scholarly journals Network Constraints on Longitudinal Grey Matter Changes in First Episode Psychosis

Author(s):  
Sidhant Chopra ◽  
Stuart Oldham ◽  
Ashlea Segal ◽  
Alexander Holmes ◽  
Kristina Sabaroedin ◽  
...  

Background: Different regions of the brain's grey matter are connected by a complex structural network of white matter fibres which are responsible for the propagation of action potentials and the transport of trophic and other molecules. In neurodegenerative disease, these connections constrain the way in which grey matter volume loss progresses. Here, we investigated whether connectome architecture also shapes the spatial pattern of longitudinal grey matter volume changes attributable to illness and antipsychotic medication in first episode psychosis (FEP). Methods: We conducted a triple-blind randomised placebo-control MRI study where 62 young adults with first episode psychosis received either an atypical antipsychotic or placebo over 6-months. A healthy control group was also recruited. Anatomical MRI scans were acquired at baseline, 3-months and 12-months. Deformation-based morphometry was used to estimate illness-related and antipsychotic-related grey matter volume changes over time. Representative functional and structural brain connectivity patterns were derived from an independent healthy control group using resting-state functional MRI and diffusion-weighted imaging. We used neighbourhood deformation models to predict the extent of brain change in a given area by the changes observed in areas to which it is either structurally connected or functionally coupled. Results: At baseline, we found that empirical illness-related regional volume differences were strongly correlated with predicted differences using a model constrained by structural connectivity weights (ρ = .541; p < .001). At 3-months and 12-months, we also found a strong correlation between longitudinal regional illness-related (ρ > .516; p < .001) and antipsychotic-related volume change (ρ > .591; p < .001) with volumetric changes in structurally connected areas. These correlations were significantly greater than those observed across various null models accounting for lower-order spatial and network properties of the data. Associations between empirical and predicted volume change estimates were much lower for models that only considered binary structural connectivity (all ρ < .376), or which were constrained by inter-regional functional coupling (all ρ < .436). Finally, we found that potential epicentres of volume change emerged posteriorly early in the illness and shifted to the prefrontal cortex by later illness stages. Conclusion: Psychosis- and antipsychotic-related grey matter volume changes are strongly shaped by anatomical brain connectivity. This result is consistent with findings in other neurological disorders and implies that such connections may constrain pathological processes causing brain dysfunction in FEP.

2010 ◽  
Vol 117 (2-3) ◽  
pp. 340
Author(s):  
J. McFarland ◽  
D. Cannon ◽  
H. Schmidt ◽  
M. Ahmed ◽  
S. Hehir ◽  
...  

2009 ◽  
Vol 194 (5) ◽  
pp. 426-433 ◽  
Author(s):  
Alex Fornito ◽  
Murat Yücel ◽  
Stephen J. Wood ◽  
Andreas Bechdolf ◽  
Simon Carter ◽  
...  

BackgroundThe anterior cingulate cortex is frequently implicated in the pathophysiology of bipolar disorder, but magnetic resonance imaging (MRI) studies have reported variable findings owing to a reliance on patient samples with chronic illness and to limited appreciation of the region's heterogeneity.AimsTo characterise anterior cingulate cortex abnormalities in patients with bipolar disorder experiencing their first episode of psychosis while accounting for regional anatomical variability.MethodGrey matter volume, surface area and cortical thickness were measured in six anterior cingulate cortex subregions per hemisphere using MRI scans acquired from 26 patients with bipolar I disorder experiencing first-episode psychosis and 26 healthy controls matched for age, gender and regional morphological variability.ResultsRelative to controls, male patients displayed increased thickness in the right subcallosal limbic anterior cingulate cortex. No significant differences were identified in females for grey matter volume or surface area measures. The findings were not attributable to medication effects.ConclusionsThese data suggest that first-episode psychosis in bipolar disorder is associated with a gender-specific, right-lateralised thickness increase in anterior cingulate cortex subregions known to play a role in regulating physiological stress responses.


2018 ◽  
Vol 23 (3) ◽  
pp. 165-179 ◽  
Author(s):  
Geoff Davies ◽  
Charlotte L. Rae ◽  
Sarah N. Garfinkel ◽  
Anil K. Seth ◽  
Nick Medford ◽  
...  

2009 ◽  
Vol 40 (7) ◽  
pp. 1137-1147 ◽  
Author(s):  
K. D. Morgan ◽  
P. Dazzan ◽  
C. Morgan ◽  
J. Lappin ◽  
G. Hutchinson ◽  
...  

BackgroundAfrican-Caribbean and black African people living in the UK are reported to have a higher incidence of diagnosed psychosis compared with white British people. It has been argued that this may be a consequence of misdiagnosis. If this is true they might be less likely to show the patterns of structural brain abnormalities reported in white British patients. The aim of this study therefore was to investigate whether there are differences in the prevalence of structural brain abnormalities in white and black first-episode psychosis patients.MethodWe obtained dual-echo (proton density/T2-weighted) images from a sample of 75 first-episode psychosis patients and 68 healthy controls. We used high resolution magnetic resonance imaging and voxel-based methods of image analysis. Two separate analyses were conducted: (1) 34 white British patients were compared with 33 white British controls; (2) 41 African-Caribbean and black African patients were compared with 35 African-Caribbean and black African controls.ResultsWhite British patients and African-Caribbean/black African patients had ventricular enlargement and increased lenticular nucleus volume compared with their respective ethnic controls. The African-Caribbean/black African patients also showed reduced global grey matter and increased lingual gyrus grey-matter volume. The white British patients had no regional or global grey-matter loss compared with their normal ethnic counterparts but showed increased grey matter in the left superior temporal lobe and right parahippocampal gyrus.ConclusionsWe found no evidence in support of our hypothesis. Indeed, the finding of reduced global grey-matter volume in the African-Caribbean/black African patients but not in the white British patients was contrary to our prediction.


2010 ◽  
Vol 41 (8) ◽  
pp. 1677-1689 ◽  
Author(s):  
M. S. Schaufelberger ◽  
J. M. Lappin ◽  
F. L. S. Duran ◽  
P. G. P. Rosa ◽  
R. R. Uchida ◽  
...  

BackgroundSome neuroimaging studies have supported the hypothesis of progressive brain changes after a first episode of psychosis. We aimed to determine whether (i) first-episode psychosis patients would exhibit more pronounced brain volumetric changes than controls over time and (ii) illness course/treatment would relate to those changes.MethodLongitudinal regional grey matter volume and ventricle:brain ratio differences between 39 patients with first-episode psychosis (including schizophrenia and schizophreniform disorder) and 52 non-psychotic controls enrolled in a population-based case-control study.ResultsWhile there was no longitudinal difference in ventricle:brain ratios between first-episode psychosis subjects and controls, patients exhibited grey matter volume changes, indicating a reversible course in the superior temporal cortex and hippocampus compared with controls. A remitting course was related to reversal of baseline temporal grey matter deficits.ConclusionsOur findings do not support the hypothesis of brain changes indicating a progressive course in the initial phase of psychosis. Rather, some brain volume abnormalities may be reversible, possibly associated with a better illness course.


Author(s):  
Sidhant Chopra ◽  
Alex Fornito ◽  
Shona M. Francey ◽  
Brian O’Donoghue ◽  
Vanessa Cropley ◽  
...  

AbstractChanges in brain volume are a common finding in Magnetic Resonance Imaging (MRI) studies of people with psychosis and numerous longitudinal studies suggest that volume deficits progress with illness duration. However, a major unresolved question concerns whether these changes are driven by the underlying illness or represent iatrogenic effects of antipsychotic medication. In this study, 62 antipsychotic-naïve patients with first-episode psychosis (FEP) received either a second-generation antipsychotic (risperidone or paliperidone) or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n = 27) was also recruited. Structural MRI scans were obtained at baseline, 3 months and 12 months. Our primary aim was to differentiate illness-related brain volume changes from medication-related changes within the first 3 months of treatment. We secondarily investigated long-term effects at the 12-month timepoint. From baseline to 3 months, we observed a significant group x time interaction in the pallidum (p < 0.05 FWE-corrected), such that patients receiving antipsychotic medication showed increased volume, patients on placebo showed decreased volume, and healthy controls showed no change. Across the entire patient sample, a greater increase in pallidal grey matter volume over 3 months was associated with a greater reduction in symptom severity. Our findings indicate that psychotic illness and antipsychotic exposure exert distinct and spatially distributed effects on brain volume. Our results align with prior work in suggesting that the therapeutic efficacy of antipsychotic medications may be primarily mediated through their effects on the basal ganglia.


2020 ◽  
Author(s):  
Sidhant Chopra ◽  
Alex Fornito ◽  
Shona M. Francey ◽  
Brian O’Donoghue ◽  
Vanessa Cropley ◽  
...  

AbstractBackgroundPsychotic disorders are associated with reductions in brain volume, but the timing and causes of these reductions remain unclear. In particular, the effects of antipsychotic medication and illness have been difficult to disentangle due to a lack of prospective, longitudinal, randomized placebo-controlled designs.MethodsWe conducted a triple-blind randomised placebo-controlled trial where 62 antipsychotic naïve patients with first episode psychosis (FEP) received either an atypical antipsychotic or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n=27) was also recruited. Structural MRI scans were obtained at baseline, 3-months and 12-months. Our primary aim was to differentiate illness-related brain volume changes from medication-related changes within the first 3 months of treatment. We secondarily investigated long-term effects at the 12-month timepoint.OutcomeFrom baseline to 3 months, we observed a significant group × time interaction in the pallidum, such that patients receiving atypical antipsychotics showed increased volume, patients on placebo showed decreased volume, and healthy controls showed no change. In patients, a greater increase in pallidal grey matter volume over 3 months was associated with a greater reduction in symptom severity, consistent with a neuroprotective effect of atypical antipsychotics. We additionally found preliminary evidence for illness-related volume reductions in prefrontal cortices at 12 months and putative antipsychotic-related neurotoxicity in cerebellum at both 3-months and 12-months.InterpretationOur findings indicate that psychotic illness and antipsychotic exposure exert distinct and spatially distributed effects on brain volume. Our results align with prior work in suggesting that the therapeutic efficacy of antipsychotics may be primarily mediated through their effects on the basal ganglia.Trial registrationACTRN12607000608460.


2012 ◽  
Vol 43 (3) ◽  
pp. 591-602 ◽  
Author(s):  
A. M. Dean ◽  
E. Goodby ◽  
C. Ooi ◽  
P. J. Nathan ◽  
B. R. Lennox ◽  
...  

BackgroundPsychotic disorders are highly heritable such that the unaffected relatives of patients may manifest characteristics, or endophenotypes, that are more closely related to risk genes than the overt clinical condition. Facial affect processing is dependent on a distributed cortico-limbic network that is disrupted in psychosis. This study assessed facial affect processing and related brain structure as a candidate endophenotype of first-episode psychosis (FEP).MethodThree samples comprising 30 FEP patients, 30 of their first-degree relatives and 31 unrelated healthy controls underwent assessment of facial affect processing and structural magnetic resonance imaging (sMRI) data. Multivariate analysis (partial least squares, PLS) was used to identify a grey matter (GM) system in which anatomical variation was associated with variation in facial affect processing speed.ResultsThe groups did not differ in their accuracy of facial affect intensity rating but differed significantly in speed of response, with controls responding faster than relatives, who responded faster than patients. Within the control group, variation in speed of affect processing was significantly associated with variation of GM density in amygdala, lateral temporal cortex, frontal cortex and cerebellum. However, this association between cortico-limbic GM density and speed of facial affect processing was absent in patients and their relatives.ConclusionsSpeed of facial affect processing presents as a candidate endophenotype of FEP. The normal association between speed of facial affect processing and cortico-limbic GM variation was disrupted in FEP patients and their relatives.


2013 ◽  
Vol 44 (6) ◽  
pp. 1279-1291 ◽  
Author(s):  
J. M. Lappin ◽  
C. Morgan ◽  
S. Chalavi ◽  
K. D. Morgan ◽  
A. A. T. S. Reinders ◽  
...  

BackgroundHippocampal pathology has been proposed to underlie clinical, functional and cognitive impairments in schizophrenia. The hippocampus is a highly plastic brain region; examining change in volume, or change bilaterally, over time, can advance understanding of the substrate of recovery in psychosis.MethodMagnetic resonance imaging and outcome data were collected at baseline and 6-year follow-up in 42 first-episode psychosis subjects and 32 matched controls, to investigate whether poorer outcomes are associated with loss of global matter and hippocampal volumes. Bilateral hippocampal increase (BHI) over time, as a marker of hippocampal plasticity was hypothesized to be associated with better outcomes. Regression analyses were performed on: (i) clinical and functional outcomes with grey matter volume change and BHI as predictor variables; and (ii) cognitive outcome with BHI as predictor.ResultsBHI was present in 29% of psychosis participants. There was no significant grey matter loss over time in either patient or control groups. Less severe illness course and lesser symptom severity were associated with BHI, but not with grey matter change. Employment and global function were associated with BHI and with less grey matter loss. Superior delayed verbal recall was also associated with BHI.ConclusionsBHI occurs in a minority of patients following their first psychotic episode and is associated with good outcome across clinical, functional and cognitive domains.


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