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Background: Despite reports of altered brain morphology in established bipolar disorder (BD), there is limited understanding of when these morphological abnormalities emerge. Assessment of patients during the early course of illness can help to address this gap, but few studies have examined surface-based brain morphology in patients at this illness stage., Methods: We completed a secondary analysis of baseline data from a randomised control trial of BD individuals stabilised after their first episode of mania (FEM). The magnetic resonance imaging scans of n = 35 FEM patients and n = 29 age-matched healthy controls were analysed. Group differences in cortical thickness, surface area and gyrification were assessed at each vertex of the cortical surface using general linear models. Significant results were identified at p < 0.05 using cluster-wise correction., Results: The FEM group did not differ from healthy controls with regards to cortical thickness or gyrification. However, there were two clusters of increased surface area in the left hemisphere of FEM patients, with peak coordinates falling within the lateral occipital cortex and pars triangularis., Conclusions: Cortical thickness and gyrification appear to be intact in the aftermath of a first manic episode, whilst cortical surface area in the inferior/middle prefrontal and occipitoparietal cortex is increased compared to age-matched controls. It is possible that increased surface area in the FEM group is the outcome of abnormalities in a premorbidly occurring process. In contrast, the findings raise the hypothesis that cortical thickness reductions seen in past studies of individuals with more established BD may be more attributable to post-onset factors., Competing Interests: Declaration of Competing Interest Dr. Van Rheenen has received grants unrelated to the current study from Club Melbourne, the Henry Freeman Trust, Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation and the Society of Mental Health Research. Professor Berk has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, National Health and Medical Research Council, Medical Research Futures Fund, Beyond Blue, Rotary Health, A2 milk company, Meat and Livestock Board, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Astra Zeneca, Lundbeck, Merck, Pfizer, and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Lundbeck Merck, Pfizer and Servier. Prof Yücel also received philanthropic donations from the David Winston Turner Endowment Fund, Wilson Foundation, as well as payments in relation to court-, expert witness-, and/or expert review-reports; the funding sources had no role in the design, management, data analysis, presentation, or interpretation and write-up of the data. Professor Pantelis has been on advisory boards for AstraZeneca, Janssen-Cilag, Lundbeck and Servier; and he has received honoraria for talks presented at educational meetings organized by AstraZeneca, Eli Lilly, Janssen-Cilag, Lundbeck, Pfizer and Shire. Prof Cotton, Dr. Dandash, Miss Ringin, Miss Cooper, Dr. Daglas-Georgiou, A/Prof Allott, Dr. Chye, Dr. Suo, Dr. MacNeil, Dr. Hasty, Dr. Hallam, Prof McGorry and Prof Fornito do not have any disclosures., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Lithium and quetiapine are effective treatments for bipolar disorder, but their potential neuroprotective effects in humans remain unclear. A single blinded equivalence randomized controlled maintenance trial was conducted in a prospective cohort of first-episode mania (FEM) patients (n=26) to longitudinally compare the putative protective effects of lithium and quetapine on grey and white matter volume. A healthy control sample was also collected (n=20). Using structural MRI scans, voxel-wise grey and white matter volumes at baseline and changes over time in response to treatment were investigated. Patients were assessed at three time points (baseline, 3 and 12-month follow-up), whereas healthy controls were assessed at two time points (baseline and 12-month follow-up). Patients were randomized to lithium (serum level 0.6 mmol l -1 , n=20) or quetiapine (flexibly dosed up to 800 mg per day, n=19) monotherapy. At baseline, compared with healthy control subjects, patients with FEM showed reduced grey matter in the orbitofrontal cortex, anterior cingulate, inferior frontal gyrus and cerebellum. In addition, patients had reduced internal capsule white matter volume bilaterally (t 1,66 >3.20, P<0.01). Longitudinally, there was a significant treatment × time effect only in the white matter of the left internal capsule (F 2,112 =8.54, P<0.01). Post hoc testing showed that, compared with baseline, lithium was more effective than quetiapine in slowing the progression of white matter volume reduction after 12 months (t 1,24 =3.76, P<0.01). Our data support the role of lithium but not quetiapine therapy in limiting white matter reduction early in the illness course after FEM.

Objectives: Cognitive deficits are apparent in the early stages of bipolar disorder; however, the timing and trajectory of cognitive functioning following a first episode of mania remains unclear. The aim of this study was to assess the trajectory of cognitive functioning in people following a first episode of mania over a 12-month period, relative to healthy controls., Method: The cohort included 61 participants who had recently stabilised from a first treated manic episode, and 21 demographically similar healthy controls. These groups were compared on changes observed over time using an extensive cognitive battery, over a 12-month follow-up period., Results: A significant group by time interaction was observed in one measure of processing speed (Trail Making Test - part A,) and immediate verbal memory (Rey Auditory Verbal Learning Test - trial 1), with an improved performance in people following a first episode of mania relative to healthy controls. On the contrary, there was a significant group by time interaction observed on another processing speed task pertaining to focussed reaction time (Go/No-Go, missed go responses), with first episode of mania participants performing significantly slower in comparison with healthy controls. Furthermore, a significant group by time interaction was observed in inhibitory effortful control (Stroop effect), in which healthy controls showed an improvement over time relative to first episode of mania participants. There were no other significant interactions of group by time related to other measures of cognition over the 12-month period., Conclusion: Our findings revealed cognitive change in processing speed, immediate memory and one measure of executive functioning over a 12-month period in first episode of mania participants relative to healthy controls. There was no evidence of change over time for all other cognitive domains. Further studies focussed on the at-risk period, subgroup analysis, and the effects of medication on the cognitive trajectory following first episode of mania are needed., (© The Royal Australian and New Zealand College of Psychiatrists 2015.)

Background: Cognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania., Methods: The design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points., Results: There was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition., Conclusion: Although the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)