Search

Machine learning can be used to define subtypes of psychiatric conditions based on shared biological foundations of mental disorders. Here we analyzed cross-sectional brain images from 4,222 individuals with schizophrenia and 7038 healthy subjects pooled across 41 international cohorts from the ENIGMA, non-ENIGMA cohorts and public datasets. Using the Subtype and Stage Inference (SuStaIn) algorithm, we identify two distinct neurostructural subgroups by mapping the spatial and temporal ‘trajectory’ of gray matter change in schizophrenia. Subgroup 1 was characterized by an early cortical-predominant loss with enlarged striatum, whereas subgroup 2 displayed an early subcortical-predominant loss in the hippocampus, striatum and other subcortical regions. We confirmed the reproducibility of the two neurostructural subtypes across various sample sites, including Europe, North America and East Asia. This imaging-based taxonomy holds the potential to identify individuals with shared neurobiological attributes, thereby suggesting the viability of redefining existing disorder constructs based on biological factors.

Cognitively impaired and spared patient subgroups were identified in psychosis and depression, and in clinical high-risk for psychosis (CHR). Studies suggest differences in underlying brain structural and functional characteristics. It is unclear whether cognitive subgroups are transdiagnostic phenomena in early stages of psychotic and affective disorder which can be validated on the neural level. Patients with recent-onset psychosis (ROP; N = 140; female = 54), recent-onset depression (ROD; N = 130; female = 73), CHR (N = 128; female = 61) and healthy controls (HC; N = 270; female = 165) were recruited through the multi-site study PRONIA. The transdiagnostic sample and individual study groups were clustered into subgroups based on their performance in eight cognitive domains and characterized by gray matter volume (sMRI) and resting-state functional connectivity (rsFC) using support vector machine (SVM) classification. We identified an impaired subgroup (NROP = 79, NROD = 30, NCHR = 37) showing cognitive impairment in executive functioning, working memory, processing speed and verbal learning (all p < 0.001). A spared subgroup (NROP = 61, NROD = 100, NCHR = 91) performed comparable to HC. Single-disease subgroups indicated that cognitive impairment is stronger pronounced in impaired ROP compared to impaired ROD and CHR. Subgroups in ROP and ROD showed specific symptom- and functioning-patterns. rsFC showed superior accuracy compared to sMRI in differentiating transdiagnostic subgroups from HC (BACimpaired = 58.5%; BACspared = 61.7%, both: p < 0.01). Cognitive findings were validated in the PRONIA replication sample (N = 409). Individual cognitive subgroups in ROP, ROD and CHR are more informative than transdiagnostic subgroups as they map onto individual cognitive impairment and specific functioning- and symptom-patterns which show limited overlap in sMRI and rsFC.

BACKGROUND: Cardiometabolic disease risk factors are disproportionately prevalent in bipolar disorder (BD) and are associated with cognitive impairment. It is, however, unknown which health risk factors for cardiometabolic disease are relevant to cognition in BD. This study aimed to identify the cardiometabolic disease risk factors that are the most important correlates of cognitive impairment in BD; and to examine whether the nature of the relationships vary between mid and later life. METHODS: Data from the UK Biobank were available for 966 participants with BD, aged between 40 and 69 years. Individual cardiometabolic disease risk factors were initially regressed onto a global cognition score in separate models for the following risk factor domains; (1) health risk behaviors (physical activity, sedentary behavior, smoking, and sleep) and (2) physiological risk factors, stratified into (2a) anthropometric and clinical risk (handgrip strength, body composition, and blood pressure), and (2b) cardiometabolic disease risk biomarkers (CRP, lipid profile, and HbA1c). A final combined multivariate regression model for global cognition was then fitted, including only the predictor variables that were significantly associated with cognition in the previous models. RESULTS: In the final combined model, lower mentally active and higher passive sedentary behavior, higher levels of physical activity, inadequate sleep duration, higher systolic and lower diastolic blood pressure, and lower handgrip strength were associated with worse global cognition. CONCLUSIONS: Health risk behaviors, as well as blood pressure and muscular strength, are associated with cognitive function in BD, whereas other traditional physiological cardiometabolic disease risk factors are not.

BACKGROUND: Research supports an association between threatening experiences in childhood and psychosis. It is possible that early threat exposure disrupts the development of emotion recognition (specifically, producing a bias for facial expressions relating to threat) and the brain structures subserving it, contributing to psychosis development. METHODS: Using data from the Philadelphia Neurodevelopmental Cohort, we examined associations between threat exposure and both the misattribution of facial expressions to fear/anger in an emotion recognition task, and gray matter volumes in key emotion processing regions. Our sample comprised youth with psychosis spectrum symptoms (N = 304), control youth (N = 787), and to evaluate specificity, youth with internalizing symptoms (N = 92). The moderating effects of group and sex were examined. RESULTS: Both the psychosis spectrum and internalizing groups had higher levels of threat exposure than controls. In the total sample, threat exposure was associated with lower left medial prefrontal cortex (mPFC) volume but not misattributions to fear/anger. The effects of threat exposure did not significantly differ by group or sex. CONCLUSIONS: The findings of this study provide evidence for an effect of threat exposure on mPFC morphology, but do not support an association between threat exposure and a recognition bias for threat-related expressions, that is particularly pronounced in psychosis. Future research should investigate factors linking transdiagnostic alterations related to threat exposure with psychotic symptoms, and attempt to clarify the mechanisms underpinning emotion recognition misattributions in threat-exposed youth.

Despite a growing body of research, there is yet to be a cohesive synthesis of studies examining differences in brain morphology according to patterns of cognitive function among both schizophrenia-spectrum disorder (SSD) and bipolar disorder (BD) individuals. We aimed to provide a systematic overview of the morphological differences-inclusive of grey and white matter volume, cortical thickness, and cortical surface area-between cognitive subgroups of these disorders and healthy controls, and between cognitive subgroups themselves. An initial search of PubMed and Scopus databases resulted in 1486 articles of which 20 met inclusion criteria and were reviewed in detail. The findings of this review do not provide strong evidence that cognitive subgroups of SSD or BD map to unique patterns of brain morphology. There is preliminary evidence to suggest that reductions in cortical thickness may be more strongly associated with cognitive impairment, whilst volumetric deficits may be largely tied to the presence of disease.

The role that vitamin D plays in the cognitive and clinical characteristics of bipolar disorder (BD) is unclear. We examined differences in the levels and deficiency status of vitamin D in an Australian sample of BD patients compared to healthy controls; and determined the extent to which vitamin D is associated with clinical variables and cognitive function in the sample. 22 healthy controls and 55 stable outpatients with a diagnosis of BD and low-grade mood symptomatology provided a sample of blood and completed cognitive tests and clinical measures. Plasma concentrations of 25-hydroxyvitamin D (vitamin D) were assayed and used to segregate participants into subgroups with sufficient or deficient levels of vitamin D. Subgroups were then compared in terms of global cognition and a range of sociodemographic and clinical factors (number of past mood episodes, illness duration, seasonal mood pattern, mood symptom severity), while mean levels of vitamin D were compared between patients and controls. Although almost 27% of the current sample were vitamin D deficient, no significant differences in mean vitamin D levels or the prevalence of vitamin D deficiency were evident between BD patients and controls. Vitamin D was not associated with global cognition in either patients or controls, nor any of the clinical measures assessed in the study. In conclusion, we observed no difference in the vitamin D levels and deficiency status of an Australian sample of healthy individuals and BD patients with low grade mood symptomatology compared to controls. Clinical symptoms and global cognition also appear to be independent of vitamin D levels in BD.

OBJECTIVE: Cognitive impairment is consistently reported in bipolar disorder (BD), but few studies have characterised which memory component processes are affected. Further, it is unknown whether the component processes underlying memory impairment are moderated by sex. The present study examined diagnosis and sex differences in both verbal and visual memory/learning domains in patients with BD and psychiatrically healthy controls. METHOD: Verbal and visual memory/learning were measured using the Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R). 114 patients with BD (n = 50 males, n = 64 females), were compared to 105 psychiatrically healthy controls (n = 42 males, n = 63 females). RESULTS: Patients with BD had worse performance in verbal and visual immediate and total recall, verbal and visual delayed free recall, and verbal recognition discrimination scores, but there were no group differences in learning slopes and cumulative learning index scores. There were trends for BD females to outperform BD males in visual memory/learning free recall and cumulative learning, but these results did not survive multiple testing correction. These findings did not change in a secondary sensitivity analysis comparing only strictly euthymic BD patients to controls (n = 64). CONCLUSION: The present study found trait-like verbal and visual memory/learning impairment in BD that was attributable to deficient encoding and/or consolidation processes rather than deficits in learning. We did not find marked sex differences in either visual or verbal memory/learning measures, although some trend level effects were apparent and deserve exploration in future studies.

Type 2 diabetes (T2D) is disproportionately prevalent in bipolar disorder (BD) and is associated with cognitive deficits in psychiatrically healthy cohorts. Whether there is an interaction effect between T2D and BD on cognition remains unclear. Using the UK Biobank, we explored interactions between T2D, BD and cognition during mid and later life; and examined age-related cognitive performance effects in BD as a function of T2D. Data were available for 1511 participants with BD (85 T2D), and 81,162 psychiatrically healthy comparisons (HC) (3430 T2D). BD and T2D status were determined by validated measures created specifically for the UK Biobank. Diagnostic and age-related associations between T2D status and cognition were tested using analyses of covariance or logistic regression. There was a negative association of T2D with visuospatial memory that was specific to BD. Processing speed and prospective memory performance were negatively associated with T2D, irrespective of BD diagnosis. Cognitive deficits were evident in BD patients with T2D compared to those without, with scores either remaining the same (processing speed) or improving (visuospatial memory) as a function of participant age. In contrast, cognitive performance in BD patients without T2D was worse as participant age increased, although the age-related trajectory remained broadly equivalent to the HC group. BD and T2D associated with cognitive performance deficits across the mid-life period; indicating comorbid T2D as a potential risk factor for cognitive dysfunction in BD. In comparison to BD participants without T2D and HCs, age-independent cognitive impairments in BD participants with comorbid T2D suggest a potential premature deterioration of cognitive functioning compared to what would normally be expected.

BACKGROUND: Verbal memory (VM) is impaired in schizophrenia (SZ) and bipolar disorder (BD), and predicts psychosocial functioning. However, there is a lack of research exploring the role of VM component processes, including semantic clustering, in these disorders. Semantic clustering might impact this association, as effective semantic memory strategies may reflect unimpaired executive control, leading to an adequate functioning. We aimed to investigate VM components in SZ and BD, and the role of semantic clustering in the relationship between VM and functioning. METHODS: We included 495 participants (156 SZ, 172 BD, and 167 healthy controls (HC)) that underwent an assessment using the Hopkins Verbal Learning Test - Revised for VM and the Functioning Assessment Short Test for psychosocial functioning. We compared groups through ANOVAs and investigated the effect of semantic clustering in the relationship between VM total immediate free recall and functioning through linear regression models. RESULTS: SZ had worse overall VM performance compared to BD, which performed worse than HCs. HCs used more semantic clustering than SZ and BD, but there were no differences between the two clinical groups. In HCs, semantic clustering impacted the relationship between VM performance and functioning, while no interaction was observed in SZ or BD. LIMITATIONS: Cross-sectional design; no medication effects or other cognitive functions were assessed. CONCLUSIONS: SZ and BD may use an alternative cognitive pathway in which the relationship between VM and functioning is independent of complex cognitive processes such as semantic clustering, supporting the cognitive remediation targeting of VM in these disorders.

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.

In 2021, the International Society for Bipolar Disorders (ISBD) launched a new global initiative to support researchers and clinicians specializing in bipolar disorder who are still in the process of establishing their careers. To capture the needs of this group, an Early and Mid-Career Committee (EMCC) was formed and tasked with the development of activities and initiatives to address this objective. To this end, the committee conducted a needs assessment survey in early 2022 that was distributed and completed worldwide. This paper, authored by members of the committee, outlines the rationale, process, goals, and aspirations of the EMCC and summarizes the development of the needs survey.

OBJECTIVE: Evidence shows impaired theory of mind (ToM) in patients with bipolar disorder (BD), yet research examining its cognitive and affective components simultaneously is sparse. Moreover, recognition of socially competitive 'fortune of others' emotions (e.g. envy/gloat) may be related to ToM, but has not been assessed in BD. Finally, if and how ToM and 'fortune of others' emotions relate to affective empathy in BD is currently unclear. This study aimed to address these points. METHODS: 64 BD patients and 34 healthy controls completed the Yoni task, a visual task assessing first- and second-order cognitive and affective ToM as well as 'fortune of others' emotions. The Toronto Empathy Questionnaire was used to assess self-reported affective empathy. RESULTS: Patients with BD showed no deficits in cognitive and affective ToM or recognition of 'fortune of others' emotions. The ability to infer 'fortune of others' emotions correlated with several ToM measures, indicating that these functions are part of the same system. Patients with BD reported similar levels of affective empathy to healthy controls, and this was not related to ToM or 'fortune of others' emotions, suggesting that affective empathy represents a separate social domain. CONCLUSIONS: These findings highlight areas of spared social functioning in BD, which may be utilized in therapeutic strategies. PRACTITIONER POINTS: Our results suggest theory of mind and empathy may represent areas of potentially spared cognitive functioning in BD. As many BD patients have experienced adversity during developmental periods in which theory of mind and empathy develop, our findings suggest that these abilities may be markers of resilience in the disorder. Our findings are important for the formulation of therapeutic interventions for BD, which may include considering practical ways that a patients' knowledge of intact ToM and empathy could be utilized to reduce self-stigma and promote self-efficacy, improved well-bein

Increasing evidence suggests that facial emotion recognition is impaired in bipolar disorder (BD). However, patient-control differences are small owing to ceiling effects on the tasks used to assess them. The extant literature is also limited by a relative absence of attention towards identifying patterns of emotion misattribution or understanding whether neutral faces are mislabelled in the same way as ones displaying emotion. We addressed these limitations by comparing facial emotion recognition performance in BD patients and healthy controls on a novel and challenging task. Thirty-four outpatients with BD I and 32 demographically matched healthy controls completed a facial emotion recognition task requiring the labelling of neutral and emotive faces displayed at low emotional intensities. Results indicated that BD patients were significantly less accurate at labelling faces than healthy controls, particularly if they displayed fear or neutral expressions. There were no between-group differences in response times or patterns of emotion mislabelling, with both groups confusing sad and neutral faces, although BD patients also mislabelled sad faces as angry. Task performance did not significantly correlate with mood symptom severity in the BD group. These findings suggest that facial emotion recognition impairments in BD extend to neutral face recognition. Emotion misattribution occurs in a similar, albeit exaggerated manner in patients with BD compared to healthy controls. Future behavioural and neuroimaging research should reconsider the use of neutral faces as baseline stimuli in their task designs.

BACKGROUND: Cognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence-based pro-cognitive treatments indicated for patients in remission. With this systematic review of randomised controlled trials (RCTs), the International Society for Bipolar Disorders (ISBD) Targeting Cognition Task force provides an update of the most promising treatments and methodological recommendations. METHODS: The review included RCTs of candidate pro-cognitive interventions in fully or partially remitted patients with major depressive disorder or bipolar disorder. We followed the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE and Cochrane Library from January 2015, when two prior systematic reviews were conducted, until February 2021. Two independent authors reviewed the studies with the Revised Cochrane Collaboration's Risk of Bias tool for Randomised trials. RESULTS: We identified 16 RCTs (N = 859) investigating cognitive remediation (CR; k = 6; N = 311), direct current or repetitive magnetic stimulation (k = 3; N = 127), or pharmacological interventions (k = 7; N = 421). CR showed most consistent cognitive benefits, with two trials showing improvements on primary outcomes. Neuromodulatory interventions revealed no clear efficacy. Among pharmacological interventions, modafinil and lurasidone showed early positive results. Sources of bias included small samples, lack of pre-screening for objective cognitive impairment, no primary outcome and no information on allocation sequence masking. CONCLUSIONS: Evidence for pro-cognitive treatments in mood disorders is emerging. Recommendations are to increase sample sizes, pre-screen for impairment in targeted domain(s), select one primary outcome, aid transfer to real-world functioning, investigate multimodal interventions and include neuroimaging.

The mental health consequences of the COVID-19 pandemic have been significant in Australia. The aim of this study was to investigate coping strategies that individuals have adopted to assist them through this stressful period. Survey data collected in September and December 2020 as part of a larger study (the COLLATE project) were analysed. The number of adaptive coping strategies endorsed by respondents had a significant negative relationship with depression and a significant positive relationship with resilience. Females tended to use more of these strategies than men, as did people who said their mental health had improved rather than deteriorated because of the COVID-19 restrictions imposed by government. Specific adaptive coping strategies differed for those with and without a mental illness. People with a mental illness were more likely to seek professional and online help, while people without a mental illness were more likely to use self-help. Focusing on what one is grateful for and keeping oneself productively occupied ("using the time to do things around the house") were the most beneficial coping strategies in terms of alleviating depression, anxiety and stress. Public health messaging promoting adaptive coping strategies may be useful in bolstering the mental health of individuals during lockdown periods. In particular, the promotion of coping flexibility should be recommended rather than the frequent use of the same coping strategies.

BACKGROUND: Developing treatments for cognitive impairment is key to improving the functioning of people with mood disorders. Neuroimaging may assist in identifying brain-based efficacy markers. This systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force examines the evidence from neuroimaging studies of pro-cognitive interventions. METHODS: We included magnetic resonance imaging (MRI) studies of candidate interventions in people with mood disorders or healthy individuals, following the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE, Cochrane Library, and Clinicaltrials.gov from inception to 30th April 2021. Two independent authors reviewed the studies using the National Heart, Lung, Blood Institutes of Health Quality Assessment Tool for Controlled Intervention Studies and the quality of neuroimaging methodology assessment checklist. RESULTS: We identified 26 studies (N = 702). Six investigated cognitive remediation or pharmacological treatments in mood disorders (N = 190). In healthy individuals, 14 studies investigated pharmacological interventions (N = 319), 2 cognitive training (N = 73) and 4 neuromodulatory treatments (N = 120). Methodologies were mostly rated as 'fair'. 77% of studies investigated effects with task-based fMRI. Findings varied but most consistently involved treatment-associated cognitive control network (CCN) activity increases with cognitive improvements, or CCN activity decreases with no cognitive change, and increased functional connectivity. In mood disorders, treatment-related default mode network suppression occurred. CONCLUSIONS: Modulation of CCN and DMN activity is a putative efficacy biomarker. Methodological recommendations are to pre-declare intended analyses and use task-based fMRI, paradigms probing the CCN, longitudinal assessments, mock scanning, and out

Considerable cognitive heterogeneity is present within the schizophrenia spectrum disorder (SSD) population. Several subgroups characterised by more homogenous cognitive profiles have been identified. It is not yet clear however, whether these subgroups represent different points along a continuum of cognitive symptom severity, or whether they reflect unique profiles of the disorder. One way to determine this is by comparing subgroups on their non-cognitive characteristics. The aim of the present review was to systematically summarise our current understanding of the non-cognitive features of the cognitive subgroups of schizophrenia spectrum disorder (SSD). Thirty-five relevant studies were identified from January 1980 to March 2020. Cognitive subgroups were consistently compared on age, sex, education, age of illness onset, illness duration, positive, negative and disorganised symptoms, depression and psychosocial functioning. It was revealed that subgroups were consistently distinguished by education, negative symptom severity and degree of functional impairment; with subgroups characterised by worse cognitive functioning performing/rated worse on these characteristics. The lack of consistent subgroup differences for the majority of the non-cognitive characteristics provides partial support for the notion that cognitive subgrouping in SSD is not simply reflecting a rehash of previously identified clinical subtypes. However, as subgroups were consistently distinguished by three characteristics known to be associated with cognition, our understanding of the extent to which the cognitive subgrouping approach is representing separate subtypes versus subdivisions along a continuum of symptom severity is still not definitive.

OBJECTIVE: Suicide is a major cause of death amongst individuals with schizophrenia spectrum disorders (SSD). Despite numerous risk factors being identified, accurate prediction of suicidality and provision of tailored and effective treatment is difficult. One factor that may warrant particular attention as a contributor to increased psychopathology and suicidality in SSD is disturbed sleep. Sleep disturbances have been reliably linked to greater levels of suicidal ideation and are highly prevalent amongst individuals with SSD. This study aimed to examine if reduced sleep duration and psychopathology are associated with increased suicidal ideation. METHOD: One-hundred and eighteen adults with chronic SSD living within the community participated in this cross-sectional study. Psychosis symptoms were assessed using the Positive and Negative Syndrome Scale. Items 4 and 10 from the Montgomery-Asperg Depression Rating Scale and Item 2 from the Calgary Depression Scale for Schizophrenia were used to assess reduced sleep duration, current suicidal ideation, and hopelessness, respectively. All measures were rated concurrently. RESULTS: A hierarchical logistic regression revealed that greater acute sleep disturbances were associated with increased suicidal ideation and this relationship was found to be uniquely mediated by both positive symptom severity and hopelessness. CONCLUSION: These results suggest that individuals with SSD who exhibited disrupted or disordered sleep, positive symptoms and/or hopelessness should be routinely screened for suicidal thinking. Furthermore, interventions that effectively target sleep disruptions may provide much-needed action against suicidal ideation.HIGHLIGHTSReduced sleep found to be associated with increased suicidal ideationThis was uniquely mediated by both hopelessness and positive symptomsMore regular screening of sleep problems in schizophrenia is needed.

The coronavirus (COVID-19) pandemic has caused major disruptions to social and other forms of functioning, which may influence schizotypy expression. The current study aimed to explore possible distal and proximal predictors contributing to schizotypy in a sample of the Australian general population during the COVID-19 pandemic. The COvid-19 and you: mentaL heaLth in AusTralia now survEy (COLLATE) project is an online mental health study aimed at tracking key mental health indicators over the progression of the pandemic. Adults residing in Australia were invited to take part using non-discriminative snowball sampling. Demographic-clinical information was collected for 850 participants in either October 2020 or January 2021. To assess schizotypy facets, the Launay-Slade Hallucinations Scale-Extended (LSHS-E) and Peters Delusions Inventory (PDI-21) were used to measure hallucination and delusion proneness respectively. Generalised linear models (with gamma and negative binomial distributions) were employed. Age, negative emotions and loneliness significantly contributed to both hallucination and delusion proneness; gender, education and religiosity also significantly contributed to delusion proneness, in the final regression models. Our study corroborated the specific contribution of loneliness, amongst other factors, in the prediction of schizotypy facets. Tackling loneliness represents a public health challenge that needs to be urgently addressed, especially in the face of the ongoing COVID-19 pandemic.

BACKGROUND: While physical inactivity is associated with adverse psychological outcomes, less is known about the psychological outcomes associated with sedentary behaviour, and specifically, its mentally active and passive forms. The COVID-19 pandemic represents a unique opportunity to study associations between these variables in light of widespread stay-at-home mandates and restrictions on outdoor exercise/social activities. Using a cross-sectional dataset acquired during the COVID-19 pandemic in Australia, we examined whether physical activity and sedentary behaviour were associated with subjective quality of life (sQoL) and subjective cognitive dysfunction, and whether these associations were mediated by depressive symptoms. METHODS: 658 participants (males = 169, females = 489) self-reported data on physical activity and sedentary behaviour in an online survey during May 2020-May 2021. Data on physical activity and sedentary behaviour (both mentally active and passive types) was compared according to whether it was collected during or out of a lockdown period. Regression models were used to test associations of physical activity and sedentary behaviour with sQoL and subjective cognitive dysfunction, and whether these associations were mediated by depression severity. RESULTS: Physical activity was beneficially associated with sQoL, whereas sedentary behaviour (both total hours and the reduction of mentally active/increase in mentally passive behaviour) was detrimentally associated with sQoL. These associations were mediated by depression severity. Physical activity and sedentary behaviour were also indirectly associated with subjective cognitive dysfunction by virtue of their associations with depression severity. CONCLUSIONS: There are important differences in the psychological correlates of mentally passive and active sedentary behaviours. Our findings suggest that health promotion strategies should focus on not only increasing physical activity but also redu

BACKGROUND: The aim of this cross-sectional study was to investigate dispositional mindfulness and its association with depression and manic tendencies, and subjective life quality in bipolar disorder (BD). Furthermore, this study sought to examine the potential mediating effects of emotion regulation difficulties on these relationships. METHOD: Twenty-eight healthy controls (HC) and 66 clinically stable outpatients with a DSM-IV-TR diagnosis of BD completed the Mindfulness Attention Awareness Scale (MAAS), Difficulties in Emotion Regulation Scale (DERS), Seven Up (7 Up) Seven Down (7 Down) and the Quality of Life in Bipolar Disorder Questionnaire (QoL.BD). These variables were compared between groups and entered into a series of mediation analyzes using PROCESS in the BD group only. RESULTS: Lower MAAS scores were detected amongst the BD patients compared to HCs. Lower MAAS scores in BD patients predicted higher 7 Up, 7 Down and lower QoL.BD scores. For the 7 Down and QoL.BD, the associations were completely mediated by DERS scores, with difficulties in strategy use and emotional clarity mediating the association between mindfulness and depressive tendencies and quality of life, respectively. No significant direct or indirect effects were detected for the 7 Up model. LIMITATIONS: The cross-sectional design precludes causal inference. The MAAS conceptualises mindfulness as unidimensional. Self-report scales of depressive and manic tendencies utilised. CONCLUSIONS: This study detected a significant association between dispositional mindfulness and depressive tendencies and life quality in BD, and found that these associations were influenced by emotion regulation difficulties. These findings encourage further investigation of mindfulness-based interventions in BD.

BACKGROUND: There has been relatively limited work focused on understanding whether relatives of individuals with bipolar disorder (BD) have difficulties in the regulation of emotion, particularly in relation to perceptions about whether emotions can be effectively regulated, or trait behaviours that acknowledge emotions as self-regulators themselves. In this study, we assessed the presence and extent of difficulties in these dimensions of emotion regulation in individuals with BD compared to unaffected first-degree biological relatives (FDR) for the first time. METHODS: In total, 161 participants, including euthymic individuals with BD, unaffected FDRs, and healthy controls, were compared on the Difficulties in Emotion Regulation Scale (DERS) - a multi-dimensional measure of habitual emotion regulation. Clinical data were also collected and examined in relation to DERS scores in a secondary analysis. RESULTS: In the BD group, difficulties were evident for most dimensions of emotion regulation as measured by the DERS; and correlated with an earlier onset of illness and more mood episodes. FDRs displayed generally normal emotion regulation, except in terms of their beliefs that emotions can be effectively regulated; on this dimension, their reported difficulty was intermediate to the BD group and controls. CONCLUSION: Habitual emotion regulation difficulties in BD persist irrespective of mood state, are related to the course of illness, and should be targeted in psychological interventions. Further, the perception that emotions cannot be effectively regulated during times of distress seems to represent an endophenotype for BD.

Sex differences in symptoms and executive control across schizophrenia spectrum disorders (SSD) are consistently reported. Similarly, these findings of sex differences are also observed in schizotypy, that is, schizophrenia-like features occurring in healthy individuals in the absence of a clinical diagnosis. This study aimed to examine the relationships between performance on three major domains of executive control: performance monitoring, response inhibition, and cognitive set-shifting, and schizotypy factor scores in both SSD patients and healthy controls (HCs), and whether sex moderated any relationships observed. A total of 111 (67 males and 44 females) patients with SSD and 258 (129 males and 129 females) HCs were included in this study. Schizotypal personality traits (in both SSD and HC) was assessed using the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE). Executive control performance was assessed using seven tasks. Stepwise linear regressions revealed that performance on cognitive set-shifting tasks was significantly associated with the introvertive anhedonia, cognitive disorganisation, and unusual experiences subscales of the O-LIFE. When sex was examined as a moderator, it was not a significant moderator of any of the relationships between cognitive set-shifting tasks and schizotypy factors. The results suggest that independent of sex, cognitive set-shifting ability is associated to an increased vulnerability to schizotypal personality traits, although performance monitoring and response inhibition did not.

Owning a pet has often been associated with improved mental health among owners, including enhanced quality of life, and decreased levels of depression and loneliness. The aim of this study was to identify whether owning a cat and/or dog was associated with better psychological wellbeing during a strict lockdown period in Victoria, Australia, during the COVID-19 pandemic. Data were analysed from a large-scale mental health study: the COvid-19 and you: mentaL heaLth in AusTralia now survEy (COLLATE). The impact of pet ownership on levels of resilience, loneliness and quality of life were examined in a sample of 138 pet owners and 125 non-pet owners. Hierarchical linear regression analyses indicated that pet ownership was significantly associated with poorer quality of life, but not significantly associated with resilience or loneliness, after accounting for situational factors (e.g. job loss) and mood states. Contrary to expectations, the findings suggest that during a specific situation such as a pandemic, pets may contribute to increased burden among owners and contribute to poorer quality of life.

Iron has been increasingly implicated in the pathology of neurodegenerative diseases. In the past decade, development of the new magnetic resonance imaging technique, quantitative susceptibility mapping (QSM), has enabled for the more comprehensive investigation of iron distribution in the brain. The aim of this systematic review was to provide a synthesis of the findings from existing QSM studies in neurodegenerative diseases. We identified 80 records by searching MEDLINE, Embase, Scopus, and PsycInfo databases. The disorders investigated in these studies included Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Wilson's disease, Huntington's disease, Friedreich's ataxia, spinocerebellar ataxia, Fabry disease, myotonic dystrophy, pantothenate-kinase-associated neurodegeneration, and mitochondrial membrane protein-associated neurodegeneration. As a general pattern, QSM revealed increased magnetic susceptibility (suggestive of increased iron content) in the brain regions associated with the pathology of each disorder, such as the amygdala and caudate nucleus in Alzheimer's disease, the substantia nigra in Parkinson's disease, motor cortex in amyotrophic lateral sclerosis, basal ganglia in Huntington's disease, and cerebellar dentate nucleus in Friedreich's ataxia. Furthermore, the increased magnetic susceptibility correlated with disease duration and severity of clinical features in some disorders. Although the number of studies is still limited in most of the neurodegenerative diseases, the existing evidence suggests that QSM can be a promising tool in the investigation of neurodegeneration.

The novel coronavirus disease (COVID-19) poses mental health challenges globally; however, to date, there is limited community level data. This study reports on the COLLATE project (COvid-19 and you: mentaL heaLth in AusTralia now survEy), an ongoing study aimed at understanding the impact of the COVID-19 pandemic on Australian mental health and well-being. We addressed prevailing primary concerns related to the COVID-19 pandemic, current levels of negative emotions and risk factors predicting negative emotions. On April 1st to 4th 2020, 5158 adults from the general public completed an online survey. Participants ranked their top ten current primary concerns about COVID-19, and completed standardized measures of negative emotions. The top three primary concerns were related to health and well-being of family and loved ones. Levels of negative emotion were high. Modelling of predictors of negative emotions established several risk factors related to demographic variables, personal vulnerabilities, financial stresses, and social distancing perceptions; particularly being young, female, or having a mental illness diagnosis. The data provides important characterization of the current Australian mental health. It appears that specific groups may need special attention to ensure their mental health is protected. These results may provide direction for international researchers characterizing similar issues.

Cognitive dysfunction is a major predictor of functional outcomes, and loss of occupational functioning is usually linked with a higher cost of illness. However, the association between cognitive impairment and consumption of health resources has not been studied in bipolar disorder to date. This study aims to examine this relationship. This is an observational, retrospective study of a representative sample of euthymic outpatients between 18 and 55 years, fulfilling DSM 5 criteria for bipolar disorder and recruited at a catchment area in Spain. Cognitive performance was screened with the Spanish version of the Screen for Cognitive Impairment in Psychiatry (SCIP-S), and several variables of health resources consumption during the previous year were registered. A total of 72 patients were assessed. Cognitive impairment according to the SCIP-S was significantly associated with the number of scheduled clinical appointments (p < 0.005) and hospital admissions (p < 0.04) but not with other health resources consumption variables. These results need to be interpreted with caution given that neither a control group nor a comprehensive, objective neuropsychological battery were used. However, despite these limitations, this study shows that in euthymic outpatients with bipolar disorder, those with suspected cognitive impairment had consumed a higher number of health resources over the previous year. These preliminary results may foster similar studies on the relationship between mental healthcare resource use and cognitive dysfunction in bipolar disorder and other psychiatric disorders.

PURPOSE: The COVID-19 global pandemic has resulted in a significant mental health toll, and recent findings suggest that individuals with an eating disorder (ED) history may be particularly vulnerable. The current study aimed to: (1) identify changes in the pattern of mental health symptoms over the first six months of the pandemic between individuals with an ED history, compared to a community sample without an ED history (non-ED); and (2) identify differences in mental health symptoms and concerns between two waves of the virus and associated lockdowns. METHOD: Data from 4915 respondents - 231 with an ED history - were compared across monthly time points from April to September 2020 on psychological symptoms including negative mood, quality of life, coping and hopefulness, as well as changes to eating and exercise behaviours. RESULTS: Mental health symptoms were increased in the ED group, but generally did not differ from non-ED in the pattern of symptoms reported over time. Increased depressive symptoms and restrictive eating behaviours were found across both groups in relation to the second wave/lockdown, as well as decreased hopefulness and quality of life. Respondents in both groups also reported coping worse during the second wave of the virus compared to the first wave. CONCLUSION: Although non-ED and ED groups tended to generally show the same pattern of symptoms, the mental health status of the ED group was significantly poorer than the non-ED group throughout the pandemic, and exacerbations in some symptoms (i.e. increased food restriction and depressive symptoms) is cause for concern.

The novel coronavirus (COVID-19) has necessitated many healthcare workers operating on the frontlines. Another segment of the population whose mental well-being is being tested are the 'other essential workers' (e.g. supermarket workers). The current study aimed to compare the mental health of healthcare versus other essential workers in the early stages of the COVID-19 outbreak. The COVID-19 and you: mentaL heaLth in AusTralia now survEy (COLLATE) project is a nationwide online mental health survey launched on 1 April 2020, aimed at identifying key mental health concerns. Adults currently living in Australia were invited to take part, and non-discriminative snowball sampling was employed. Participants were partitioned into healthcare workers (HCW; n=905), other essential workers (OEW; n=810), and the general population (GNP; n=3443). Across all groups, top COVID-19 related concerns were primarily associated with the health and well-being of loved ones. In terms of current levels of depression, anxiety, stress and quality of life, HCWs fared the best, and OEWs fared the worst (with the GNP falling in between). In the face of this medical crisis, Australian HCWs seem to be managing their mental health relatively well, but more supports need to be devoted to OEWs to safeguard their mental well-being.

Processing speed (PS) impairment is one of the most severe and common cognitive deficits in schizophrenia. Previous studies have reported correlations between PS and white matter diffusion properties, including fractional anisotropy (FA), in several fiber bundles in schizophrenia, suggesting that white matter alterations could underpin decreased PS. In schizophrenia, white matter alterations are most prevalent within inter-hub connections of the rich club. However, the spatial and topological characteristics of this association between PS and FA have not been investigated in patients. In this context, we tested whether structural connections comprising the rich club network would underlie PS impairment in 298 patients with schizophrenia or schizoaffective disorder and 190 healthy controls from the Australian Schizophrenia Research Bank. PS, measured using the digit symbol coding task, was largely (Cohen's d = 1.33) and significantly (P < .001) reduced in the patient group when compared with healthy controls. Significant associations between PS and FA were widespread in the patient group, involving all cerebral lobes. FA was not associated with other cognitive measures of phonological fluency and verbal working memory in patients, suggesting specificity to PS. A topological analysis revealed that despite being spatially widespread, associations between PS and FA were over-represented among connections forming the rich club network. These findings highlight the need to consider brain network topology when investigating high-order cognitive functions that may be spatially distributed among several brain regions. They also reinforce the evidence that brain hubs and their interconnections may be particularly vulnerable parts of the brain in schizophrenia.

OBJECTIVES: Cognitive dysfunction affects a significant proportion of people with bipolar disorder (BD), but the cause, trajectory and correlates of such dysfunction remains unclear. Increased understanding of these factors is required to progress treatment development for this symptom dimension. METHODS: This paper provides a critical overview of the literature concerning the trajectories and emerging correlates of cognitive functioning in BD. It is a narrative review in which we provide a qualitative synthesis of current evidence concerning clinical, molecular, neural and lifestyle correlates of cognitive impairment in BD across the lifespan (in premorbid, prodromal, early onset, post-onset, elderly cohorts). RESULTS: There is emerging evidence of empirical links between cognitive impairment and an increased inflammatory state, brain structural abnormalities and reduced neuroprotection in BD. However, evidence regarding the progressive nature of cognitive impairment is mixed, since consensus between different cross-sectional data is lacking and does not align to the outcomes of the limited longitudinal studies available. Increased recognition of cognitive heterogeneity in BD may help to explain some inconsistencies in the extant literature. CONCLUSIONS: Large, longitudinally focussed studies of cognition and its covariation alongside biological and lifestyle factors are required to better define cognitive trajectories in BD, and eventually pave the way for the application of a precision medicine approach for individual patients in clinical practice.

During this unprecedented novel coronavirus (COVID-19) pandemic, there is an urgent need for empirical data to characterise its impact on the mental health and well-being of Australians. In this viewpoint, we outline a number of considerations for research on this topic, highlighting areas necessitating special attention, consideration of particular vulnerable groups and the need for longitudinal studies to track mental health fluctuations in the general population. We conclude by introducing the COLLATE (COvid-19 and you: mentaL heaLth in AusTralia now survEy) project, outlining its aims, addressing some considerations raised herein and detailing avenues for future research. Since the World Health Organization (WHO) declared the novel coronavirus (COVID-19) outbreak a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 (WHO, 2020), the COVID-19 pandemic has caused major upheaval both in Australia and globally. While the search for a vaccine continues, current efforts towards tackling the virus and limiting contagion in several nations have focused on social distancing and the shutdown of non-essential services. In Australia, the first case was reported on 13 January 2020 (COVID-19 National Incident Room Surveillance Team, 2020), the first death occurred on 24 February and a spate of progressive restrictions were enforced throughout the 2 weeks leading up to 31 March 2020 (COVID-19 National Incident Room Surveillance Team, 2020a).

AIM: The effects of social isolation measures used to control the spread of COVID-19 are negatively impacting the mental health of many. One of the consequences of exposure to disasters/pandemics is an increase in alcohol use. The current study aimed to examine what predisposing (distal) and pandemic-related (proximal) factors were associated with increased drinking in the wake of the COVID-19 pandemic. METHODS: On 1 April 2020, 5158 Australians completed a survey from the COvid-19 and you: mentaL heaLth in AusTralia now survEy (COLLATE) project, a nationwide study aimed at tracking key mental health concerns. Using logistic regression, distal (demographics and previous drinking behaviors) and proximal (employment, lifestyle factors, and mood) factors were assessed for their association with increased drinking since the onset of the COVID-19 pandemic. RESULTS: Distal factors, including heavier drinking pre-pandemic, middle age, and average or higher income, and proximal factors, including job loss, eating more, changes to sleep as well as stress and depression, were all associated with increased drinking in the COVID-19 pandemic environment. Female sex and self-reported history of mental illness became nonsignificant after proximal measures were added to the model. Living alone, exercise, anxiety, and status as an essential or health-care worker were not associated with increased drinking. CONCLUSION: These results provide guidance as to who might be targeted to receive support based on predisposing demographic factors and pre-pandemic drinking behavior. Second, they indicate what behaviors/factors accompany increased alcohol use and provide targets for psychosocial and psychoeducational supports to address these proximal factors.

OBJECTIVE: Emerging evidence suggests that the coronavirus (COVID-19) pandemic may be negatively impacting mental health. The impact on eating and exercise behaviors is, however, currently unknown. This study aimed to identify changes in eating and exercise behaviors in an Australian sample among individuals with an eating disorder, and the general population, amidst the COVID-19 pandemic outbreak. METHOD: A total of 5,469 participants, 180 of whom self-reported an eating disorder history, completed questions relating to changes in eating and exercise behaviors since the emergence of the pandemic, as part of the COLLATE (COvid-19 and you: mentaL heaLth in AusTralia now survEy) project; a national survey launched in Australia on April 1, 2020. RESULTS: In the eating disorders group, increased restricting, binge eating, purging, and exercise behaviors were found. In the general population, both increased restricting and binge eating behaviors were reported; however, respondents reported less exercise relative to before the pandemic. DISCUSSION: The findings have important implications for providing greater monitoring and support for eating disorder patients during the COVID-19 pandemic. In addition, the mental and physical health impacts of changed eating and exercise behaviors in the general population need to be acknowledged and monitored for potential long-term consequences.

BACKGROUND: Physical-distancing strategies during the coronavirus (COVID-19) pandemic may be particularly detrimental to the mental health of individuals with a pre-existing mood disorder. Data on the mental health status of these individuals during the current pandemic is sparse, and their current mental health needs unclear. METHOD: We characterised COVID-19 related lifestyle changes, primary concerns and psychological distress in n=1292 respondents self-reporting a mood disorder (either bipolar disorder or depressive disorder) and n=3167 respondents without any reported mental disorder from the COLLATE (COvid-19 and you: mentaL heaLth in AusTralia now survEy) project; an Australian national survey launched on April 1st 2020. RESULTS: Psychological distress was heightened in the mood disorder group compared to the group with no mental disorder, with stress and depression further elevated in respondents with bipolar disorder compared to those with depressive disorder; and men with bipolar disorder having even higher levels of depression than women with bipolar disorder. Respondents with bipolar disorder were particularly concerned about financial issues associated with COVID-19 compared to those with depressive disorder and those with no mental disorder. Adverse changes to lifestyle behaviours were more prevalent in respondents with a mood disorder and linked to higher levels of distress. LIMITATIONS: Mood disorder was self-reported and was not clinically verified. CONCLUSIONS: Current psychological distress levels are elevated in individuals with mood disorder and are associated with maladaptive situational and lifestyle changes occurring in response to COVID-19.

Antidepressant medications are the first-line treatment option for moderate to severe major depressive disorder. However, most antidepressants have numerous documented adverse events, including cardiometabolic effects and weight gain, which are major public health concerns. Antidepressant agents provide varying risk of associated weight gain, including significant within-class differences. Some agents, such as mirtazapine, show significant levels of weight gain, while others, such as bupropion, demonstrate weight-loss effects. Current findings suggest the role of histamine and serotonin off-target appetite-promoting pathways in adverse weight-gain effects. Therefore, controlling for undesired weight effects is an important consideration for the selection of antidepressants.

Our research team was asked to consider the relationship of the neuroscience of sensorimotor control to the language of emotions and feelings. Actions are the principal means for the communication of emotions and feelings in both humans and other animals, and the allostatic mechanisms controlling action also apply to the regulation of emotional states by the self and others. We consider how motor control of hierarchically organised, feedback-based, goal-directed action has evolved in humans, within a context of consciousness, appraisal and cultural learning, to serve emotions and feelings. In our linguistic analysis, we found that many emotion and feelings words could be assigned to stages in the sensorimotor learning process, but the assignment was often arbitrary. The embodied nature of emotional communication means that action words are frequently used, but that the meanings or senses of the word depend on its contextual use, just as the relationship of an action to an emotion is also contextually dependent.

OBJECTIVE: The current study aimed to compare specific cognitive profiles corresponding to auditory verbal hallucinations (AVH) status and elucidate which pattern of cognitive deficits may predict voice-hearing status. METHOD: Clinical participants with schizophrenia spectrum disorders were partitioned into: (i) current voice-hearers (n = 46), (ii) past voice-hearers (n = 37) and (iii) never voice-hearers (n = 40), and compared with 319 non-clinical controls. Cognitive assessment employed the MATRICS Consensus Cognitive Battery (MCCB), supplemented by the Delis-Kaplan Executive Function System (D-KEFS) Colour-Word Interference Test (Stroop) as a robust measure of executive function. RESULTS: On the Visual Learning domain, current and past voice-hearers had significantly poorer performance relative to never voice-hearers, who in turn had significantly poorer performance than non-clinical controls. Current and never voice-hearers had significantly poorer performance on the Social Cognition domain relative to non-clinical controls. Current voice-hearers also had significantly poorer performance on the Inhibition domain relative to non-clinical controls. Binary logistic regression revealed that Visual Learning was the only significant cognitive predictor of AVH presence. CONCLUSION: Visual learning, and potentially inhibition, may be viable therapeutic targets when addressing cognitive mechanisms associated with AVHs. Future research should focus on investigating additional cognitive mechanisms, employing diverse voice-hearing populations and embarking on related longitudinal studies.

BACKGROUND: Impairments in affective cognition are part of the neurocognitive profile and possible treatment targets in bipolar disorder (BD), but the findings are heterogeneous. The International Society of Bipolar Disorder (ISBD) Targeting Cognition Task Force conducted a systematic review to (i) identify the most consistent findings in affective cognition in BD, and (ii) provide suggestions for affective cognitive domains for future study and meta-analyses. METHODS: The review included original studies reporting behavioral measures of affective cognition in BD patients vs controls following the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement. Searches were conducted on PubMed/MEDLINE, EMBASE, and PsychInfo from inception until November 2018. RESULTS: A total of 106 articles were included (of which nine included data for several affective domains); 41 studies assessed emotional face processing; 23 studies investigated reactivity to emotional words and images; 3 investigated explicit emotion regulation; 17 assessed implicit emotion regulation; 31 assessed reward processing and affective decision making. In general, findings were inconsistent. The most consistent findings were trait-related difficulties in facial emotion recognition and implicit emotion regulation, and impairments in reward processing and affective decision making during mood episodes. Studies using eye-tracking and facial emotion analysis revealed subtle trait-related abnormalities in emotional reactivity. CONCLUSION: The ISBD Task Force recommends facial expression recognition, implicit emotion regulation, and reward processing as domains for future research and meta-analyses. An important step to aid comparability between studies in the field would be to reach consensus on an affective cognition test battery for BD.

OBJECTIVE: The personality characteristics and symptoms observed in schizophrenia are postulated to lie on a continuum, with non-clinical manifestations referred to as schizotypy. High schizotypy behaviours are argued to correspond with the three main clusters of symptoms in schizophrenia: positive, negative and cognitive/disorganised symptoms, yet there is limited empirical evidence to support this. This study aimed to investigate whether schizotypy dimensions significantly correlate with their respective schizophrenia symptomatology in the largest sample to date. METHODS: A total of 361 adults (103 patients with schizophrenia/schizoaffective disorder and 258 healthy controls) were assessed for schizotypy using the Oxford-Liverpool Inventory of Feelings and Experiences. The MATRICS Consensus Cognitive Battery supplemented by the Stroop task and Wisconsin Card Sorting Test was administered to all participants to obtain objective measurements of cognition. Schizophrenia symptomatology was assessed using the Positive and Negative Syndrome Scale in patients only. RESULTS: The results demonstrated significant correlations between the Oxford-Liverpool Inventory of Feelings and Experiences positive and negative subscales and their respective Positive and Negative Syndrome Scale subscales only, indicating that positive and negative schizotypy dimensions across patients and controls accurately reflect the respective schizophrenia symptomatology observed in patients. Cognitive performance did not correlate with cognitive/disorganised symptom dimensions of the Oxford-Liverpool Inventory of Feelings and Experiences or the Positive and Negative Syndrome Scale, indicating that cognitive impairment is an independent symptom dimension that requires objective cognitive testing. CONCLUSION: Collectively, the findings provide empirical evidence for the continuum theory and support the use of schizotypy as a model for investigating schizophrenia.

In this review, we describe the sex differences in prevalence, onset, symptom profiles, and disease outcome that are evident in schizophrenia, bipolar disorder, and post-traumatic stress disorder. Women with schizophrenia tend to exhibit less disease impairment than men. By contrast, women with post-traumatic stress disorder are more affected than men. The most likely candidates to explain these sex differences are gonadal hormones. This review details the clinical evidence that oestradiol and progesterone are dysregulated in these psychiatric disorders. Notably, existing data on oestradiol, and to a lesser extent, progesterone, suggest that low levels of these hormones may increase the risk of disease development and worsen symptom severity. We argue that future studies require a more inclusive, considered analysis of gonadal steroid hormones and the intricacies of the interactions between them, with methodological rigour applied, to enhance our understanding of the roles of steroid hormones in psychiatric disorders. LINKED ARTICLES: This article is part of a themed section on The Importance of Sex Differences in Pharmacology Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.21/issuetoc.