Endophenotype For Bipolar Disorder Research Articles

Neurocognitive functions in siblings of patients with bipolar disorder

ObjectivesSome studies suggest that there are deficits in neurocognitive functions in the euthymic phase of bipolar disorder and healthy relatives of patients with bipolar disorder and that these neurocognitive disorders may be the endophenotype for bipolar disorder. This study aimed to evaluate the neurocognitive functions of unaffected siblings of patients with bipolar disorder compared with the healthy controls. MethodsThe study included the unaffected siblings of patients with bipolar disorder (n = 75) and healthy volunteers without a family history of bipolar disorder (n = 50). The Structured Clinical Interview for DSM-IV (SCID-I) was administered to each individual to investigate the diagnosis of Axis-I psychiatric disorders according to DSM-IV. The Judgment of Line Orientation Test, the Auditory Verbal Learning Test, the Serial Digit Learning Test, the Stroop Color Word Test, and the Trail Making Test were used to evaluate neurocognitive functions. ResultsOur study found no difference between the groups regarding processing speed, set-shifting, and mental flexibility. However, unaffected siblings of patients with bipolar disorder had significantly worse performance than healthy controls in verbal learning and memory, response inhibition, and visuospatial function. ConclusionsThis study suggests that visuospatial function, response inhibition, verbal learning, and memory may be endophenotypic markers for bipolar disorder.

Processing speed - A potential candidate cognitive endophenotype for bipolar disorder.

Bipolar disorder (BD) is a chronic multifactorial disorder that presents with cognitive impairment as one of its main features, in patients as well as in their first-degree relatives. However, the profile of cognitive dysfunction in BD patients and their relatives is not yet well defined. Various neurocognitive deficits have been proposed as endophenotypes for BD. In the present study, we explored the susceptibility to neurocognitive deficits in BD patients and their siblings compared to healthy controls. A sample consisting of patients diagnosed with BD (N=37), their unaffected siblings (N=30) and a healthy control group (N=39) was assessed using the Brief Assessment of Cognition for Affective Disorders (BAC-A) battery of tests in various cognitive domains: memory, processing speed, working memory, reasoning and problem solving, and affective processing. Compared to healthy controls, BD patients and their unaffected siblings showed deficits in attention and motor speed, or processing speed as measured by the Symbol coding task (p = 0.008), as well as a similar degree of impairment (p = 1.000). The lack of statistically significant findings in the other cognitive domains could be related to differences in task difficulty. Most patients were taking psychotropic medication with varying effects on cognition and being treated as outpatients, implying a currently higher level of functioning, which may limit extrapolation of the sample to the general population of BD patients. These results support the view of considering processing speed as an endophenotype for bipolar disorder.

Assessment of the validity and feasibility of a novel virtual reality test of emotion regulation in patients with bipolar disorder and their unaffected relatives

BackgroundEmotion dysregulation has been suggested as an endophenotype of bipolar disorder (BD). Neuroimaging studies show aberrant neural activity during emotion regulation in remitted patients with BD and their unaffected first-degree relatives (UR) compared to healthy controls (HC). However, behavioural studies produce conflicting - generally negative findings - possibly due to limited sensitivity and ecological validity of current behavioural paradigms. MethodsThis study aimed to explore emotion regulation in BD (n = 30) and UR (n = 26) relative to HC (n = 47) by using a novel emotion regulation task in virtual reality (VR). Participants were instructed to either react naturally to, or dampen, their emotional response to highly positive or highly negative scenarios presented in first-person 360-degree spherically camera-recorded VR environments. Participants also completed a more traditional computerised task of emotion regulation for comparison purposes. ResultsPatients with BD exhibited difficulties with down-regulating their negative emotions in the VR paradigm compared to HC and UR (ps ≤ .04), whereas UR did not differ from HC (p = .97). There was no emotion regulation difference between groups in the more traditional computerised task (ps ≥ .40). LimitationsThe small sample size limits generalisability. ConclusionsThe results suggest trait-related reduced ability to down-regulate negative emotions in BD patients compared to HC in the VR paradigm, but not in the more traditional task of emotion regulation. This may indicate that VR provides a more sensitive measure relative to traditional paradigms. The findings provided no support for aberrant emotional regulation as an endophenotype of BD given the normal emotion regulation performance in UR.

The Influence of 5-HTTLPR, BDNF Rs6265 and COMT Rs4680 Polymorphisms on Impulsivity in Bipolar Disorder: The Role of Gender.

Impulsivity has been proposed as an endophenotype for bipolar disorder (BD); moreover, impulsivity levels have been shown to carry prognostic significance and to be quality-of-life predictors. To date, reports about the genetic determinants of impulsivity in mood disorders are limited, with no studies on BD individuals. Individuals with BD and healthy controls (HC) were recruited in the context of an observational, multisite study (GECOBIP). Subjects were genotyped for three candidate single-nucleotide polymorphisms (SNPs) (5-HTTLPR, COMT rs4680, BDNF rs6265); impulsivity was measured through the Italian version of the Barratt Impulsiveness Scale (BIS-11). A mixed-effects regression model was built, with BIS scores as dependent variables, genotypes of the three polymorphisms as fixed effects, and centers of enrollment as random effect. Compared to HC, scores for all BIS factors were higher among subjects with euthymic BD (adjusted β for Total BIS score: 5.35, p < 0.001). No significant interaction effect was evident between disease status (HC vs. BD) and SNP status for any polymorphism. Considering the whole sample, BDNF Met/Met homozygosis was associated with lower BIS scores across all three factors (adjusted β for Total BIS score: −10.2, p < 0.001). A significant 5-HTTLPR x gender interaction was found for the SS genotype, associated with higher BIS scores in females only (adjusted β for Total BIS score: 12.0, p = 0.001). Finally, COMT polymorphism status was not significantly associated with BIS scores. In conclusion, BD diagnosis did not influence the effect on impulsivity scores for any of the three SNPs considered. Only one SNP—the BDNF rs6265 Met/Met homozygosis—was independently associated with lower impulsivity scores. The 5-HTTLPR SS genotype was associated with higher impulsivity scores in females only. Further studies adopting genome-wide screening in larger samples are needed to define the genetic basis of impulsivity in BD.

Prefrontal-limbic-striatum dysconnectivity associated with negative emotional endophenotypes in bipolar disorder during depressive episodes

BackgroundThe prefrontal-limbic-subcortical network has been suggested as an important circuitry in the pathophysiology underlying bipolar disorder during depressive episodes (BDD). However, the relationships between disrupted prefrontal-limbic-subcortical connection and the emotional endophenotypes in BDD patients remain largely unclear. MethodsForty-three BDD patients and 63 matched healthy controls (HCs) underwent the resting-state functional magnetic resonance imaging scan. The altered clusters were first identified by using a spatial pairwise clustering method and then were extracted as regions of interest to calculate the functional connectivity (FC). Group comparisons were conducted to identify the abnormal FCs. Classification analysis was employed to examine whether the altered FCs could distinguish BDD from HCs. The relationships between FC alterations and the emotional endophenotypes as measured by the Affective Neuroscience Personality Scales (ANPS) were further detected in BDD. ResultsCompared with HCs, BDD patients showed abnormal FCs in the prefrontal-limbic-striatum circuit. Importantly, the altered FCs yielded 84.91% accuracy (p< 1/5000) with 93.65% sensitivity and 72.09% specificity in differentiating between BDD and HCs. Moreover, the decreased FCs in the prefrontal-striatum and prefrontal-limbic systems were positively correlated with negative emotional endophenotypes of Sadness and Fear scores. ConclusionsThe findings demonstrated that prefrontal-limbic-striatum disconnection may be identified as a potential effective biomarker for BDD, which could help further explain the neurobiological mechanisms underlying BDD.

Is processing speed a valid neurocognitive endophenotype in bipolar disorder? Evidence from a longitudinal, family study

BackgroundSubstantial evidence supports the existence of neurocognitive endophenotypes in bipolar disorder (BD), but very few longitudinal studies have included unaffected relatives. In a 5-year, follow-up, family study, we have recently suggested that deficits in manual motor speed and visual memory could be endophenotype candidates for BD. We aimed to explore whether this also applies to processing speed. MethodsA sample of 348 individuals, including 163 BD patients, 65 unaffected first-degree relatives (BD-Rel) and 120 genetically unrelated healthy controls (HC), was assessed with the Digit Symbol Substitution Test (DSST) on two occasions over a 2-year period (T1, T2). DSST values were controlled for age, years of education, occupational status, and subsyndromic mood symptoms. Differences between groups were evaluated with ANCOVAs. ResultsAt T1 BD performed significantly worse than HC (p < 0.001; Cohen's d = 1.38) and BD-Rel (p < 0.001; Cohen's d = 0.82). BD-Rel showed an intermediate performance with significant differences with HC (p < 0.01; Cohen's d = 0.50). Similarly, at T2 BD performed significantly worse than HC (p < 0.001; Cohen's d = 1.44) and BD-Rel (p < 0.01; Cohen's d = 0.51). BD-Rel performance was intermediate and significantly lower than that of HC (p < 0.01; Cohen's d = 0.97). A Repeated Measures ANOVA revealed no significant between-group differences in performance over time (p > 0.05). ConclusionsThe results of this longitudinal, family study suggest that impaired processing speed may represent a suitable cognitive endophenotype for BD. Further research on the field is required to confirm these preliminary findings.

For whom the circadian clock ticks? Investigation of PERIOD and CLOCK gene variants in bipolar disorder

ABSTRACT Clock genes play significant roles in the regulation of circadian rhythms, which are thought to be involved in the pathophysiology of neurodegenerative and psychiatric diseases. We aimed to investigate the association of five gene polymorphisms (PER3 VNTR (rs57875989), PER2 rs2304672, CLOCK rs1801260, CLOCK rs10462028, CLOCK rs11932595) with PCR-based methods as potential risk factors in bipolar disorder (BD). We used a multiple testing methodology in BD patients (n = 121) and healthy control individuals (n = 121) of Turkish descent to analyze the effects of these gene variants both as risk factors for the disorder and for the evaluation of these variants in the patient group with multiple subscales. We evaluated the circadian rhythm disturbances and seasonal variations in mood and behavior in BD patients using the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) and Seasonal Pattern Assessment Questionnaire (SPAQ) to enlighten the possible links between these scores and the studied circadian gene variants. The results of our study revealed significant associations: PER3 VNTR (rs57875989) 5/5 repeat genotype displayed a protective effect against BD when compared with 4/4 repeat genotype. Moreover, patients with PER3 VNTR 5/5 repeat genotype displayed a higher ratio of hypomania. PER2 rs2304672 G allele frequency increased the risk for BD. There was no association in terms of genotype/allele frequency comparisons between patients and controls for CLOCK gene variants. However, significant associations were found in patients in terms of clinical and behavioral patterns such as mean age at disease onset and BRIAN total scores enabling some risk stratifications for patients. Our results indicate the significance of circadian gene variants in BD, which need to be confirmed in different studies with larger samples. Thus, the possible endophenotypes of BD can be enlightened and advanced chronotherapeutics approaches can be manipulated in the future for clinical benefit.

Response Processes to Looming Appetitive and Aversive Cues in Euthymic Bipolar Patients and Their First-Degree Relatives: An Exploratory Study.

Background:Patients with bipolar disorder demonstrate increased sensitivity to appetitive/rewarding stimuli even during euthymia. On presentation of arousing pictures, they show a peculiar response, suggesting heightened vigilance. While responding to looming arousing cues, studies show subjects with anxiety spectrum disorders exhibit increased reaction time (RT), explained by the “looming-vulnerability model.” This study aimed to investigate the responses to looming arousing cues in euthymic bipolar patients and their first-degree relatives, as compared to healthy controls.Method:A looming appetitive and aversive cue paradigm was designed for assessing the RT of patients to process appetitive and aversive cues. The behavioral inhibition/activation and sensitivity to reward/punishment amongst the groups were also assessed.Results:The bipolar group showed significantly longer RT to process appetitive cues irrespective of the looming condition. Aversive cues elicited significantly longer RT in both the bipolar group and in first-degree relatives, but only when presented with the looming condition. Significant looming bias was elicited in the bipolar group which suggested a particular cognitive style to looming cues. A composite measure of RT along with sensitivity to reward/punishment distinguishes the bipolar group and their first-degree relatives from the healthy controls.Conclusion:The looming vulnerability model may provide important insights for future exploration of cognitive endophenotypes in bipolar disorder.

Social Cognition and Neuro-cognition in Patients with Bipolar Disorder, Their First-Degree Relatives and Healthy Controls.

Background:Studies focusing on assessing social cognition deficits in schizophrenia have been expanded to bipolar disorder considering the similarities shared between the two conditions. Existing research has identified significant deficits in social cognitive skills independent of mood states and neurocognitive deficits, which could indicate the potentiality of this domain to be an endophenotype for bipolar disorder.Methods:The current study assesses the impairments in social cognition in patients with bipolar disorder and their first degree relatives, simultaneously testing for neurocognition as well, and comparing their performance to healthy controls. Fifty four participants were recruited, with 18 participants in each group. MATRICS Consensus Cognitive Battery was used to test neurocognition and Social Cognition Rating Tool in Indian Setting was administered for testing social cognition.Results:Significant deficits were found in social cognition and neurocognition (at p<.01) in the patient group when compared to both probands and healthy controls but no difference between probands and healthy controls. This finding established impairments in socio-cognitive functioning in remitted patients. Conclusion: The study has identified persistent deficits in social and neuro-cognition despite remission, having significant clinical implications in terms developing remediation programs for social cognition and planning early intervention as social cognition deficits have been identified as potential risk factors.

White Matter Microstructure in Individuals With and At Risk for Bipolar Disorder: Evidence for an Endophenotype From a Voxel-Based Meta-analysis

BackgroundAberrant white matter (WM) microstructure has been proposed as a mechanism underlying bipolar disorder (BD). Given the strong genetic underpinnings of both WM microstructure and BD, such WM aberrations may be not only a disease marker, but also an endophenotype of BD. If so, they should be observable in individuals at risk for BD (AR) (i.e., first-degree relatives). This meta-analysis integrates evidence on perturbed WM microstructure in individuals with or at risk for BD. MethodsA comprehensive search of literature published through April 2020 identified diffusion tensor imaging studies that used a voxel-based approach to compare fractional anisotropy (FA) and radial diffusivity between individuals with BD and/or AR individuals and healthy volunteers. Effect size comparison and conjunction analysis allowed identification of endophenotypes and disease markers of BD. Effects of age, sex, mood state, and psychotropic medication were explored using meta-regressions. ResultsWe included 57 studies in individuals with BD (N = 4631) and 10 in AR individuals (N = 753). Both individuals with and at risk for BD were associated with lower FA in the body and splenium of the corpus callosum. In the BD group, decreased FA and increased radial diffusivity comprised the entire corpus callosum, anterior thalamic radiation, fronto-orbito-polar tracts, and superior longitudinal fasciculus, and were influenced by age, sex, and mood state. Studies with higher proportions of individuals taking lithium or antipsychotics reported smaller FA reductions in BD. ConclusionsFindings suggest that abnormalities in the body and splenium of the corpus callosum may be an endophenotype for BD, and they associate BD with WM tracts relevant for working memory performance, attention, and reward processing.

Non-Affective Memory and Visuomotor Performance as Possible Endophenotypes for Bipolar Disorder

Cognitive impairment is a serious problem in the treatment of bipolar disorder (BD) affective functional recovery. Neuropsychological deficits have been considered as possible intermediate phenotypes for BD. We conducted a cross-sectional study on neuropsychological performance of BD patients, their non-bipolar siblings, and healthy controls (HC).

Does Cognitive Dysfunction in Bipolar Disorder Qualify as a Diagnostic Intermediate Phenotype?-A Perspective Paper.

The present perspective paper addresses and discusses whether cognitive dysfunction in bipolar disorder qualifies as a diagnostic intermediate phenotype using the Robin and Guze criteria of diagnostic validity. The paper reviews current data within (1) delineation of the clinical intermediate phenotype, (2) associations of the intermediate phenotype with para-clinical data such as brain imaging and blood-based data, (3) associations to family history / genetics, (4) characteristics during long-term follow-up, and (5) treatment effects on cognition. In this way, the paper identifies knowledge gaps and suggests recommendations for future research within each of the five areas. Based on the current state of knowledge, we conclude that cognitive dysfunction does not qualify as a diagnostic intermediate phenotype or endophenotype for bipolar disorder, although promising new evidence points to emotion and reward processing abnormalities as possible putative endophenotypes.

The Functional Connectivity Between the Nucleus Accumbens and the Ventromedial Prefrontal Cortex as an Endophenotype for Bipolar Disorder

BackgroundAlterations in functional connectivity between the nucleus accumbens (NAcc) and frontal cortices have been previously associated with the presence of psychiatric syndromes, including bipolar disorder (BD). Whether these alterations are a consequence or a risk factor for mental disorders remains unresolved. MethodsThis study included 35 patients with BD, 30 nonaffected siblings of patients with BD, and 23 healthy control subjects to probe functional connectivity at rest between NAcc and the rest of the brain in a cross-sectional design. Blood oxygen level–dependent time series at rest from NAcc were used as seed region in a voxelwise correlational analysis. The strength of the correlations found was compared across groups after Fisher’s Z transformation. ResultsWe found increased functional connectivity between the NAcc and the ventromedial prefrontal cortex—comprising mainly the subgenual anterior cingulate—in patients compared with healthy control subjects. Participants at increased genetic risk but yet resilient—nonaffected siblings—showed functional connectivity values midway between the former two groups. ConclusionsOur results are indicative of the potential for the connectivity between NAcc and the ventromedial prefrontal cortex to represent an endophenotype for BD.

Comparison of Cognitive Controls in Patients with Bipolar I Disorder and Their Unaffected First-Degree Relatives

Objectives This study intended to identify the deficits of cognitive control among patients with bipolar I disorder and their first-degree relatives, and identify the possibility of cognitive control as an endophenotype of bipolar disorder. Methods The study included three groups: euthymic states pa...

Polygenic Risk Scores and Bipolar Disorder

Bipolar disorder is an affective disorder with mood swings between the pole of depression and the pole of mania. The mechanism of those mood swings has not been completely elucidated yet. According to current scientific knowledge affective episodes are caused by a concatenation between a genetic predisposition and biopsychosocial triggers. Even though diverse genome wide associated gene variants (e.g., single nucleotide polymorphisms of CACNA1C, ANK3 or NCAN) were associated with Bipolar disorder in the last decade, there is still missing heritability. Thus, innovative approaches and endophenotypes of Bipolar disorder must be used to decipher the underlying disease mechanisms of Bipolar disorder. Recently, the Polygenic Risk Score for Schizophrenia was investigated in the lithium response endophenotype of Bipolar disorder. The polygenic score for Schizophrenia was inversely associated with the lithium response phenotype in study participants with Bipolar disorder. Furthermore, there are genetic overlaps between psychiatric diseases, which also demonstrates the importance of cross-disorder design studies to elucidate the missing heritability of Bipolar disorder.

All stressed out? Introducing a German version of the perceived stress scale: Validation, psychometric properties and sample differences in healthy and clinical populations

Heightened impulsivity has been suggested as a possible risk factor for bipolar disorder (BD). However, studies on high-risk populations are scarce and have mainly focused on individuals with a genetic risk. The present study investigated two high-risk samples for BD with regard to several aspects of the impulsivity construct.Unaffected relatives of BD patients (genetically defined high-risk group, N=29) and participants scoring high on the Hypomanic Personality Scale (psychometrically defined high-risk sample, N=25) were being compared to respective control groups (N=27 and N=25) using a multi-method approach. Participants were accessed on the Barratt Impulsiveness Scale-11 (BIS-11, trait impulsivity), the Stop Signal Task (response inhibition), and the Cambridge Gambling Task (impulsive behavior in decision-making processes).Both high-risk groups reported heightened impulsivity on the BIS-11, as well as impulsive decision-making, whereas no significant group differences in response inhibition were observed.Limitations were the lack in specificity of the results for BD and the cross-sectional study design, which does not allow conclusions about the influence of impulsivity on the development of or resilience for BD in risk groups.Our findings support the assumption that increased trait impulsivity and impulsive decision-making are a vulnerability marker for and an endophenotype of BD.

The effect of stimulus strength on binocular rivalry rate in healthy individuals: Implications for genetic, clinical and individual differences studies

Binocular rivalry (BR) occurs when conflicting images concurrently presented to corresponding retinal locations of each eye stochastically alternate in perception. Anomalies of BR rate have been examined in a range of clinical psychiatric conditions. In particular, slow BR rate has been proposed as an endophenotype for bipolar disorder (BD) to improve power in large-scale genome-wide association studies. Examining the validity of BR rate as a BD endophenotype however requires large-scale datasets (n=1000s to 10,000s), a standardized testing protocol, and optimization of stimulus parameters to maximize separation between BD and healthy groups. Such requirements are indeed relevant to all clinical psychiatric BR studies. Here we address the issue of stimulus optimization by examining the effect of stimulus parameter variation on BR rate and mixed-percept duration (MPD) in healthy individuals. We aimed to identify the stimulus parameters that induced the fastest BR rates with the least MPD. Employing a repeated-measures within-subjects design, 40 healthy adults completed four BR tasks using orthogonally drifting grating stimuli that varied in drift speed and aperture size. Pairwise comparisons were performed to determine modulation of BR rate and MPD by these stimulus parameters, and individual variation of such modulation was also assessed. From amongst the stimulus parameters examined, we found that 8cycles/s drift speed in a 1.5° aperture induced the fastest BR rate without increasing MPD, but that BR rate with this stimulus configuration was not substantially different to BR rate with stimulus parameters we have used in previous studies (i.e., 4cycles/s drift speed in a 1.5° aperture). In addition to contributing to stimulus optimization issues, the findings have implications for Levelt's Proposition IV of binocular rivalry dynamics and individual differences in such dynamics.

Evidence that eye-movement profiles do not explain slow binocular rivalry rate in bipolar disorder: support for a perceptual endophenotype.

Presenting conflicting images simultaneously, one to each eye, produces perceptual alternations known as binocular rivalry (BR). Slow BR rate has been proposed as an endophenotype for bipolar disorder (BD) for use in large-scale genome-wide association studies. However, the trait could conceivably reflect eye movement (EM) dysfunction in BD rather than anomalous perceptual processing per se. To address this question, we examined the relationship between EM profiles and BR rate for various stimulus types in BD and healthy subjects. We also examined differences in EM profiles between these groups. Employing a repeated-measures within-subjects design, 20 BD outpatients and 20 age- and sex-matched healthy controls completed EM tasks and separate BR tasks involving a range of stimuli with different drift speeds. The association between each EM measure and BR rate was examined with correlational analyses for all stimulus conditions in both groups. Between-group comparisons were performed to determine any differences in those EM measures. Corresponding Bayesian analyses were also conducted. There were no EM measures that showed a significant relationship with BR rate in either the BD group or the healthy group (P≥7.87×10-3 ), where those EM measures were also significantly different between the BD and healthy groups (P≥1.32×10-2 ). These findings were verified with Bayes factors. The results provide evidence that EM profiles do not explain the slow BR endophenotype for BD, thus indicating that the trait reflects anomalous perceptual processing per se. This perceptual trait can be employed in clinical, genetic, mechanistic and pathophysiological studies.

White matter volumes in youth offspring of bipolar parents

BackgroundStudying youth at high risk of developing bipolar disorder may clarify neurobiological factors associated with vulnerability to this illness. We present here a baseline characterization of brain structure in youth at-risk for bipolar disorder. MethodsMagnetic resonance images were obtained from 115 child and adolescent offspring of bipolar disorder type I subjects and 57 healthy child and adolescent offspring of healthy parents (healthy control offspring). Offspring of parents with bipolar disorder were divided into healthy bipolar offspring (n=47) or symptomatic bipolar offspring (n=68), according to presence or absence of childhood-onset psychopathology. All bipolar offspring were free of major mood and psychotic disorders. Gray (GM) and white matter (WM) volumes were compared between groups using voxel-based morphometry. ResultsNo differences in GM volumes were found across groups. Healthy bipolar offspring presented with decreased WM volumes in areas of the right frontal, temporal and parietal lobes, and in the left temporal and parietal lobes compared to healthy control offspring. Symptomatic bipolar offspring did not present with any differences in WM volumes compared to either healthy bipolar offspring or healthy control offspring. LimitationsCross-sectional design and heterogeneous sample of symptomatic bipolar offspring. ConclusionsWM volume decreases in areas of the frontal, occipital, and parietal lobes are present in bipolar offspring prior to the development of any psychiatric symptoms, and may be a correlate of familial risk to bipolar disorder. In this large cohort, we have not found evidence for regional GM volume abnormalities as an endophenotype for bipolar disorder.

Sleep-wake cycle phenotypes in young people with familial and non-familial mood disorders.

Converging evidence identifies that the offspring of parents with bipolar disorder (BD), individuals at clinical high risk of BD, and young people with recent onset BD may differ from other clinical cases or healthy controls in terms of sleep-wake profiles. However, it is possible that these differences may reflect current mental state, subtype of mood disorder, or familial traits. This study aimed to determine objective and subjective sleep-wake profiles in individuals aged 15-25years with a current major depressive episode, in relation to familial traits. Frequency matching was employed to ensure that each individual with a confirmed family history of BD (FH+) could be compared to four controls who did not have a familial mood disorder (FH-). Pre-selected objective actigraphy and subjective Pittsburgh Sleep Quality Index (PSQI) ratings were compared using one-way analysis of variance (ANOVA) and applying the Benjamini-Hochberg (BH) correction for false discoveries. The sample comprised 60 individuals with a mean age of 19years. The FH+ (n=12) and FH- groups (n=48) differed on three key sleep parameters: mean sleep duration on week nights (P=.049), variability in waking after sleep onset (P=.038), and daily disturbances (PSQI dimension of sleep disturbance and daytime dysfunction; P=.01). The sleep profiles we identified in this study, especially the daily disturbances phenotype, provide support for research into endophenotypes for BD. Also, the findings may offer the opportunity for more tailored, personalized interventions that target specific components of the sleep-wake cycle in individuals with a family history of BD.