Examining cognition across the bipolar/schizophrenia diagnostic spectrum

Lynham, Amy; Hubbard, Leon; Tansey, Katherine E.; Hamshere, Marian L.; Legge, Sophie E.; Jones, Ian; Walters, James

doi:10.1503/jpn.170076

Cited by 56 publications

(25 citation statements)

References 47 publications

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“…There was no difference in age between the groups ( P > .1). Participants were recruited from the Cognition in Psychosis study (Schizophrenia Working Group of the Psychiatric Genomics Consortium 17 ), with full details of the case sample recruitment and procedures are provided in Lynham et al 18 Controls were recruited primarily through an advert placed on the Cardiff University Noticeboard system and opportunistically from CUBRIC, Cardiff University. This study was approved by the NHS ethics Board and also the Cardiff University School of Psychology Ethics Board.…”

Section: Methodsmentioning

confidence: 99%

Oscillatory, Computational, and Behavioral Evidence for Impaired GABAergic Inhibition in Schizophrenia

Shaw

Knight

Freeman

et al. 2019

Schizophrenia Bulletin

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The dysconnection hypothesis of schizophrenia (SZ) proposes that psychosis is best understood in terms of aberrant connectivity. Specifically, it suggests that dysconnectivity arises through aberrant synaptic modulation associated with deficits in GABAergic inhibition, excitation–inhibition balance and disturbances of high-frequency oscillations. Using a computational model combined with a graded-difficulty visual orientation discrimination paradigm, we demonstrate that, in SZ, perceptual performance is determined by the balance of excitation–inhibition in superficial cortical layers. Twenty-eight individuals with a DSM-IV diagnosis of SZ, and 30 age- and gender-matched healthy controls participated in a psychophysics orientation discrimination task, a visual grating magnetoencephalography (MEG) recording, and a magnetic resonance spectroscopy (MRS) scan for GABA. Using a neurophysiologically informed model, we quantified group differences in GABA, gamma measures, and the predictive validity of model parameters for orientation discrimination in the SZ group. MEG visual gamma frequency was reduced in SZ, with lower peak frequency associated with more severe negative symptoms. Orientation discrimination performance was impaired in SZ. Dynamic causal modeling of the MEG data showed that local synaptic connections were reduced in SZ and local inhibition correlated negatively with the severity of negative symptoms. The effective connectivity between inhibitory interneurons and superficial pyramidal cells predicted orientation discrimination performance within the SZ group; consistent with graded, behaviorally relevant, disease-related changes in local GABAergic connections. Occipital GABA levels were significantly reduced in SZ but did not predict behavioral performance or oscillatory measures. These findings endorse the importance, and behavioral relevance, of GABAergic synaptic disconnection in schizophrenia that underwrites excitation–inhibition balance.

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Section: Methodsmentioning

confidence: 99%

Oscillatory, Computational, and Behavioral Evidence for Impaired GABAergic Inhibition in Schizophrenia

Shaw

Knight

Freeman

et al. 2019

Schizophrenia Bulletin

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“…Although current statistical evidence for specific risk CNVs in BD is weak, some CNVs have similar effect sizes to those observed in MDD (Supplementary Table S1), suggesting that larger samples may identify robust associations. However, the lack of robust CNV associations in BD could also, in part, be due to the less severe impairments in cognitive function that are found in BD patients when compared with other psychiatric disorders, such as schizophrenia [ 23 , 24 ], given neuropsychiatric CNVs have been associated with reduced cognitive function in the general population [ 25 ]. In support of this hypothesis, a recent study evaluated CNVs across different BD subphenotypes and found a significant enrichment of CNVs only in schizoaffective bipolar (SAB) cases compared to controls [ 26 • ], and patients diagnosed with SAB have greater cognitive impairments compared with patients with a diagnosis of BD type I or II [ 23 ].…”

Section: Neuropsychiatric Cnv Locimentioning

confidence: 99%

“…However, the lack of robust CNV associations in BD could also, in part, be due to the less severe impairments in cognitive function that are found in BD patients when compared with other psychiatric disorders, such as schizophrenia [ 23 , 24 ], given neuropsychiatric CNVs have been associated with reduced cognitive function in the general population [ 25 ]. In support of this hypothesis, a recent study evaluated CNVs across different BD subphenotypes and found a significant enrichment of CNVs only in schizoaffective bipolar (SAB) cases compared to controls [ 26 • ], and patients diagnosed with SAB have greater cognitive impairments compared with patients with a diagnosis of BD type I or II [ 23 ]. Studies of common alleles in BD have also found evidence for genetic heterogeneity across BD subphenotypes, where significant elevations of schizophrenia PRS are found in SAB compared with other BD subphenotypes [ 27 , 28 ].…”

Section: Neuropsychiatric Cnv Locimentioning

confidence: 99%

Copy number variation and neuropsychiatric illness

Rees

Kirov

2021

Current Opinion in Genetics & Development

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Graphical abstract Identification of neuropsychiatric CNVs. A) Schematic of a deletion and duplication. B) Example of a locus enriched for deletions in cases. C) Number of risk CNVs implicated in published studies of neuropsychiatric disorders. The number of cases included in each study is shown on the x axis, and larger points represent studies with more control samples (see Table 1 for further details). SCZ = schizophrenia, ASD = autism spectrum disorder, ID = intellectual disability, MDD = major depressive disorder, ADHD = attention-deficit hyperactivity disorder, TS = Tourette syndrome, OCD = obsessive compulsive disorder, BD = bipolar disorder.

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“…Control participants were neurologically and psychology healthy, and matched patients on age and gender. Patients were recruited through the Cognition and Psychosis study (i.e., from the Schizophrenia Working Group of the Psychiatric Genomics Consortium; details of the case sample recruitment and procedures are provided in ( Lynham et al, 2018 )), while controls were primarily recruited through ads using the Cardiff University Noticeboard and opportunistically from CUBRIC, Cardiff University. One patient was excluded due to the quality of their recording, and three controls were excluded due to the lack of a complete set of recording conditions.…”

Section: Methodsmentioning

confidence: 99%

Patient, interrupted: MEG oscillation dynamics reveal temporal dysconnectivity in schizophrenia

Alamian

Pascarella

Lajnef

et al. 2020

NeuroImage: Clinical

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Highlights Temporal autocorrelation is attenuated in the neural dynamics of schizophrenia. Alterations are primarily observed in the alpha and beta frequency bands. Machine-learning significantly classified patients and controls with 82% accuracy. Brain regions showing disrupted temporal connectivity include (para)limbic areas. Long-range temporal correlation informs on temporal dysconnectivity in schizophrenia.

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Examining cognition across the bipolar/schizophrenia diagnostic spectrum

Cited by 56 publications

References 47 publications

Oscillatory, Computational, and Behavioral Evidence for Impaired GABAergic Inhibition in Schizophrenia

Oscillatory, Computational, and Behavioral Evidence for Impaired GABAergic Inhibition in Schizophrenia

Copy number variation and neuropsychiatric illness

Patient, interrupted: MEG oscillation dynamics reveal temporal dysconnectivity in schizophrenia

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