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BACKGROUND: People with bipolar disorder (BD) tend to show widespread cognitive impairment compared to healthy controls. Impairments in processing speed (PS), attention and executive function (EF) may represent 'core' impairments that have a role in wider cognitive dysfunction. Cognitive impairments appear to relate to structural brain abnormalities in BD, but whether core deficits are related to particular brain regions is unclear and much of the research on brain-cognition associations is limited by univariate analysis and small samples. METHODS: Euthymic BD patients (n = 56) and matched healthy controls (n = 26) underwent T1-weighted MRI scans and completed neuropsychological tests of PS, attention and EF. We utilised public datasets to develop normative models of cortical thickness (n = 5977) to generate robust estimations of cortical abnormalities in patients. Canonical correlation analysis was used to assess multivariate brain-cognition associations in BD, controlling for age, sex and premorbid IQ. RESULTS: BD showed impairments on tests of PS, attention and EF, and abnormal cortical thickness in several brain regions compared to healthy controls. Impairments in tests of PS and EF were most strongly associated with cortical thickness in the left inferior temporal, right entorhinal and right temporal pole areas. CONCLUSION: Impairments in PS, attention and EF can be observed in euthymic BD and may be related to abnormal cortical thickness in temporal regions. Future research should continue to leverage normative modelling and multivariate methods to examine complex brain-cognition associations in BD. Future research may benefit from exploring covariance between traditional brain structural morphological metrics such as cortical thickness, cortical volume and surface area.
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ABSTRACTDeficits in episodic memory have been reported in various psychiatric conditions, including Major Depressive Disorder (MDD). Many widely used episodic memory tests do not have the ability to distinguish between impaired memory of separate components of a real-life event (e.g., what happened, where it happened and when), and impaired binding of such real-life features. To address this issue, a naturalistic, real-world What-Where-When memory task was employed to assess the nature of episodic memory impairments in MDD. A validation study established that the task is sensitive to age-related episodic memory changes, and that intentional encoding does not invalidate the task. The main study then compared the performance of patients with depression and control participants on the intentionally encoded WWW task. Patients with MDD presented an overall episodic memory impairment arising from deficits in object memory and the ability to bind objects to temporal context. Taken together, our study confirms the episodic memory impairment in MDD, by providing evidence of deficient object memory and reduced ability to bind temporal context to objects in patients.â¯Our naturalistic WWW task presents a promising approach for thorough identification of the nature of episodic memory impairments, under a real-world environment, in various conditions, including MDD.
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Dieulafoy lesions (DL) are an uncommon cause of gastrointestinal bleeding which is often difficult to diagnose due to the rarity of the condition and varying clinical presentations. This case describes an unusual presentation of upper gastrointestinal bleeding in an 85-year-old female with findings on two separate gastroscopies of both a gastric ulcer and duodenal DL. The pathophysiology of DL remains poorly understood and despite shared risk factors, these two pathologies are rarely reported concurrently. The presence of a concomitant gastric ulcer further complicated the diagnosis and treatment of the duodenal DL in this case. This highlights the importance of clinician awareness of this pathology and its presentation and the need for early repeat endoscopy.
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Mechanical stereochemistry arises when the interlocking of stereochemically trivial covalent subcomponents results in a stereochemically complex object. Although this general concept was identified in 1961, the stereochemical description of these molecules is still under development to the extent that new forms of mechanical stereochemistry are still being identified. Here, we present a simple analysis of rotaxane and catenane stereochemistry that allowed us to identify the final missing simple mechanical stereogenic unit, an overlooked form of rotaxane geometric isomerism, and demonstrate its stereoselective synthesis.
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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.
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Trastorno por Déficit de Atención con Hiperactividad , Trastorno Bipolar , Estimulantes del Sistema Nervioso Central , Disfunción Cognitiva , Humanos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno Bipolar/tratamiento farmacológico , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Estimulantes del Sistema Nervioso Central/efectos adversos , Estimulantes del Sistema Nervioso Central/uso terapéutico , Uso Fuera de lo Indicado , Metilfenidato/efectos adversos , Metilfenidato/uso terapéuticoRESUMEN
In 1971, Schill recognized that a prochiral macrocycle encircling an oriented axle led to geometric isomerism in rotaxanes. More recently, we identified an overlooked chiral stereogenic unit in rotaxanes that arises when a prochiral macrocycle encircles a prochiral axle. Here, we show that both stereogenic units can be accessed using equivalent strategies, with a single weak stereodifferentiating interaction sufficient for moderate to excellent stereoselectivity. Using this understanding, we demonstrated the first direct enantioselective (70% ee) synthesis of a mechanically axially chiral rotaxane.
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Background: Fatigue is a prominent symptom in many diseases and is strongly associated with impaired daily function. The measurement of daily function is currently almost always done with questionnaires, which are subjective and imprecise. With the recent advances of digital wearable technologies, novel approaches to evaluate daily function quantitatively and objectively in real-life conditions are increasingly possible. This also creates new possibilities to measure fatigue-related changes of daily function using such technologies. Summary: This review examines which digitally assessable parameters in immune-mediated inflammatory and neurodegenerative diseases may have the greatest potential to reflect fatigue-related changes of daily function. Key Messages: Results of a standardized analysis of the literature reporting about perception-, capacity-, and performance-evaluating assessment tools indicate that changes of the following parameters: physical activity, independence of daily living, social participation, working life, mental status, cognitive and aerobic capacity, and supervised and unsupervised mobility performance have the highest potential to reflect fatigue-related changes of daily function. These parameters thus hold the greatest potential for quantitatively measuring fatigue in representative diseases in real-life conditions, e.g., with digital wearable technologies. Furthermore, to the best of our knowledge, this is a new approach to analysing evidence for the design of performance-based digital assessment protocols in human research, which may stimulate further systematic research in this area.
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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.
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OBJECTIVES: Cognitive impairment is a core feature of bipolar disorder (BD) and major depressive disorder (MDD). Deficits in processing speed (PS) and sustained attention (SA) may be particularly impaired and may underpin a broader profile of deficits, however current knowledge of the nature of these impairments is limited by heterogeneous results in the literature. Few reviews to date have attempted to disentangle sources of heterogeneity to assess the presence and magnitude of impairments in PS and SA in BD and MDD. METHODS: One hundred and three studies were reviewed to examine performance in tests of PS and SA in BD (n = 3452) and MDD (n = 5461) compared to healthy controls (n = 8016). Neuropsychological methodology used in the literature was summarised. Data were meta-analysed to assess impairments in PS and SA for each neuropsychological test separately. Subgroup analysis was performed across mood states to investigate sources of heterogeneity. RESULTS: Impairments were found across most neuropsychological tests, with small to large effect sizes for BD (range: d = 0.19-0.96) and MDD (range: d = 0.29-0.86). Impairments were present in symptomatic states and euthymia in most cases. Some outcome measures were not impaired in euthymia. Heterogeneity was observed for most neuropsychological tests and remained after separating by mood state. There inadequate data to meta-analyse some outcome measures, particularly for symptomatic groups. CONCLUSION: Impairments in PS and SA in BD and MDD can be observed across most neuropsychological tests. Future research should further investigate the nature of these impairments across mood states, controlling for clinical confounds.
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Trastorno Bipolar , Disfunción Cognitiva , Trastorno Depresivo Mayor , Humanos , Trastorno Bipolar/complicaciones , Trastorno Bipolar/psicología , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/psicología , Velocidad de Procesamiento , Atención , Pruebas NeuropsicológicasRESUMEN
OBJECTIVE: Attentional impairments are common in dementia with Lewy bodies and its prodromal stage of mild cognitive impairment (MCI) with Lewy bodies (MCI-LB). People with MCI may be capable of compensating for subtle attentional deficits in most circumstances, and so these may present as occasional lapses of attention. We aimed to assess the utility of a continuous performance task (CPT), which requires sustained attention for several minutes, for measuring attentional performance in MCI-LB in comparison to Alzheimer's disease (MCI-AD), and any performance deficits which emerged with sustained effort. METHOD: We included longitudinal data on a CPT sustained attention task for 89 participants with MCI-LB or MCI-AD and 31 healthy controls, estimating ex-Gaussian response time parameters, omission and commission errors. Performance trajectories were estimated both cross-sectionally (intra-task progress from start to end) and longitudinally (change in performance over years). RESULTS: While response times in successful trials were broadly similar, with slight slowing associated with clinical parkinsonism, those with MCI-LB made considerably more errors. Omission errors were more common throughout the task in MCI-LB than MCI-AD (OR 2.3, 95% CI: 1.1-4.7), while commission errors became more common after several minutes of sustained attention. Within MCI-LB, omission errors were more common in those with clinical parkinsonism (OR 1.9, 95% CI: 1.3-2.9) or cognitive fluctuations (OR 4.3, 95% CI: 2.2-8.8). CONCLUSIONS: Sustained attention deficits in MCI-LB may emerge in the form of attentional lapses leading to omissions, and a breakdown in inhibitory control leading to commission errors.
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Unit human capital resources (HCR) are vital to performance across organizational levels. Crucially, the benefits of unit HCR often hinge on resource access and effective resource management. Yet, how units manage HCR remains unclear. We first review findings from human resource management (HRM) and unit leadership literatures relating to unit HCR, which have evolved separately despite their shared goals. Using our review as a foundation, we offer an integrative model highlighting the ways unit leaders can leverage HRM practices and their leadership behaviors for the greatest impact on unit HCR. In so doing, we identify a potentially potent nexus for scholars of both disciplines to focus their integrative efforts on-unit leaders-given their responsibility for HRM practice delivery (e.g., implementing a job rotation program) and their own leadership behaviors (e.g., composing teams). We conclude by highlighting future research questions, opportunities for theoretical integration, and expanding empirical examination. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Liderazgo , Conducta Social , Humanos , Recursos HumanosRESUMEN
BACKGROUND: Autonomic nervous system (ANS) dysregulation might be relevant to the pathophysiology of fatigue and cognitive impairment in depression and perhaps should be considered when making prescribing decisions. AIMS: To determine the relationship of self-reported ANS symptoms with fatigue, cognition and prescribed medication in people with a diagnosis of depression, in comparators without depression but with other mental health, neurodevelopmental or neurodegenerative disorders (active controls) and in healthy controls. METHOD: Cross-sectional analysis of an opportunistic sample from England. Self-reported data were collected on demographics, diagnosis, medication, ANS symptoms (Composite Autonomic Symptom Scale-31, COMPASS-31) and fatigue (Visual Analogue Scale for Fatigue, VAS-F). A subsample completed cognitive tests (THINC-it), including the subjective Perceived Deficits Questionnaire five-item version (PDQ-5). Spearman's correlation and mediation models were used to explore the relationship between COMPASS-31, VAS-F and PDQ-5 scores. RESULTS: Data were obtained for 3345 participants, 22% with depression. The depression group had significantly (P < 0.01) more severe autonomic dysregulation as measured by COMPASS-31 scores (median 30) than active (median 23) and healthy controls (median 10). The depression group had significantly higher symptom severity (P < 0.01) than both control groups on the VAS-F and PDQ-5. Overall, there was a significantly positive correlation (P < 0.01) between COMPASS-31, VAS-F scores (Spearman's rho rs = 0.44) and PDQ-5 scores (rs = 0.56). COMPASS-31 scores mediated greater symptom severity on the VAS-F and PDQ-5 for those with depression. COMPASS-31 scores remained significantly different between the depression group and both control groups independently of medication. CONCLUSIONS: People with a diagnosis of depression report worse fatigue and cognition than active and healthy comparators; this appears to be mediated by ANS dysregulation.
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OBJECTIVES: Fatigue is one of the most important symptoms needing improvement in Primary Sjögren's syndrome (PSS). Previous data from our group suggest that noninvasive stimulation of the vagus nerve (nVNS) may improve symptoms of fatigue. This experimental medicine study uses the gammaCore device (electroCore) and a sham device to investigate the relationship between nVNS and fatigue in PSS, and to explore potential mechanisms involved. MATERIALS AND METHODS: Forty participants with PSS were randomly assigned to use active (n = 20) or sham (n = 20) nVNS devices twice daily for 54 days in a double-blind manner. Patient-reported measures of fatigue were collected at baseline and day 56: Profile of Fatigue (PRO-F)-Physical, PRO-F-Mental and Visual Analogue Scale of abnormal fatigue (fVAS). Neurocognitive tests, immunologic responses, electroencephalography alpha reactivity, muscle acidosis, and heart rate variability were compared between devices from baseline to day 56 using analysis of covariance. RESULTS: PRO-F-Physical, PRO-F-Mental, and fVAS scores were significantly reduced at day 56 in the active group only (p = 0.02, 0.02, and 0.04, respectively). Muscle bioenergetics and heart rate variability showed no change between arms. There were significant improvements in digit span and a neurocognitive test (p = 0.03), and upon acute nVNS stimulation, frontal region alpha reactivity showed a significant negative relationship with fatigue scores in the active group (p < 0.01). CONCLUSIONS: We observed significant improvements in three measures of fatigue at day 56 with the active device but not the sham device. Directly after device use, fatigue levels correlate with measures of alpha reactivity, suggesting modulation of cholinergic system integrity as a mechanism of action for nVNS.
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Fatiga , Síndrome de Sjögren , Estimulación del Nervio Vago , Humanos , Fatiga/diagnóstico , Fatiga/etiología , Fatiga/terapia , Dimensión del Dolor , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/terapia , Resultado del Tratamiento , Estimulación del Nervio Vago/métodosRESUMEN
Acute pancreatitis (AP) is a rare complication in the post-operative period and the incidence following colorectal surgery is unknown. Although benign hyperamylasaemia following colonic resection is a documented phenomenon, clinically significant AP in the post-operative setting is poorly described in the literature and little is understood about the underlying pathophysiology. Additionally, while gastrointestinal fistulae are a well-recognized complication of bowel surgery, nil previous reports discuss the possible contribution of post-operative AP to their development. We present a case of AP complicated by enterocutaneous fistula following extended right hemicolectomy and describe the possible mechanisms leading to these conditions.
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Prostate cancer (PCa) is the second leading cause of cancer death for men in the United States. While organ-confined disease has reasonable expectation of cure, metastatic PCa is universally fatal upon recurrence during hormone therapy, a stage termed castration-resistant prostate cancer (CRPC). Until such time as molecularly defined subtypes can be identified and targeted using precision medicine, it is necessary to investigate new therapies that may apply to the CRPC population as a whole. The administration of ascorbate, more commonly known as ascorbic acid or Vitamin C, has proved lethal to and highly selective for a variety of cancer cell types. There are several mechanisms currently under investigation to explain how ascorbate exerts anti-cancer effects. A simplified model depicts ascorbate as a pro-drug for reactive oxygen species (ROS), which accumulate intracellularly and generate DNA damage. It was therefore hypothesized that poly(ADP-ribose) polymerase (PARP) inhibitors, by inhibiting DNA damage repair, would augment the toxicity of ascorbate. Results: Two distinct CRPC models were found to be sensitive to physiologically relevant doses of ascorbate. Moreover, additional studies indicate that ascorbate inhibits CRPC growth in vitro via multiple mechanisms including disruption of cellular energy dynamics and accumulation of DNA damage. Combination studies were performed in CRPC models with ascorbate in conjunction with escalating doses of three different PARP inhibitors (niraparib, olaparib, and talazoparib). The addition of ascorbate augmented the toxicity of all three PARP inhibitors and proved synergistic with olaparib in both CRPC models. Finally, the combination of olaparib and ascorbate was tested in vivo in both castrated and non-castrated models. In both cohorts, the combination treatment significantly delayed tumor growth compared to monotherapy or untreated control. Conclusions: These data indicate that pharmacological ascorbate is an effective monotherapy at physiological concentrations and kills CRPC cells. Ascorbate-induced tumor cell death was associated with disruption of cellular energy dynamics and accumulation of DNA damage. The addition of PARP inhibition increased the extent of DNA damage and proved effective at slowing CRPC growth both in vitro and in vivo. These findings nominate ascorbate and PARPi as a novel therapeutic regimen that has the potential to improve CRPC patient outcomes.
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Necrotising fasciitis (NF) is a rapidly progressive infection of soft tissue and fascia. Early diagnosis and prompt extensive surgical debridement decrease mortality. This remains a challenge for rural surgeons who have limited experience with the disease, in a setting where patient transfers to tertiary centres are lengthy and often delayed. To assist clinical decision making in this setting, a case series of five NF presentations in a rural Australian hospital were retrospectively analysed for presentation, investigation, treatment and clinical outcomes. Three underwent abdominal wall debridement and two underwent below knee amputation. Results demonstrate early recognition of NF and the extent of surgical intervention prior to acute transfer are key to successful outcomes. Expedient diagnosis and early extensive debridement at the initial contact reduce mortality and should be the goal of management in this setting.
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BACKGROUND: The relationship between major depressive disorder (MDD) and personality disorders is complex, with implications for diagnosis and treatment. We sought to explore the relationship between these disorders quantitatively in an inpatient setting. METHODS: We conducted a structured observational study exploring symptoms of depression and selected neurocognitive functions over the span of an inpatient admission in those with depression and personality disorders. Sixty inpatients presenting with symptoms of depression completed ratings of mood and neurocognitive function. Diagnosis was confirmed by structured clinical interview (SCID-5-RV) at discharge and used to allocate patients to one of the two groups for analysis: those with MDD-only and those with a personality disorder (with or without MDD). RESULTS: On admission, observer-based ratings of depression were significantly higher in the MDD-only group while subjective ratings were higher in the personality disorder group. Depression rating scores lessened in both groups during the admission, but at discharge, the personality disorder group continued to report higher subjective ratings. The personality disorder group also rated themselves as more cognitively impaired than the MDD-only group and unlike the MDD-only group, they did not report subjective improvements in cognitive function over the course of admission. Objective assessment of cognitive function demonstrated improvements in both groups. CONCLUSIONS: In this study, the presence of a personality disorder was associated with greater subjective severity of depressive symptomatology and selected neurocognitive functioning, despite similar or lower objective severity in comparison with those with MDD. This finding has implications for understanding the patient journey through health care settings.
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Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/psicología , Pacientes Internos , Depresión , Escalas de Valoración Psiquiátrica , Trastornos de la Personalidad/diagnóstico , PersonalidadRESUMEN
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.
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Trastorno Bipolar , Disfunción Cognitiva , Trastorno Bipolar/diagnóstico por imagen , Trastorno Bipolar/tratamiento farmacológico , Cognición , Disfunción Cognitiva/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Trastornos del Humor/diagnóstico por imagen , Trastornos del Humor/tratamiento farmacológicoRESUMEN
Chirality typically arises in molecules because of a rigidly chiral arrangement of covalently bonded atoms. Less generally appreciated is that chirality can arise when molecules are threaded through one another to create a mechanical bond. For example, when two macrocycles with chemically distinct faces are joined to form a catenane, the structure is chiral, although the rings themselves are not. However, enantiopure mechanically axially chiral catenanes in which the mechanical bond provides the sole source of stereochemistry have not been reported. Here we re-examine the symmetry properties of these molecules and in doing so identify a straightforward route to access them from simple chiral building blocks. Our analysis also led us to identify an analogous but previously unremarked upon rotaxane stereogenic unit, which also yielded to our co-conformational auxiliary approach. With methods to access mechanically axially chiral molecules in hand, their properties and applications can now be explored.
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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.