Bipolar Phenotype Research Articles

Rewarding Subjective Effects of the NMDAR Antagonist Nitrous Oxide (Laughing Gas) Are Moderated by Impulsivity and Depressive Symptoms in Healthy Volunteers.

BackgroundNitrous oxide (N2O) is an anesthetic gas with both therapeutic and abuse potential. Because N2O is an NMDA receptor (NMDAR) antagonist, its effects are expected to resemble those of the prototypical NMDAR antagonist, ketamine. In this study, we examined the subjective rewarding effects of N2O using measures previously employed in studies of ketamine. We also tested for moderation of these effects by bipolar phenotype, depressive symptoms, and impulsivity.MethodsHealthy volunteers were randomly assigned to either 50% N2O (n = 40) or medical air (n = 40). Self-reported rewarding (liking and wanting), and alcohol-like effects were assessed pre-, peri- and post inhalation.ResultsEffect sizes for the various rewarding/alcohol-like effects of N2O were generally similar to those reported in studies of moderate-dose ketamine. Impulsivity moderated the subjective reinforcing (liking) effects of inhaled gas, while depressive symptoms moderated motivational (wanting [more]) effects. However, depression and impulsivity had opposite directional influences, such that higher impulsivity was associated with higher N2O liking, and higher depression, with lower N2O wanting.ConclusionTo the extent that static (versus longitudinal) subjective rewarding effects are a reliable indicator of future problematic drug use, our findings suggests that impulsivity and depression may predispose and protect, respectively, against N2O abuse. Future studies should examine if these moderators are relevant for other NMDAR antagonists, including ketamine, and novel ketamine-like therapeutic and recreational drugs. Similarities between moderate-dose N2O and moderate-dose ketamine in the intensity of certain subjective effects suggest that N2O may, at least to some extent, serve as substitute for ketamine as a safe and easily implemented experimental tool for probing reward-related NMDAR function and dysfunction in humans.

Quantitative Phase Imaging of Spreading Fibroblasts Identifies the Role of Focal Adhesion Kinase in the Stabilization of the Cell Rear.

Cells attaching to the extracellular matrix spontaneously acquire front–rear polarity. This self-organization process comprises spatial activation of polarity signaling networks and the establishment of a protruding cell front and a non-protruding cell rear. Cell polarization also involves the reorganization of cell mass, notably the nucleus that is positioned at the cell rear. It remains unclear, however, how these processes are regulated. Here, using coherence-controlled holographic microscopy (CCHM) for non-invasive live-cell quantitative phase imaging (QPI), we examined the role of the focal adhesion kinase (FAK) and its interacting partner Rack1 in dry mass distribution in spreading Rat2 fibroblasts. We found that FAK-depleted cells adopt an elongated, bipolar phenotype with a high central body mass that gradually decreases toward the ends of the elongated processes. Further characterization of spreading cells showed that FAK-depleted cells are incapable of forming a stable rear; rather, they form two distally positioned protruding regions. Continuous protrusions at opposite sides results in an elongated cell shape. In contrast, Rack1-depleted cells are round and large with the cell mass sharply dropping from the nuclear area towards the basal side. We propose that FAK and Rack1 act differently yet coordinately to establish front–rear polarity in spreading cells.

Identifying novel associations in GWAS by hierarchical Bayesian latent variable detection of differentially misclassified phenotypes

BackgroundHeterogeneity in the definition and measurement of complex diseases in Genome-Wide Association Studies (GWAS) may lead to misdiagnoses and misclassification errors that can significantly impact discovery of disease loci. While well appreciated, almost all analyses of GWAS data consider reported disease phenotype values as is without accounting for potential misclassification.ResultsHere, we introduce Phenotype Latent variable Extraction of disease misdiagnosis (PheLEx), a GWAS analysis framework that learns and corrects misclassified phenotypes using structured genotype associations within a dataset. PheLEx consists of a hierarchical Bayesian latent variable model, where inference of differential misclassification is accomplished using filtered genotypes while implementing a full mixed model to account for population structure and genetic relatedness in study populations. Through simulations, we show that the PheLEx framework dramatically improves recovery of the correct disease state when considering realistic allele effect sizes compared to existing methodologies designed for Bayesian recovery of disease phenotypes. We also demonstrate the potential of PheLEx for extracting new potential loci from existing GWAS data by analyzing bipolar disorder and epilepsy phenotypes available from the UK Biobank. From the PheLEx analysis of these data, we identified new candidate disease loci not previously reported for these datasets that have value for supplemental hypothesis generation.ConclusionPheLEx shows promise in reanalyzing GWAS datasets to provide supplemental candidate loci that are ignored by traditional GWAS analysis methodologies.

Eye-gaze processing in the broader bipolar phenotype revealed by electrical neuroimaging

Previous studies have documented atypical brain responses to faces in individuals with bipolar disorder (BD) and in their relatives. In view of previous findings of atypical face processing in youths at risk for BD, the aim of this study was to examine whether BD patients and offspring would show differential activation in networks of the social brain when processing eye-gaze.Data from 18 euthymic BD patients and 18 offspring, as well as 36 age-matched healthy controls, were collected using a delayed face-matching paradigm, event related potentials and electrical neuroimaging methods.The P200 component, which is implicated in facial cues decoding, differentiated the BD groups from their age-matched controls. P200 source reconstruction indicates impairments conveyed by eye-contact in a network involved in experiencing others’ social intentions in BD patients (supplementary motor cortex, precentral gyrus, inferior parietal lobe), and the engagement of compensatory prefrontal mechanisms for modulating these functions in BD offspring. When viewing faces that had an averted gaze, BD patients and offspring showed a hypo-activation, compared to controls, particularly in regions involved in experiencing others’ feelings (post-central gyrus in BD patients / ventral premotor cortex in offspring). Therefore, the neural mechanism for decoding shifts in eye-gaze may be a familial characteristic of BD.

RGC-32 regulates expression of insulin-like growth factor binding proteins in astrocytes

Abstract Response gene to complement (RGC)-32 plays an important role in the mediation of TGF-β downstream effects and activation of cell cycle. During experimental autoimmune encephalomyelitis (EAE), RGC-32 knock-out (KO) mouse astrocytes displayed an elongated, bipolar phenotype, resembling immature astrocytes and glial progenitors whereas those from wild-type (WT) mice had a reactive, hypertrophied phenotype, suggesting a role for RGC-32 in astrocyte differentiation. To gain more insight into the role played by RGC-32 in astrocytes, we investigated the transcriptional profile induced by TGF-β in astrocytes using qPCR arrays. The majority of genes differentially expressed were related to cell growth, extracellular matrix remodeling and signal transduction. Among them, a group of genes belonging to the family of insulin-like growth factor binding proteins (IGFBPs) and insulin-like growth factors (IGFs) were found to be most significantly regulated by RGC-32. The IGFBP category includes IGFBP2, IGFBP3, IGFBP6 and connective tissue growth factor (CTGF). Using Real-time PCR and Western Blotting, we confirmed the differential expression of these genes in RGC-32 KO astrocytes after TGF-β stimulation. When glial fibrillary acidic protein (GFAP) and CTGF levels were compared between WT and KO astrocytes after TGF-β stimulation, significantly lower levels of mRNA and protein expression were found in RGC-32 KO astrocytes. These data suggest that TGF-β stimulation of CTGF is RGC-32 dependent and that RGC-32 plays a role in the regulation of CTGF downstream effects. The differential regulation of IGFBPs and GFAP suggests that they might be responsible for the lack of astrocyte differentiation seen in RGC-32 KO mice during EAE.

F84. Subjective Responses to Amphetamine in Adolescents With a Bipolar Phenotype

Individuals vary in their acute subjective responses drugs in ways that influence future use and misuse. One source of variation is psychiatric symptomatology. There is epidemiological and laboratory-based evidence that adolescents who report high rates of hypomania are at risk for drug abuse. In the present study, we examined subjective and physiological responses to acute oral d-amphetamine in 18-19-year-olds self-reporting a bipolar phenotype (BPP).

RGC-32 regulates reactive astrocytosis and extracellular matrix deposition in experimental autoimmune encephalomyelitis

Extracellular matrix (ECM) deposition in active demyelinating multiple sclerosis (MS) lesions may impede axonal regeneration and can modify immune reactions. Response gene to complement (RGC)-32 plays an important role in the mediation of TGF-β downstream effects, but its role in gliosis has not been investigated. To gain more insight into the role played by RGC-32 in gliosis, we investigated its involvement in TGF-β-induced ECM expression and the upregulation of the reactive astrocyte markers α-smooth muscle actin (α-SMA) and nestin. In cultured neonatal rat astrocytes, collagens I, IV, and V, fibronectin, α-SMA, and nestin were significantly induced by TGF-β stimulation, and RGC-32 silencing resulted in a significant reduction in their expression. Using astrocytes isolated from RGC-32 knock-out (KO) mice, we found that the expression of TGF-β-induced collagens I, IV, and V, fibronectin, and α-SMA was significantly reduced in RGC-32 KO mice when compared with wild-type (WT) mice. SIS3 inhibition of Smad3 phosphorylation was also associated with a significant reduction in RGC-32 nuclear translocation and TGF-β-induced collagen I expression. In addition, during experimental autoimmune encephalomyelitis (EAE), RGC-32 KO mouse astrocytes displayed an elongated, bipolar phenotype, resembling immature astrocytes and glial progenitors whereas those from WT mice had a reactive, hypertrophied phenotype. Taken together, our data demonstrate that RGC-32 plays an important role in mediating TGF-β-induced reactive astrogliosis in EAE. Therefore, RGC-32 may represent a new target for therapeutic intervention in MS.

Morphometric analysis of spread platelets identifies integrin \u03b1IIb\u03b23-specific contractile phenotype

Haemostatic platelet function is intimately linked to cellular mechanics and cytoskeletal morphology. How cytoskeletal reorganizations give rise to a highly contractile phenotype that is necessary for clot contraction remains poorly understood. To elucidate this process in vitro, we developed a morphometric screen to quantify the spatial organization of actin fibres and vinculin adhesion sites in single spread platelets. Platelets from healthy donors predominantly adopted a bipolar morphology on fibrinogen and fibronectin, whereas distinguishable, more isotropic phenotypes on collagen type I or laminin. Specific integrin αIIbβ3 inhibitors induced an isotropic cytoskeletal organization in a dose-dependent manner. The same trend was observed with decreasing matrix stiffness. Circular F-actin arrangements in platelets from a patient with type II Glanzmann thrombasthenia (GT) were consistent with the residual activity of a small number of αIIbβ3 integrins. Cytoskeletal morphologies in vitro thus inform about platelet adhesion receptor identity and functionality, and integrin αIIbβ3 mechanotransduction fundamentally determines the adoption of a bipolar phenotype associated with contraction. Super-resolution microscopy and electron microscopies further confirmed the stress fibre-like contractile actin architecture. For the first time, our assay allows the unbiased and quantitative assessment of platelet morphologies and could help to identify defective platelet behaviour contributing to elusive bleeding phenotypes.

DeepBipolar: Identifying genomic mutations for bipolar disorder via deep learning.

Bipolar disorder, also known as manic depression, is a brain disorder that affects the brain structure of a patient. It results in extreme mood swings, severe states of depression, and overexcitement simultaneously. It is estimated that roughly 3% of the population of the United States (about 5.3 million adults) suffers from bipolar disorder. Recent research efforts like the Twin studies have demonstrated a high heritability factor for the disorder, making genomics a viable alternative for detecting and treating bipolar disorder, in addition to the conventional lengthy and costly postsymptom clinical diagnosis. Motivated by this study, leveraging several emerging deep learning algorithms, we design an end-to-end deep learning architecture (called DeepBipolar) to predict bipolar disorder based on limited genomic data. DeepBipolar adopts the Deep Convolutional Neural Network (DCNN) architecture that automatically extracts features from genotype information to predict the bipolar phenotype. We participated in the Critical Assessment of Genome Interpretation (CAGI) bipolar disorder challenge and DeepBipolar was considered the most successful by the independent assessor. In this work, we thoroughly evaluate the performance of DeepBipolar and analyze the type of signals we believe could have affected the classifier in distinguishing the case samples from the control set.

Wnt and GSK3 Signaling Pathways in Bipolar Disorder: Clinical and Therapeutic Implications.

The neurobiology of bipolar disorder, a chronic and systemic ailment is not completely understood. The bipolar phenotype manifests in myriad ways, and psychopharmacological agents like lithium have long term beneficial effects. The enzyme glycogen synthase kinase 3 (GSK3) has come into focus, as lithium and several other mood stabilizing medications inhibit its activity. This kinase and its key upstream modulator, Wnt are dysregulated in mood disorders and there is a growing impetus to delineate the chief substrates involved in the development of these illnesses. In May 2016, a comprehensive literature search was undertaken which revealed that there is over activity of GSK3 in bipolar disorder with deleterious downstream effects like proinflammatory status, increased oxidative stress, and circadian dysregulation leading to declining neurotrophic support and enhanced apoptosis of neural elements. By developing specific GSK3 inhibitors the progressive worsening in bipolar disorder can be forestalled with improved prospects for the sufferers.

M25 - Investigation of Relationships Between Bipolar Disorder Phenotypes And Genome-Wide Significant Loci From PGC2 Schizophrenia

Background Schizophrenia (SZ) and Bipolar disorder (BD) show evidence for partial overlap in phenotypic and genetic influences based on family, twins, adoption and Psychiatric Genetic Consortium (PGC) studies. They have lifetime prevalence of about 1% and 2.4%, and heritability estimates of 60-80% and 40-70%, respectively. In the last decade BD has been investigated using dimensional structuring of psychoses based on symptomatic-functional checklists that provides reliable approach to phenotypic assessment. Recent research suggests moving towards developing Phenotype-based Genetic Association Studies. In this approach, patients will only be put into groups consisting of others with symptoms similar to their own. Canonical Correlation Analysis (CCA) is statistical technique designed to identify relationships (usually hidden) between two sets of variables. We use CCA to combine genotypic and phenotypic variables and measure correlation between those sets. This analysis estimates canonical correlation between psychotic symptoms measured using validated item check list (OPCRIT), and genome-wide significant (GWS) loci from PGC2 schizophrenia. Methods For our analysis we used phenotype and genetic data for 5,507 BD cases. Imputation of genetic data was performed with 1000Genomes (Phase 3, 2014) then quality control was applied (INFO>0.8, HWE>1e-6, MAF>0.01). Additional quality control was performed on phenotypic symptom coverage. CCA was employed as implemented in R, using package “CCA” with GWS loci from PGC2 SZ and OPCRIT items. SNPs were standardised and adjusted for 10 population covariates calculated from imputed data using principal component approach prior to CCA. Results Canonical correlation analysis was run on 4422 cases on 89 available GWS PGC2 SZ SNPs or their proxies (with r2>0.6). 60 phenotypic variables were taken from OPCRIT measurements including mood disturbance, biological indices, atypical depression, substance use, psychosis and social functioning. We found no significant canonical correlations indicating absence of hidden sub-clusters at individual symptom level of BD associated with SZ GWS loci. Discussion Our analysis was focused to find correlation from bipolar phenotype by using OPCRIT questionnaire and GWS SZ loci from PGC2. We have shown that there were no significant canonical correlation coefficients suggesting that there is no direct association between SZ associated genetic loci and BP at individual symptom level. CCA is canonical correlation analysis is one of potential of data-driven approaches to identify hidden genotype-phenotype relationships. It provides opportunities to generate and test different hypotheses and understand more about complex architecture of psychiatric disorders. In the next stage we plan to extend our analysis to more fine grained systematic descriptors of BD and test for correlation with genetic profiles from a number of co-morbid disorders, as well as the full range of phenotypic and genetic data that are available.

Conditional Knockout of Ankyrin-G In The Mouse Forebrain Results In Bipolar-Like Behavior

Background To date, few animal models of bipolar disorder have been developed, and fewer still are based on genetic loci despite the fact that genome wide association studies (GWAS) have now identified a number of candidate genes. Across studies, one of the most consistent findings is in ANK3, which encodes Ankyrin-G, a protein that organizes sodium and potassium channels at the axon initial segments (AIS). To explore the potential pathophysiological role of Ankyrin-G in bipolar disorder, we generated a mouse model with conditional deletion of all major isoforms of Ank3 in the adult forebrain. Methods Ank3 flox mice (Ank3 flox/flox) were crossed with Camk2a-Cre mice, which begin to express Cre in the forebrain at post-natal day 19. Beginning at 3 months of age, the behaviors of conditional knockout mice and control littermates were assessed in a 24 hour locomotor activity test, open field, elevated plus maze, forced swim test, and prepulse inhibition test. In a second cohort, behavioral effects of two mood-stabilizers, lithium and valproic acid, as well as the stimulant methylphenidate were assessed. In separate cohorts, mice were exposed to 14 day cycles of social defeat stress, a commonly used paradigm that results in a depression-like phenotype among wild-type mice. Finally, the behavior of heterozygous mice was characterized at baseline and then after exposure to social defeat stress and treatment with the antidepressant fluoxetine. Results Conditional knockout of Ank3 (cKO) resulted in striking hyperactivity, sleep-cycle disruption, and decreased anxiety-like behaviors. Ank3 cKO mice were indistinguishable from controls in prepulse inhibition, where deficits are often found in models of schizophrenia. Consistent with a mania-like phenotype, the hyperactivity of Ank3 cKO mice was normalized by treatment with lithium and valproic acid. When treated with methylphenidate, both Ank3 cKO and control mice displayed increased locomotor activity. After 14 days of social defeat, Ank3 and control mice displayed a depression-like phenotype. Consistent with a bipolar depression-like phenotype, Ank3 cKO mice expose to social defeat were indistinguishable from socially defeated controls. When allowed to recover for 14 days and then re-exposed to social defeat, Ank3 cKO mice, but not controls, displayed evidence of ‘cycling’ between mania and depression-like behaviors. Finally, we found that Ank3 heterozygous mice are indistinguishable from controls at baseline. However, Ank3 heterozygous mice appear to be more sensitive to both social defeat stress and the antidepressant fluoxetine. Discussion Overall cKO of Ank3, a genetic loci that has repeatedly been implicated in human bipolar disorder and is involved in organization of the axon initial segment, recapitulates major aspects of both bipolar mania and bipolar depression. We believe that this novel genetic model may provide a better understanding of the role of of Ankyrin-G in the brain, further insights into the molecular biology of bipolar disorder, and allow for the development of novel therapeutic approaches.

Screening the risk of bipolar spectrum disorders: Validity evidence of the Mood Disorder Questionnaire in adolescents and young adults

The aim of this study was to gather sources of validity evidence of the Mood Disorder Questionnaire (MDQ) in young adults for its use as a screening tool for bipolar spectrum disorders. The sample was composed of 1002 participants, 268 men (26.7%). The mean age of participants was 21.1 years (SD=3.9). The results showed that between 3 and 59% of the sample reported some hypomanic experience. Gender differences were found in the total score of the MDQ. The analysis of the internal structure by exploratory factor analysis yielded 2 factors, called Energy-Activity and Disinhibition-Attention. This dimensional structure was replicated in the exploratory structural equation modelling (ESEM), and also had factorial equivalence by gender. Participants who met the cut-off points of the MDQ reported a worse perceived mental health status and more consummatory and anticipatory pleasure, compared to the low scores group. These findings indicate that the MDQ has adequate psychometric properties in non-clinical samples, and could be useful as a screening tool in psychopathology, with the possibility of optimising strategies for early identification and prevention in individuals at high risk for bipolar disorders. Future studies should further explore the role of subclinical bipolar phenotype and conduct longitudinal studies in samples of the general population.

Self-images in the present and future: Role of affect and the bipolar phenotype

BackgroundBipolar Spectrum Disorder (BPSD) is associated with changes in self-related processing and affect, yet the relationship between self-image and affect in the BPSD phenotype is unclear. Methods47 young adults were assessed for hypomanic experiences (BPSD phenotype) using the Mood Disorders Questionnaire. Current and future self-images (e.g. I am… I will be…) were generated and rated for emotional valence, stability, and (for future self-images only) certainty. The relationship between self-image ratings and measures of affect (depression, anxiety and mania) were analysed in relation to the BPSD phenotype. ResultsThe presence of the BPSD phenotype significantly moderated the relationship between (1) affect and stability ratings for negative self-images, and (2) affect and certainty ratings for positive future self-images. Higher positivity ratings for current self-images were associated with lower depression and anxiety scores. LimitationsThis was a non-clinical group of young adults sampled for hypomanic experiences, which limits the extension of the work to clinical levels of psychopathology. This study cannot address the causal relationships between affect, self-images, and BPSD. Future work should use clinical samples and experimental mood manipulation designs. ConclusionsBPSD phenotype can shape the relationship between affect and current and future self-images. This finding will guide future clinical research to elucidate BPSD vulnerability mechanisms and, consequently, the development of early interventions.

Screening the risk of bipolar spectrum disorders: Validity evidence of the Mood Disorder Questionnaire in adolescents and young adults.

The aim of this study was to gather sources of validity evidence of the Mood Disorder Questionnaire (MDQ) in young adults for its use as a screening tool for bipolar spectrum disorders. The sample was composed of 1,002 participants, 268 men (26.7%). The mean age of participants was 21.1 years (SD=3.9). The results showed that between 3 and 59% of the sample reported some hypomanic experience. Gender differences were found in the total score of the MDQ. The analysis of the internal structure by exploratory factor analysis yielded 2 factors, called Energy-Activity and Disinhibition-Attention. This dimensional structure was replicated in the exploratory structural equation modeling (ESEM), and also had factorial equivalence by gender. Participants who met the cut-off points of the MDQ reported a worse perceived mental health status and more consummatory and anticipatory pleasure, compared to the low scores group. These findings indicate that the MDQ has adequate psychometric properties in non-clinical samples, and could be useful as a screening tool in psychopathology, with the possibility of optimizing strategies for early identification and prevention in individuals at high risk for bipolar disorders. Future studies should further explore the role of subclinical bipolar phenotype and conduct longitudinal studies in samples of the general population.

S.21.03 The bipolar phenotypes and big data – future potential

S.21.03 The bipolar phenotypes and big data – future potential

Blurred boundaries in diagnostic criteria present a challenge to optimal treatment

Early, accurate diagnosis may hold the key to achieving significant improvements in the prospects for patients with bipolar disorder. However, the broad characterisation of the bipolar phenotype to encompass bipolar spectrum and bipolar not otherwise specified (NOS) makes differential diagnosis more challenging. These issues were among those explored at the 13th Latest Advances in Psychiatry Symposium held in London in March, which took biopsychosocial approaches to psychiatry as its overarching theme. Steve Titmarsh reports.

Leprosy as a Model of Immunity

Leprosy displays a spectrum of clinical manifestations, such as lepromatous and tuberculoid leprosy, and type I and II lepra reactions, which are thought to be a reflection of the host's immunological response against Mycobacterium leprae. Therefore, differential recognition of M. leprae, as well as its degraded components, and subsequent activation of cellular immunity will be an important factor for the clinical manifestation of leprosy. Although M. leprae mainly parasitizes tissue macrophages in the dermis and the Schwann cells of peripheral nerves, the presence of M. leprae in other organs, such as the liver, may also play important roles in the further modification of seesaw-like bipolar phenotypes of leprosy. Thus, leprosy is an exciting model for investigating the role of the human immune system in host defense and susceptibility to infection.

A systematic review of gender‐specific rates of unipolar and bipolar disorders in community studies of pre‐pubertal children

Gender-specific rates of unipolar and bipolar disorders are well established for cases with post-pubertal onset. However, there is less certainty about these rates in pre-pubertal children. We undertook a systematic review of community studies that report gender-specific rates for unipolar and bipolar disorders in young children, particularly cases of major depression and mania. Computer databases (Medline, EMBASE, Index to Theses, and PsychInfo) were searched for non-clinical observational studies using recognized diagnostic criteria to identify unipolar and bipolar disorders in children aged ≤ 12 years. A meta-analysis was undertaken to calculate pooled odds ratios (ORs) for caseness for major depression by gender. The limited data on bipolar disorder were summarized. Analysis of 12 studies (>15,000 children), indicated that the community prevalence of unipolar disorders was higher in boys (1.3%) than in girls (0.8%). Rates of major depression were low (0.61%), but boys were significantly more likely to meet diagnostic criteria than girls (OR = 1.61; 95% confidence interval: 1.11-2.35). Five studies, assessing >5,000 children, identified only one case with a probable diagnosis of mania. This systematic review suggests that boys aged ≤ 12 years are significantly more likely to experience major depression than girls. However, in younger children, community rates of major depression are low, and it is frequently suggested (but not proven) that most cases are comorbid. The absence of mania suggests either that childhood bipolar phenotypes do not resemble post-pubertal onset cases or that there are problems of case ascertainment.

Daily rest-activity patterns in the bipolar phenotype: A controlled actigraphy study

This study assessed daily rest-activity patterns in euthymic, medication-naïve bipolar phenotype individuals. The Mood Disorder Questionnaire was used to identify 19 bipolar phenotype individuals and 21 controls. Participants wore an Actiwatch-L for 2 weeks to assess their sleep behaviour and circadian rest-activity rhythmicity. Bipolar phenotype individuals had increased movement during sleep, as assessed by the fragmentation index, greater activity levels during their least active 5 h (2 am–7 am), and lower circadian relative amplitude compared to controls. Higher activity levels during sleep affecting circadian amplitude in young adults with the bipolar phenotype may be associated with vulnerability for developing mood disorder.