Differential correlates of criticism versus emotional overinvolvement towards patients with schizophrenia living in halfway houses or with their families.

PURPOSE: This study systematically searched for differential correlates of criticism vs. emotional overinvolvement (EOI) towards patients with schizophrenia in families and halfway houses, which have only incidentally been reported in previous research. Identified patterns were compared across settings. METHODS: We included 40 inpatients with schizophrenia living in halfway houses and 40 outpatients living with their families and recorded the expressed emotion (EE) of 22 psychiatric nurses or 56 parents, respectively, through Five Minutes Speech Samples. Each nurse rated 1-12 inpatients and each inpatient was rated by 2-5 nurses. Each outpatient was rated by one or both parents. As EE ratings had a multilevel structure, weighted Spearman correlations of criticism and EOI with various patient- and caregiver-related characteristics were calculated and compared with Meng's z-test. RESULTS: Criticism was weakly negatively correlated with EOI in nurses but negligibly in parents. Distinct patterns of significant differential correlates arose across settings. Outpatients' aggressive behavior and parents' related burden were mainly associated with higher criticism. Inpatients' symptoms (agitation/aggression, negative and other psychotic symptoms) and nurses' burnout (Depersonalization) were mainly associated with lower EOI. Inpatients' perceived criticism and outpatients' previous suicide attempts were equally associated with higher criticism and lower EOI (mirror correlations). Finally, various inpatient attributes (older age, chronicity, unemployment and smoking) triggered higher EOI only. Inpatients' age, psychopathology (esp. agitation/aggression and negative symptoms) and perceived criticism survived adjustment for multiple comparisons. CONCLUSION: Our findings suggest setting-specific pathogenetic pathways of criticism and EOI and might help customize psychoeducational interventions to staff and families.

Forensic investigation of complex and complicated suicides in Attica, Greece: a 12-year retrospective study.

The purpose of this study was to examine the prevalence and characteristics (victims' profiles, circumstances surrounding the incidents, and methods employed) of complex and complicated suicides over a 12-year period in the broader area of Athens, Greece. A retrospective analysis of 5,568 autopsy cases performed at the Department of Forensic Medicine and Toxicology of the National and Kapodistrian University of Athens from January 1, 2011, to December 31, 2022, was carried out. Out of a total sample of 5,568 autopsies, 360 suicide cases were identified, among which 14 (3.9%) were classified as complex suicides, and one case (0.3%) was identified as complicated suicide. Among the victims, 78.6% were males. The age range of the victims varied between 25 and 82 years old. The most prevalent method of complex suicide was the use of sharp objects followed by jumping from a height (42.8%). The next most common combination of methods was poisoning (21.4%) along with hanging. Prior suicidal attempts and suicide note were mentioned in 16.7% and 8.3% of the cases respectively. Overall, a total of 9 different methods were used in the above 14 cases. Only half (50.0%) of the victims had an established psychiatric diagnosis. In determining the cause of death in cases of a complex or complicated suicides, it is of utmost importance for the forensic pathologist to gather and analyze all available information provided by the police, the victim's relatives along with a thorough investigation of the scene, a detailed autopsy and a toxicological analysis.

Does omega-3 supplementation improve the inflammatory profile of patients with heart failure? a systematic review and meta-analysis.

Omega-3 fatty acids are potential anti-inflammatory agents that may exert beneficial outcomes in diseases characterised by increased inflammatory profile. The purpose of this study was to comprehensively evaluate the existing research on the effectiveness of n-3 fatty acid supplementation in lowering levels of circulating inflammatory cytokines in patients with heart failure (HF). From the beginning until October 2022, randomised controlled trials (RCTs) were the subject of PubMed, Scopus, Web of Science, and Cochrane Library literature search. Omega-3 fatty acid supplementation vs. placebo were compared in eligible RCTs to see how they affected patients with HF in terms of inflammation, primarily of tumour necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), and c-reactive protein (CRP). A meta-analysis employing the random effects inverse-variance model and standardised mean differences was performed to assess group differences. Ten studies were included in this systematic review and meta-analysis. Our main analysis (k = 5) revealed a beneficial response of n-3 fatty acid supplementation on serum TNF-a (SMD: - 1.13, 95% CI: - 1.75- - 0.50, I2 = 81%, P = 0.0004) and IL-6 levels (k = 4; SMD: - 1.27, 95% CI: - 1.88- - 0.66, I2 = 81%, P < 0.0001) compared to placebo; however, no changes were observed in relation to CRP (k = 6; SMD: - 0.14, 95% CI: - 0.35-0.07, I2 = 0%, P = 0.20). Omega-3 fatty acid supplementation may be a useful strategy for reducing inflammation in patients with HF, but given the paucity of current studies, future studies may increase the reliability of these findings.

Gender, age at onset, and duration of being ill as predictors for the long-term course and outcome of schizophrenia: an international multicenter study.

BACKGROUND: The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia. METHODS: Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects. RESULTS: There was a 3-year later age at onset for females (P < .001) and lower rates of negative symptoms (P < .01) and higher depression/anxiety measures (P < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness. DISCUSSION: Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.

Executive Dysfunction, Social Cognition Impairment, and Gray Matter Pathology in Myotonic Dystrophy Type 2: A Pilot Study.

BACKGROUND: In contrast to myotonic dystrophy type 1, the cognitive and radiologic profile of myotonic dystrophy type 2 (DM2) is relatively poorly characterized. OBJECTIVE: To conduct a pilot study to systematically evaluate cognitive and radiologic features in a cohort of Greek individuals with DM2. METHOD: Eleven genetically confirmed individuals with DM2 and 26 age- and education-matched healthy controls were administered the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS) to screen for impairment in multiple cognitive domains. MRI data were evaluated by morphometric analyses to identify disease-specific gray and white matter alterations. The following statistical thresholds were used for cognitive comparisons: PFDR < 0.05 and Bayes factor (BF 10 ) >10. RESULTS: The DM2 group exhibited cognitive impairment (ECAS Total score; PFDR = 0.001; BF 10 = 108.887), which was dominated by executive impairment ( PFDR = 0.003; BF 10 = 25.330). A trend toward verbal fluency impairment was also identified. No significant impairments in memory, language, or visuospatial function were captured. The analysis of subscores revealed severe impairments in social cognition and alternation. Voxel-based morphometry identified widespread frontal, occipital, and subcortical gray matter atrophy, including the left superior medial frontal gyrus, right medial orbitofrontal gyrus, right operculum, right precuneus, bilateral fusiform gyri, and bilateral thalami. CONCLUSION: DM2 may be associated with multifocal cortical and thalamic atrophy, which is likely to underpin the range of cognitive manifestations mostly characterized by executive impairment and specifically by impaired social cognition.

The impact of different forms of exercise on circulating endothelial progenitor cells in cardiovascular and metabolic disease.

Circulating endothelial progenitor cells (EPCs) contribute to vascular repair and their monitoring could have prognostic clinical value. Exercise is often prescribed for the management of cardiometabolic diseases, however, it is not fully understood how it regulates EPCs. OBJECTIVES: to systematically examine the acute and chronic effects of different exercise modalities on circulating EPCs in patients with cardiovascular and metabolic disease. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. RESULTS: six electronic databases and reference lists of eligible studies were searched to April 2021. Thirty-six trials met the inclusion criteria including 1731 participants. Acute trials: in chronic heart failure (CHF), EPC mobilisation was acutely increased after high intensity interval or moderate intensity continuous exercise training, while findings were inconclusive after a cardiopulmonary cycling exercise test. Maximal exercise tests acutely increased EPCs in ischaemic or revascularized coronary artery disease (CAD) patients. In peripheral arterial disease (PAD), EPC levels increased up to 24 h post-exercise. In patients with compromised metabolic health, EPC mobilisation was blunted after a single exercise session. Chronic trials: in CHF and acute coronary syndrome, moderate intensity continuous protocols, with or without resistance exercise or calisthenics, increased EPCs irrespective of EPC identification phenotype. Findings were equivocal in CAD regardless of exercise mode, while in severe PAD disease EPCs increased. High intensity interval training increased EPCs in hypertensive metabolic syndrome and heart failure reduced ejection fraction. CONCLUSION: the clinical condition and exercise modality influence the degree of EPC mobilisation and magnitude of EPC increases in the long term.

The impact of different forms of exercise on endothelial progenitor cells in healthy populations.

Circulating endothelial progenitor cells (EPCs) contribute to vascular healing and neovascularisation, while exercise is an effective means to mobilise EPCs into the circulation. OBJECTIVES: to systematically examine the acute and chronic effects of different forms of exercise on circulating EPCs in healthy populations. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. RESULTS: thirty-one articles met the inclusion criteria including 747 participants aged 19 to 76 years. All included trials used flow cytometry for identification of circulating EPCs. Eight and five different EPC phenotypes were identified in the acute and chronic trials, respectively. In the acute trials, moderate intensity continuous (MICON), maximal, prolonged endurance, resistance and high intensity interval training (HIIT) exercise protocols were utilised. Prolonged endurance and resistance exercise had the most profound effect on circulating EPCs followed by maximal exercise. In the chronic trials, MICON exercise, HIIT, HIIT compared to MICON and MICON compared to exergame (exercise modality based on an interactive video game) were identified. MICON exercise had a positive effect on circulating EPCs in older sedentary individuals which was accompanied by improvements in endothelial function and arterial stiffness. Long-stage HIIT (4 min bouts) appears to be an effective means and superior than MICON exercise in mobilising circulating EPCs. In conclusion, both in acute and chronic trials the degree of exercise-induced EPC mobilisation depends upon the exercise regime applied. In future, more research is warranted to examine the dose-response relationship of different exercise forms on circulating EPCs using standardised methodology and EPC phenotype.

Polygenic risk scores for neuropsychiatric, inflammatory, and cardio-metabolic traits highlight possible genetic overlap with suicide attempt and treatment-emergent suicidal ideation.

Suicide is the second cause of death among youths. Genetics may contribute to suicidal phenotypes and their co-occurrence in other neuropsychiatric and medical conditions. Our study aimed to investigate the association of polygenic risk scores (PRSs) for 24 neuropsychiatric, inflammatory, and cardio-metabolic traits/diseases with suicide attempt (SA) or treatment-worsening/emergent suicidal ideation (TWESI). PRSs were computed based on summary statistics of genome-wide association studies. Regression analyses were performed between PRSs and SA or TWESI in four clinical cohorts. Results were then meta-analyzed across samples, including a total of 688 patients with SA (Neff  = 2,258) and 214 with TWESI (Neff  = 785). Stratified genetic covariance analyses were performed to investigate functionally cross-phenotype PRS associations. After Bonferroni correction, PRS for major depressive disorder (MDD) was associated with SA (OR = 1.24; 95% CI = 1.11-1.38; p = 1.73 × 10-4 ). Nominal associations were shown between PRSs for coronary artery disease (CAD) (p = 4.6 × 10-3 ), loneliness (p = .009), or chronic pain (p = .016) and SA, PRSs for MDD or CAD and TWESI (p = .043 and p = .032, respectively). Genetic covariance between MDD and SA was shown in 86 gene sets related to drugs having antisuicidal effects. A higher genetic liability for MDD may underlie a higher SA risk. Further, but milder, possible modulatory factors are genetic risk for loneliness and CAD.

Cortisol to Dehydroepiandrosterone Sulphate Ratio and Executive Function in Bipolar Disorder.

INTRODUCTION: Bipolar disorder (BD) is associated with impairment in cognitive domains such as verbal memory and executive functions. Very few studies have assessed dehydroepiandrosterone sulphate (DHEA-S) in BD and its relation to cognitive functioning despite evidence showing its regulatory effects on glucocorticoid action. The aim of our study was to explore the association of cortisol, DHEA-S, and cortisol to DHEA-S ratio with visuospatial memory and executive functioning in BD. METHODS: Cognitive performance of 60 bipolar I patients and 30 healthy subjects was evaluated by using Cambridge Neuropsychological Test Automated Battery tasks targeting visuospatial memory (spatial recognition memory) and executive functions (planning [Stockings of Cambridge; SOC] and attentional set shifting [ID/ED]). Morning serum cortisol and DHEA-S levels were measured in patients. Main effects of cortisol, DHEA-S, and cortisol/DHEA-S ratio for each neurocognitive task were explored in multiple regression analyses correcting for demographic and clinical parameters as well as treatment-related factors (current use of antipsychotic and mood stabilizer medication). RESULTS: Bipolar patients showed poorer performance than healthy subjects in planning and attentional set shifting but not in visuospatial memory. Cortisol to DHEA-S ratio predicted worse performance in planning (SOC). CONCLUSIONS: This is the first study to assess memory and executive function in BD in relation to DHEA-S and cortisol to DHEA-S ratio. We report an association of cortisol to DHEA-S ratio with worse performance in planning in bipolar I patients, which warrants further investigation.

Modeling psychological function in patients with schizophrenia with the PANSS: an international multi-center study.

BACKGROUND: The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model. METHODS: Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed. RESULTS: The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage. CONCLUSIONS: The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct "cores" of schizophrenia, the "Positive" and the "Negative," while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.

Personality dimensions could explain resilience in patients with eating disorders.

PURPOSE: Resilience can be defined as the ability to maintain health in the face of adversity. Resilience has been associated with personality traits. Personality traits in the context of Eating Disorders (ED) have also been examined. However, the relationship between resilience and personality profile in patients with ED has not been studied. The aim of this study is to investigate whether personality dimensions impact on resilience, in patients with ED, compared to healthy participants. METHODS: Connor and Davidson resilience scale, as a measure of resilience and temperament-character inventory, as a measure of personality dimensions, were completed by 100 participants: 50 (50%) healthy University students (controls subgroup) and 50 (50%) patients with ED, matched on age and gender. RESULTS: Patients with ED showed lower resilience than healthy participants and scored higher on harm avoidance, and lower on reward dependence, self-directedness and cooperativeness than controls. Lower harm avoidance, higher persistence and higher self-directedness were associated with resilience in both subgroups. Self-directedness and persistence predicted resilience in both subgroups. Only Harm Avoidance predicted resilience in patients' subgroup. CONCLUSION: To our knowledge, there are no existing data examining the effect of personality dimensions in resilience, in the context of ED. We found that only the effect of Harm Avoidance in resilience was different among the participants' subgroups. In conclusion, Harm Avoidance could explain differences in resilience between healthy participants and patients with ED. LEVEL OF EVIDENCE: Level III: case-control analytic study.

Familial aggregation analysis of cognitive performance in early-onset bipolar disorder.

We analysed the familial aggregation (familiality) of cognitive dimensions and explored their role as liability markers for early-onset bipolar disorder (EOBD). The sample comprised 99 subjects from 26 families, each with an offspring diagnosed with EOBD. Four cognitive dimensions were assessed: reasoning skills; attention and working memory; memory; and executive functions. Their familiality was investigated in the total sample and in a subset of healthy relatives. The intra-family resemblance score (IRS), a family-based index of the similarity of cognitive performance among family members, was calculated. Familiality was detected for the attention and working memory (AW) dimension in the total sample (ICC = 0.37, p = 0.0004) and in the subsample of healthy relatives (ICC = 0.37, p = 0.016). The IRS reflected that there are families with similar AW mean scores (either high or low) and families with heterogeneous scores. Families with the most common background for the AW dimension (IRS > 0) were selected and dichotomized in two groups according to the mean family AW score. This allowed differentiating families whose members had similar high scores than those with similar low scores: both patients (t = - 4.82, p = 0.0005) and relatives (t = - 5.04, p < 0.0001) of the two groups differed in their AW scores. AW dimension showed familial aggregation, suggesting its putative role as a familial vulnerability marker for EOBD. The IRS estimation allowed the identification of families with homogeneous scores for this dimension. This represents a first step towards the investigation of the underlying mechanisms of AW dimension and the identification of etiological subgroups.

Staging of Schizophrenia With the Use of PANSS: An International Multi-Center Study.

INTRODUCTION: A specific clinically relevant staging model for schizophrenia has not yet been developed. The aim of the current study was to evaluate the factor structure of the PANSS and develop such a staging method. METHODS: Twenty-nine centers from 25 countries contributed 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Analysis of covariance, Exploratory Factor Analysis, Discriminant Function Analysis, and inspection of resultant plots were performed. RESULTS: Exploratory Factor Analysis returned 5 factors explaining 59% of the variance (positive, negative, excitement/hostility, depression/anxiety, and neurocognition). The staging model included 4 main stages with substages that were predominantly characterized by a single domain of symptoms (stage 1: positive; stages 2a and 2b: excitement/hostility; stage 3a and 3b: depression/anxiety; stage 4a and 4b: neurocognition). There were no differences between sexes. The Discriminant Function Analysis developed an algorithm that correctly classified >85% of patients. DISCUSSION: This study elaborates a 5-factor solution and a clinical staging method for patients with schizophrenia. It is the largest study to address these issues among patients who are more likely to remain affiliated with mental health services for prolonged periods of time.

Guilt Delusional Beliefs Increase the Risk of Suicidal Attempt in Elderly Unipolar Psychotic Depressives.

The aim of this study was to investigate the differential effect of various delusion categories, namely, guilt, paranoid, impending disaster, and somatic on suicidal attempts in elderly patients experiencing unipolar psychotic major depression (PMD), because the evidence on this is scarce. The sample consisted of 65 consecutively admitted patients 60 years or older, experiencing PMD, and assessed by means of Structured Clinical Interview for DSM-4 (Patient Edition), Hamilton Depression Rating Scale, Mini-Mental Status Examination (MMSE), and by a physical impairment rating scale. Patients with guilt delusional beliefs had 5.31 times higher odds (95% confidence interval, 1.37-25.40) of a suicidal attempt than the patients without guilt delusional beliefs, controlling for sex, age, prior history of suicide attempt, MMSE, and hallucinations. In addition, 17 PMD patients with lifetime suicidal attempt compared with 48 PMD patients without lifetime suicidal attempt presented only higher age of disorder onset (p = 0.008). Of the four categories of delusions assessed, only guilt delusions were associated with an increased risk for suicidal attempt.

Well-being in Patients with Affective Disorders Compared to Nonclinical Participants: A Multi-Model Evaluation of the Mental Health Continuum-Short Form.

OBJECTIVES: The Mental Health Continuum-Short Form (MHC-SF), measuring emotional, social, and psychological well-being, has scarcely been validated in clinical populations. We evaluated MHC-SF in 203 patients with affective disorders and 163 nonclinical participants. METHOD: Traditional confirmatory factor analysis (CFA), bifactor CFA, three-factor exploratory structural equation modeling (ESEM), and bifactor ESEM models were compared. Convergent/discriminant validity was tested against classic well-being validators and current mood state. RESULTS: All three subscales were significantly lower in patients. Test-retest reliability in patients was moderate. Bifactor ESEM fitted data best and displayed full scalar gender and partial scalar invariance across groups. Factor strength indices suggested that MHC-SF is primarily unidimensional, especially in patients. However, subscales differed considerably on size, internal consistency, distinctness, discriminant validity, and temporal stability. CONCLUSIONS: MHC-SF was valid and reliable for monitoring well-being in both clinical and nonclinical samples, but further research is needed before safely concluding on its dimensionality.

Major Depression and the Degree of Suicidality: Results of the European Group for the Study of Resistant Depression (GSRD).

Background: This European multicenter study aimed to elucidate suicidality in major depressive disorder. Previous surveys suggest a prevalence of suicidality in major depressive disorder of ≥50%, but little is known about the association of different degrees of suicidality with socio-demographic, psychosocial, and clinical characteristics. Methods: We stratified 1410 major depressive disorder patients into 3 categories of suicidality based on the Hamilton Rating Scale for Depression item 3 (suicidality) ratings (0=no suicidality; 1-2=mild/moderate suicidality; 3-4=severe suicidality). Chi-squared tests, analyses of covariance, and Spearman correlation analyses were applied for the data analyses. Results: The prevalence rate of suicidality in major depressive disorder amounted to 46.67% (Hamilton Rating Scale for Depression item 3 score ≥1). 53.33% were allocated into the no, 38.44% into the mild/moderate, and 8.23% into the severe suicidality patient group. Due to the stratification of our major depressive disorder patient sample according to different levels of suicidality, we identified some socio-demographic, psychosocial, and clinical variables differentiating from the patient group without suicidality already in presence of mild/moderate suicidality (depressive symptom severity, treatment resistance, psychotic features, add-on medications in general), whereas others separated only when severe suicidality was manifest (inpatient treatment, augmentation with antipsychotics and benzodiazepines, melancholic features, somatic comorbidities). Conclusions: As even mild/moderate suicidality is associated with a failure of achieving treatment response, adequate recognition of this condition should be ensured in the clinical practice.

The Relationship between Hopelessness and Clinical Characteristics of Hospitalized Patients with Recent Suicide Attempt.

This study aimed to assess hopelessness in 170 hospitalized individuals with recent suicide attempt and examine its association with patients' characteristics, with a view to improving awareness in health professionals and especially nurses, who are among the first to take care of these patients. Participants completed Beck Hopelessness Scale and Beck Depression Inventory. More than half (51.18%) experienced moderate-to-severe hopelessness. A multiple linear regression analysis showed that age, attempted suicide method, past suicide attempt, and psychiatric diagnosis contributed statistically significantly to hopelessness prediction. Hopelessness assessment could efficiently help health professionals to minimize both inpatient suicide and suicidal acts after discharge.

Clinical and treatment-related predictors of cognition in bipolar disorder: focus on visual paired associative learning.

Bipolar disorder (BD) is associated with impairment in cognitive domains such as verbal memory and executive functions. However, visual paired associative learning (PAL) has been far less researched. Neurocognitive dysfunction in BD patients has been related to several clinical factors, but data on the effect of medication are relatively scarce and inconsistent. The aim of our study was to explore the effect of clinical and treatment-related parameters on executive functions and visual memory/learning, including PAL, in BD. Cognitive performance of 60 bipolar I patients and 30 healthy subjects was evaluated by using CANTAB battery tasks targeting spatial recognition memory, PAL and executive functions (set shifting, planning, inhibitory control). Bipolar patients showed poorer performance in PAL, set shifting, planning and inhibitory control than healthy subjects; however, only differences in PAL and planning survived correction for multiple comparisons. Number of previous manic episodes and illness duration predicted worse performance in set shifting and PAL, respectively, whereas current treatment with valproate predicted better performance in PAL. This is one of the first studies to assess clinical and treatment-related predictors of PAL in BD. We report a possibly beneficial effect of valproate on PAL, which warrants further investigation.

Validating a two-dimensional bipolar spectrum model integrating DSM-5's mixed features specifier for Major Depressive Disorder.

INTRODUCTION: The literature on DSM-5's 'Major Depressive Disorder with lifetime mixed features' (MDD-MF) is limited. This study investigated MDD-MF's potential inclusion into a bipolar spectrum. METHODS: We recruited 287 patients with Bipolar I disorder (BD-I), BD-II, MDD-MF or 'MDD without lifetime mixed features' (MDD-noMF); most (N=280) were stabilized for at least one year on medication. Sixteen validators (clinical features, psychiatric family history, temperament, stabilizing treatment) were compared across groups and subjected to trend analyses. Two discriminant function analyses (DFA; primary and secondary), excluding or including, respectively, treatment-related predictors, explored latent dimensions maximizing between-group discrimination; mahalanobis distances between group 'centroids' were calculated. RESULTS: Eleven validators differed significantly across groups; nine varied monotonically along a bipolar diathesis gradient with significant linear trends; two peaked at MDD-MF and displayed significant quadratic trends. In the primary DFA, apart from a classic bipolarity dimension, correlating with hospitalizations, early age at onset, lifetime psychosis and lower anxious temperament scores, on which groups ranked along a bipolar propensity gradient, a second dimension was also significant, peaking at BD-II and MDD-MF (challenging the classic bipolar ranking), which correlated with lifetime psychiatric comorbidities, suicidality, lower lifetime psychosis rates, female gender, higher cyclothymic and lower depressive temperament scores; MDD-MF was equipoised amidst BD-II and MDD-noMF. After including treatment-related predictors (secondary DFA), discrimination improved overall but BD-II and MDD-MF were closest than any other pair, suggesting similar treatment patterns for these two groups at this naturalistic setting. CONCLUSIONS: To our knowledge, this is the first time a two-dimensional bipolar spectrum based on classic external validators is proposed, fitting the data better than a unidimensional model. Additional predictors are warranted to improve BD-II/MDD-MF discrimination.