Major depressive disorder (MDD) is the leading cause of disability globally, with moderate heritability and well-established socio-environmental risk factors. Genetic studies have been mostly restricted to European settings, with polygenic scores (PGS) demonstrating low portability across diverse global populations.

This study examines genetic architecture, polygenic prediction, and socio-environmental correlates of MDD in a family-based sample of 10 032 individuals from Nepal with array genotyping data. We used genome-based restricted maximum likelihood to estimate heritability, applied S-LDXR to estimate the cross-ancestry genetic correlation between Nepalese and European samples, and modeled PGS trained on a GWAS meta-analysis of European and East Asian ancestry samples.

We estimated the narrow-sense heritability of lifetime MDD in Nepal to be 0.26 (95% CI 0.18–0.34, p = 8.5 × 10−6). Our analysis was underpowered to estimate the cross-ancestry genetic correlation (rg = 0.26, 95% CI −0.29 to 0.81). MDD risk was associated with higher age (beta = 0.071, 95% CI 0.06–0.08), female sex (beta = 0.160, 95% CI 0.15–0.17), and childhood exposure to potentially traumatic events (beta = 0.050, 95% CI 0.03–0.07), while neither the depression PGS (beta = 0.004, 95% CI −0.004 to 0.01) or its interaction with childhood trauma (beta = 0.007, 95% CI −0.01 to 0.03) were strongly associated with MDD.

Estimates of lifetime MDD heritability in this Nepalese sample were similar to previous European ancestry samples, but PGS trained on European data did not predict MDD in this sample. This may be due to differences in ancestry-linked causal variants, differences in depression phenotyping between the training and target data, or setting-specific environmental factors that modulate genetic effects. Additional research among under-represented global populations will ensure equitable translation of genomic findings.

Alzheimer’s Disease (AD) and dementia present major and escalating public health concerns for the U.S., especially among ethnoculturally diverse (e.g., Latinx, non-Latinx Black [NLB]) populations who represent an increasing percentage of the older adult population in the US and bear greater AD burden compared to non-Latinx Whites (NLWs). Notably, neurocognition and functional status are highly correlated in those with AD. However, little has been done to understand these associations and validate functional measures across geographically diverse, multiethnic samples. The aims of this study were to characterize the neurocognition and functional status of a large, multiethnic sample and subsequently examine any associations between neurocognition and functional status among Latinx, NLB, and NLW older adults.

This cross-sectional, retrospective study utilized archival data drawn from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). ADNI is a national, longitudinal, multi-site, observational study aiming to measure the progression of AD (see https://adni-info.org). Study measures included the: 1) Alzheimer’s Disease Assessment Scale Cognitive subscale (ADAS-cog; 13-items), a global neurocognitive battery evaluating neurocognition in people with AD; 2) Functional Activities Questionnaire (FAQ; 10-item questionnaire) to assess functional status; 3) Geriatric Depression Scale (GDS; 15-item questionnaire) for depression; and 4) American National Adult Reading Test (ANART; 50-word test) for reading level. The sample included 1537 older adults who completed baseline visits for the ADNI study, 1333 of whom were NLW, 123 NLB, and 81 Latinx. The average age of the sample was 73 years, average 16 years of education, and 53% male. Compared to the NLW group, the NLB and Latinx groups were significantly younger and had a higher percentage of female participants. Compared to NLW and Latinx groups, the NLB group also had significantly fewer years of education and lower reading scores. Potential confounds (i.e., demographic variables, depression) were identified a priori based on the literature and subsequently analyzed for inclusion as covariates in the primary analyses. Analyses revealed variables were non-normally distributed, therefore Independent Samples Kruskal-Wallis tests and Spearman’s Correlations were computed to examine differences and correlations between ethnocultural groups.

After controlling for age and education, Latinx and NLB groups had significantly higher ADAS-cog and FAQ scores than the NLW group (Hs = 9.50-21.53, ps < .05). Spearman’s partial correlations controlling for age, education, gender, and depression revealed that higher ADAS-cog scores were associated with higher FAQ scores within Latinx (p=.49, p<.001), NLB (p=.66, p<.001), and NLW (p=.60, p<.001) groups.

Findings indicate that neurocognition is positively associated with functional status and support the ecological and external validity of the ADAS-cog and FAQ for use with NLB and Latinx older adults, in addition to previously established work with more homogenous samples. Study strengths include the overall sample size, geographic diversity, and standardization of research approaches. Study limitations include high education level and low comorbidity rates present in the sample, limiting the generalizability of the results, in addition to the unbalanced ethnocultural groups, further emphasizing the need for increased inclusion efforts of ethnoculturally diverse older adults into brain health research studies.

Generalized anxiety disorder (GAD) is a highly prevalent mental illness that is associated with clinically significant distress, functional impairment, and poor emotional regulation. Primary functional magnetic resonance imaging (fMRI) studies of GAD report neural abnormalities in comparison to healthy controls. However, many of these findings in the primary literature are inconsistent, and it is unclear whether they are specific to GAD or shared transdiagnostically across related disorders.

This meta-analysis seeks to establish the most reliable neural abnormalities observed in individuals with GAD, as reported in the primary fMRI activation literature.

We conducted an exhaustive literature search in PubMed to identify primary studies that met our pre-specified inclusion criteria and then extracted relevant data from primary, whole-brain fMRI activation studies of GAD that reported coordinates in Talairach or MNI space. We then used multilevel kernel density analysis (MKDA) with ensemble thresholding to examine the differences between adults with GAD and healthy controls in order to identify brain regions that reached statistical significance across primary studies.

Patients with GAD showed statistically significant (α=0.05–0.0001; family-wise-error-rate corrected) neural activation in various regions of the cerebral cortex and basal ganglia across a variety of experimental tasks.

These results inform our understanding of the neural basis of GAD and are interpreted using a frontolimbic model of anxiety as well as specific clinical symptoms of this disorder and its relation to other mood and anxiety disorders. These results also suggest possible novel targets for emerging neurostimulation therapies (e.g., transcranial magnetic stimulation) and may be used to advance our understanding of the effects of current pharmaceutical treatments and ways to improve treatment selection and symptom-targeting for patients diagnosed with GAD.

None Declared

Functional magnetic resonance imaging (fMRI) has been used to identify the neural activity of both youth and adults diagnosed with major depressive disorder (MDD) in comparison to healthy age-matched controls. Previously reported abnormalities in depressed youth appear to mostly align with those found in depressed adults; however, some of the reported aberrant brain activity in youth has not been consistent with what is observed in adults, and to our knowledge there has not yet been a formal, quantitative comparison of these two groups. In addition, it is not known whether these observed differences between youth and adults with depression are attributable to developmental age or length-of-illness.

The aim of this study is to elucidate the similarities and differences in patterns of abnormal neural activity between adults and youth diagnosed with MDD and to then determine whether these observed differences are due to either developmental age or length-of-illness.

We used multilevel kernel density analysis (MKDA) with ensemble thresholding and triple subtraction to separately determine neural abnormalities throughout the whole brain in primary studies of depressed youth and depressed adults and then directly compare the observed abnormalities between each of those age groups. We then conducted further comparisons between multiple subgroups to control for age and length-of-illness and thereby determine the source of the observed differences between youth and adults with depression.

Adults and youth diagnosed with MDD demonstrated reliable, differential patterns of abnormal activation in various brain regions throughout the cerebral cortex that are statistically significant (p < .05; FWE-corrected). In addition, several of these brain regions that exhibited differential patterns of neural activation between the two age groups can be reliably attributed to either developmental age or length-of-illness.

These findings indicate that there are common and disparate patterns of brain activity between youth and adults with MDD, several of which can be reliably attributed to developmental age or length-of-illness. These results expand our understanding of the neural basis of depression across development and course of illness and may be used to inform the development of new, age-specific clinical treatments as well as prevention strategies for this disorder.

None Declared

Stevens-Johnson Syndrome is a rare life-threatening condition characterized by severe mucocutaneous epidermal necrolysis and detachment of the epidermis. The condition centers around a delayed-type hypersensitivity reaction with a complex etiology stemming from a variety of causes.

To present the case of a patient with a diagnosis of intellectual disability, bipolar disorder and epilepsy who, 14 days after starting treatment with Cariprazine, presented with pseudovesicular skin lesions suggestive of Steven-Johnson syndrome.

A non-systematic literature review on PubMed database on Steven-Johnson syndrome and other autoimmune processes in patients with bipolar disorder, and the impact on the affective symptoms of the former, was conducted. The clinical case report was prepared through the review of clinical records of the patient.

The authors present the case of a 50-year-old woman, undergoing psychiatric follow-up for more than 30 years with a diagnosis of bipolar disorder. She has a moderate intellectual disability and generalized epilepsy diagnosed at the age of 13. Since the age of 20, the patient has presented clinical manifestations compatible with bipolar disorder.

On a dermatological level, the patient had medical records of hypersensitivity reaction to amoxicillin-clavulanic acid, intolerance to carbamazepine; and toxicoderma and hepatitis after treatment with Lamotrigine, compatible with DRESS syndrome.

At the time of the study, psychopharmacological treatment consisted in valproic acid, lithium and cariprazine (the latter being introduced 14 days earlier). Pseudovesicular and papular skin lesions were observed, with a dianiform appearance and central necrosis.

Prior to the debut of the dermatological condition, the patient showed a decompensation of her bipolar disorder, with escalating irritability, soliloquies, verbosity and hostility towards her parents, with episodes of psychomotor agitation.

After the appearance of the skin lesions, a striking clinical change was observed, with an almost complete remission of affective symptoms, temporally coincident with DRESS syndrome and cariprazine withdrawal.

In recent years, research on autoimmune diseases and their relationship with mental disorders, such as bipolar disorder, schizophrenia and depression, has become increasingly abundant. The conclusions point to the fact that both disorders could be interrelated even at an etiopathogenic level. In this case report, we discuss a patient with a diagnosis of bipolar disorder with an important component of autoimmune response to different drugs, which seems to have influenced the clinical course of the mental illness.

None Declared

Major depressive disorder (MDD) is a highly prevalent mental illness that frequently originates in early development and is pervasive during adolescence. Despite its high prevalence and early age of onset, our understanding of the potentially unique neural basis of MDD in this age group is still not well understood, and the existing primary literature on the topic includes many new and divergent results. This limited understanding of MDD in youth presents a critical need to further investigate its neural basis in youth and presents an opportunity to also improve clinical treatments that target its neural abnormalities.

The present study aims to advance our understanding of the neural basis of MDD in youth by identifying abnormal functional activation in various brain regions compared with healthy controls.

We conducted a meta-analysis of functional magnetic resonance imaging (fMRI) studies of MDD by using a well-established method, multilevel kernel density analysis (MKDA) with ensemble thresholding, to quantitatively combine all existing whole-brain fMRI studies of MDD in youth compared with healthy controls. This method involves a voxel-wise, whole-brain approach, that compares neural activation of patients with MDD to age-matched healthy controls across variations of task-based conditions, which we subcategorize into affective processing, executive functioning, positive valence, negative valence, and symptom provocation tasks.

Youth with MDD exhibited statistically significant (p<0.05; FWE-corrected) hyperactivation and hypoactivation in multiple brain regions compared with age-matched healthy controls. These results include significant effects that are stable across various tasks as well as some that appear to depend on task conditions.

This study strengthens our understanding of the neural basis of MDD in youth and may also be used to help identify possible similarities and differences between youth and adults with depression. It may also help inform the development of new treatment interventions and tools for predicting unique treatment responses in youth with depression.

None Declared

Major depressive disorder (MDD) is a highly prevalent mental illness that often first occurs or persists into adulthood and is considered the leading cause of disability and disease burden worldwide. Unfortunately, individuals diagnosed with MDD who seek treatment often experience limited symptom relief and may not achieve long-term remission, which is due in part to our limited understanding of its underlying pathophysiology. Many studies that use task-based functional magnetic resonance imaging (fMRI) have found abnormal activation in brain regions in adults diagnosed with MDD, but those findings are often inconsistent; in addition, previous meta-analyses that quantitatively integrate this large body literature have found conflicting results.

This meta-analysis aims to advance our understanding of the neural basis of MDD in adults, as measured by fMRI activation studies, and address inconsistencies and discrepancies in the empirical literature.

We employed multilevel kernel density analysis (MKDA) with ensemble thresholding, a well-established method for voxel-wise, whole-brain meta-analyses, to conduct a quantitative comparison of all relevant primary fMRI activation studies of adult patients with MDD compared to age-matched healthy controls.

We found that adults with MDD exhibited a reliable pattern of statistically significant (p<0.05; FWE-corrected) hyperactivation and hypoactivation in several brain regions compared to age-matched healthy controls across a variety of experimental tasks.

This study supports previous findings that there is reliable neural basis of MDD that can be detected across heterogenous fMRI studies. These results can be used to inform development of promising treatments for MDD, including protocols for personalized interventions. They also provide the opportunity for additional studies to examine the specificity of these effects among various populations-of-interest, including youth vs. adults with depression as well as other related mood and anxiety disorders.

None Declared

41 years-old man diagnosed of schizophrenia and peripheral spondyloarthropathy HLA-B27 (-) in treatment with methotrexate. Psychiatric background: First psychotic episode at 18, with no further medical monitoring. In 2018 he underwent a new episode consisting in auditory hallucinations, delusional ideas and clinophilia of months of evolution. He was sent to a Psychiatric Rehabilitation Unit and prescribed aripiprazole 20mg. The routine blood analysis revealed triglycerides level of 414mg/dL, with previous normal levels (123 mg/dL), without no other cause to justify it.

To study the relationship between aripiprazole treatment and acute hypertriglyceridemia.

A clinical case is presented and available bibliography about the relation between aripiprazole and acute hypertriglyceridemia is reviewed.

Hypertriglyceridemia was confirmed in the second analysis, so we concluded it was due to the start of aripiprazole, after rejecting other potential causes. Aripiprazole was replaced by cariprazine 3mg because of its similar profile. The analysis was repeated after a month and the normalization of the triglyceridemia (159mg/dL) was verified, while cholesterol levels remain stable. Moreover, the patient experienced an improvement in akathisia and sedation.

Although metabolic impact is not expected with aripiprazole, after reviewing the bibliography we have found a clinical trial and a case series that described this adverse effect. Our case highlights the importance of closely monitoring of patients in whom an antipsychotic treatment is started due to the high mortality and morbidity related to cardiovascular diseases.

No significant relationships.

The mounting evidence for effective delivery of psychological interventions by non-specialists in low- and middle-income settings has led to a rapid expansion of mental health and psychosocial support trainings globally. As such, there is a demand for strategies on how to train and implement these services to attain adequate quality. This study aims to evaluate the added value of a competency-driven approach to training of facilitators for a group intervention for children with severe emotional distress in Lebanon.

In a controlled before and after study, 24 trainees were randomly allocated to participate in either a competency-driven training (CDT) or training-as-usual (TAU) (1 : 1) for a psychological intervention for children with severe emotional distress. We assessed the change in demonstrated competencies, using standardised role-plays, before and after the training. Measures included the 13-item Working with children-Assessment of Competencies Tool (WeACT), the 15-item ENhancing Assessment of Common Therapeutic factors (ENACT) and the 6-item Group facilitation: Assessment of Competencies Tool (GroupACT). The trainer in the experimental arm used pre-training and during training competency assessment scores to make real-time adjustment to training delivery. Due to COVID-19 pandemic restrictions, all activities were done remotely.

CDT resulted in significantly better outcomes on increasing competencies on the WeACT (repeated measures analysis of variance; F(1, 22) = 6.49, p < 0.018) and on the GroupACT (Mann–Whitney U = 22, p < 0.003), though not statistically significant on the ENACT. There is no significant between-group difference on the reduction of harmful behaviours, mainly because both forms of training appear equally successful in eliminating such behaviours.

This proof-of-concept study demonstrates the potential of CDT, using standardised assessment of trainee competencies, to contribute to better training outcomes without extending the duration of training. CDT can result in up to 18% greater increase in adequate competency, when compared to TAU. The study also yields recommendations for further enhancing the benefits of competency-driven strategies. A fully powered trial is needed to confirm these findings.

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.

There is a scarcity of evaluated tools to assess whether non-specialist providers achieve minimum levels of competency to effectively and safely deliver psychological interventions in low- and middle-income countries. The objective of this study was to evaluate the reliability and utility of the newly developed Working with children – Assessment of Competencies Tool (WeACT) to assess service providers’ competencies in Gaza, Palestine.

The study evaluated; (1) psychometric properties of the WeACT based on observed role-plays by trainers/supervisors (N = 8); (2) sensitivity to change among service provider competencies (N = 25) using pre-and-post training WeACT scores on standardized role-plays; (3) in-service competencies among experienced service providers (N = 64) using standardized role-plays.

We demonstrated moderate interrater reliability [intraclass correlation coefficient, single measures, ICC = 0.68 (95% CI 0.48–0.86)] after practice, with high internal consistency (α = 0.94). WeACT assessments provided clinically relevant information on achieved levels of competencies (55% of the competencies were scored as adequate pre-training; 71% post-training; 62% in-service). Pre-post training assessment saw significant improvement in competencies (W = −3.64; p < 0.001).

This study demonstrated positive results on the reliability and utility of the WeACT, with sufficient inter-rater agreement, excellent internal consistency, sensitivity to assess change, and providing insight needs for remedial training. The WeACT holds promise as a tool for monitoring quality of care when implementing evidence-based care at scale.