/-) prevented formation of the subcommissural organ (SCO), resulting in congenital hydrocephalus, whereas interruption of two alleles (homozygous, -/-) caused fatal failure of dorsal midline brain structure formation. These mutagenesis studies implicated RFX4_v3 in early brain development as well as the genesis of the SCO. Rfx4_v3 deficiency presumably causes abnormalities in brain by altering the expression levels of many genes that are crucial for brain morphogenesis, such as the signaling components in the Wnt, bone morphogenetic protein, and retinoic acid pathways. RFX4_v3 might affect these critical signaling pathways in brain development. Cx3cl1, a chemokine gene highly expressed in brain, was identified as a direct target for RFX4_v3, indicating that RFX4_v3 possesses trans-acting activity to stimulate gene expression. Rfx4_v3 is highly expressed in the suprachiasmatic nucleus and might be involved in regulating the circadian clock. One haplotype in RFX4_v3 gene is linked to a higher risk of bipolar disorder, suggesting that this protein might contribute to the pathogenesis of the disease. This Mini-Review describes our current knowledge about RFX4_v3, an important protein that appears to be involved in many aspects of brain development and disease.

Temperament, life events, and psychopathology among the offspring of bipolar parents

The present study examines the relationship between temperament, recent and remote life events, and psychopathology among the offspring of parents with bipolar disorder and well comparisons. Offspring of bipolar and well parents were clinically assessed using KSADS-PL format interviews. Lifetime psychiatric diagnoses were made on a blind consensus basis in accordance with DSM-IV criteria. Depending on offspring age, either the child or their parent on their behalf, completed a semi-structured interview quantifying the number and impact of recent life events and remote permanent losses, as well as a measure of temperament. In this study, there was an association between psychopathology and the number of recent negative life events, but no association between psychopathology and the number of early losses. Emotionality was positively correlated with recent life events. However, in stepwise regression analyses, only emotionality significantly contributed to lifetime psychopathology in general and emotionality and age contributed to the risk of mood disorder in particular. These findings, replicate in a sample of offspring at high risk for bipolar disorder, previously reported associations between high emotionality and unipolar depression. In this population, any effect of undesirable life events would appear to be mediated through the association with emotionality.

A Pilot Study of Antidepressant-Induced Mania in Pediatric Bipolar Disorder: Characteristics, Risk Factors, and the Serotonin Transporter Gene

Antidepressant-induced mania (AIM) has been described in bipolar disorder (BD) and has been associated with the short-allele of the serotonin transporter gene (5-HTT). We wished to investigate the frequency of and risk factors for AIM in pediatric patients with or at high risk for BD. Fifty-two children and adolescents (30 with BD and 22 with subthreshold manic symptoms, 15.1 +/- 3.4 years old), all with a parent with BD, were interviewed with their parents for manic/depressive symptoms occurring before and after past antidepressant treatment. The 47 subjects with serotonin reuptake inhibitor (SSRI) exposure were genotyped for the 5-HTT polymorphism. Fifty percent of subjects were AIM+ and 25.5% had new onset of suicidal ideation. The AIM+ and AIM- groups did not differ significantly in relation to allele (p = .36) or genotype (p = .53) frequencies of the 5-HTT polymorphism. The AIM+ subjects were more likely to have more comorbidities (3.2 vs. 2.4; p = .02) and be BD type I (p = .04) than AIM- subjects. Youth with or at high risk for BD may be particularly vulnerable to SSRI AIM and thus should be monitored if given SSRIs. In this preliminary study, we did not find that the 5-HTT polymorphism significantly influenced vulnerability to AIM.

Divalproex Sodium Reduces Overall Aggression in Youth at High Risk for Bipolar Disorder

The psychopharmacology of aggression in youth is relatively unexplored, even though such maladaptive aggression manifests across many different diagnoses. This study was a 12-week, open-label trial with divalproex sodium (DVPX) in 24 bipolar offspring 6-18 years of age (mean age = 11.3 years; 17 boys) with mixed diagnoses of major depression, cyclothymia, attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD). The Overt Aggression Scale (OAS) was used to measure aggression in 4-week intervals. We measured serum gamma-butyric acid (GABA) and glutamate levels at baseline and week 12. Seventy-one percent of evaluable subjects were considered responders to DVPX treatment by the OAS. There was a significant correlation between the Young Mania Rating Scale (YMRS) and OAS scores at week 0 (p = 0.036) and week 12 (p = 0.025). Serum DVPX level did not correlate with treatment response. These youths who are at high risk for bipolar disorder experienced an overall decrease in aggressive behavior in response to DVPX. Age or gender did not predict a positive response to DVPX. This study is the first report of treatment efficacy of a mood stabilizer for aggression in youth at high risk for bipolar disorder.

Obstetrical complications in children at high risk for bipolar disorder

Objective To examine obstetrical complications as a risk factor for developing bipolar disorder (BPD). We hypothesized that children with a bipolar parent would be at greater risk for obstetrical complications than demographically matched children of healthy adults. Additionally, within this “at-risk” (AR) sample, we hypothesized that obstetrical complications would be associated with the development of psychiatric disorders. Methods The Washington University in St. Louis Kiddie-Schedule for Affective Disorders and Schizophrenia (WASH-U KSADS) was administered to children (AR) who had at least one parent with BPD ( N = 36) and children of healthy parents (HC) ( N = 27), by raters who were blind to diagnostic category. To assess obstetrical risk history, the Rochester Research Obstetrical Scale (ROS) was administered to parents of AR and HC children. Results Children at familial risk for BPD had greater total ( p = 0.02) and prenatal ( p = 0.006) obstetrical complication scores than children of healthy parents. However, obstetrical complications were not associated with the development of affective, anxiety, or disruptive behavioral disorders within the at-risk group. Conclusion Our data suggest that compared with children of families without BPD, children of parents with BPD may be at greater risk for obstetrical complications, particularly those that occur during the prenatal period; however, at this early follow-up period factors other than obstetrical complications appear to contribute to the differences in rates of psychiatric disorders between these groups.

Creativity in familial bipolar disorder

Studies have demonstrated relationships between creativity and bipolar disorder (BD) in individuals, and suggested familial transmission of both creativity and BD. However, to date, there have been no studies specifically examining creativity in offspring of bipolar parents and clarifying mechanisms of intergenerational transmission of creativity. We compared creativity in bipolar parents and their offspring with BD and bipolar offspring with attention-deficit/hyperactivity disorder (ADHD) with healthy control adults and their children. 40 adults with BD, 20 bipolar offspring with BD, 20 bipolar offspring with ADHD, and 18 healthy control parents and their healthy control children completed the Barron–Welsh Art Scale (BWAS), an objective measure of creativity. Adults with BD compared to controls scored significantly (120%) higher on the BWAS Dislike subscale, and non-significantly (32%) higher on the BWAS Total scale. Mean BWAS Dislike subscale scores were also significantly higher in offspring with BD (107% higher) and offspring with ADHD (91% higher) than in healthy control children. Compared to healthy control children, offspring with BD had 67% higher and offspring with ADHD had 40% higher BWAS Total scores, but these differences failed to reach statistical significance when adjusted for age. In the bipolar offspring with BD, BWAS Total scores were negatively correlated with duration of illness. The results of this study support an association between BD and creativity and contribute to a better understanding of possible mechanisms of transmission of creativity in families with genetic susceptibility for BD. This is the first study to show that children with and at high risk for BD have higher creativity than healthy control children. The finding in children and in adults was related to an enhanced ability to experience and express dislike of simple and symmetric images. This could reflect increased access to negative affect, which could yield both benefits with respect to providing affective energy for creative achievement, but also yield liabilities with respect to quality of interpersonal relationships or susceptibility to depression.

Trouble déficitaire attentionnel avec hyperactivité et trouble bipolaire. Une revue

The future of children suffering from Attention Deficit Hyperactivity Disorder (ADHD) remains discussed. This article questions about ADHD being a prodromal sign of adults'Bipolar Disorder (BD). Therefore we aim to clarify the links between these two disorders. It appears that there is an association between them. This is shown by an elevated comorbidity, a familial association, a higher risk of BD in the future of the ADHD patients. The presence of an ADHD (especially some sub-types) can be considered as a clinical predictive factor for a later BD. Moreover, BDs present some common features in this context. Finally, data from genetic familial studies suggest that the ADHD + BD association is a distinct familial sub-type and may be related to what some have termed childhood-onset BD. Thus these links raise nosological questions and may have important practical impacts.