Dealing with heterogeneity of cognitive dysfunction in acute depression : a clustering approach

Heterogeneity in cognitive functioning among major depressive disorder (MDD) patients could have been the reason for the small-to-moderate differences reported so far when it is compared to other psychiatric conditions or to healthy controls. Additionally, most of these studies did not take into account clinical and sociodemographic characteristics that could have played a relevant role in cognitive variability. This study aims to identify empirical clusters based on cognitive, clinical and sociodemographic variables in a sample of acute MDD patients. In a sample of 174 patients with an acute depressive episode, a two-step clustering analysis was applied considering potentially relevant cognitive, clinical and sociodemographic variables as indicators for grouping. Treatment resistance was the most important factor for clustering, closely followed by cognitive performance. Three empirical subgroups were obtained: cluster 1 was characterized by a sample of non-resistant patients with preserved cognitive functioning (n = 68, 39%); cluster 2 was formed by treatment-resistant patients with selective cognitive deficits (n = 66, 38%) and cluster 3 consisted of resistant (n = 23, 58%) and non-resistant (n = 17, 42%) acute patients with significant deficits in all neurocognitive domains (n = 40, 23%). The findings provide evidence upon the existence of cognitive heterogeneity across patients in an acute depressive episode. Therefore, assessing cognition becomes an evident necessity for all patients diagnosed with MDD, and although treatment resistant is associated with greater cognitive dysfunction, non-resistant patients can also show significant cognitive deficits. By targeting not only mood but also cognition, patients are more likely to achieve full recovery and prevent new relapses

Patient-ventilator asynchronies during mechanical ventilation: current knowledge and research priorities

Background: Mechanical ventilation is common in critically ill patients. This life-saving treatment can cause complications and is also associated with long-term sequelae. Patient-ventilator asynchronies are frequent but underdiagnosed, and they have been associated with worse outcomes.Main body: Asynchronies occur when ventilator assistance does not match the patient's demand. Ventilatory overassistance or underassistance translates to different types of asynchronies with different effects on patients. Underassistance can result in an excessive load on respiratory muscles, air hunger, or lung injury due to excessive tidal volumes. Overassistance can result in lower patient inspiratory drive and can lead to reverse triggering, which can also worsen lung injury. Identifying the type of asynchrony and its causes is crucial for effective treatment.Mechanical ventilation and asynchronies can affect hemodynamics. An increase in intrathoracic pressure during ventilation modifies ventricular preload and afterload of ventricles, thereby affecting cardiac output and hemodynamic status. Ineffective efforts can decrease intrathoracic pressure, but double cycling can increase it. Thus, asynchronies can lower the predictive accuracy of some hemodynamic parameters of fluid responsiveness.New research is also exploring the psychological effects of asynchronies. Anxiety and depression are common in survivors of critical illness long after discharge. Patients on mechanical ventilation feel anxiety, fear, agony, and insecurity, which can worsen in the presence of asynchronies. Asynchronies have been associated with worse overall prognosis, but the direct causal relation between poor patient-ventilator interaction and worse outcomes has yet to be clearly demonstrated.Critical care patients generate huge volumes of data that are vastly underexploited. New monitoring systems can analyze waveforms together with other inputs, helping us to detect, analyze, and even predict asynchronies. Big data approaches promise to help us understand asynchronies better and improve their diagnosis and management.Conclusions: Although our understanding of asynchronies has increased in recent years, many questions remain to be answered. Evolving concepts in asynchronies, lung crosstalk with other organs, and the difficulties of data management make more efforts necessary in this field

Virtual Reality-Based Early Neurocognitive Stimulation in Critically Ill Patients : A Pilot Randomized Clinical Trial

This study focuses on the application of a non-immersive virtual reality (VR)-based neurocognitive intervention in critically ill patients. Our aim was to assess the feasibility of direct outcome measures to detect the impact of this digital therapy on patients' cognitive and emotional outcomes. Seventy-two mechanically ventilated adult patients were randomly assigned to the "treatment as usual" (TAU, n = 38) or the "early neurocognitive stimulation" (ENRIC, n = 34) groups. All patients received standard intensive care unit (ICU) care. Patients in the ENRIC group also received adjuvant neurocognitive stimulation during the ICU stay. Outcome measures were a full neuropsychological battery and two mental health questionnaires. A total of 42 patients (21 ENRIC) completed assessment one month after ICU discharge, and 24 (10 ENRIC) one year later. At one-month follow-up, ENRIC patients had better working memory scores (p = 0.009, d = 0.363) and showed up to 50% less non-specific anxiety (11.8% vs. 21.1%) and depression (5.9% vs. 10.5%) than TAU patients. A general linear model of repeated measures reported a main effect of group, but not of time or group-time interaction, on working memory, with ENRIC patients outperforming TAU patients (p = 0.008, η 2 = 0.282). Our results suggest that non-immersive VR-based neurocognitive stimulation may help improve short-term working memory outcomes in survivors of critical illness. Moreover, this advantage could be maintained in the long term. An efficacy trial in a larger sample of participants is feasible and must be conducted

Patient-ventilator asynchronies during mechanical ventilation : current knowledge and research priorities

Mechanical ventilation is common in critically ill patients. This life-saving treatment can cause complications and is also associated with long-term sequelae. Patient-ventilator asynchronies are frequent but underdiagnosed, and they have been associated with worse outcomes. Asynchronies occur when ventilator assistance does not match the patient's demand. Ventilatory overassistance or underassistance translates to different types of asynchronies with different effects on patients. Underassistance can result in an excessive load on respiratory muscles, air hunger, or lung injury due to excessive tidal volumes. Overassistance can result in lower patient inspiratory drive and can lead to reverse triggering, which can also worsen lung injury. Identifying the type of asynchrony and its causes is crucial for effective treatment. Mechanical ventilation and asynchronies can affect hemodynamics. An increase in intrathoracic pressure during ventilation modifies ventricular preload and afterload of ventricles, thereby affecting cardiac output and hemodynamic status. Ineffective efforts can decrease intrathoracic pressure, but double cycling can increase it. Thus, asynchronies can lower the predictive accuracy of some hemodynamic parameters of fluid responsiveness. New research is also exploring the psychological effects of asynchronies. Anxiety and depression are common in survivors of critical illness long after discharge. Patients on mechanical ventilation feel anxiety, fear, agony, and insecurity, which can worsen in the presence of asynchronies. Asynchronies have been associated with worse overall prognosis, but the direct causal relation between poor patient-ventilator interaction and worse outcomes has yet to be clearly demonstrated. Critical care patients generate huge volumes of data that are vastly underexploited. New monitoring systems can analyze waveforms together with other inputs, helping us to detect, analyze, and even predict asynchronies. Big data approaches promise to help us understand asynchronies better and improve their diagnosis and management. Although our understanding of asynchronies has increased in recent years, many questions remain to be answered. Evolving concepts in asynchronies, lung crosstalk with other organs, and the difficulties of data management make more efforts necessary in this field

If you feel you can’t, you won’t: the role of subjective and objective cognitive competence on psychosocial functioning in depression

BackgroundThe purpose of this exploratory study is to examine the role of sociodemographic, clinical, and cognitive - both objective and subjective - factors in overall and in specific domains of psychosocial functioning, in patients with depression at different clinical states of the disease (remitted and non-remitted).MethodsA sample of 325 patients with major depressive disorder, 117 in remission and 208 in non-remission, were assessed with a semi-structured interview collecting sociodemographic, clinical, cognitive (with neuropsychological tests and the Perceived Deficit Questionnaire), and functional (Functioning Assessment Short Test) characteristics. Backward regression models were conducted to determine associations of global and specific areas of functioning with independent factors, for both clinical states.ResultsResidual depressive symptomatology and self-appraisal of executive competence were significantly associated with psychosocial functioning in remitted patients, in overall and some subdomains of functioning, particularly cognitive and interpersonal areas. While depressive symptoms, executive deficits and self-appraisal of executive function were significantly related to functional outcomes in non-remitted patients, both in overall functioning and in most of subdomains.DiscussionThis study evidences the strong association of one's appraisal of executive competence with psychosocial functioning, together with depressive symptoms, both in remitted and non-remitted patients with depression. Therefore, to achieve full recovery, clinical management of patients should tackle not only the relief of core depressive symptoms, but also the cognitive ones, both those that are objectified with neuropsychological tests and those that are reported by the patients themselves

Group and sex differences in social cognition in bipolar disorder, schizophrenia/schizoaffective disorder and healthy people

Background: Impairment of social cognition is documented in bipolar disorder (BD) and schizophrenia/schizoaffective disorder (SCH). In healthy individuals, women perform better than men in some of its sub-domains. However, in BD and SCH the results are mixed. Our aim was to compare emotion recognition, affective Theory of Mind (ToM) and first- and second-order cognitive ToM in BD, SCH and healthy subjects, and to investigate sex-related differences. Methods: 120 patients (BD = 60, SCH = 60) and 40 healthy subjects were recruited. Emotion recognition was assessed by the Pictures of Facial Affect (POFA) test, affective ToM by the Reading the Mind in the Eyes Test (RMET) and cognitive ToM by several false-belief stories. Group and sex differences were analyzed using parametric (POFA, RMET) and non-parametric (false-belief stories) tests. The impact of age, intelligence quotient (IQ) and clinical variables on patient performance was examined using a series of linear/logistic regressions. Results: Both groups of patients performed worse than healthy subjects on POFA, RMET and second-order false-belief (p < 0.001), but no differences were found between them. Instead, their deficits were related to older age and/or lower IQ (p < 0.01). Subthreshold depression was associated with a 6-fold increased risk of first-order false-belief failure (p < 0.001). Sex differences were only found in healthy subjects, with women outperforming men on POFA and RMET (p ≤ 0.012), but not on first/second-order false-belief. Limitations: The cross-sectional design does not allow for causal inferences. Conclusion: BD and SCH patients had deficits in emotion recognition, affective ToM, and second-order cognitive ToM, but their performance was comparable to each other, highlighting that the differences between them may be subtler than previously thought. First-order cognitive ToM remained intact, but subthreshold depression altered their normal functioning. Our results suggest that the advantage of healthy women in the emotional and affective aspects of social cognition would not be maintained in BD and SCH

Group and sex differences in social cognition in bipolar disorder, schizophrenia/schizoaffective disorder and healthy people

Background: Impairment of social cognition is documented in bipolar disorder (BD) and schizophrenia/schizoaffective disorder (SCH). In healthy individuals, women perform better than men in some of its sub-domains. However, in BD and SCH the results are mixed. Our aim was to compare emotion recognition, affective Theory of Mind (ToM) and first- and second-order cognitive ToM in BD, SCH and healthy subjects, and to investigate sex-related differences. Methods: 120 patients (BD = 60, SCH = 60) and 40 healthy subjects were recruited. Emotion recognition was assessed by the Pictures of Facial Affect (POFA) test, affective ToM by the Reading the Mind in the Eyes Test (RMET) and cognitive ToM by several false-belief stories. Group and sex differences were analyzed using parametric (POFA, RMET) and non-parametric (false-belief stories) tests. The impact of age, intelligence quotient (IQ) and clinical variables on patient performance was examined using a series of linear/logistic regressions. Results: Both groups of patients performed worse than healthy subjects on POFA, RMET and second-order falsebelief (p < 0.001), but no differences were found between them. Instead, their deficits were related to older age and/or lower IQ (p < 0.01). Subthreshold depression was associated with a 6-fold increased risk of first-order false-belief failure (p < 0.001). Sex differences were only found in healthy subjects, with women outperforming men on POFA and RMET (p ≤ 0.012), but not on first/second-order false-belief. Limitations: The cross-sectional design does not allow for causal inferences. Conclusion: BD and SCH patients had deficits in emotion recognition, affective ToM, and second-order cognitive ToM, but their performance was comparable to each other, highlighting that the differences between them may be subtler than previously thought. First-order cognitive ToM remained intact, but subthreshold depression altered their normal functioning. Our results suggest that the advantage of healthy women in the emotional and affective aspects of social cognition would not be maintained in BD and SCH

Objective and subjective cognition in survivors of COVID-19 one year after ICU discharge : the role of demographic, clinical, and emotional factors

Altres ajuts: This research was also supported by CIBER -Consorcio Centro de Investigación Biomédica en Red- CB06/06/1097, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea - European Regional Development Fund.Intensive Care Unit (ICU) COVID-19 survivors may present long-term cognitive and emotional difficulties after hospital discharge. This study aims to characterize the neuropsychological dysfunction of COVID-19 survivors 12 months after ICU discharge, and to study whether the use of a measure of perceived cognitive deficit allows the detection of objective cognitive impairment. We also explore the relationship between demographic, clinical and emotional factors, and both objective and subjective cognitive deficits. Critically ill COVID-19 survivors from two medical ICUs underwent cognitive and emotional assessment one year after discharge. The perception of cognitive deficit and emotional state was screened through self-rated questionnaires (Perceived Deficits Questionnaire, Hospital Anxiety and Depression Scale and Davidson Trauma Scale), and a comprehensive neuropsychological evaluation was carried out. Demographic and clinical data from ICU admission were collected retrospectively. Out of eighty participants included in the final analysis, 31.3% were women, 61.3% received mechanical ventilation and the median age of patients was 60.73 years. Objective cognitive impairment was observed in 30% of COVID-19 survivors. The worst performance was detected in executive functions, processing speed and recognition memory. Almost one in three patients manifested cognitive complaints, and 22.5%, 26.3% and 27.5% reported anxiety, depression and post-traumatic stress disorder (PTSD) symptoms, respectively. No significant differences were found in the perception of cognitive deficit between patients with and without objective cognitive impairment. Gender and PTSD symptomatology were significantly associated with perceived cognitive deficit, and cognitive reserve with objective cognitive impairment. One-third of COVID-19 survivors suffered objective cognitive impairment with a frontal-subcortical dysfunction 12 months after ICU discharge. Emotional disturbances and perceived cognitive deficits were common. Female gender and PTSD symptoms emerged as predictive factors for perceiving worse cognitive performance. Cognitive reserve emerged as a protective factor for objective cognitive functioning. Trial registration : ClinicalTrials.gov Identifier: NCT04422444; June 9, 2021. The online version contains supplementary material available at 10.1186/s13054-023-04478-7

Experience sampling methods for the personalised prediction of mental health problems in Spanish university students: protocol for a survey-based observational study within the PROMES-U project

IntroductionThere is a high prevalence of mental health problems among university students. Better prediction and treatment access for this population is needed. In recent years, short-term dynamic factors, which can be assessed using experience sampling methods (ESM), have presented promising results for predicting mental health problems.Methods and analysisUndergraduate students from five public universities in Spain are recruited to participate in two web-based surveys (at baseline and at 12-month follow-up). A subgroup of baseline participants is recruited through quota sampling to participate in a 15-day ESM study. The baseline survey collects information regarding distal risk factors, while the ESM study collects short-term dynamic factors such as affect, company or environment. Risk factors will be identified at an individual and population level using logistic regressions and population attributable risk proportions, respectively. Machine learning techniques will be used to develop predictive models for mental health problems. Dynamic structural equation modelling and multilevel mixed-effects models will be considered to develop a series of explanatory models for the occurrence of mental health problems.Ethics and disseminationThe project complies with national and international regulations, including the Declaration of Helsinki and the Code of Ethics, and has been approved by the IRB Parc de Salut Mar (2020/9198/I) and corresponding IRBs of all participating universities. All respondents are given information regarding access mental health services within their university and region. Individuals with positive responses on suicide items receive a specific alert with indications for consulting with a health professional. Participants are asked to provide informed consent separately for the web-based surveys and for the ESM study. Dissemination of results will include peer-reviewed scientific articles and participation in scientific congresses, reports with recommendations for universities’ mental health policy makers, as well as a well-balanced communication strategy to the general public

Diferencias de grupo y sexo en la cognición social en el trastorno bipolar, la esquizofrenia y las personas sanas

Introducció. L'alteració de la cognició social, inclosa la capacitat de reconèixer emocions bàsiques (processament emocional) i d'interpretar estats mentals (teoria de la ment, ToM), està documentada en el trastorn bipolar i l'esquizofrènia. Alguns estudis suggereixen que els pacients amb trastorn bipolar obtenen millors resultats que els pacients amb esquizofrènia en aquesta funció cognitiva. No obstant això, aquesta diferència no s'observa de forma consistent en tots els estudis. En persones sanes, les dones tendeixen a superar els homes en certs aspectes de la cognició social. En el trastorn bipolar i l'esquizofrènia els resultats són contradictoris. Objectius. Objectiu principal: comparar les diferències en el processament emocional i la ToM entre el trastorn bipolar, l'esquizofrènia i les persones sanes, i investigar les diferències relacionades amb el sexe. Objectius secundaris: explorar la relació entre els diferents subdominis de la cognició social i la influència que les variables sociodemogràfiques, clíniques i cognitives no socials exerceixen sobre el processament emocional i la ToM. Mètode. S'inclouen pacients amb trastorn bipolar I/II [estudis 2 i 3] i pacients amb esquizofrènia/trastorn esquizoafectiu [estudis 1, 2 i 3] aparellats per edat i anys d'educació amb un grup control de persones sanes [estudis 1 i 2]. El processament emocional s'examina mitjançant el Pictures of Facial Affect test (POFA), la ToM cognitiva de primer i segon ordre mitjançant històries de falsa creença, la ToM cognitiva d'ordre superior mitjançant la Hinting Task (HT) i la ToM afectiva mitjançant el Reading the Mind in the Eyes Test (RMET). Les diferències de grup i sexe s'analitzen mitjançant proves paramètriques (POFA, HT i RMET) i no paramètriques (històries de falsa creença). La relació entre els diferents subdominis de la cognició social i la influència de les variables sociodemogràfiques, clíniques i cognitives no socials s'exploren mitjançant regressions lineals/logístiques. Resultats. Ambdós grups de pacients obtenen pitjors resultats que les persones sanes en el POFA, la falsa creença de segon ordre, la HT i el RMET. Els pacients amb trastorn bipolar només obtenen millors resultats que els pacients amb esquizofrènia en la HT. Les diferències de sexe únicament s'observen en les persones sanes, sent les dones les que superen els homes en el POFA i el RMET. Més enllà de la malaltia, el POFA i la falsa creença de segon ordre emergeixen com els principals predictors del RMET. Una major edat, una intel·ligència general més baixa, els símptomes depressius subclínics, una pitjor memòria verbal i una velocitat de processament més lenta es relacionen amb dèficits més greus en la cognició social. Limitacions. El disseny transversal no permet fer inferències causals. Conclusió. Els pacients amb trastorn bipolar i esquizofrènia mostren dèficits en el processament emocional, la ToM cognitiva de segon ordre, la ToM cognitiva d'ordre superior i la ToM afectiva però no en la ToM cognitiva de primer ordre, que roman preservada en la majoria dels pacients. No obstant això, patir depressió subclínica es relaciona amb un major risc de dèficits sobrevinguts en aquesta funció cognitiva. Els pacients amb trastorn bipolar només superen els pacients amb esquizofrènia en la ToM cognitiva d'ordre superior. Per tant, les diferències entre aquestes dues poblacions clíniques poden ser més subtils del que suggereixen les investigacions anteriors i afectar únicament a aspectes específics de la ToM. Els nostres resultats indiquen que l'avantatge de les dones sanes en els aspectes emocionals i afectius de la cognició social pot perdre's en el trastorn bipolar i l'esquizofrènia a causa de l'efecte de la malaltia. La vinculació entre el processament emocional i la ToM apunta a una possible relació jeràrquica entre els diferents subdominis de la cognició social.Introducción. La alteración de la cognición social, incluida la capacidad de reconocer emociones básicas (procesamiento emocional) y de interpretar estados mentales (teoría de la mente, ToM), está documentada en el trastorno bipolar y la esquizofrenia. Algunos estudios sugieren que los pacientes con trastorno bipolar obtienen mejores resultados que los pacientes con esquizofrenia en esta función cognitiva. Sin embargo, esta diferencia no se observa de forma consistente en todos los estudios. En personas sanas, las mujeres tienden a superar a los hombres en ciertos aspectos de la cognición social. En el trastorno bipolar y la esquizofrenia los resultados son contradictorios. Objetivos. Objetivo principal: comparar las diferencias en el procesamiento emocional y la ToM entre el trastorno bipolar, la esquizofrenia y las personas sanas, e investigar las diferencias relacionadas con el sexo. Objetivos secundarios: explorar la relación entre los diferentes subdominios de la cognición social y la influencia que las variables sociodemográficas, clínicas y cognitivas no sociales ejercen sobre el procesamiento emocional y la ToM. Método. Se incluyen pacientes con trastorno bipolar I/II [estudios 2-3] y pacientes con esquizofrenia/trastorno esquizoafectivo [estudios 1-3] emparejados por edad y años de educación con un grupo control de personas sanas [estudios 1-2]. El procesamiento emocional se examina mediante el Pictures of Facial Affect test (POFA), la ToM cognitiva de primer y segundo orden mediante historias de falsa creencia, la ToM cognitiva de orden superior mediante la Hinting Task (HT) y la ToM afectiva mediante el Reading the Mind in the Eyes Test (RMET). Las diferencias de grupo y sexo se analizan mediante pruebas paramétricas (POFA, HT y RMET) y no paramétricas (historias de falsa creencia). La relación entre los diferentes subdominios de la cognición social y la influencia de las variables sociodemográficas, clínicas y cognitivas no sociales se exploran mediante regresiones lineales/logísticas. Resultados. Ambos grupos de pacientes obtienen peores resultados que las personas sanas en el POFA, la falsa creencia de segundo orden, la HT y el RMET. Los pacientes con trastorno bipolar sólo obtienen mejores resultados que los pacientes con esquizofrenia en la HT. Las diferencias de sexo únicamente se observan en las personas sanas, siendo las mujeres las que superan a los hombres en el POFA y el RMET. Más allá de la enfermedad, el POFA y la falsa creencia de segundo orden emergen como los principales predictores del RMET. Una mayor edad, una menor inteligencia general, los síntomas depresivos subclínicos, una peor memoria verbal y una velocidad de procesamiento más lenta se relacionan con déficits más graves en la cognición social. Limitaciones. El diseño transversal no permite hacer inferencias causales. Conclusión. Los pacientes con trastorno bipolar y esquizofrenia muestran déficits en el procesamiento emocional, la ToM cognitiva de segundo orden, la ToM cognitiva de orden superior y la ToM afectiva pero no en la ToM cognitiva de primer orden, que permanece preservada en la mayoría de los pacientes. Sin embrago, sufrir depresión subclínica se relaciona con un mayor riesgo de déficits sobrevenidos en esta función cognitiva. Los pacientes con trastorno bipolar sólo superan a los pacientes con esquizofrenia en la ToM cognitiva de orden superior. Por lo tanto, las diferencias entre estas dos poblaciones clínicas pueden ser más sutiles de lo que sugieren las investigaciones anteriores y afectar únicamente a aspectos específicos de la ToM. Nuestros resultados indican que la ventaja de las mujeres sanas en los aspectos emocionales y afectivos de la cognición social puede perderse en el trastorno bipolar y la esquizofrenia debido al efecto de la enfermedad. La vinculación entre el procesamiento emocional y la ToM apunta a una posible relación jerárquica entre los diferentes subdominios de la cognición social.Introduction. Impaired social cognition, including the ability to recognize basic emotions (emotional processing) and to interpret mental states (theory of mind, ToM), is documented in bipolar disorder and schizophrenia. Some studies suggest that patients with bipolar disorder perform better than patients with schizophrenia in this cognitive function. However, this difference is not consistently reported across studies. In healthy people, women tend to outperform men on certain aspects of social cognition. In bipolar disorder and schizophrenia, the results are contradictory. Objectives. Primary objective: to compare differences in emotional processing and ToM between bipolar disorder, schizophrenia and healthy people, and to investigate sex-related differences. Secondary aims: to explore the relationship between the different subdomains of social cognition and the influence that sociodemographic, clinical and non-social cognitive variables exert on emotional processing and ToM. Method. Included are patients with bipolar disorder I/II [studies 2 and 3] and patients with schizophrenia/schizoaffective disorder [studies 1, 2 and 3] matched for age and years of education with a control group of healthy people [studies 1 and 2]. Emotional processing is examined using the Pictures of Facial Affect test (POFA), first- and second-order cognitive ToM using false belief stories, higher-order cognitive ToM using the Hinting Task (HT) and affective ToM using the Reading the Mind in the Eyes Test (RMET). Group and sex differences are analyzed using parametric (POFA, HT and RMET) and non-parametric (false belief stories) tests. The relationship between the different subdomains of social cognition and the influence of sociodemographic, clinical, and non-social cognitive variables are explored using linear/logistic regressions. Results. Both groups of patients perform worse than healthy people on the POFA, the second-order false belief, the HT and the RMET. Patients with bipolar disorder only perform better than patients with schizophrenia on the HT. Sex differences are only found in healthy people, with women outperforming men on the POFA and the RMET. Beyond illness, the POFA and the second-order false belief emerge as the main predictors of the RMET. Older age, lower general intelligence, subclinical depressive symptoms, worse verbal memory, and slower processing speed are related to more severe deficits in social cognition. Limitations. The cross-sectional design does not allow for causal inferences. Conclusion. Patients with bipolar disorder and schizophrenia show deficits in emotional processing, second-order cognitive ToM, higher-order cognitive ToM and affective ToM but not in first-order cognitive ToM, which remains preserved in most patients. However, suffering from subclinical depression is associated with an increased risk of supervening deficits in this cognitive function. Patients with bipolar disorder only outperform patients with schizophrenia in higher-order cognitive ToM. Thus, the differences between these two clinical populations may be subtler than previous research suggests and affect only specific aspects of ToM. Our results indicate that the advantage of healthy women in emotional and affective aspects of social cognition may be lost in bipolar disorder and schizophrenia due to the effect of the illness. The link between emotional processing and ToM points to a possible hierarchical relationship between different subdomains of social cognition