Abnormalities In Bipolar Disorder Research Articles

Reduced myelin content in bipolar disorder: A study of inhomogeneous magnetization transfer

BackgroundPrevious neuroimaging and pathological studies have found myelin-related abnormalities in bipolar disorder (BD), which prompted the use of magnetic resonance (MR) imaging technology sensitive to neuropathological changes to explore its neuropathological basis. We holistically investigated alterations in myelin within BD patients by inhomogeneous magnetization transfer (ihMT), which is sensitive and specific to myelin content. MethodsThirty-one BD and 42 healthy controls (HC) were involved. Four MR metrics, i.e., ihMT ratio (ihMTR), pseudo-quantitative ihMT (qihMT), magnetization transfer ratio and pseudo-quantitative magnetization transfer (qMT), were compared between groups using analysis methods based on whole-brain voxel-level and white matter regions of interest (ROI), respectively. ResultsThe voxel-wise analysis showed significantly inter-group differences of ihMTR and qihMT in the corpus callosum. The ROI-wise analysis showed that ihMTR, qihMT, and qMT values in BD group were significantly lower than that in HC group in the genu and body of corpus callosum, left anterior limb of the internal capsule, left anterior corona radiate, and bilateral cingulum (p < 0.001). And the qihMT in genu of corpus callosum and right cingulum were negatively correlated with depressive symptoms in BD group. LimitationsThis study is based on cross-sectional data and the sample size is limited. ConclusionThese findings suggest the reduced myelin content of anterior midline structure in the bipolar patients, which might be a critical pathophysiological feature of BD.

Inflammatory Biomarkers, Cognitive Functioning, and Brain Imaging Abnormalities in Bipolar Disorder: A Systematic Review.

Recent studies have pointed to neuroinflammation and neurotrophic factors as crucial mediators in the pathophysiology origins of mood disorders. The aim of this review is to assess the potential association between cognitive impairment, brain imaging abnormalities, and inflammatory biomarkers in patients affected by bipolar disorder (BD). Following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, we systematically searched PubMed, Google Scholar, Scopus, and Web of Science databases, with no year restriction, up until August 2023, for human studies that examined the relationship between inflammatory markers and cognitive impairment in BD patients. Studies based on neuroimaging, such as MRI, DTI, and fMRI, were also included, along with those examining the moderating role of specific inflammatory markers in the alteration of the brain. 59 human clinical studies satisfied the criteria for consideration. Most of the studies reviewed concur that inflammatory state, measured by peripheral blood levels of CRP and cytokines, constitutes an important contributor to cognitive impairment observed in patients with BD. Robust evidence indicates an association between cognitive impairment and CRP, IL-1RA, IL-6, and TNF-α with its receptors, whereas there is no convincing evidence for the involvement of other neuroinflammatory biomarkers. Neuroimaging studies suggest that brain structural/functional abnormalities seen in BD could also be linked to a neuroinflammatory condition. Current data provide evidence of a link between cognitive impairments observed in BD patients and mechanisms of neuroinflammation. Emerging evidence indicates that systemic inflammation might also play an important role in the deterioration of brain structures critical to cognitive functions in patients with BD. The convergence of findings across these studies strengthens our understanding of the complex neurobiological underpinnings of these disorders. Identification of BD specific inflammatory markers may be of assistance for future early therapeutic interventions.

Marked alteration of phosphoinositide signaling-associated molecules in postmortem prefrontal cortex with bipolar disorder.

The etiology of bipolar disorder (BD) remains unknown; however, lipid abnormalities in BD have received increasing attention in recent years. In this study, we examined the expression levels of enzyme proteins associated with the metabolic pathway of phosphoinositides (PIs) and their downstream effectors, protein kinase B (Akt1) and glycogen synthase kinase 3β (GSK3β), which have been assumed to be the targets of mood stabilizers such as lithium, in the postmortem brains of patients with BD. The protein expression levels of phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1C), phosphatidylinositol 4-kinase alpha (PIK4CA), phosphatase and tensin homolog deleted from chromosome 10 (PTEN), Akt1, and GSK3β were measured using enzyme-linked immunosorbent assays and multiplex fluorescent bead-based immunoassays in the prefrontal cortex (PFC). Specifically, PTEN, Akt1, GSK3β, and PIP5K1C were measured in seven BD patients and 48 controls. Additionally, PIK4CA was analyzed in 10 cases and 34 controls. PTEN expression levels were markedly decreased in the PFCs of patients with BD, whereas those of Akt and GSK3β were prominently elevated. Moreover, patients medicated with lithium exhibited higher Akt1 expression levels and lower PTEN expression levels in comparison with the untreated group. Our results suggest that the expression levels of Akt1/GSK3β and its upstream regulator PTEN are considerably altered.

Supra-second interval timing in bipolar disorder: examining the role of disorder sub-type, mood, and medication status

BackgroundWidely reported by bipolar disorder (BD) patients, cognitive symptoms, including deficits in executive function, memory, attention, and timing are under-studied. Work suggests that individuals with BD show impairments in interval timing tasks, including supra-second, sub-second, and implicit motor timing compared to the neuronormative population. However, how time perception differs within individuals with BD based on disorder sub-type (BDI vs II), depressed mood, or antipsychotic medication-use has not been thoroughly investigated. The present work administered a supra-second interval timing task concurrent with electroencephalography (EEG) to patients with BD and a neuronormative comparison group. As this task is known to elicit frontal theta oscillations, signal from the frontal (Fz) lead was analyzed at rest and during the task.ResultsResults suggest that individuals with BD show impairments in supra-second interval timing and reduced frontal theta power during the task compared to neuronormative controls. However, within BD sub-groups, neither time perception nor frontal theta differed in accordance with BD sub-type, depressed mood, or antipsychotic medication use.ConclusionsThis work suggests that BD sub-type, depressed mood status or antipsychotic medication use does not alter timing profile or frontal theta activity. Together with previous work, these findings point to timing impairments in BD patients across a wide range of modalities and durations indicating that an altered ability to assess the passage of time may be a fundamental cognitive abnormality in BD.

Along-Tract Statistical Mapping of Microstructural Abnormalities in Bipolar Disorder: A Pilot Study.

Investigating brain circuitry involved in bipolar disorder (BD) is key to discovering brain biomarkers for genetic and interventional studies of the disorder. Even so, prior research has not provided a fine-scale spatial mapping of brain microstructural differences in BD. In this pilot diffusion MRI dataset, we used BUndle ANalytics (BUAN)-a recently developed analytic approach for tractography-to extract, map, and visualize the profile of microstructural abnormalities on a 3D model of fiber tracts in people with BD (N=38) and healthy controls (N=49), and investigate along-tract white matter (WM) microstructural differences between these groups. Using the BUAN pipeline, BD was associated with lower mean fractional anisotropy (FA) in fronto-limbic and interhemispheric pathways and higher mean FA in posterior bundles relative to controls.Clinical Relevance- BUAN combines tractography and anatomical information to capture distinct along-tract effects on WM microstructure that may aid in classifying diseases based on anatomical differences.

Widespread intra-axonal signal fraction abnormalities in bipolar disorder from multicompartment diffusion MRI: Sensitivity to diagnosis, association with clinical features and pharmacologic treatment.

Despite diffusion tensor imaging (DTI) evidence for widespread fractional anisotropy (FA) reductions in the brain white matter of patients with bipolar disorder, questions remain regarding the specificity and sensitivity of FA abnormalities as opposed to other diffusion metrics in the disorder. We conducted a whole-brain voxel-based multicompartment diffusion MRI study on 316 participants (i.e., 158 patients and 158 matched healthy controls) employing four diffusion metrics: the mean diffusivity (MD) and FA estimated from DTI, and the intra-axonal signal fraction (IASF) and microscopic axonal parallel diffusivity (Dpar) derived from the spherical mean technique. Our findings provide novel evidence about widespread abnormalities in other diffusion metrics in BD. An extensive overlap between the FA and IASF results suggests that the lower FA in patients may be caused by a reduced intra-axonal volume fraction or a higher macromolecular content in the intra-axonal water. We also found a diffuse alteration in MD involving white and grey matter tissue and more localised changes in Dpar. A Machine Learning analysis revealed that FA, followed by IASF, were the most helpful metric for the automatic diagnosis of BD patients, reaching an accuracy of 72%. Number of mood episodes, age of onset/duration of illness, psychotic symptoms, and current treatment with lithium, antipsychotics, antidepressants, and antiepileptics were all significantly associated with microstructure abnormalities. Lithium treatment was associated with less microstructure abnormality.

Personality Traits Interact With Sleep and Biological Rhythm in Patients With Bipolar Disorder.

Sleep disturbances and circadian rhythm changes in bipolar disorder (BD) may have behavioral components as well as biological components. This study aimed to examine the relationship between personality traits, sleep and circadian rhythm in BD. A total of 150 participants with BD, and 150 healthy controls completed the Big Five Personality Test-50 (B5PT-50-TR), Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN), Functioning Assessment Short Test (FAST), Pittsburgh Sleep Quality Index (PSQI), Young Mania Rating Scale and Beck Depression Inventory. In the BD group, B5PT-50-TR emotional stability and openness subscale scores were significantly lower in comparison with the healthy control group. Agreeableness and emotional stability subscales were covariates for the BRIAN sleep subscale and emotional stability was a covariate for PSQI total score. Emotional instability might be a vulnerability factor for sleep disorders and biological rhythm abnormalities in BD. Improvement in emotional instability may relieve sleep disorders and biological rhythm, thereby leading to better treatment outcomes in BD.

Efficacy of automatic pupillometry as a screening technique to detect autonomic dysfunction in bipolar disorder

ABSTRACT Clinical relevance Autonomic nervous system abnormalities in the pathophysiology of bipolar disorder are controversial. Pupillary features may be affected as a result of autonomic nervous system abnormalities in bipolar disorder. Small changes in pupillary responses may not be noticeable on clinical examination. Automated pupillemetries can be helpful in demonstrating these changes reliably and quantitatively. Background The aim of this study was to compare the static and dynamic pupillary responses of bipolar patients with healthy controls. In addition, pupillary response differences between mania, depression and remission stages were investigated. Methods The bipolar patient group consisted of 39 eyes of 39 patients with 13 patients in each of the stages: mania, depression and remission. The control group consisted of 39 eyes of 39 healthy volunteers. After the ophthalmic examination, static and dynamic pupillometry measurements were made. The mean pupil dilatation speed was calculated according to dynamic measurements. Static pupillometry measurements including scotopic, mesopic and photopic pupil diameters; the first dynamic measurements at 0th second and pupillary dilatation speed were used for statistical analysis. Results There was no difference static and the first dynamic pupillometry measurements between the bipolar and control groups (p > 0.05 for all parameters), but there was a significant difference in mean pupil dilatation speed (p = 0.041). No significant differences were found between the 3 groups for all static and the first dynamic pupillometry measurements and the mean pupil dilatation speed (p > 0.05). Conclusion Static and the first dynamic measurements of bipolar patients were not different from healthy controls. The mean pupil dilatation speed of bipolar patients was significantly lower, but this difference had a low effect size.

Precision neuroimaging biomarkers for bipolar disorder

Bipolar disorder (BD) is a severe mental illness associated with alterations in brain organization. Neuroimaging studies have generated a large body of knowledge regarding brain morphological and functional abnormalities in BD. Current advances in the field have focussed on the need for more precise neuroimaging biomarkers. Here we present a selective overview of precision neuroimaging biomarkers for BD, focussing on personalized metrics and novel neuroimaging methods aiming to provide mechanistic insights into the brain alterations associated with BD. The evidence presented covers (a) machine learning techniques applied to neuroimaging data to differentiate patients with BD from healthy individuals or other clinical groups; (b) the ‘brain-age-gap-estimation (brainAGE), which is an individualized measure of brain health; (c) diffusional kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI) and Positron Emission Tomography (PET) techniques that open new opportunities to measure microstructural changes in neurite/synaptic integrity and function.

Alterations in resting-state whole-brain functional connectivity pattern similarity in bipolar disorder patients.

BackgroundPrevious neuroimaging studies have extensively demonstrated many signs of functionally spontaneous local neural activity abnormalities in bipolar disorder (BD) patients using resting‐state functional magnetic resonance imaging (rs‐fMRI). However, how to identify the changes of voxel‐wise whole‐brain functional connectivity pattern and its corresponding functional connectivity changes remain largely unclear in BD patients. The current study aimed to investigate the voxel‐wise changes of functional connectivity patterns in BD patients using publicly available data from the UCLA CNP LA5c Study.MethodsA total of 45 BD patients and 115 healthy control subjects were finally included and whole‐brain functional connectivity homogeneity (FcHo) was calculated from their rs‐fMRI. Moreover, the alterations of corresponding functional connectivity were subsequently identified using seed‐based resting‐state functional connectivity analysis.ResultsIndividuals with BD exhibited significantly lower FcHo values in the left middle temporal gyrus (MTG) when compared with controls. Functional connectivity findings further indicated decreased functional connectivities between left MTG and cluster 1 (left superior temporal gyrus, extend to middle temporal gyrus, rolandic operculum), cluster 2 (right postcentral, extend to right precentral) in BD patients. The mean FcHo values of left MTG were positively correlated with insomnia, middle scores and appetite increase scores. The mean functional connectivities of left MTG to cluster 1 were negatively correlated with grandiose delusions scores. While the functional connections between left MTG with cluster 2 were negatively correlated with delusions of reference and positively correlated with insomnia, middle scores in BD patients.ConclusionsOur findings suggested that abnormal FcHo and functional connections in those areas of the brain involving DMN and SMN networks might play a crucial role in the neuropathology of BD.

Brain-Based Abnormalities in Bipolar Disorder: Neuroprogression (and Neurodevelopment)

SEE CORRESPONDING ARTICLE ON PAGE 582 Longitudinal Structural Brain Changes in Bipolar Disorder: A Multicenter Neuroimaging Study of 1232 Individuals by the ENIGMA Bipolar Disorder Working GroupBiological PsychiatryVol. 91Issue 6PreviewBipolar disorder (BD) is associated with cortical and subcortical structural brain abnormalities. It is unclear whether such alterations progressively change over time, and how this is related to the number of mood episodes. To address this question, we analyzed a large and diverse international sample with longitudinal magnetic resonance imaging (MRI) and clinical data to examine structural brain changes over time in BD. Full-Text PDF Open Access

Aberrant Subnetwork and Hub Dysconnectivity in Adult Bipolar Disorder: A Multicenter Graph Theory Analysis.

Neuroimaging evidence implicates structural network-level abnormalities in bipolar disorder (BD); however, there remain conflicting results in the current literature hampered by sample size limitations and clinical heterogeneity. Here, we set out to perform a multisite graph theory analysis to assess the extent of neuroanatomical dysconnectivity in a large representative study of individuals with BD. This cross-sectional multicenter international study assessed structural and diffusion-weighted magnetic resonance imaging data obtained from 109 subjects with BD type 1 and 103 psychiatrically healthy volunteers. Whole-brain metrics, permutation-based statistics, and connectivity of highly connected nodes were used to compare network-level connectivity patterns in individuals with BD compared with controls. The BD group displayed longer characteristic path length, a weakly connected left frontotemporal network, and increased rich-club dysconnectivity compared with healthy controls. Our multisite findings implicate emotion and reward networks dysconnectivity in bipolar illness and may guide larger scale global efforts in understanding how human brain architecture impacts mood regulation in BD.

Emotion Processing Deficit in Euthymic Bipolar Disorder: A Potential Endophenotype.

Background:Emotion processing deficits have been described in patients with bipolar disorder (BD) and are considered one of the core cognitive abnormalities in BD with endophenotype potential. However, the literature on specific impairments in emotion processing cognitive strategies (directive/cortical/higher versus intuitive/limbic/lower) in euthymic adult BD patients and healthy first-degree relatives/high-risk (HR) subjects in comparison with healthy controls (HCs) is sparse.Methods:We examined facial emotion recognition deficits (FERD) in BD (N = 30), HR (N = 21), and HC (N = 30) matched for age (years), years of education, and sex using computer-administered face emotions–Matching And Labeling Task (eMALT).Results:The three groups were significantly different based on labeling accuracy scores for fear and anger (FA) (P < 0.001) and sad and disgust (SD) (P < 0.001). On post-hoc analysis, HR subjects exhibited a significant deficit in the labeling accuracy of FA facial emotions (P < 0.001) compared to HC. The BD group was found to have significant differences in all FA (P = 0.004) and SD (P = 0.003) emotion matching as well as FA (P = 0.001) and SD (P < 0.001) emotion labeling accuracy scores.Conclusions:BD in remission exhibits FERD in general, whereas specific labeling deficits of fear and anger emotions, indicating impaired directive higher order aspect of emotion processing, were demonstrated in HR subjects. This appears to be a potential endophenotype. These deficits could underlie the pathogenesis in BD, with possible frontolimbic circuitry impairment. They may have potential implications in functional recovery and prognosis of BD.

Time-Frequency Characterization of Resting Brain in Bipolar Disorder during Euthymia-A Preliminary Study.

The goal of this paper is to investigate the baseline brain activity in euthymic bipolar disorder (BD) patients by comparing it to healthy controls (HC) with the use of a variety of resting state functional magnetic resonance imaging (rs-fMRI) analyses, such as amplitude of low frequency fluctuations (ALFF), fractional ALFF (f/ALFF), ALFF-based functional connectivity (FC), and r egional homogeneity (ReHo). We hypothesize that above-mentioned techniques will differentiate BD from HC indicating dissimilarities between the groups within different brain structures. Forty-two participants divided into two groups of euthymic BD patients (n = 21) and HC (n = 21) underwent rs-fMRI evaluation. Typical band ALFF, slow-4, slow-5, f/ALFF, as well as ReHo indexes were analyzed. Regions with altered ALFF were chosen as ROI for seed-to-voxel analysis of FC. As opposed to HC, BD patients revealed: increased ALFF in left insula; increased slow-5 in left middle temporal pole; increased f/ALFF in left superior frontal gyrus, left superior temporal gyrus, left middle occipital gyrus, right putamen, and bilateral thalamus. There were no significant differences between BD and HC groups in slow-4 band. Compared to HC, the BD group presented higher ReHo values in the left superior medial frontal gyrus and lower ReHo values in the right supplementary motor area. FC analysis revealed significant hyper-connectivity within the BD group between left insula and bilateral middle frontal gyrus, right superior parietal gyrus, right supramarginal gyrus, left inferior parietal gyrus, left cerebellum, and left supplementary motor area. To our best knowledge, this is the first rs-fMRI study combining ReHo, ALFF, f/ALFF, and subdivided frequency bands (slow-4 and slow-5) in euthymic BD patients. ALFF, f/ALFF, slow-5, as well as REHO analysis revealed significant differences between two studied groups. Although results obtained with the above methods enable to identify group-specific brain structures, no overlap between the brain regions was detected. This indicates that combination of foregoing rs-fMRI methods may complement each other, revealing the bigger picture of the complex resting state abnormalities in BD.

Associations and limited shared genetic aetiology between bipolar disorder and cardiometabolic traits in the UK Biobank.

People with bipolar disorder (BPD) are more likely to die prematurely, which is partly attributed to comorbid cardiometabolic traits. Previous studies report cardiometabolic abnormalities in BPD, but their shared aetiology remains poorly understood. This study examined the phenotypic associations and shared genetic aetiology between BPD and various cardiometabolic traits. In a subset of the UK Biobank sample (N = 61 508) we investigated phenotypic associations between BPD (ncases = 4186) and cardiometabolic traits, represented by biomarkers, anthropometric traits and cardiometabolic diseases. To determine shared genetic aetiology in European ancestry, polygenic risk scores (PRS) and genetic correlations were calculated between BPD and cardiometabolic traits. Several traits were significantly associated with increased risk for BPD, namely low total cholesterol, low high-density lipoprotein cholesterol, high triglycerides, high glycated haemoglobin, low systolic blood pressure, high body mass index, high waist-to-hip ratio; and stroke, coronary artery disease and type 2 diabetes diagnosis. BPD was associated with higher polygenic risk for triglycerides, waist-to-hip ratio, coronary artery disease and type 2 diabetes. Shared genetic aetiology persisted for coronary artery disease, when correcting PRS associations for cardiometabolic base phenotypes. Associations were not replicated using genetic correlations. This large study identified increased phenotypic cardiometabolic abnormalities in BPD participants. It is found that the comorbidity of coronary artery disease may be based on shared genetic aetiology. These results motivate hypothesis-driven research to consider individual cardiometabolic traits rather than a composite metabolic syndrome when attempting to disentangle driving mechanisms of cardiometabolic abnormalities in BPD.

Inflammation is correlated with abnormal functional connectivity in unmedicated bipolar depression: an independent component analysis study of resting-state fMRI.

Inflammation might play a role in bipolar disorder (BD), but it remains unclear the relationship between inflammation and brain structural and functional abnormalities in patients with BD. In this study, we focused on the alterations of functional connectivity (FC), peripheral pro-inflammatory cytokines and their correlations to investigate the role of inflammation in FC in BD depression. In this study, 42 unmedicated patients with BD II depression and 62 healthy controls (HCs) were enrolled. Resting-state-functional magnetic resonance imaging was performed in all participants and independent component analysis was used. Serum levels of Interleukin-6 (IL-6) and Interleukin-8 (IL-8) were measured in all participants. Correlation between FC values and IL-6 and IL-8 levels in BD was calculated. Compared with the HCs, BD II patients showed decreased FC in the left orbitofrontal cortex (OFC) implicating the limbic network and the right precentral gyrus implicating the somatomotor network. BD II showed increased IL-6 (p = 0.039), IL-8 (p = 0.002) levels. Moreover, abnormal FC in the right precentral gyrus were inversely correlated with the IL-8 (r = -0.458, p = 0.004) levels in BD II. No significant correlation was found between FC in the left OFC and cytokines levels. Our findings that serum IL-8 levels are associated with impaired FC in the right precentral gyrus in BD II patients suggest that inflammation might play a crucial role in brain functional abnormalities in BD.

Frontolimbic brain volume abnormalities in bipolar disorder with suicide attempts

Over 2.3 million people in the United States live with bipolar disorder. Sixty percent of those with a bipolar disorder diagnosis attempt suicide at least once in their lifetime and up to 19% die by suicide. However, the neurobiology of suicide attempts in bipolar disorder remains unclear. We studied the gray matter volume (GMV) of 81 participants with a bipolar-I diagnosis (age-range: 14-34 years old) and 40 healthy participants (age-range 14.7-32 years old) to compare their neuroanatomy and histories of suicide attempt. In the bipolar group, 42 were manic with ages ranging from 14-30.6 years, and 39 were depressed with ages ranging from 14-34.3 years). Twenty three bipolar participants had a suicide attempt history, and 58 had no suicide attempt history. All participants completed behavioral/diagnostic assessments and MRI. We focused on a predefined frontolimbic circuitry in bipolar disorder versus controls to first identify diagnostic GMV correlates and to specifically identify GMV correlates for suicide attempt history. We found reduced GMV in bipolar diagnosis versus controls in the subgenual cingulate and dorsolateral prefrontal cortices. Our observed regional GMV reductions were associated with histories of suicide attempts and measures of individual variations in current suicidal ideation at the time of scanning.

Comparison of first-episode and multiple-episode bipolar disorder: A surface-based morphometry study

It is still unclear whether the structural abnormalities in Bipolar disorder (BD) are static or progressive. We aimed to compare differences in cortical thickness, surface area, and volume between patients with BD and healthy volunteers (HV) and to examine whether there are differences between patients who have had a single manic episode and those with multiple episodes. We recruited 30 patients with Type I BD and 30 age and sex matched HV. All participants underwent structural magnetic resonance imaging. Cortical volume, thickness, and surface area were measured using the QDEC tool from the Freesurfer software with age and intracranial volume as covariates. Study groups were comparable across age, sex distribution, and intracranial volume. Patients had significantly lower surface area in bilateral cuneus, right postcentral gyrus, and rostral middle frontal gyri; and lower cortical volume in the left middle temporal gyrus, right postcentral gyrus, and right cuneus. BD patients with multiple episodes had lower cortical measures while those with single episode had cortical measures comparable to HV. Findings indicate that the pathophysiological processes in BD are possibly progressive in nature. Our findings underscore the potential importance of early diagnosis and intervention in preventing deterioration and improving functional recovery.

Will machine learning applied to neuroimaging in bipolar disorder help the clinician? A critical review and methodological suggestions.

The existence of anatomofunctional brain abnormalities in bipolar disorder (BD) is now well established by magnetic resonance imaging (MRI) studies. To create diagnostic and prognostic tools, as well as identifying biologically valid subtypes of BD, research has recently turned towards the use of machine learning (ML) techniques. We assessed both supervised ML and unsupervised ML studies in BD to evaluate their robustness, reproducibility and the potential need for improvement. We systematically searched for studies using ML algorithms based on MRI data of patients with BD until February 2019. We identified 47 studies, 45 using supervised ML techniques and 2 including unsupervised ML analyses. Among supervised studies, 43 focused on diagnostic classification. The reported accuracies for classification of BD ranged between (a) 57% and 100%, for BD vs healthy controls; (b) 49.5% and 93.1% for BD vs patients with major depressive disorder; and (c) 50% and 96.2% for BD vs patients with schizophrenia. Reported accuracies for discriminating subjects genetically at risk for BD (either from control or from patients with BD) ranged between 64.3% and 88.93%. Although there are strong methodological limitations in previous studies and an important need for replication in large multicentric samples, the conclusions of our review bring hope of future computer-aided diagnosis of BD and pave the way for other applications, such as treatment response prediction. To reinforce the reliability of future results we provide methodological suggestions for good practice in conducting and reporting MRI-based ML studies in BD.

Exploring the Relationship of Transdiagnostic Mood and Psychosis Symptom Domains with Motor Dysfunction

Background: A number of motor abnormalities have been reported in psychotic disorders, including dyskinesia and psychomotor slowing. There is also evidence for many of the same motor abnormalities in biological first-degree relatives and accruing evidence for motor abnormalities in bipolar disorder. In addition to motor dysfunction, there are also shared symptom domains amongst these populations. Objectives: We explored the associations of (1) current and lifetime psychosis and mood symptom domains and (2) domains of psychosis proneness with various domains of motor function in a transdiagnostic sample (n = 149). Method: Individuals with schizophrenia, schizoaffective disorder, or bipolar disorder, biological first-degree relatives of individuals with a psychotic disorder, and controls completed measures of psychomotor speed and movement fluidity, and neural activity related to motor preparation (stimulus-locked lateralized readiness potential, S-LRP) and execution (response-locked LRP) was assessed using EEG. All participants completed the Brief Psychiatric Rating Scale; patients were additionally assessed for lifetime psychosis and mood episode symptoms, and relatives and controls completed the Chapman psychosis proneness scales. Results: Multiple regression revealed levels of current negative symptoms and mania were significantly positively associated with psychomotor slowing even after accounting for current antipsychotic medication dosage and duration of illness. S-LRP onset latency was significantly positively associated with magical ideation. Conclusion: Domains of motor function are associated with various mood and psychosis symptom domains in a transdiagnostic sample, which may provide insight into brain abnormalities relevant to the expression of symptoms across disorders.