Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.

Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.

We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

Male rectal and anal cancer patients demonstrate high rates of sexual dysfunction. This pilot randomized controlled trial tested a psychoeducational intervention designed to improve psychosexual adjustment.

Rectal or anal cancer patients were randomized to a Sexual Health Intervention for Men (intervention) or to a referral and information control (control). The intervention included control activities plus 4 sexual health intervention sessions every 4–6 weeks and 3 brief telephone calls timed between these sessions. Assessments were completed pre-intervention (baseline) and 3 months (follow-up 1) and 8 months (follow-up 2) post-intervention. Differences were assessed with statistical significance and Cohen’s d effect sizes (d = 0.2, small effect; d = 0.5, moderate effect; d = 0.8, large effect).

Ninety subjects enrolled. Forty-three participants completed at least 1 follow-up assessment (intervention, n = 14; control n = 29). At follow-up 1, men in intervention, compared to control, improved on all domains of the International Index of Erectile Function (IIEF) (p < 0.001 to p < 0.05) and demonstrated large effects (d = 0.8 to d = 1.5). Similarly, at follow-up 2, changes in all domains of the IIEF except the orgasm domain were either statistically significant or marginally statistically significant (p = 0.01 to p = 0.08) and demonstrated moderate to large treatment effects for intervention versus control (d = 0.5 to d = 0.8). Men in the intervention, compared to control, demonstrated decreased sexual bother at follow-up 1 (p = 0.009, d = 1.1), while Self-Esteem and Relationship (SEAR) total scores and the SEAR sexual relationship subscale demonstrated moderate increases for intervention versus control (d = 0.4 to d = 0.6).

This study provides initial evidence for combining a psychoeducational intervention with medical interventions to address sexual dysfunction following rectal and anal cancer. Trials register number: NCT00712751 (date of registration: 7/10/2008).

Identifying neuroimaging biomarkers of antidepressant response may help guide treatment decisions and advance precision medicine.

To examine the relationship between anhedonia and functional neurocircuitry in key reward processing brain regions in people with major depressive disorder receiving aripiprazole adjunct therapy with escitalopram.

Data were collected as part of the CAN-BIND-1 study. Participants experiencing a current major depressive episode received escitalopram for 8 weeks; escitalopram non-responders received adjunct aripiprazole for an additional 8 weeks. Functional magnetic resonance imaging (on weeks 0 and 8) and clinical assessment of anhedonia (on weeks 0, 8 and 16) were completed. Seed-based correlational analysis was employed to examine the relationship between baseline resting-state functional connectivity (rsFC), using the nucleus accumbens (NAc) and anterior cingulate cortex (ACC) as key regions of interest, and change in anhedonia severity after adjunct aripiprazole.

Anhedonia severity significantly improved after treatment with adjunct aripiprazole.

There was a positive correlation between anhedonia improvement and rsFC between the ACC and posterior cingulate cortex, ACC and posterior praecuneus, and NAc and posterior praecuneus. There was a negative correlation between anhedonia improvement and rsFC between the ACC and anterior praecuneus and NAc and anterior praecuneus.

Eight weeks of aripiprazole, adjunct to escitalopram, was associated with improved anhedonia symptoms. Changes in functional connectivity between key reward regions were associated with anhedonia improvement, suggesting aripiprazole may be an effective treatment for individuals experiencing reward-related deficits. Future studies are required to replicate our findings and explore their generalisability, using other agents with partial dopamine (D2) agonism and/or serotonin (5-HT2A) antagonism.

Having a family member admitted in Intensive Care Unit (ICU) can cause a severe psychological stress, and various psychological disorders gathered into the notion of Post intensive care syndrome-family (PICS-F). In this way, Family-centered care in ICU represents the aim of international accepted recommendations focusing on a partnership approach to health care decision-making between the family and health care provider to prevent PICS-F. During the first SARS-CoV-2 linked lockdown, social restrictions impaired the right application of these recommendations, increasing risk of PICS-F, particularly Post-Traumatic Stress Disorder (PTSD).

The main objective was to compare the PTSD prevalence at 6 months in a group of relatives including during OLAF implementation with a control group in a cohort of ICU-patient relatives.

Considering this, the psychiatric team and the ICU team of the Toulouse University, France, proposed the creation of a temporary device called OLAF (Opération de Liaison et d’Aide aux Familles in French), aiming to bring a psychological phone support to ICU-patient relatives. Besides this operational approach we designed a research approach that aimed to investigate the impact of OLAF device on PICS-F.

We noted that 12 participants (11.5 %) presented a PTSD at 6 months without statistically significant differences between the groups (p=0.8). Considering that OLAF group presented higher PDI (Peritraumatric Distress Inventory) score at screening we also considered a mediation model suggesting that OLAF could have played a role to diminish the PCL-5 score as a covariable. In the multinomial logistic regression analysis, we found that the only factor associated with the PTSD diagnosis was the level of Anxiety and Depression Signs measured with HADS (Hospital Anxiety and Depression Scale) at screening (OR= 1.2, p<0.001).

We found no difference in PTSD prevalence according to OLAF intervention. Nevertheless, our result suggested that the intervention could have play a role in reducing PTSD by acting on anxiety and peri traumatic distress in a mediated model. We found that anxiety score could serve as a risk marker to predict PTSD and should probably be precociously screened and treated in this population.

None Declared

Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.

We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.

BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.

We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.

Prediction of treatment outcomes is a key step in improving the treatment of major depressive disorder (MDD). The Canadian Biomarker Integration Network in Depression (CAN-BIND) aims to predict antidepressant treatment outcomes through analyses of clinical assessment, neuroimaging, and blood biomarkers.

In the CAN-BIND-1 dataset of 192 adults with MDD and outcomes of treatment with escitalopram, we applied machine learning models in a nested cross-validation framework. Across 210 analyses, we examined combinations of predictive variables from three modalities, measured at baseline and after 2 weeks of treatment, and five machine learning methods with and without feature selection. To optimize the predictors-to-observations ratio, we followed a tiered approach with 134 and 1152 variables in tier 1 and tier 2 respectively.

A combination of baseline tier 1 clinical, neuroimaging, and molecular variables predicted response with a mean balanced accuracy of 0.57 (best model mean 0.62) compared to 0.54 (best model mean 0.61) in single modality models. Adding week 2 predictors improved the prediction of response to a mean balanced accuracy of 0.59 (best model mean 0.66). Adding tier 2 features did not improve prediction.

A combination of clinical, neuroimaging, and molecular data improves the prediction of treatment outcomes over single modality measurement. The addition of measurements from the early stages of treatment adds precision. Present results are limited by lack of external validation. To achieve clinically meaningful prediction, the multimodal measurement should be scaled up to larger samples and the robustness of prediction tested in an external validation dataset.

Multiple treatments are effective for major depressive disorder (MDD), but the outcomes of each treatment vary broadly among individuals. Accurate prediction of outcomes is needed to help select a treatment that is likely to work for a given person. We aim to examine the performance of machine learning methods in delivering replicable predictions of treatment outcomes.

Of 7732 non-duplicate records identified through literature search, we retained 59 eligible reports and extracted data on sample, treatment, predictors, machine learning method, and treatment outcome prediction. A minimum sample size of 100 and an adequate validation method were used to identify adequate-quality studies. The effects of study features on prediction accuracy were tested with mixed-effects models. Fifty-four of the studies provided accuracy estimates or other estimates that allowed calculation of balanced accuracy of predicting outcomes of treatment.

Eight adequate-quality studies reported a mean accuracy of 0.63 [95% confidence interval (CI) 0.56–0.71], which was significantly lower than a mean accuracy of 0.75 (95% CI 0.72–0.78) in the other 46 studies. Among the adequate-quality studies, accuracies were higher when predicting treatment resistance (0.69) and lower when predicting remission (0.60) or response (0.56). The choice of machine learning method, feature selection, and the ratio of features to individuals were not associated with reported accuracy.

The negative relationship between study quality and prediction accuracy, combined with a lack of independent replication, invites caution when evaluating the potential of machine learning applications for personalizing the treatment of depression.

Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.

We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.

We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).

Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.

To evaluate the National Health Safety Network (NHSN) hospital-onset Clostridioides difficile infection (HO-CDI) standardized infection ratio (SIR) risk adjustment for general acute-care hospitals with large numbers of intensive care unit (ICU), oncology unit, and hematopoietic cell transplant (HCT) patients.

Retrospective cohort study.

Eight tertiary-care referral general hospitals in California.

We used FY 2016 data and the published 2015 rebaseline NHSN HO-CDI SIR. We compared facility-wide inpatient HO-CDI events and SIRs, with and without ICU data, oncology and/or HCT unit data, and ICU bed adjustment.

For these hospitals, the median unmodified HO-CDI SIR was 1.24 (interquartile range [IQR], 1.15–1.34); 7 hospitals qualified for the highest ICU bed adjustment; 1 hospital received the second highest ICU bed adjustment; and all had oncology-HCT units with no additional adjustment per the NHSN. Removal of ICU data and the ICU bed adjustment decreased HO-CDI events (median, −25%; IQR, −20% to −29%) but increased the SIR at all hospitals (median, 104%; IQR, 90%–105%). Removal of oncology-HCT unit data decreased HO-CDI events (median, −15%; IQR, −14% to −21%) and decreased the SIR at all hospitals (median, −8%; IQR, −4% to −11%).

For tertiary-care referral hospitals with specialized ICUs and a large number of ICU beds, the ICU bed adjustor functions as a global adjustment in the SIR calculation, accounting for the increased complexity of patients in ICUs and non-ICUs at these facilities. However, the SIR decrease with removal of oncology and HCT unit data, even with the ICU bed adjustment, suggests that an additional adjustment should be considered for oncology and HCT units within general hospitals, perhaps similar to what is done for ICU beds in the current SIR.

Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.

To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.

The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.

These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.

Patients with major depressive disorder (MDD) display cognitive deficits in acutely depressed and remitted states. Childhood maltreatment is associated with cognitive dysfunction in adults, but its impact on cognition and treatment related cognitive outcomes in adult MDD has received little consideration. We investigate whether, compared to patients without maltreatment and healthy participants, adult MDD patients with childhood maltreatment display greater cognitive deficits in acute depression, lower treatment-associated cognitive improvements, and lower cognitive performance in remission.

Healthy and acutely depressed MDD participants were enrolled in a multi-center MDD predictive marker discovery trial. MDD participants received 16 weeks of standardized antidepressant treatment. Maltreatment and cognition were assessed with the Childhood Experience of Care and Abuse interview and the CNS Vital Signs battery, respectively. Cognitive scores and change from baseline to week 16 were compared amongst MDD participants with (DM+, n = 93) and without maltreatment (DM−, n = 90), and healthy participants with (HM+, n = 22) and without maltreatment (HM−, n = 80). Separate analyses in MDD participants who remitted were conducted.

DM+ had lower baseline global cognition, processing speed, and memory v. HM−, with no significant baseline differences amongst DM−, HM+, and HM− groups. There were no significant between-group differences in cognitive change over 16 weeks. Post-treatment remitted DM+, but not remitted DM−, scored significantly lower than HM− in working memory and processing speed.

Childhood maltreatment was associated with cognitive deficits in depressed and remitted adults with MDD. Maltreatment may be a risk factor for more severe and persistent cognitive deficits in adult MDD.

Although executive and other cognitive deficits have been found in patients with borderline personality disorder (BPD), whether these have brain functional correlates has been little studied. This study aimed to examine patterns of task-related activation and de-activation during the performance of a working memory task in patients with the disorder.

Sixty-seven DSM-IV BPD patients and 67 healthy controls underwent fMRI during the performance of the n-back task. Linear models were used to obtain maps of within-group activations and areas of differential activation between the groups.

On corrected whole-brain analysis, there were no activation differences between the BPD patients and the healthy controls during the main 2-back v. baseline contrast, but reduced activation was seen in the precentral cortex bilaterally and the left inferior parietal cortex in the 2-back v. 1-back contrast. The patients showed failure of de-activation affecting the medial frontal cortex and the precuneus, plus in other areas. The changes did not appear to be attributable to previous history of depression, which was present in nearly half the sample.

In this study, there was some, though limited, evidence for lateral frontal hypoactivation in BPD during the performance of an executive task. BPD also appears to be associated with failure of de-activation in key regions of the default mode network.

In an effort to optimize patient outcomes, considerable attention is being devoted to identifying patient characteristics associated with major depressive disorder (MDD) and its responsiveness to treatment. In the current study, we extend this work by evaluating whether early change in these sensitivities is associated with response to antidepressant treatment for MDD.

Participants included 210 patients with MDD who were treated with 8 weeks of escitalopram and 112 healthy comparison participants. Of the original 210 patients, 90 non-responders received adjunctive aripiprazole for an additional 8 weeks. Symptoms of depression and anhedonia were assessed at the beginning of treatment and 8 weeks later in both samples. Reward and punishment sensitivity were assessed using the BIS/BAS scales measured at the initiation of treatment and 2 weeks later.

Individuals with MDD exhibited higher punishment sensitivity and lower reward sensitivity compared with healthy comparison participants. Change in reward sensitivity during the first 2 weeks of treatment was associated with improved depressive symptoms and anhedonia following 8 weeks of treatment with escitalopram. Similarly, improvement in reward responsiveness during the first 2 weeks of adjunctive therapy with aripiprazole was associated with fewer symptoms of depression at post-treatment.

Findings highlight the predictive utility of early change in reward sensitivity during antidepressant treatment for major depression. In a clinical setting, a lack of change in early reward processing may signal a need to modify a patient's treatment plan with alternative or augmented treatment approaches.