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Neuropsychological and social cognitive function in young people at genetic risk of bipolar disorder
McCormack, C; Green, M J; Rowland, J E; Roberts, G; Frankland, A; Hadzi-Pavlovic, D; Joslyn, C; Lau, P; Wright, A; Levy, F; Lenroot, R K; Mitchell, P B
BACKGROUND:Impairments in key neuropsychological domains (e.g. working memory, attention) and social cognitive deficits have been implicated as intermediate (endo) phenotypes for bipolar disorder (BD), and should therefore be evident in unaffected relatives. METHOD/METHODS:Neurocognitive and social cognitive ability was examined in 99 young people (age range 16-30 years) with a biological parent or sibling diagnosed with the disorder [thus deemed to be at risk (AR) of developing BD], compared with 78 healthy control (HC) subjects, and 52 people with a confirmed diagnosis of BD. RESULTS:Only verbal intelligence and affective response inhibition were significantly impaired in AR relative to HC participants; the BD participants showed significant deficits in attention tasks compared with HCs. Neither AR nor BD patients showed impairments in general intellectual ability, working memory, visuospatial or language ability, relative to HC participants. Analysis of BD-I and BD-II cases separately revealed deficits in attention and immediate memory in BD-I patients (only), relative to HCs. Only the BD (but not AR) participants showed impaired emotion recognition, relative to HCs. CONCLUSIONS:Selective cognitive deficits in the capacity to inhibit negative affective information, and general verbal ability may be intermediate markers of risk for BD; however, the extent and severity of impairment in this sample was less pronounced than has been reported in previous studies of older family members and BD cases. These findings highlight distinctions in the cognitive profiles of AR and BD participants, and provide limited support for progressive cognitive decline in association with illness development in BD.
PMID: 26621494
ISSN: 1469-8978
CID: 5275812
What clinical features precede the onset of bipolar disorder?
Perich, Tania; Lau, Phoebe; Hadzi-Pavlovic, Dusan; Roberts, Gloria; Frankland, Andrew; Wright, Adam; Green, Melissa; Breakspear, Michael; Corry, Justine; Radlinska, Basia; McCormack, Clare; Joslyn, Cassandra; Levy, Florence; Lenroot, Rhoshel; Nurnberger Jnr, John I; Mitchell, Philip B
Despite a growing number of reports, there is still limited knowledge of the clinical features that precede the onset of bipolar disorder (BD). To explore this, we investigated baseline data from a prospectively evaluated longitudinal cohort of subjects aged 12-30 years to compare: first, lifetime rates of clinical features between a) subjects at increased genetic risk for developing BD ('AR'), b) participants from families without mental illness ('controls'), and c) those with established BD; and, second, prior clinical features that predict the later onset of affective disorders in these same three groups. This is the first study to report such comparisons between these three groups (though certainly not the first to compare AR and control samples). 118 AR participants with a parent or sibling with BD (including 102 with a BD parent), 110 controls, and 44 BD subjects were assessed using semi-structured interviews. AR subjects had significantly increased lifetime risks for depressive, anxiety and behavioural disorders compared to controls. Unlike prior reports, preceding anxiety and behavioural disorders were not found to increase risk for later onset of affective disorders in the AR sample, perhaps due to limited sample size. However, preceding behavioural disorders did predict later onset of affective disorders in the BD sample. The findings that i) AR subjects had higher rates of depressive, anxiety and behavioural disorders compared to controls, and ii) prior behavioural disorders increased the risk to later development of affective disorders in the BD group, suggest the possibility of therapeutic targeting for these disorders in those at high genetic risk for BD.
PMID: 25700556
ISSN: 1879-1379
CID: 5262352
Expert and competent non-expert visual cues during simulated diagnosis in intensive care
McCormack, Clare; Wiggins, Mark W; Loveday, Thomas; Festa, Marino
The aim of this study was to examine the information acquisition strategies of expert and competent non-expert intensive care physicians during two simulated diagnostic scenarios involving respiratory distress in an infant. Specifically, the information acquisition performance of six experts and 12 competent non-experts was examined using an eye-tracker during the initial 90 s of the assessment of the patient. The results indicated that, in comparison to competent non-experts, experts recorded longer mean fixations, irrespective of the scenario. When the dwell times were examined against specific areas of interest, the results revealed that competent non-experts recorded greater overall dwell times on the nurse, where experts recorded relatively greater dwell times on the head and face of the manikin. In the context of the scenarios, experts recorded differential dwell times, spending relatively more time on the head and face during the seizure scenario than during the coughing scenario. The differences evident between experts and competent non-experts were interpreted as evidence of the relative availability of task-specific cues or heuristics in memory that might direct the process of information acquisition amongst expert physicians. The implications are discussed for the training and assessment of diagnostic skills.
PMCID:4144005
PMID: 25206348
ISSN: 1664-1078
CID: 5262342
Reduced inferior frontal gyrus activation during response inhibition to emotional stimuli in youth at high risk of bipolar disorder
Roberts, Gloria; Green, Melissa J; Breakspear, Michael; McCormack, Clare; Frankland, Andrew; Wright, Adam; Levy, Florence; Lenroot, Rhoshel; Chan, Herng Nieng; Mitchell, Philip B
BACKGROUND:Functional brain imaging of young people at increased genetic risk for bipolar disorder provides a means of identifying potential endophenotypes for this condition. Dysfunctional neural mechanisms for the cognitive control of emotion are implicated in the genetic predisposition to bipolar disorder, with aberrant activity in frontocortical, striatal, and limbic brain regions previously reported in subjects with established bipolar disorder during inhibitory and emotion processing tasks. METHODS:Functional brain activity during inhibition of emotional material in young people at increased genetic risk for bipolar disorder was investigated using a facial-emotion go/no-go task during functional magnetic resonance imaging. Data from 47 genetically high-risk individuals aged 18 to 30 years with at least one first-degree relative with bipolar disorder were compared with 49 control subjects (within the same age range but without a family history of bipolar disorder or other severe mental illness). RESULTS:Whole-brain corrected analyses revealed a highly specific and significant lack of recruitment of the inferior frontal gyrus when inhibiting responses to fearful faces in the high-risk participants compared with control subjects (p = .011, family-wise error, peak voxel). CONCLUSIONS:Impaired inhibitory function of the inferior frontal cortex may represent a trait marker of vulnerability to bipolar disorder. That this finding was revealed during inhibition of emotional material further implicates dysregulated frontolimbic brain networks as a potential neurocognitive endophenotype for bipolar disorder and provides evidence for pre-existing functional disturbances in those at high genetic risk for bipolar disorder.
PMID: 23245750
ISSN: 1873-2402
CID: 5262332
Size and Shape of the Thalamus and Hippocampus in Young People at High Genetic Risk of Developing Bipolar Disorder [Meeting Abstract]
Roberts, Gloria; Wen, Wei; Lenroot, Rhoshel; Jiang, Jiyang; Breakspear, Michael; Green, Melissa; Joslyn, Cassandra; McCormack, Clare; Frankland, Andrew; Mitchell, Philip
ISI:000318671800581
ISSN: 0006-3223
CID: 5262662
Social cognition in young people at-risk for bipolar disorder: associations with neurocognition and emotion regulation [Meeting Abstract]
Green, M. J.; Roberts, G.; McCormack, C.; Frankland, A.; Wright, A.; Rowland, Jesseca; Hadzi-Pavlovic, Dusan; Levy, F.; Lenroot, R.; Mitchell, P. B.
ISI:000301531000177
ISSN: 1398-5647
CID: 5262652
Reduced inferior frontal gyrus activation during emotion inhibition in young people at increased genetic risk for bipolar disorder [Meeting Abstract]
Mitchell, P. B.; Roberts, G.; Green, M. J.; Breakspear, M.; McCormack, C.; Frankland, A.; Wright, A.; Levy, F.; Lenroot, R.; Chan, H. N.
ISI:000301531000078
ISSN: 1398-5647
CID: 5262642
Reduced inferior frontal gyrus activation during emotion inhibition in young people at increased genetic risk for bipolar disorder [Meeting Abstract]
Mitchell, P.; Roberts, G.; Green, M.; Breakspear, M.; Frankland, A.; McCormack, C.; Wright, A.; Levy, F.; Lenroot, R.; Chan, H.
ISI:000209062500312
ISSN: 1461-1457
CID: 5262612
Impaired inferior frontal gyrus response to an emotional inhibition task in young first-degree relatives of bipolar disorder patients compared to controls [Meeting Abstract]
Roberts, G.; Green, M. J.; Breakspear, M.; McCormack, C.; Frankland, A.; Wright, A.; McCue, C.; Hadzi-Pavlovic, D.; Levy, F.; Lino, B.; Lenroot, R.; Corry, J.; Mitchell, P. B.
ISI:000300102400198
ISSN: 1398-5647
CID: 5262632
Impaired Inferior Frontal Gyrus Response to an Emotional Inhibition Task in Young First-degree Relatives of Bipolar Disorder Patients Compared to Controls [Meeting Abstract]
Roberts, Gloria; Green, Melissa; Breakspear, Michael; McCormack, Clare; Frankland, Andrew; Wright, Adam; McCue, Caitlin; Hadzi-Pavlovic, Dusan; Levy, Florence; Lino, Bianca; Lenroot, Rhoshel; Corry, Justine; Mitchell, Philip
ISI:000290641800553
ISSN: 0006-3223
CID: 5262622