Thalamocortical Anatomical Connectivity in Schizophrenia and Psychotic Bipolar Disorder

Abstract Background Anatomical connectivity between the thalamus and cortex, including the prefrontal cortex (PFC), is abnormal in schizophrenia. Overlapping phenotypes, including deficits in executive cognitive abilities dependent on PFC-thalamic circuitry, suggest dysrupted thalamocortical anatomical connectivity may extend to psychotic bipolar disorder. We tested this hypothesis and examined the impact of illness stage to inform when in the illness course thalamocortical dysconnectivity emerges. Methods Diffusion-weighted imaging data were collected on 70 healthy individuals and 124 people with a psychotic disorder (schizophrenia spectrum = 75; psychotic bipolar disorder = 49), including 62 individuals in the early stage of psychosis. Anatomical connectivity between major divisions of the cortex and thalamus was quantified using probabilistic tractography and compared between groups. Associations between PFC-thalamic anatomical connectivity and executive cognitive abilities were examined using regression analysis. Results Psychosis was associated with lower PFC-thalamic and elevated somatosensory-thalamic anatomical connectivity. Follow-up analyses established that lower PFC-thalamic and elevated somatosensory-thalamic anatomical connectivity were present in both schizophrenia and psychotic bipolar disorder. Lower PFC-thalamic anatomical connectivity was also present in early-stage and chronic psychosis. Contrary to expectations, lower PFC-thalamic anatomical connectivity was not associated with impaired executive cognitive abilities. Conclusions Altered thalamocortical anatomical connectivity, especially reduced PFC-thalamic connectivity, is a transdiagnostic feature of psychosis detectable in the early stage of illness. Further work is required to elucidate the functional consequences of the full spectrum of thalamocortical connectivity abnormalities in psychosis.

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Thalamocortical Anatomical Connectivity in Schizophrenia and Psychotic Bipolar Disorder

Biological Psychiatry ◽

10.1016/j.biopsych.2020.02.1139 ◽

2020 ◽

Vol 87 (9) ◽

pp. S447-S448

Author(s):

Julia Sheffield ◽

Anna Huang ◽

Baxter Rogers ◽

Monica Giraldo-Chica ◽

Bennett Landman ◽

...

Keyword(s):

Bipolar Disorder ◽

Anatomical Connectivity ◽

Psychotic Bipolar Disorder

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Relational memory in the early stage of psychotic bipolar disorder

Psychiatry Research ◽

10.1016/j.psychres.2020.113508 ◽

2020 ◽

Vol 294 ◽

pp. 113508

Author(s):

Rachel A. McKinney ◽

Suzanne N. Avery ◽

Kristan Armstrong ◽

Jennifer Urbano Blackford ◽

Neil D. Woodward ◽

...

Keyword(s):

Bipolar Disorder ◽

Early Stage ◽

Relational Memory ◽

Psychotic Bipolar Disorder

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Relational Memory in the Early Stage of Psychotic Bipolar Disorder

Biological Psychiatry ◽

10.1016/j.biopsych.2020.02.560 ◽

2020 ◽

Vol 87 (9) ◽

pp. S215-S216

Author(s):

Rachel A. McKinney ◽

Suzanne N. Avery ◽

Kristan Armstrong ◽

Stephan Heckers

Keyword(s):

Bipolar Disorder ◽

Early Stage ◽

Relational Memory ◽

Psychotic Bipolar Disorder

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EPA guidance on physical activity as a treatment for severe mental illness: a meta-review of the evidence and Position Statement from the European Psychiatric Association (EPA), supported by the International Organization of Physical Therapists in Mental Health (IOPTMH)

European Psychiatry ◽

10.1016/j.eurpsy.2018.07.004 ◽

2018 ◽

Vol 54 ◽

pp. 124-144 ◽

Cited By ~ 119

Author(s):

Brendon Stubbs ◽

Davy Vancampfort ◽

Mats Hallgren ◽

Joseph Firth ◽

Nicola Veronese ◽

...

Keyword(s):

Physical Activity ◽

Bipolar Disorder ◽

Mental Illness ◽

Health Outcomes ◽

Schizophrenia Spectrum Disorders ◽

Schizophrenia Spectrum ◽

Meta Review ◽

Spectrum Disorders ◽

The Impact

AbstractPhysical activity (PA) may be therapeutic for people with severe mental illness (SMI) who generally have low PA and experience numerous life style-related medical complications. We conducted a meta-review of PA interventions and their impact on health outcomes for people with SMI, including schizophrenia-spectrum disorders, major depressive disorder (MDD) and bipolar disorder. We searched major electronic databases until January 2018 for systematic reviews with/without meta-analysis that investigated PA for any SMI. We rated the quality of studies with the AMSTAR tool, grading the quality of evidence, and identifying gaps, future research needs and clinical practice recommendations. For MDD, consistent evidence indicated that PA can improve depressive symptoms versus control conditions, with effects comparable to those of antidepressants and psychotherapy. PA can also improve cardiorespiratory fitness and quality of life in people with MDD, although the impact on physical health outcomes was limited. There were no differences in adverse events versus control conditions. For MDD, larger effect sizes were seen when PA was delivered at moderate-vigorous intensity and supervised by an exercise specialist. For schizophrenia-spectrum disorders, evidence indicates that aerobic PA can reduce psychiatric symptoms, improves cognition and various subdomains, cardiorespiratory fitness, whilst evidence for the impact on anthropometric measures was inconsistent. There was a paucity of studies investigating PA in bipolar disorder, precluding any definitive recommendations. No cost effectiveness analyses in any SMI condition were identified. We make multiple recommendations to fill existing research gaps and increase the use of PA in routine clinical care aimed at improving psychiatric and medical outcomes.

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Emotion recognition deficits in schizophrenia-spectrum disorders and psychotic bipolar disorder: Findings from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study

Schizophrenia Research ◽

10.1016/j.schres.2014.07.001 ◽

2014 ◽

Vol 158 (1-3) ◽

pp. 105-112 ◽

Cited By ~ 45

Author(s):

Anthony C. Ruocco ◽

James L. Reilly ◽

Leah H. Rubin ◽

Alex R. Daros ◽

Elliot S. Gershon ◽

...

Keyword(s):

Bipolar Disorder ◽

Emotion Recognition ◽

Schizophrenia Spectrum Disorders ◽

Intermediate Phenotypes ◽

Schizophrenia Spectrum ◽

Spectrum Disorders ◽

Psychotic Bipolar Disorder

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Results of the 2nd Planned Interim Analysis of the RAPID Trial (involved field radiotherapy versus no further treatment) in Patients with Clinical Stages 1A and 2A Hodgkin Lymphoma and a ‘negative’ FDG-PET Scan after 3 Cycles ABVD

Blood ◽

10.1182/blood.v112.11.369.369 ◽

2008 ◽

Vol 112 (11) ◽

pp. 369-369 ◽

Cited By ~ 15

Author(s):

John Radford ◽

Michael O’Doherty ◽

Sally Barrington ◽

Wendi Qian ◽

Philippa Patrick ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Interim Analysis ◽

Early Stage ◽

Randomised Trial ◽

Pet Scan ◽

Imaging Data ◽

Early Stage Disease ◽

Involved Field ◽

The Impact ◽

Involved Field Radiotherapy

Abstract The goal of response adapted treatment in Hodgkin lymphoma (HL) is to maximise the number of cures whilst minimising the effects of late toxicity on the incidence of endocrine dysfunction, infertility, second cancers and cardiovascular disease. In early stage disease abbreviated chemotherapy (CT) followed by involved field radiotherapy (RT) is the current standard of care but some patients (pts) may be cured by CT alone. If it were possible to identify this population, RT and associated toxicity could then be avoided in a proportion of pts using a response adapted approach. 18FDG-positron emission tomography (PET) provides an opportunity to identify pts with an excellent prognosis after CT but the impact on disease control of de-escalating treatment (no consolidation RT) based on these imaging data requires careful evaluation. Here we present results of the 2nd planned interim analysis of an ongoing randomised trial (RAPID) comparing no further treatment with involved field RT following 3 cycles ABVD and a ‘negative’ (-ve) PET scan. Consenting pts with histologically proven, previously untreated HL, stages 1A and 2A above the diaphragm are eligible for trial entry. Following 3 cycles ABVD, responders have a PET scan performed at one of 13 UK imaging centres (all calibrated for quality control purposes by phantom imaging) and if this is reported -ve for HL (score 1 or 2 on a 5 point scale) following central review at the Core Lab in London, pts are randomised between involved field RT and no further treatment. Those with a PET scan ‘positive’ (+ve) for HL (score 3, 4 or 5) have a 4th cycle of ABVD and involved field RT. When 320 PET -ve pts have been randomised the trial is powered to exclude a 10% difference in PFS with 90% power. At the time of analysis in May 2008, 369 pts (190 male, 179 female; median age 34.5 yrs) had been registered since trial activation in October 2003. Following 3 cycles ABVD, 331 have had a PET scan which at central review has been allocated a score of 1 (n=203, 61%), 2 (n=58, 18%), 3 (n=35, 11%), 4 (n=20, 6%) or 5 (n=15, 4%) giving an overall PET -ve rate (score 1 or 2) of 79%. 255 PET -ve pts have been randomised to receive involved field RT (n=125, 49%) or no further treatment (n=130, 51%). 6 pts have not been randomised (pt choice, 2; randomization data entered after database frozen for analysis, 2; clinician choice, 1; error, 1). After a median of 13 months from randomisation, 245 of 255 (96%) pts are alive and progression free, 6 (2%) have progressed and 4 (1.5%) have died (HL, 1; treatment related, 1; other 2). In this the 2nd planned, interim analysis of RAPID, we have shown that designation of PET -ve/+ve status at Core Lab review is feasible and patients are willing to undergo randomisation to answer a de-escalation of therapy question. The PET +ve rate of 21% after 3 cycles ABVD is at the upper end of the expected range and the event rate after short follow-up is very low. Accrual continues with an extended recruitment target of 535 to facilitate exclusion of a 7% difference between the randomised arms. This is based on views obtained from a survey undertaken at the 7th International Symposium on Hodgkin lymphoma (Cologne, Germany, 2007)1 1 Capturing expert opinion at an international meeting (IM) to understand what constitutes a practice changing result in an NCRN clinical trial featuring de-escalation of treatment in Hodgkin lymphoma (HL). Radford J et al, NCRI conference, Birmingham UK, October 2008

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S169. THE IMPACT OF PSYCHOSIS IN ADOLESCENT-ONSET BIPOLAR DISORDER: A STRUCTURAL MRI STUDY

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa031.235 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S101-S101

Author(s):

Cristian Llach ◽

Adriana Fortea ◽

Isabel Valli ◽

Iria Mendez ◽

Sara Lera ◽

...

Keyword(s):

Bipolar Disorder ◽

Cortical Thickness ◽

Orbitofrontal Cortex ◽

Child And Adolescent ◽

Psychotic Symptoms ◽

Adolescent Patients ◽

Bipolar Patients ◽

Psychotic Features ◽

The Impact ◽

Psychotic Bipolar Disorder

Abstract Background Bipolar Disorder (BD) is a major psychiatric illness defined by episodic mood changes, which in approximately 50% of cases is associated with psychotic features. Over the past decades, a large amount of research has identified brain structural and functional alterations in patients with this mental disorder. Some findings have been found to be specific to patients with psychotic symptoms, raising suggestions that this could represent a biological subtype of the disorder. Recent interest has been addressed to Early-Onset Bipolar Disorder (EOBD, onset prior to age 18). Latest reviews in EOBD samples have pointed to abnormalities in the frontal lobe and limbic structures, with some inconsistencies in the reported results possibly caused by differences in the methodology. In addition, no study so far has examined the neural structural correlates of psychotic symptoms in adolescent-onset bipolar disorder (AOBD). The aim of the present study is to examine the impact of psychosis on the neurobiological architecture in a sample of patients with AOBD. To our knowledge, this is the first study comparing gray matter structure between AOBD patients with or without psychotic features. Methods We conducted a cross-sectional study collecting T1-weighted structural magnetic resonance neuroimaging (3T-MRI) data in patients diagnosed with Bipolar Disorder type I or II between 12 and 19 years old (N=46, mean age (SD)=15.89 (1.94), gender=52.2% females). All patients were recruited from child and adolescent mental health services of the Hospital Clinic of Barcelona, Spain. Diagnoses were confirmed with a semi-structured clinical interview (Kiddie-Sads present and lifetime version) by child and adolescent psychiatrists. Images were pre-processed employing FreeSurfer 5.3.0, and data corresponding to Cortical Thickness (CTH) and Subcortical Volumes (SCV) was obtained. Groups were compared according to whether patients had experienced psychotic symptoms at any point during their illness: Non-Psychotic Bipolar Disorder (NPSBD, N=25) and Psychotic Bipolar Disorder (PSBD, N=21). No differences in age (t=0.498, p=0.621) or sex (χ2=0.001, p=0.979). Group effects in relation to both CT and SCV were examined with a general linear model. The main effect of group on CTH and SCV, was performed for the whole brain, performing a correction for multiple comparisons (Montecarlo correction, threshold = 0.05). Results Between-group analyses showed smaller CTH in a cluster in the left medial orbitofrontal cortex (cluster size= 1142.58 mm2) in PSBD relative to NPSBD (x, y, z: 25.63, 89.61, -42.74; p=0.002). In addition, we observed a smaller right hippocampus volume (p=0.025) in PSBD relative to NPSBD. No other statistically significant differences were obtained. Discussion PSBD showed smaller cortical thickness in the left medial orbitofrontal cortex, as well as a volumetric reduction in the right hippocampal volume. Similar results have been reported in a study comparing adolescent patients with psychotic BD and healthy controls. These results add evidence about the role of these two structures in the genesis of psychotic symptoms in a population diagnosed with AOBD. Interestingly, one study has reported a surface area decreased of the orbitofrontal cortex in adolescent patients with a non-bipolar psychotic disorder, which suggests that they may be a common substrate to psychotic symptoms during adolescence regardless of co-occurring affective symptoms. In summary, this study points to the existence of a distinct biological nature between bipolar patients according to psychotic symptoms, underpinned by a different neurobiological architecture. Future research should focus on replication and on examining the clinical value of this finding.

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T56. RISKY DECISION-MAKING IMPAIRMENT IN EARLY-STAGE PSYCHOTIC BIPOLAR DISORDER

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa029.616 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S252-S253

Author(s):

Mary Chung Man Ng ◽

Joe Kwun Nam Chan ◽

Martha Luk ◽

Cheuk Fei Wong ◽

Sui Fung Wo ◽

...

Keyword(s):

Decision Making ◽

Bipolar Disorder ◽

Early Stage ◽

Healthy Controls ◽

Risky Decision Making ◽

Risky Decision ◽

Cumulative Score ◽

Study Results ◽

Adjusted Score ◽

Psychotic Bipolar Disorder

Abstract Background Previous research suggests that bipolar disorder may be associated with increased risk-taking / impulsivity. Risky decision-making paradigm is an objective, performance-based measure which has been increasingly applied in bipolar disorder research examining. Nonetheless, literature focused only on chronically ill samples, with illness chronicity, clinical heterogeneity and prolonged medication exposure being potential confounding factors of study results. The current study aimed to explore whether patients with early-stage psychotic bipolar disorder (BDP) exhibit impaired risky decision-making relative to healthy controls, using a well-validated, widely-applied experimental paradigm of Balloon Analogue Risk Task (BART). Methods Thirty-nine patients with early-stage BDP (defined by having received psychiatric treatment for first-episode BDP within 3 years since service entry) and 36 demographically matched healthy controls were recruited. BART was administered to examine risky decision-making performance. Deliberative risky behavior was operationalized as the willingness to inflate balloons as each pump was accompanied by an extra point gained in the temporary repository or balloon explosion. Three performance-based indices (adjusted score, explosion rate and cumulative score) were derived and analyzed. Results There were no significant differences between patients and controls in age, gender and educational levels. Independent samples t-tests illustrated that patients had significantly lower adjusted score (t = -3.45, p = .001, d = .791), explosion rate (t = -2.75, p = .007, d = .631) and cumulative score (t = -3.07, p = .003, d = .714) in BART compared to controls. Similar findings were obtained when comparison analyses were restricted to patients who were treated with antipsychotic medications at the time of study assessment (n = 30). No significant correlations between BART performance-based indices and measures of clinical and treatment variables were found in patient sample. Discussion Our results demonstrated that early-stage BDP patients displayed suboptimal risky decision-making compared with controls. Abnormal risky decision-making observed in the euthymic state of patients in early stage of bipolar disorder suggests that such impairment might represent a trait factor in the disorder. Further prospective research is warranted to clarify the longitudinal course of risky decision-making impairment in bipolar disorder.

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S82. REINFORCEMENT LEARNING IMPAIRMENT IN PATIENTS WITH EARLY-STAGE PSYCHOTIC BIPOLAR DISORDER

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa031.148 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S65-S65

Author(s):

Joe Kwun Nam Chan ◽

Mary Chung Man Ng ◽

Cheuk Fei Wong ◽

Sui Fung Wo ◽

Corine Sau Man Wong ◽

...

Keyword(s):

Bipolar Disorder ◽

Reinforcement Learning ◽

Negative Reinforcement ◽

Early Stage ◽

Reward Sensitivity ◽

Learning Performance ◽

Loss Avoidance ◽

Learning Measures ◽

Learning Impairment ◽

Psychotic Bipolar Disorder

Abstract Background Abnormal reward sensitivity is a biosignature to mood disorders spectrum. Recent data suggested either elevated or preserved positive but impaired negative reinforcement learning in patients with bipolar disorder. Functional MRI studies provided extra evidence on heightened reward sensitivity in manic patients. Of note, these investigations mostly rest on chronically ill samples, conditions of whom may have been confounded by prolonged exposure to medications. This study aims to examine reinforcement learning performance and its relationship with symptomology in patients with early-stage psychotic bipolar disorder (BDP). Methods This study is based on 38 patients with early-stage BDP (defined by having received psychiatric treatment for first-episode BDP within 3 years since service entry) who have been euthymic for at least eight weeks and 40 demographically-matched controls. Reinforcement learning performance was evaluated using Gain-vs-Loss-Avoidance Task (GLAT), which measured the correct responses in both gain and loss-avoidance pairs with reinforcement probability at either 90% or 80% across four blocks in the training phase and one block in the test/transfer phase. Comparison analyses on reinforcement learning performance were conducted on two groups. Associations of reinforcement learning measures with symptom scores, cognitive functions and functioning measures were also tested. Results There was no group difference in gender, age or education level. Repeated-measures analysis of variance (ANOVA) showed significant main effects of group (F=6.52, p=0.013), block (F=43.71, p<0.001), probability (F= 5.58, p<0.001), and block x group (F=2.87, p=0.040) interaction. Post-hoc tests revealed that controls performed better than patients across blocks (p<0.05). Patients also showed a lower lose-shift rate (t= 2.21, p=0.03) and punishment-driven learning accuracy rates (t=2.42, p=0.018) than controls. Marginally significant main effect of stimulus pair (F=3.98, p=0.05) was revealed in the test phase, with controls showing a significantly higher preference in Frequent Winner vs Frequent Loser (FWFL) pair than patients (t=-2.25, p=0.028). No significant correlations between learning measures and any of the symptom dimensions in patient sample. Discussion Our preliminary findings provided a brief evidence on the negative reinforcement learning impairment in early-stage BDP patients. Further investigation is required to verify and confirm our results of impaired negative reinforcement learning in the initial course of bipolar disorder.

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