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Background: Brain networks involved in language, attentional and response processes are detectable by fMRI during lexical decision (LD). Here, we investigated possible abnormalities in the functional networks involved in LD in patients with bipolar disorder (BD)., Methods: fMRI and behavioural data were compared between BD (n = 25) and control (n = 21), with groups matched for age and sex. The functional brain networks involved in LD were extracted by manipulating the "word-likeness" of LD stimuli and using a multidimensional analysis method., Results: Attentional, response and language processes were captured in separate function-specific brain networks (default mode network, response network, linguistic processing network, respectively) in the BD and control groups, replicating the results of our previous study in an independent group of healthy adults. Behaviourally, the BD group showed higher performance than the control group in the LD task. Activity in the default mode network (DMN) and the linguistic processing network (LPN) did not differ between the groups, but the BD group had higher activation than the control group in the response network (RESP)., Limitations: Due to the small sample, the study is underpowered, capable of only detecting large effects., Conclusions: The results suggest that BD may be associated with sustained activity in the RESP network, which might contribute to psychomotor dysfunction in BD. Future studies should investigate the possible link between altered RESP activation and psychomotor disturbances in BD, as well as the basis for altered RESP activity in BD., (Copyright © 2022 Elsevier B.V. All rights reserved.)

First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10 -5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

White matter pathology likely contributes to the pathogenesis of bipolar disorder (BD). Most studies of white matter in BD have used diffusion tensor imaging (DTI), but the advent of more advanced multi-shell diffusion MRI imaging offers the possibility to investigate other aspects of white matter microstructure. Diffusion kurtosis imaging (DKI) extends the DTI model and provides additional measures related to diffusion restriction. Here, we investigated white matter in BD by applying whole-brain voxel-based analysis (VBA) and a network-based connectivity approach using constrained spherical deconvolution tractography to assess differences in DKI and DTI metrics between BD (n = 25) and controls (n = 24). The VBA showed lower mean kurtosis in the corona radiata and posterior association fibers in BD. Regional differences in connectivity were indicated by lower mean kurtosis and kurtosis anisotropy in streamlines traversing the temporal and occipital lobes, and lower mean axial kurtosis in the right cerebellar, thalamo-subcortical pathways in BD. Significant differences were not seen in DTI metrics following FDR-correction. The DKI findings indicate altered connectivity across cortical, subcortical and cerebellar areas in BD. DKI is sensitive to different microstructural properties and is a useful complementary technique to DTI to more fully investigate white matter in BD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: A domain of cognition that has been found to be impaired in bipolar disorder across mood states is working memory. Working memory can be separated into two components, maintenance and manipulation. Bipolar patients also demonstrate structural brain abnormalities in prefrontal and parietal regions, which are regions associated with working memory processes. Despite the understanding that working memory consists of multiple separable cognitive processes, no study to date has differentiated maintenance and manipulation, and associated them with underlying structural brain regions in bipolar disorder., Methods: Twenty-six bipolar patients and 24 controls completed a visuospatial working memory task and structural neuroimaging. Prefrontal and parietal gray matter volume, surface area, and cortical thickness were obtained using FreeSurfer. The relationship between working memory performance, structural integrity, symptoms, and functioning were investigated., Results: Bipolar patients were less accurate on the working memory task compared to controls, without a greater deficit in the manipulation condition. Controls had thicker prefrontal and parietal cortices than bipolar patients. In bipolar patients, thicker prefrontal cortices had a small association with greater accuracy on the maintenance condition, as well as greater depression., Limitations: This study could have benefitted from a larger sample size., Conclusions: Bipolar patients demonstrated both poorer accuracy on the visuospatial working memory task compared to controls and thinner cortices in areas associated with working memory, namely the prefrontal and parietal cortices. This demonstrates an underlying relationship between brain and behavior in bipolar disorder., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Deficits in response inhibition have been observed in schizophrenia and bipolar disorder; however, the neural origins of the abnormalities and their relevance to genetic liability for psychosis are unknown. We used a stop-signal task to examine motor inhibition and associated neural processes in schizophrenia patients (n = 57), bipolar disorder patients (n = 21), first-degree biological relatives of patients with schizophrenia (n = 34), and healthy controls (n = 56). Schizophrenia patients demonstrated motor control deficits reflected in longer stop-signal reaction times and elongated reaction times. With the possibility of needing to inhibit a button press, both schizophrenia and bipolar disorder patients showed diminished reductions of the P300 brain response and only the healthy controls demonstrated adjustments in response execution time, as measured by response-locked lateralized readiness potentials. Schizotypal traits in the biological relatives were associated with less P300 modulation consistent with the motor-related anomalies being associated with subtle schizophrenia-spectrum symptomatology in family members. The two patient groups had elongated response selection processes as manifest in the delayed onset of the stimulus-locked lateralized readiness potential. The bipolar disorder group was unique in showing significantly diminished neural responses to the stop-signal to inhibit a response. Antipsychotic medication dosage was related to worse motor inhibition, thus motor inhibition deficits in schizophrenia may be partially explained by the effect of pharmacological agents. Failed modulation of brain processes in relation to response inhibition probability and the lengthening of motor response selection appear to be transdiagnostic abnormalities spanning schizophrenia and bipolar disorder., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Background: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects., Methods: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects., Results: FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects., Conclusions: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Anxiety symptoms and anxiety disorders are common in both mood and psychotic disorders. However, limited comparative information exists regarding the long-term course of anxiety in schizoaffective disorder, bipolar disorder, and major depressive disorder. Prospective evaluation of the 20-year trajectory of self-reported anxiety and somatic-related anxiety in three major diagnostic groups, 43 schizoaffective patients, 47 bipolar patients, and 109 major depression patients was conducted. The patients were recruited at an index phase of hospitalization, and then reassessed longitudinally at six subsequent follow-ups over 20-years. The sample was well characterized with symptom, recovery and functioning data being available. This study found that in the earlier years of illness, self-reported anxiety was greater in schizoaffective and major depression patients than bipolar patients. The three groups were similar for anxiety symptoms during the 20-year course of their illness. Last, we found in all patients, self-reported anxiety in the early years predicted having a period of recovery and lower global functioning in the future. Our data provides unique information regarding the comparative course of anxiety in related mood and psychotic disorders. Both clinicians and researchers should focus on assessing, diagnosing, and treating anxiety in mood and psychotic disorders, as a means to improve outcomes and quality of life in these individuals., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The present study investigated self-reported impulsivity in gambling disorder (GD) and bipolar disorder (BD). Participants with GD (n = 31), BD (n = 19), and community controls (n = 68) completed diagnostic interviews and symptom severity and functioning assessments. Participants also completed the UPPS-P Impulsive Behavior Scale composed of five dimensions including urgency (i.e., acting rashly under conditions of negative or positive emotion), lack of perseverance (i.e., inability to maintain focus), lack of premeditation (i.e., inability to consider negative consequences), and sensation seeking (i.e., tendency to pursue novel and exciting activities). Multivariate analysis of variance showed overall significant differences among the diagnostic groups on the UPPS-P subscales. Follow-up analyses of variance showed that the groups differed on all subscales except sensation seeking. The gambling and bipolar groups had significantly higher levels of self-reported impulsivity on all subscales when compared to controls. In addition, the BD group showed higher levels of positive urgency when compared to the GD group. Positive and negative urgency showed the strongest association with GD and BD. Impaired emotion regulation mechanisms may underlie self-reported impulsivity in both disorders. Lack of premeditation and perseverance may be related to dysfunctional cognitive processes.

Hallucinations are a salient feature of both psychotic and mood disorders. Currently there is a call for more research on the phenomenology of different forms of hallucinations, in a broader array of disorders, to further both theoretical knowledge and clinical utility. We investigated auditory, visual, and olfactory hallucinations at index hospitalization and auditory and visual hallucinations prospectively for 20years in 150 young patients, namely 51 schizophrenia, 25 schizoaffective, 28 bipolar, and 79 unipolar depression. For the index hospitalization, the data showed schizophrenia and schizoaffective patients had a greater rate of auditory and visual hallucinations than bipolar and depression patients. However, over the longitudinal trajectory of their illness, a greater percentage of schizophrenia patients had auditory and visual hallucinations than schizoaffective patients, as well as bipolar and depression patients. Also, in contrast to the initial period, schizoaffective patients did not differentiate themselves over the follow-up period from bipolar patients. Bipolar and depression patients did not significantly differ at index hospitalization or at follow-up. We found visual hallucinations differentiated the groups to a greater degree over the 20year course than did auditory hallucinations. These findings suggest the longitudinal course is more important for differentiating schizophrenia and schizoaffective disorder, whereas the initial years may be more useful to differentiate schizoaffective disorder from bipolar disorder. Furthermore, we found that the early presence of auditory hallucinations was associated with a reduced likelihood for a future period of recovery. No olfactory hallucinations were present at the index hospitalization in any patients. Over the course of 20years, a minority of schizophrenia patients presented with olfactory hallucinations, and very few schizoaffective and bipolar patients presented with olfactory hallucinations. This study underscores the importance of the longitudinal course of symptoms to understand the relationship between related disorders and recovery., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The ability to accurately judge facial expressions is important in social interactions. Individuals with bipolar disorder have been found to be impaired in emotion recognition; however, the specifics of the impairment are unclear. This study investigated whether facial emotion recognition difficulties in bipolar disorder reflect general cognitive, or emotion-specific, impairments. Impairment in the recognition of particular emotions and the role of processing speed in facial emotion recognition were also investigated., Methods: Clinically stable bipolar patients (n = 17) and healthy controls (n = 50) judged five facial expressions in two presentation types, time-limited and self-paced. An age recognition condition was used as an experimental control., Results: Bipolar patients' overall facial recognition ability was unimpaired. However, patients' specific ability to judge happy expressions under time constraints was impaired., Conclusions: Findings suggest a deficit in happy emotion recognition impacted by processing speed. Given the limited sample size, further investigation with a larger patient sample is warranted.

Schizophrenia and bipolar disorder are typically separated in diagnostic systems. Behavioral, cognitive, and brain abnormalities associated with each disorder nonetheless overlap. We evaluated the diagnostic specificity of facial emotion recognition deficits in schizophrenia and bipolar disorder to determine whether select aspects of emotion recognition differed for the two disorders. The investigation used an experimental task that included the same facial images in an emotion recognition condition and an age recognition condition (to control for processes associated with general face recognition) in 27 schizophrenia patients, 16 bipolar I patients, and 30 controls. Schizophrenia and bipolar patients exhibited both shared and distinct aspects of facial emotion recognition deficits. Schizophrenia patients had deficits in recognizing angry facial expressions compared to healthy controls and bipolar patients. Compared to control participants, both schizophrenia and bipolar patients were more likely to mislabel facial expressions of anger as fear. Given that schizophrenia patients exhibited a deficit in emotion recognition for angry faces, which did not appear due to generalized perceptual and cognitive dysfunction, improving recognition of threat-related expression may be an important intervention target to improve social functioning in schizophrenia., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Schizophrenia and bipolar disorder, although diagnostically separate, likely share elements of their genetic etiology. This study assessed whether the COMT Val158Met polymorphism has shared or specific associations with clinical phenotypes evident in schizophrenia and bipolar disorder. Schizophrenia and bipolar patients completed a clinical assessment encompassing premorbid functioning and current and lifetime symptomatology. Multivariate analyses yielded a three-way interaction of diagnosis, COMT genotype for lifetime symptomatology. The COMT Val allele was associated with greater positive symptomatology in schizophrenia, whereas Met homozygosity was associated with greater positive symptomatology in bipolar disorder. Findings support the COMT Val158Met polymorphism conferring vulnerability for different clinical phenotypes in schizophrenia and bipolar disorder. Lifetime symptomatology may be particularly useful in determining the relationship between genes and clinical phenotypes across mental disorders.

Schizophrenia has been reliably associated with impairments in backward masking performance, while bipolar disorder has less consistently been tied to such a deficit. To examine the genetic determinants of visual perception abnormalities in schizophrenia and bipolar disorder, this study evaluated the diagnostic specificity of backward masking performance deficits and whether masking deficits were associated with catechol-O-methyl transferase (COMT) genotype. A location-based backward masking task, which equated participants on the perceptual intensity of stimuli, was completed by 41 schizophrenia outpatients, 28 bipolar outpatients, and 43 nonpsychiatric controls. COMT genotype data were available for 39 schizophrenia outpatients, 28 bipolar outpatients, and 20 nonpsychiatric controls. Schizophrenia patients demonstrated impaired backward masking performance compared to controls and bipolar patients. A group by COMT genotype interaction was detected with schizophrenia Met homozygotes performing more poorly than control and bipolar Met homozygotes, and worse than Val homozygote and heterozygote schizophrenia patients. This study provides novel evidence for differential effects of the COMT gene on neural systems underlying visual perception in schizophrenia and bipolar disorder. The COMT Met allele may be associated with deficits in schizophrenia that are unrelated to neural systems supporting sustained attention or working memory., ((c) 2007 Wiley-Liss, Inc.)

First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.