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The substantial individual heterogeneity that characterizes people with mental illness is often ignored by classical case-control research, which relies on group mean comparisons. Here we present a comprehensive, multiscale characterization of the heterogeneity of gray matter volume (GMV) differences in 1,294 cases diagnosed with one of six conditions (attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, depression, obsessive-compulsive disorder and schizophrenia) and 1,465 matched controls. Normative models indicated that person-specific deviations from population expectations for regional GMV were highly heterogeneous, affecting the same area in <7% of people with the same diagnosis. However, these deviations were embedded within common functional circuits and networks in up to 56% of cases. The salience-ventral attention system was implicated transdiagnostically, with other systems selectively involved in depression, bipolar disorder, schizophrenia and attention-deficit/hyperactivity disorder. Phenotypic differences between cases assigned the same diagnosis may thus arise from the heterogeneous localization of specific regional deviations, whereas phenotypic similarities may be attributable to the dysfunction of common functional circuits and networks., (© 2023. The Author(s).)

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.)

A recent review on the use of electroconvulsive therapy (ECT) in obsessive-compulsive-related disorders (OCRDs) identified reports of trichotillomania (TTM) in only three patients, but it did not describe the specific effect of ECT on hair-pulling behaviors. The authors present a case report of Mrs. A, a 77-year-old widowed housewife with a lifelong history of episodic TTM and bipolar disorder who was effectively treated with ECT. However, on each attempt to withdraw ECT, her condition deteriorated. Eventually, a decision was made to maintain ECT (one session every week), which resulted in no further relapse over the followup period. ECT shows some potential promise for reducing hair-pulling behaviors in the context of severe depression.

Mood disturbances seen in first-episode mania (FEM) are linked to disturbed functional connectivity of the striatum. Lithium and quetiapine are effective treatments for mania but their neurobiological effects remain largely unknown. We conducted a single-blinded randomized controlled maintenance trial in 61 FEM patients and 30 healthy controls. Patients were stabilized for a minimum of 2 weeks on lithium plus quetiapine then randomly assigned to either lithium (serum level 0.6 mmol/L) or quetiapine (dosed up to 800 mg/day) treatment for 12 months. Resting-state fMRI was acquired at baseline, 3 months (patient only) and 12 months. The effects of treatment group, time and their interaction, on striatal functional connectivity were assessed using voxel-wise general linear modelling. At baseline, FEM patients showed reduced connectivity in the dorsal (p = 0.05) and caudal (p = 0.008) cortico-striatal systems when compared to healthy controls at baseline. FEM patients also showed increased connectivity in a circuit linking the ventral striatum with the medial orbitofrontal cortex, cerebellum and thalamus (p = 0.02). Longitudinally, we found a significant interaction between time and treatment group, such that lithium was more rapid, compared to quetiapine, in normalizing abnormally increased functional connectivity, as assessed at 3-month and 12-month follow-ups. The results suggest that FEM is associated with reduced connectivity in dorsal and caudal corticostriatal systems, as well as increased functional connectivity of ventral striatal systems. Lithium appears to act more rapidly than quetiapine in normalizing hyperconnectivity of the ventral striatum with the cerebellum. The study was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12607000639426). http://www.anzctr.org.au.

Background Lithium and quetiapine are considered standard maintenance agents for bipolar disorder yet it is unclear how their efficacy compares with each other. Aims To investigate the differential effect of lithium and quetiapine on symptoms of depression, mania, general functioning, global illness severity and quality of life in patients with recently stabilised first-episode mania. Method Maintenance trial of patients with first-episode mania stabilised on a combination of lithium and quetiapine, subsequently randomised to lithium or quetiapine monotherapy (up to 800 mg/day) and followed up for 1 year. (Trial registration: Australian and New Zealand Clinical Trials Registry - ACTRN12607000639426.) Results In total, 61 individuals were randomised. Within mixed-model repeated measures analyses, significant omnibus treatment × visit interactions were observed for measures of overall psychopathology, psychotic symptoms and functioning. Planned and post hoc comparisons further demonstrated the superiority of lithium treatment over quetiapine. Conclusions In people with first-episode mania treated with a combination of lithium and quetiapine, continuation treatment with lithium rather than quetiapine is superior in terms of mean levels of symptoms during a 1-year evolution., Competing Interests: Declaration of interestThis study was supported by an unrestricted grant from AstraZeneca. R.D., M.H. and K.H. worked on a study that has received research support by AstraZeneca. M.B. has received grant/research support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Rotary Health, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Meat and Livestock Board, Organon, Novartis, Mayne Pharma, Servier and Woolworths, has been a speaker for AstraZeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen-Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth, and served as a consultant to AstraZeneca, Bioadvantex, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen-Cilag, Lundbeck Merck and Servier. C.M. has received a grant/research support from Eli Lilly and AstraZeneca, Janssen Cilag and Sanofi Aventis, and served as a consultant to AstraZeneca and Eli Lilly. P.D.M. has received investigator initiated research grants from AstraZeneca, Janssen-Cilag, Eli Lilly and BMS. He has received honoraria for educational events from Janssen-Cilag, Eli Lilly, BMS, AstraZeneca, Pfizer and Lundbeck. C.P. has participated on Advisory Boards for Janssen-Cilag, AstraZeneca, Lundbeck and Servier, has received honoraria for talks presented at educational meetings organised by AstraZeneca, Janssen-Cilag, Eli-Lilly, Pfizer, Lundbeck and Shire., (© The Royal College of Psychiatrists 2017.)

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.)

There are now numerous reports of neuroanatomical abnormalities in people with bipolar disorder. However, it remains unclear whether those abnormalities predate the onset of the illness. In this cross-sectional magnetic resonance imaging study, we assessed 11 young people clinically at ultra-high risk of development of psychosis (UHR), who all developed bipolar I or II disorder by follow-up (median time to onset 328 days - UHR-BP), 11 matched UHR participants, who had no psychiatric diagnosis after at least 12 months of follow-up (UHR-Well) and 11 matched healthy controls (HC). Our main outcome measures were amygdala, hippocampus, insula, lateral ventricular and whole brain volumes. Amygdala and insula volume reductions were more pronounced in the UHR-BP than in the UHR-Well and HC group. Lateral ventricle, whole-brain and hippocampal volumes did not differ between groups. If these findings are confirmed, they suggest that imaging investigations could help to distinguish people who will subsequently develop bipolar disorder from those who will not, at least in symptomatically enriched samples., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: It has been suggested that patients with psychotic bipolar disorder (BDP+) might have more severe cognitive deficits than non-psychotic bipolar disorder patients (BDP-). However, only a handful of studies have compared cognition between BDP+ and BDP-. Our aim was to examine cognitive deficits associated with psychosis in BD using meta-analytic methods., Methods: After a systematic literature review, we conducted a meta-analysis on studies that compared cognition in bipolar disorder (BD) patients with and without a history of psychosis. In addition the effects of clinical and demographic confounder factors were examined with meta-regression analyses., Results: There were no significant differences for gender and duration of illness between groups. Compared with BDP-, BDP+ patients had more inpatient admissions, a younger onset of illness and used antipsychotics more commonly. BDP+ patients also performed significantly worse in 4 of 6 cognitive domains (planning and reasoning, working memory, verbal memory and processing speed). There were also differences for some individual tasks (List Learning, Delayed Recall, Trail Making B, Wisconsin Card Sorting Test, Digits Backwards, Stroop Interference, Semantic Fluency) with BDP+ patients showing moderately greater impairment on these tasks (d=0.30-0.55)., Conclusions: A history of psychosis is associated with greater severity of cognitive deficits in BD. However, this effect is modest, and these findings do not suggest a complete categorical distinction between BDP+ and BDP-. Psychosis in BD might reflect partly distinct neurobiological processes., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Bipolar disorder follows a staged trajectory in which persistence of illness is associated with a number of clinical features such as progressive shortening of the inter-episode interval and decreased probability of treatment response. This neuroprogressive clinical process is reflected by both progressive neuroanatomical changes and evidence of cognitive decline. The biochemical foundation of this process appears to incorporate changes in inflammatory cytokines, cortisone, neurotrophins and oxidative stress. There is a growing body of evidence to suggest that these markers may differ between the early and late stages of the disorder. The presence of a series of tangible targets raises the spectre of development of rational neuroprotective strategies, involving judicious use of current therapies and novel agents. Most of the currently used mood stabilisers share effects on oxidative stress and neurotrophins, while novel potentially neuroprotective agents are being developed. These developments need to be combined with service initiatives to maximise the opportunities for early diagnosis and intervention.

Background: Functional abnormalities of the superior temporal gyrus (STG) have been implicated in the pathophysiology of bipolar disorder, but magnetic resonance imaging (MRI) studies of this region have yielded inconsistent findings., Method: We used MRI to examine the volumes of the STG and its gray matter subregions [planum polare (PP), Heschl gyrus (HG), planum temporale (PT), and lateral STG (rostral and caudal regions)] in 26 patients with established bipolar I disorder (8 males and 18 females, mean age=38.4 years) and 24 age and gender-matched healthy controls (7 males and 17 females, mean age=38.7 years)., Results: Bipolar patients had significantly smaller volumes of the PT and caudal STG compared with controls in the left hemisphere. The STG white matter volume did not differ between the groups. There was no association between the STG volume and number of manic/depressive episodes, family history, or clinical subtype (i.e., psychotic and nonpsychotic), but daily dosage of lithium treatment at the time of scanning was positively correlated with right PP and right rostral STG volumes., Limitations: Entire clinical data (e.g., lifetime medication, symptomatology) were not available., Conclusions: These findings implicate a role for the STG gray matter, especially its left posterior regions, in the neurobiology of bipolar disorder. Our findings may also support the notion of lithium-induced gray matter expansion., (Copyright 2009 Elsevier B.V. All rights reserved.)

Background: We conducted a meta-analysis of gray matter abnormalities in bipolar disorder (BD) using voxel-based morphometry studies to help clarify the structural abnormalities underpinning this condition., Methods: A systematic review was conducted for voxel-based morphometry studies of patients with BD. Meta-analyses of gray matter differences between BD and control subjects were undertaken using "signed differential mapping," a novel method that, in contrast to previously used techniques, allows inclusion of negative findings and ensures that single studies do not exert undue influence on the results. Meta-regression and subgroup analyses were used to examine the effect of moderator variables on gray matter abnormalities., Results: A total of 21 studies comparing gray matter volumes of 660 BD patients and 770 healthy control subjects were included. Gray matter reduction in left rostral anterior cingulate cortex (ACC) and right fronto-insular cortex was associated with BD. Fronto-insular cortex abnormality was not evident in early phases of the illness. In chronic patients, longer duration of illness was associated with increased gray matter in a cluster that included basal ganglia, subgenual ACC, and amygdala. Lithium treatment was associated with enlargement of ACC gray matter volumes, which overlapped with the region where gray matter was reduced in BD., Conclusions: The most robust gray matter reductions in BD occur in anterior limbic regions, which may be related to the executive control and emotional processing abnormalities seen in this patient population. Clinical factors such as illness duration and lithium treatment also impact on case-control comparisons of gray matter volume., (Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

This structural magnetic resonance imaging study investigated insular cortex volume in 26 patients with bipolar I disorder and 24 matched controls. While insular volume did not differ between these groups, exploratory analyses demonstrated that the number of depressive episodes correlated negatively with the anterior insular volume in the patients, suggesting it may have a role in the pathophysiology of bipolar disorder., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Morphologic changes of cortico-limbic regions have been reported in bipolar disorder, but it remains unclear whether midline brain abnormalities relevant to cortico-limbic connectivity are also present., Methods: We used magnetic resonance imaging to investigate the size of the adhesio interthalamica (AI) and cavum septi pellucidi (CSP), as well as third ventricular volume, in 26 patients with bipolar I disorder and 24 matched controls., Results: CSP length and prevalence of a large CSP did not differ between the groups, but bipolar patients had significantly shorter AI and larger third ventricles compared to controls., Limitations: A comprehensive investigation of medication effects was not possible due to incomplete medication data., Conclusions: These findings implicate a role for the AI and connected brain regions in the neurobiology of bipolar disorder., (Copyright (c) 2009 Elsevier B.V. All rights reserved.)

Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has been demonstrated in bipolar disorder (BD), but previous magnetic resonance imaging (MRI) studies of pituitary gland volume in BD have reported variable findings. In this MRI study we investigated pituitary volume in 26 patients with established bipolar I disorder (8 males and 18 females, mean age=38.4 years) and 24 matched controls (7 males and 17 females, mean age=38.7 years). The BD patients had a significantly larger pituitary volume as compared with controls, but there was no association between pituitary volume and illness duration, number of manic/depressive episodes, daily medication dosage, family history, or clinical subtype (i.e., psychotic and nonpsychotic). Pituitary volume was larger in females than in males for both groups. These results support previous neuroendocrine findings that implicate HPA axis dysfunction in the core pathophysiological process of BD.

Objective: Callosal structural and functional alterations have been demonstrated in a range of neuropsychiatric illnesses, including bipolar disorder, but no study has examined regional callosal thickness in this phenotype. The aim of the present study was therefore to examine callosal size and shape in a well-defined group of bipolar affective disorder patients and controls., Methods: The participants included 24 patients with DSM-IV bipolar I disorder and 24 matched healthy controls. The corpus callosum was extracted from mid-callosal images from T1-weighted magnetic resonance imaging scans on all participants, and callosal area, length, bending angle and regional callosal thickness measures were computed from these images., Results: The callosum was thinner in the bipolar group overall, with a disproportionately reduced thickness in the splenium. Psychotic and non-psychotic patients did not differ, although patients without a family history of mood disorders had a thinner callosum., Conclusion: Callosal reductions are present in established bipolar disorder, and affect posterior regions more than anterior regions. This may reflect a primary disturbance to myelination, or a secondary effect of grey matter changes.

Purpose of Review: Although structural magnetic resonance imaging (sMRI) and neuropathological investigations offer complementary information that can be used to formulate and test hypotheses about pathophysiological mechanisms in psychiatric disorders, the findings from these two fields are seldom integrated in a systematic manner. In this study, we overview recent sMRI findings in schizophrenia and bipolar disorder and consider how they relate to neuropathological data., Recent Findings: sMRI research indicates that schizophrenia is associated with volumetric reductions in a network of frontal, temporal, limbic, striatal, and thalamic regions. Some of these abnormalities are apparent prior to psychosis onset and may progress with ongoing illness. sMRI findings in bipolar disorder have been more variable, with both volumetric increases and decreases being reported across several brain regions at different illness stages. Neuropathological studies of both patient groups suggest the cellular changes associated with these volumetric differences affect diverse tissue compartments in a regionally heterogeneous way., Summary: These findings suggest that any putative pathophysiological mechanism in schizophrenia or bipolar disorder should account for the dynamic, complex, and regionally heterogeneous brain abnormalities seen in these patients. We contend that greater integration of the findings from these two fields will facilitate more targeted and hypothesis-driven research in the future.

Background: The 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., Aims: To characterise anterior cingulate cortex abnormalities in patients with bipolar disorder experiencing their first episode of psychosis while accounting for regional anatomical variability., Method: Grey 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., Results: Relative 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., Conclusions: These 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.

Abnormalities of the anterior cingulate cortex (ACC) are thought to be involved in the pathophysiology of bipolar disorder, but structural Magnetic Resonance Imaging (MRI) studies have reported variable findings. Reasons for this include a failure to consider variability in regional cortical folding patterns and a reliance on relatively coarse measures (e.g., volume) to index anatomical change. We sought to overcome these limitations by combining a novel protocol for parcellating the ACC and adjacent paracingulate cortex (PaC) that accounts for inter-individual variations in sulcal and gyral morphology with a cortical surface-based approach that allowed calculation of regional grey matter volume, surface area and cortical thickness in 24 patients with bipolar I disorder and 24 matched controls. No changes in grey matter volume or surface area were identified in any region, but patients did show significant reductions in cortical thickness in the left rostral PaC and right dorsal PaC that were not attributable to group differences in cortical folding patterns. These findings suggest that bipolar disorder is associated with more pronounced changes in the PaC, and that reliance on volumetric measures alone may obscure more subtle differences.

An increased prevalence of duplicated Heschl's gyrus (HG) has been repeatedly demonstrated in various stages of schizophrenia as a potential neurodevelopmental marker, but it remains unknown whether other neuropsychiatric disorders also exhibit this macroscopic brain feature. The present magnetic resonance imaging study aimed to examine the disease specificity of the established finding of altered HG patterns in schizophrenia by examining independent cohorts of bipolar disorder (BD) and major depressive disorder (MDD). Twenty-six BD patients had a significantly higher prevalence of HG duplication bilaterally compared to 24 age- and sex-matched controls, while their clinical characteristics (e.g., onset age, number of episodes, and medication) did not relate to HG patterns. No significant difference was found for the HG patterns between 56 MDD patients and 33 age- and sex-matched controls, but the patients with a single HG were characterized by more severe depressive/anxiety symptoms compared to those with a duplicated HG. Thus, in keeping with previous findings, the present study suggests that neurodevelopmental pathology associated with gyral formation of the HG during the late gestation period partly overlaps between schizophrenia and BD, but that HG patterns may make a somewhat distinct contribution to the phenomenology of MDD. [ABSTRACT FROM AUTHOR]

Abnormal melatonin secretion has been demonstrated in patients with affective disorders such as major depressive disorder (MDD) and bipolar disorder (BD). However, magnetic resonance imaging (MRI) studies that previously investigated the volume of the pineal gland, which regulates circadian rhythms by secreting melatonin, in these patients reported inconsistent findings. The present study employed MRI to examine pineal gland volumes and pineal cyst prevalence in 56 MDD patients (29 currently depressed and 27 remitted patients), 26 BD patients, and matched controls (33 for MDD and 24 for BD). Pineal volumes and cyst prevalence in the current MDD, remitted MDD, and BD groups did not significantly differ from those of the healthy controls. However, pineal gland volumes were significantly smaller in the current MDD subgroup of non-melancholic depression than in the melancholic MDD subgroup. Interestingly, pineal volumes correlated negatively with the severity of loss of interest in the current MDD group. Medication and the number of affective episodes were not associated with pineal volumes in the MDD or BD group. While these results do not suggest that pineal volumes reflect abnormal melatonin secretion in affective disorders, they do point to the possibility that pineal abnormalities are associated with clinical subtypes of MDD and its symptomatology. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to examine cognitive functioning in people following first-episode mania relative to a demographically similar healthy control group. Methods: Forty-one patients, who had recently stabilised from a first manic episode, and twenty-one healthy controls, were compared in an extensive cognitive assessment. Results: First-episode mania participants had significantly lower Full-Scale IQ (FSIQ) relative to healthy controls; however, this finding could be driven by premorbid differences in intellectual functioning. There were no significant differences between groups in Verbal IQ (VIQ) and Performance IQ (PIQ). First-episode mania participants performed significantly poorer than healthy controls in processing speed, verbal learning and memory, working memory, and cognitive flexibility with medium-to-large effects. There were no group differences in other measures of cognition. Conclusions: Participants following first-episode mania have poorer global intelligence than healthy controls, and have cognitive difficulties in some, but not all areas of cognitive functioning. This highlights the importance of early intervention and cognitive assessment in the early course of the disorder. [ABSTRACT FROM AUTHOR]

BackgroundLithium and quetiapine are considered standard maintenance agents for bipolar disorder yet it is unclear how their efficacy compares with each other.AimsTo investigate the differential effect of lithium and quetiapine on symptoms of depression, mania, general functioning, global illness severity and quality of life in patients with recently stabilised first-episode mania.MethodMaintenance trial of patients with first-episode mania stabilised on a combination of lithium and quetiapine, subsequently randomised to lithium or quetiapine monotherapy (up to 800 mg/day) and followed up for 1 year. (Trial registration: Australian and New Zealand Clinical Trials Registry - ACTRN12607000639426.)ResultsIn total, 61 individuals were randomised. Within mixed-model repeated measures analyses, significant omnibus treatment × visit interactions were observed for measures of overall psychopathology, psychotic symptoms and functioning. Planned and post hoc comparisons further demonstrated the superiority of lithium treatment over quetiapine.ConclusionsIn people with first-episode mania treated with a combination of lithium and quetiapine, continuation treatment with lithium rather than quetiapine is superior in terms of mean levels of symptoms during a 1-year evolution. [ABSTRACT FROM AUTHOR]

We assessed correlates of obsessive–compulsive (OCPD), schizotypal (SPD) and borderline (BPD) personality disorders in 110 obsessive–compulsive disorder (OCD) patients. We found OCD patients with OCPD (20.9%) to exhibit higher rates of hoarding and bipolar disorders, increased severity of hoarding and symmetry, lower prevalence of unacceptable thoughts involving sex and religion and less non-planning impulsivity. Conversely, OCD patients with SPD (13.6%) displayed more frequently bipolar disorder, increased severity of depression and OCD neutralization, greater prevalence of “low-order” behaviors (i.e., touching), lower low-planning impulsivity and greater “behavioral” compulsivity. Finally, in exploratory analyses, OCD patients with BPD (21.8%) exhibited lower education, higher rates of several comorbid psychiatric disorders, greater frequency of compulsions involving interpersonal domains (e.g. reassurance seeking), increased severity of depression, anxiety and OCD dimensions other than symmetry and hoarding, more motor and non-planning impulsivity, and greater “cognitive” compulsivity. These findings highlight the importance of assessing personality disorders in OCD samples. [ABSTRACT FROM AUTHOR]

It has recently been suggested that cognitive impairment should be included in the diagnostic criteria of schizophrenia. One of the main arguments in support of this suggestion has been the hope that cognitive impairment can help distinguish schizophrenia from bipolar disorder (BD). However, recent evidence shows that cognitive deficits occur in BD and persist beyond euthymia. Further, mood disorders with psychotic features might be expected to manifest greater cognitive impairment, which further complicates the potential to differentiate these disorders. The goal of the current meta-analysis was to examine the magnitude and characteristics of cognitive impairments in affective psychoses (AP). A systematic search of the existing literature sourced 27 studies that met the inclusion criteria. These studies compared cognitive performances of 763 patients with AP (550 BD and 213 major depressive disorder) and 1823 healthy controls. Meta-regression and subgroup analyses were used to examine the effects of moderator variables. Meta-analyses of these studies showed that patients with AP were impaired in all 15 cognitive tasks with large effect sizes for most measures. There were no significant differences between the magnitude of impairments between the BD and major depressive disorder groups. The largest effect size was found for symbol coding, stroop task, verbal learning, and category fluency, reflecting impairments in elementary and complex aspects of attentional processing, as well as learning and memory. In general, the pattern of cognitive impairments in AP was similar to reported findings in euthymic patients with BD, but relatively more pronounced. [ABSTRACT FROM PUBLISHER]

It has recently been suggested that the diagnostic criteria of schizophrenia should include specific reference to cognitive impairments characterizing the disorder. Arguments in support of this assertion contend that such inclusion would not only serve to increase the awareness of cognitive deficits in affected patients, among both clinicians and researchers alike, but also increase the “point of rarity” between schizophrenia and mood disorders. The aim of the current article is to examine this latter assertion in light of the recent opinion piece provided by Keefe and Fenton (Keefe RSE, Fenton WS. How should DSM-V criteria for schizophrenia include cognitive impairment? Schizophr Bull. 2007;33:912–920). Through literature review, we explore the issue of whether cognitive deficits do in fact differentiate the major psychoses. The overall results of this inquiry suggest that inclusion of cognitive impairment criteria in Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-V) would not provide a major advancement in discriminating schizophrenia from bipolar disorder and affective psychoses. Therefore, while cognitive impairment should be included in DSM-V, it should not dictate diagnostic specificity—at least not until more comprehensive evidence-based reviews of the current diagnostic system have been undertaken. Based on this evidence, we consider several alternatives for the DSM-V definition of cognitive impairment in schizophrenia, including (1) the inclusion of cognitive impairment as a specifier and (2) the definition of cognitive impairment as a dimension within a hybrid categorical-dimensional system. Given the state of current evidence, these possibilities appear to represent the most parsimonious approaches to the inclusion of cognitive deficits in the diagnostic criteria of schizophrenia and, potentially, of mood disorders. [ABSTRACT FROM PUBLISHER]

Background: Abnormalities of the anterior cingulate cortex (ACC) are frequently implicated in the pathophysiology of psychotic disorders, but whether such changes are apparent before psychosis onset remains unclear. In this study, we characterized prepsychotic ACC abnormalities in a sample of individuals at ultra-high-risk (UHR) for psychosis. Methods: Participants underwent baseline magnetic resonance imaging and were followed-up over 12–24 months to ascertain diagnostic outcomes. Baseline ACC morphometry was then compared between UHR individuals who developed psychosis (UHR-P; n = 35), those who did not (UHR-NP; n = 35), and healthy control subjects (n = 33). Results: Relative to control subjects, UHR-P individuals displayed bilateral thinning of a rostral paralimbic ACC region that was negatively correlated with negative symptoms, whereas UHR-NP individuals displayed a relative thickening of dorsal and rostral limbic areas that was correlated with anxiety ratings. Baseline ACC differences between the two UHR groups predicted time to psychosis onset, independently of symptomatology. Subdiagnostic comparisons revealed that changes in the UHR-P group were driven by individuals subsequently diagnosed with a schizophrenia spectrum psychosis. Conclusions: These findings indicate that anatomic abnormalities of the ACC precede psychosis onset and that baseline ACC differences distinguish between UHR individuals who do and do not subsequently develop frank psychosis. They also indicate that prepsychotic changes are relatively specific to individuals who develop a schizophrenia spectrum disorder, suggesting they may represent a diagnostically specific risk marker. [Copyright &y& Elsevier]