Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force.

BACKGROUND: Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD. METHODS: We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials. RESULTS: Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment-related ADHD symptom reduction: two involved methylphenidate and one amphetamine salts. One study found a trend towards pro-cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and one a serious risk of bias. CONCLUSIONS: Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers.

The effect of age on emotion processing in individuals with mood disorders and in healthy individuals.

Introduction: Emotion processing is an essential part of interpersonal relationships and social interactions. Changes in emotion processing have been found in both mood disorders and in aging, however, the interaction between such factors has yet to be examined in detail. This is of interest due to the contrary nature of the changes observed in existing research - a negativity bias in mood disorders versus a positivity effect with aging. It is also unclear how changes in non-emotional cognitive function with aging and in mood disorders, interact with these biases. Methods and results: In individuals with mood disorders and in healthy control participants, we examined emotional processing and its relationship to age in detail. Data sets from two studies examining facial expression recognition were pooled. In one study, 98 currently depressed individuals (either unipolar or bipolar) were compared with 61 healthy control participants, and in the other, 100 people with bipolar disorder (in various mood states) were tested on the same facial expression recognition task. Repeated measures analysis of variance was used to examine the effects of age and mood disorder diagnosis alongside interactions between individual emotion, age, and mood disorder diagnosis. A positivity effect was associated with increasing age which was evident irrespective of the presence of mood disorder or current mood episode. Discussion: Results suggest a positivity effect occurring at a relatively early age but with no evidence of a bias toward negative emotions in mood disorder or specifically, in depressed episodes. The positivity effect in emotional processing in aging appears to occur even within people with mood disorders. Further research is needed to understand how this fits with negative biases seen in previous studies in mood disorders.

Racism, early psychosis, and institutional contact: A qualitative study of Indigenous experiences.

BACKGROUND: There is evidence of Indigenous and ethnic minority inequities in the incidence and outcomes of early psychosis. Racism has been implicated as having an important role. AIM: To use Indigenous experiences to develop a more detailed understanding of how racism operates to impact early psychosis outcomes. METHODS: Critical Race Theory informed the methodology used. Twenty-three Indigenous participants participated in four family focus group interviews and thirteen individual interviews, comprising of 9 Maori youth with early psychosis, 10 family members and 4 Maori mental health professionals. An analysis of the data was undertaken using deductive structural coding to identify descriptions of racism, followed by inductive descriptive and pattern coding. RESULTS: Participant experiences revealed how racism operates as a socio-cultural phenomenon that interacts with institutional policy and culture across systems pertaining to social responsiveness, risk discourse, and mental health service structures. This is described across three major themes: 1) selective responses based on racial stereotypes, 2) race related risk assessment bias and 3) institutional racism in the mental health workforce. The impacts of racism were reported as inaction in the face of social need, increased use of coercive practices and an under resourced Indigenous mental health workforce. CONCLUSION: The study illustrated the inter-related nature of interpersonal, institutional and structural racism with examples of interpersonal racism in the form of negative stereotypes interacting with organizational, socio-cultural and political priorities. These findings indicate that organizational cultures may differentially impact Indigenous and minority people and that social responsiveness, risk discourse and the distribution of workforce expenditure are important targets for anti-racism efforts.

The COVID Psychosocial Impacts Scale: A Reliable and Valid Tool to Examine the Psychosocial Impacts of the COVID-19 Pandemic.

This paper reports on the development and validation of the COVID Psychosocial Impacts Scale (CPIS), a self-report measure that comprehensively examines both positive and negative psychosocial impacts from the COVID-19 pandemic. This is the first part of the program of work in which the CPIS was administered and compared with a measure of psychological distress (Kessler Psychological Distress Scale, K-10) and wellbeing (World Health Organization Well-Being Index, WHO-5). The data were obtained online in 2020 and 2022 at two distinct time points to capture different exposures to the pandemic in the New Zealand population to a non-representative sample of 663 and 687 adults, respectively. Two hundred seventy-one participants took part in both surveys. Findings indicate a unidimensional structure within CPIS subscales and inter-relatedness among CPIS stress-related subscales. The scatter plots and correlation matrix indicate CPIS having a positive moderate correlation with K10 and a negative moderate correlation with WHO-5, indicative of construct validity. The paper outlines contextual factors surrounding CPIS development and makes suggestions for future iterations of CPIS. Further work will examine its psychometric properties across cultures.

Racism, early psychosis and institutional contact: a qualitative study of Indigenous experiences.

There is evidence of Indigenous and ethnic minority inequities in the incidence and outcomes of early psychosis. racism has an important role. This study aimed to use Indigenous experiences to develop a more detailed understanding of how racism operates to impact early psychosis. Critical Race Theory informed the methods used. Twenty-three Indigenous participants participated in 4 family focus group interviews and 13 individual interviews, comprising of 9 youth, 10 family members and 4 mental health professionals. An analysis of the data was undertaken using deductive structural coding to identify descriptions of racism, followed by inductive descriptive and pattern coding. Participant experiences revealed how racism operates as a socio-cultural phenomenon that interacts with institutional policy and culture across systems. This is described across three themes: (1) selective responses based on racial stereotypes, (2) race related risk assessment bias and (3) institutional racism in the mental health workforce. The impacts of racism were reported as inaction in the face of social need, increased coercion and an under resourced Indigenous workforce. These findings indicate that organizational cultures may differentially impact Indigenous and minority people and that social responsiveness, risk discourse and the distribution of workforce expenditure are important targets for anti-racism efforts.

Ketamine and psychotherapy for the treatment of psychiatric disorders: systematic review.

BACKGROUND: Ketamine is an effective short-term treatment for a range of psychiatric disorders. A key question is whether the addition of psychotherapy to ketamine treatment improves outcomes or delays relapse. AIM: To identify all studies combining psychotherapy with ketamine for the treatment of psychiatric disorders to summarise their effects and make recommendations for future research. METHOD: The review protocol was prospectively registered with PROSPERO (registration number CRD42022318120). Potential studies were searched for in MEDLINE, Embase, PsycINFO, SCOPUS, the Cochrane library and Google Scholar. Eligible studies combined ketamine and psychotherapy for the treatment of psychiatric disorders and did not use case reports or qualitative designs. Key findings relating to psychotherapy type, diagnosis, ketamine protocol, sequencing of psychotherapy and study design are reported. Risk of bias was assessed using modified Joanna Briggs critical appraisal tools. RESULTS: Nineteen studies evaluating 1006 patients were included in the systematic review. A variety of supportive individual and group, manualised and non-manualised psychotherapies were used. The majority of studies evaluated substance use disorders, post-traumatic stress disorder and treatment-resistant depression. Ketamine protocols and sequencing of ketamine/psychotherapy treatment varied substantially between studies. Outcomes were largely positive for the addition of psychotherapy to ketamine treatment. CONCLUSION: The combination of psychotherapy and ketamine offers promise for the treatment of psychiatric disorders, but study heterogeneity prevents definitive recommendations for their integration. Larger randomised controlled trials using manualised psychotherapies and standardised ketamine protocols are recommended to clarify the extent to which the addition of psychotherapy to ketamine improves outcomes over ketamine treatment alone.

Examining the psychosocial impacts of the COVID-19 pandemic: an international cross-sectional study protocol.

INTRODUCTION: The COVID-19 pandemic exposed people to significant and prolonged stress. The psychosocial impacts of the pandemic have been well recognised and reported in high-income countries (HICs) but it is important to understand the unique challenges posed by COVID-19 in low- and middle-income countries (LMICs) where limited international comparisons have been undertaken. This protocol was therefore devised to study the psychosocial impacts of the COVID-19 pandemic in seven LMICs using scales that had been designed for or translated for this purpose. METHODS AND ANALYSIS: This cross-sectional study uses an online survey to administer a novel COVID Psychosocial Impacts Scale (CPIS) alongside established measures of psychological distress, post-traumatic stress, well-being and post-traumatic growth in the appropriate language. Participants will include adults aged 18 years and above, recruited from Indonesia, Iraq, Iran, Malaysia, Pakistan, Somalia and Turkey, with a pragmatic target sample size of 500 in each country.Data will be analysed descriptively on sociodemographic and study variables. In addition, CPIS will be analysed psychometrically (for reliability and validity) to assess the suitability of use in a given context. Finally, within-subjects and between-subjects analyses will be carried out using multi-level mixed-effect models to examine associations between key sociodemographic and study variables. ETHICS AND DISSEMINATION: Ethical approval was granted by the Human Ethics Committee, University of Otago, New Zealand (Ref. No. 21/102). In addition, international collaborators obtained local authorisation or ethical approval in their respective host universities before data collection commenced.Participants will give informed consent before taking part. Data will be collected and stored securely on the University of Otago, New Zealand Qualtrics platform using an auto-generated non-identifiable letter-number string. Data will be available on reasonable request. Findings will be disseminated by publications in scientific journals and/or conference presentations. TRIAL REGISTRATION NUMBER: NCT05052333.

Childhood trauma and cognitive functioning in mood disorders: A systematic review.

BACKGROUND: Cognitive impairment is a core feature of mood disorders and has been identified as an important treatment target. A better understanding of the factors contributing to cognitive impairment in mood disorders would be beneficial in developing interventions to address cognitive impairment. One key factor is childhood trauma. The aim of this review was to systematically synthesise and review research examining associations between reported childhood trauma and cognitive functioning in mood disorders. METHODS: Studies in adult samples examining the relationship between objective cognitive function and reported childhood trauma in major depressive disorder and/or bipolar disorder (in-episode or euthymia) were identified. Searches were conducted on PubMed, Embase and PsycINFO until January 2022. A narrative review technique was used due to the heterogeneity of group comparisons, cognitive tests and data analysis across studies. RESULTS: Seventeen studies met the criteria for inclusion (mood disorders N = 1723, healthy controls N = 797). Evidence for childhood trauma being related to poorer cognitive functioning was consistent across global cognitive functioning and executive function domains for euthymic patients and psychomotor speed for in-episode patients. There was mixed evidence for verbal learning and memory and executive function for in-episode patients. Identification of patterns within other domains was difficult due to limited number of studies. CONCLUSION: Findings from this review suggest childhood trauma is associated with poorer cognitive functioning in people with mood disorders. Targeted interventions to improve cognition may be warranted for this group.

Evolution of first episode psychosis diagnoses and health service use among young Maori and non-Maori-A New Zealand national cohort study.

AIMS: The validity of diagnostic classification in early psychosis has important implications for early intervention; however, it is unknown if previously found disparities between Maori (Indigenous people of New Zealand) and non-Maori in first episode diagnoses persist over time, or how these differences impact service use. METHODS: We used anonymized routine mental health service data and a previously established cohort of over 2400 13-25-year-old youth diagnosed with FEP between 2009 and 2012, to explore differences in diagnostic stability of psychosis diagnoses, comorbid (non-psychosis) diagnoses, and mental health service contacts between Maori and non-Maori in the five-year period following diagnosis. RESULTS: Differences in schizophrenia and affective psychosis diagnoses between Maori and non-Maori were maintained in the five-year period, with Maori being more likely to be diagnosed with schizophrenia (51% vs. 35%), and non-Maori with bipolar disorder (28% vs. 18%). Stability of diagnosis was similar (schizophrenia 75% Maori vs. 67% non-Maori; bipolar disorder 55% Maori vs. 48% non-Maori) and those with no stable diagnosis at FEP were most likely to move towards a schizophrenia disorder diagnosis in both groups. Maori had a lower rate of diagnosed co-morbid affective and anxiety symptoms and higher rates of continued face to face contact and inpatient admission across all diagnoses. CONCLUSIONS: Indigenous differences in schizophrenia and affective psychosis diagnoses could be related to differential exposure to socio-environmental risk or assessor bias. The lower rate of co-morbid affective and anxiety disorders indicates a potential under-appreciation of affective symptoms in Maori youth with first episode psychosis.

Non-Indigenous privilege in health, justice and social services preceding first episode psychosis: A population-based cohort study.

BACKGROUND: There is evidence of disparities between non-Indigenous and Indigenous incidence of psychotic disorders. Despite these disparities being a clear signpost of the impact of structural racism, there remains a lack of evidence to target institutional factors. We aimed to investigate non-Indigenous and Indigenous differences in government service use prior to first episode diagnosis as a means of identifying points of intervention to improve institutional responses. METHODS: We used a previously established national New Zealand cohort of 2385 13 to 25-year-old youth diagnosed with psychosis between 2009 and 2012 and a linked database of individual-level multiple government agency administration data, to investigate the differences in health, education, employment, child protection and criminal-justice service use between non-Indigenous (60%) and Indigenous youth (40%) in the year preceding first episode diagnosis. Further comparisons were made with the general population. RESULTS: A high rate of health service contact did not differ between non-Indigenous and Indigenous youth (adjusted rate ratio 1.0, 95% confidence interval [0.9, 1.1]). Non-Indigenous youth had higher rates of educational enrolment (adjusted rate ratio 1.2, 95% confidence interval [1.1, 1.3]) and employment (adjusted rate ratio 1.2, 95% confidence interval [1.1, 1.3]) and were 40% less likely to have contact with child protection services (adjusted rate ratio 0.6, 95% confidence interval [0.5, 0.8]) and the criminal-justice system (adjusted rate ratio 0.6, 95% confidence interval [0.5, 0.7]). Both first episode cohorts had a higher risk of criminal justice contact compared to the general population, but the difference was greater for non-Indigenous youth (risk ratio 3.0, 95% confidence interval [2.7, 3.4] vs risk ratio 2.0, 95% confidence interval [1.8, 2.2]), explained by the lower background risk. INTERPRETATION: The results indicate non-Indigenous privilege in multiple sectors prior to first episode diagnosis. Indigenous-based social disparities prior to first episode psychosis are likely to cause further inequities in recovery and will require a response of health, education, employment, justice and political systems.

Validation of the Longitudinal Interval Follow-Up Evaluation for the Long-Term Measurement of Mood Symptoms in Bipolar Disorder.

The long-term burden of symptoms is an important outcome in bipolar disorder (BD). A method which has minimal burden of assessment uses a retrospective interview, the Longitudinal Interval Follow-up Examination (LIFE), although this may be subject to problems with recall. This study examines the relationship between the retrospective LIFE scale and concurrently-rated mood rating scales in two clinical trials of 18 months of psychotherapy for patients with BD. The Montgomery-Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) were administered every eight to nine weeks and the LIFE was carried out every 6 months. Correlations between scores on mood rating scales and at equivalent times on the LIFE were examined, as well as of potential clinical moderators. There were significant correlations between LIFE depression ratings and concurrent MADRS score (r = 0.57) and between LIFE mania ratings and YMRS score (r = 0.40). In determining "mild depression" on the MADRS, a receiver operating characteristics (ROC) analysis showed an AUC of 0.78 for LIFE scores. Correlations, particularly for depression scores, were high even when the LIFE rating was several months before the interview, suggesting that the LIFE has validity in examining the burden of mood symptoms over time, with relatively little burden of assessment. Future research should examine the relationship between symptom burden and quality of life measured in this way.

Changes in Mood, Anxiety, and Cognition with Polycystic Ovary Syndrome Treatment: A Longitudinal, Naturalistic Study.

Purpose: Individuals with polycystic ovary syndrome (PCOS) are at increased risk of depression and anxiety symptoms and impairment in aspects of cognitive function. However, there is little evidence regarding effects of standard treatment for PCOS on these features of the syndrome. The aim of this study was to examine the effect of 12 weeks of naturalistic treatment of PCOS, with usual medications, on depression symptoms, anxiety symptoms and cognitive function. Patients and Methods: Thirty-three participants with PCOS received 12 weeks of individualised treatment based on clinical presentation. Changes in depression and anxiety symptoms were assessed with the self-report Hospital Anxiety and Depression Scale at baseline and 12 weeks, and cognitive function was assessed at the same time-points with a battery of tests spanning cognitive domains of verbal learning and memory, visuospatial learning and memory, psychomotor speed, attention and executive function. Outcomes were compared with a control group of 40 healthy participants. Results: Participants with PCOS (mean age = 29.2 years; mean Body Mass Index = 27.4) were treated with a variety of medications, predominantly spironolactone (n = 22) and oral contraceptives (n = 16). Depression and anxiety symptoms improved significantly over the course of treatment, with moderate effect sizes (Cohen's d 0.43-0.55, p < 0.05). Effect sizes of the difference in change from that of the control group were moderate but did not reach statistical significance. Women undergoing PCOS treatment demonstrated significant improvements in aspects of cognitive function, but improvement did not differ significantly from controls and effect size changes were similar, suggesting practise effects in both groups. Conclusion: Our study provides preliminary evidence that treatment of PCOS may be associated with improvement in psychiatric aspects of the syndrome, particularly depressive symptoms.

Relationship between baseline cognition and 18-month treatment response in bipolar disorder.

BACKGROUND: To date, few studies have examined baseline cognitive function as a predictor of clinical outcome following treatment in bipolar disorder (BD). The aim of this analysis was therefore to examine the relationship between baseline cognitive function and treatment outcome in a sample of young adults with BD receiving Interpersonal Social Rhythm Therapy (IPSRT) or Specialist Supportive Care (SSC) with adjunctive pharmacotherapy. METHODS: Eighty-six BD patients underwent baseline cognitive testing and completed 18 months of IPSRT or SCC. Univariate analyses examined the relationship between baseline cognitive function (global and individual cognitive domains) and change in mood symptom burden, and psychosocial functioning, from baseline to treatment-end. RESULTS: Baseline global cognition was not predictive of change in mood symptom burden over 18 months of treatment. However, poorer baseline psychomotor speed performance was associated with less improvement in mood symptom burden at treatment-end. Neither baseline global cognition nor individual cognitive domain scores were associated with change in psychosocial functioning. LIMITATIONS: Due to the exploratory nature of the study, correction was not made for multiple comparisons. Data was obtained from a relatively small sample and has been the subject of prior analysis, thereby increasing the likelihood of chance findings. CONCLUSION: Although global cognition was not associated with outcome, when examining individual domains, poorer baseline psychomotor speed predicted less change in mood symptom burden following 18-months of psychotherapy and pharmacotherapy. This suggests that pre-treatment measures of psychomotor speed may help to identify those who require additional, and more targeted, intervention. Further large-scale research is required.

Can magnetic resonance imaging enhance the assessment of potential new treatments for cognitive impairment in mood disorders? A systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force.

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-of-scanner tests.

Social Rhythm Disruption is Associated with Greater Depressive Symptoms in People with Mood Disorders: Findings from a Multinational Online Survey During COVID-19.

OBJECTIVES: Societal restrictions imposed to prevent transmission of COVID-19 may challenge circadian-driven lifestyle behaviours, particularly amongst those vulnerable to mood disorders. The overarching aim of the present study was to investigate the hypothesis that, in the routine-disrupted environment of the COVID-19, amongst a sample of people living with mood disorders, greater social rhythm disruption would be associated with more severe mood symptoms. METHODS: We conducted a two-wave, multinational survey of 997 participants (MAge=39.75±13.39,Female=81.6%) who self-reported a mood disorder diagnosis (i.e., major depressive disorder or bipolar disorder). Respondents completed questionnaires assessing demographics, social rhythmicity (The Brief Social Rhythm Scale), depression symptoms (Patient Health Questionnaire-9), sleep quality and diurnal preference (The Sleep, Circadian Rhythms and Mood questionnaire) and stressful life events during the COVID-19 pandemic (The Social Readjustment Rating Scale). RESULTS: The majority of participants indicated COVID-19-related social disruption had affected the regularity of their daily routines to at least some extent (n = 788, 79.1%). As hypothesised, lower social rhythmicity was associated with greater depressive symptoms when tested cross-sectionally (standardised ß = -.25, t = -7.94, P = 0.000) and when tested using a 2-level hierarchical linear model across two time points (b = -0.14, t = -3.46, df = 264, P ≤ 0.001). CONCLUSIONS: These results are consistent with the social zeitgeber hypothesis proposing that mood disorders are sensitive to life events that disrupt social rhythms.

Domain-Based Functional Improvements in Bipolar Disorder After Interpersonal and Social Rhythm Therapy.

BACKGROUND: Studies typically report overall change in function when assessing bipolar disorder (BD) interventions, but individual domains are not analyzed. Which aspects of functioning are impacted is clearly important and may differ between treatments. METHODS: Data were analyzed from two previous clinical trials of Interpersonal and Social Rhythm Therapy (IPSRT) for BD patients. Change in total and subscale scores on the Social Adjustment Scale Self-Report (SAS-SR) from 0 to 78 weeks, were analyzed. RESULTS: 152 BD patients took part in randomized controlled trials of IPSRT (n = 38) vs. Specialist Supportive Care (SSC) (n = 43), and of IPSRT (n = 41) vs. treatment as usual (TAU) which was discharge to primary care (n = 30). IPSRT was superior to TAU on change in the social and leisure activities and extended family subscales, and SAS-SR total score over 18 months. LIMITATIONS: Studies were not designed to be pooled. Patients in study 1 were younger and symptomatic at baseline. Patients assigned to TAU were more likely to drop-out. Patients did not respond to subscales that were not personally applicable (work, marital, children). CONCLUSION: IPSRT had a positive impact on two SAS-SR subscales compared to TAU over 18 months. Other subscales were limited by the lack of respondents due to individual applicability. Different psychotherapy may have differential effects on different domains of function. Measures of function and research into functioning in BD should include domain-based measures, and report the numbers of participants who respond to questions in each domain.

Randomised controlled cognition trials in remitted patients with mood disorders published between 2015 and 2021: A systematic review by the International Society for Bipolar Disorders Targeting Cognition Task Force.

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.

Randomised controlled trial of Interpersonal and Social Rhythm Therapy and group-based Cognitive Remediation versus Interpersonal and Social Rhythm Therapy alone for mood disorders: study protocol.

BACKGROUND: Individuals with mood disorders frequently experience cognitive impairment, which impacts on the long-term trajectory of the disorders, including being associated with persisting difficulties in occupational and psychosocial functioning, residual mood symptoms, and relapse. Current first-line treatments for mood disorders do little to improve cognitive function. Targeting cognition in clinical research is thus considered a priority. This protocol outlines a prospectively-registered randomised controlled trial (RCT) which examines the impact of adding group-based Cognitive Remediation (CR) to Interpersonal and Social Rhythm Therapy (IPSRT-CR) for individuals with mood disorders. METHODS: This is a pragmatic, two-arm, single-blinded RCT comparing IPSRT-CR with IPSRT alone for adults (n = 100) with mood disorders (Major Depressive Disorder or Bipolar Disorder) with subjective cognitive difficulties, on discharge from Specialist Mental Health Services in Christchurch, New Zealand. Both treatment arms will receive a 12-month course of individual IPSRT (full dose = 24 sessions). At 6 months, randomisation to receive, or not, an 8-week group-based CR programme (Action-based Cognitive Remediation - New Zealand) will occur. The primary outcome will be change in Global Cognition between 6 and 12 months (treatment-end) in IPSRT-CR versus IPSRT alone. Secondary outcomes will be change in cognitive, functional, and mood outcomes at 6, 12, 18, and 24 months from baseline and exploratory outcomes include change in quality of life, medication adherence, rumination, and inflammatory markers between treatment arms. Outcome analyses will use an intention-to-treat approach. Sub-group analyses will assess the impact of baseline features on CR treatment response. Participants' experiences of their mood disorder, including treatment, will be examined using qualitative analysis. DISCUSSION: This will be the first RCT to combine group-based CR with an evidence-based psychotherapy for adults with mood disorders. The trial may provide valuable information regarding how we can help promote long-term recovery from mood disorders. Many issues have been considered in developing this protocol, including: recruitment of the spectrum of mood disorders, screening for cognitive impairment, dose and timing of the CR intervention, choice of comparator treatment, and choice of outcome measures. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12619001080112 . Registered on 6 August 2019.

Rate of polycystic ovary syndrome in mental health disorders: a systematic review.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with increased risk of many mental health conditions, including mood and anxiety disorders. Whether PCOS is more common in mental health conditions than in the general population is less clear. A systematic review investigating this question may provide clarity regarding whether increased prevalence of PCOS is seen in particular mental health disorders, and thus, whether screening female mental health patients for PCOS is warranted. AIMS: To systematically synthesise and review research examining rates of PCOS in mental health disorders. METHODS: Peer-reviewed articles assessing the prevalence of PCOS within a sample of reproductive-aged females with a diagnosis of Axis I or II mental health disorder were included. Key studies were identified through a comprehensive search of PubMed and Web of Science. RESULTS: Eleven studies met inclusion criteria, assessing rate of diagnosed PCOS in samples with bipolar disorder (n = 7), autism spectrum disorders (ASD; n = 2), bulimia nervosa (n = 1), and post-traumatic stress disorder (PTSD; n = 1). Overall, there was limited evidence of elevated rates of PCOS in bipolar disorder, compared with population estimates or healthy control group rates. In ASD, bulimia nervosa, and PTSD samples, significantly increased rates of PCOS were reported compared with healthy control samples, although studies were relatively small. CONCLUSIONS: This review highlights complexities and methodological considerations in this area of research. There are a limited number of studies assessing PCOS in mental health samples, and thus, important areas of future research have been identified. TRIAL REGISTRATION: This systematic review was registered on PROSPERO (ID: CRD42020151420; https://www.crd.york.ac.uk/prospero/ ) on 28 April 2020.