Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo.

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples (N = 1,384) of medication-free individuals with first-episode and recurrent MDD (N = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls (N = 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals (N = 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine-learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions that exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter (N = 290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter (N = 395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%). By contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) (ß = -18.3, 95% CI (-34.3 to -2.3), P = 0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that constitute MDD and predict treatment response.

Cross-cultural differences through subjective cognition: illustration in translatology with the SSTIC-E in the UAE.

The development of appropriate and valid multicultural and multilingual instruments research is necessary due to a growing multicultural and multilingual society in the 21st century. We explored the use of a cognitive scale related to subjective complaints, focusing on the first step: a cross-cultural and semantic validation. This study presents the translation and cross-validation process of the "Subjective Scale to Investigate Cognition in Schizophrenia" (SSTICS) for the United Arab Emirates (UAE) region via different languages used in Dubaï/Abu Dhabi. This scale measures cognitive complaints and has been validated with psychosis and used in 20 clinical trials worldwide. It evaluates areas of the illness related to self-awareness focusing on memory dysfunction and deficits of attention, language, and praxis. We described the method of cross-cultural validation, with back-translation, semantic steps, and societal contexts. The use of the Subjective Scale to Investigate Cognition in Emirates (SSTIC-E) was explored with different samples of UAE Arabic-speaking subjects. First, a pilot sample mean SSTICS total score was 16.5 (SD:16.9); (p < 0.001). The SSTIC-E was then administered to 126 patients and 84 healthy control participants. The healthy group has a lower mean score of 22.55 (SD = 12.04) vs. 34.06 (SD = 15.19). The method was extended to nine other languages, namely, Pakistani/Urdu, Hindi, Marathi, Lithuanian, Serbian, German, Romanian, Sinhala, and Russian. The scales are provided in the article. The overall aim of the translation process should be to stay close to the original version of the instrument so that it is meaningful and easily understood by the target language population. However, for construct validity, some items must be adapted at the time of translation to ensure that the questioned cognitive domain is respected. For example, cooking, an executive function, does not have the same occurrence for an Emirati male, or remembering a prime minister's name, semantic memory, requires an electoral system to appoint the leader of a country. Translation methods and processes present many challenges but applying relevant and creative strategies to reduce errors is essential to achieve semantic validation. This study aims to measure personally experienced knowledge or attitudes; such language effects can be a thorny problem.

Risk of suicidal behavior in patients with major depression and bipolar disorder - A systematic review and meta-analysis of registry-based studies.

Suicide is a health priority and one of the most common causes of death in mood disorders. One of the limitations of this type of research is that studies often establish rates of suicide behaviors in mood disorders by using diverse comparison groups or simply monitoring cohort of patients over a time period. In this registry-based systematic review, national registers were identified through searches in six academic databases, and information about the occurrence of suicide behaviors in mood disorders was systematically extracted. Odds ratios were subsequently calculated comparing rates of death by suicide in mood disorders in comparison with age and period matched rates of death by suicide in the general population obtained from country-wide national registers. The aim was to provide the most recent summary of epidemiological and clinical factors associated to suicide in mood disorders whilst calculating the likelihood of death by suicide in mood disorders in comparison with non-affected individuals according to national databases. The study follows the Preferred Reporting Guidelines for Systematic Reviews and Meta-analyses and was prespecify registered on Prospero (CRD42020186857). Results suggest that patients with mood disorders are at substantially increased risk of attempting and dying by suicide. Several epidemiological, clinical and social factors are reported to be associated with clinical populations at risk of suicide. Meta-analyses of completed deaths by suicide suggest that the likelihood for dying by suicide in mood disorders is 8.62 times higher in major depression and 8.66 times higher in bipolar disorder with higher number of untoward events in women compared to men in both conditions. The likelihood of dying by suicide in major depressive disorders is higher in the first year following discharge. Clinical guidelines might consider longer periods of monitoring following discharge from hospital. Overall, due to the higher risk of suicide in mood disorders, efforts should be made to increase detection and prevention whilst focusing on reducing risk in the most severe forms of illness with appropriate treatment to promote response and remission at the earliest convenience.

The Utility of CYP2D6 and CYP2C19 Variants to Guide Pharmacological Treatment in Complex Unipolar Major Depression: A Pilot Longitudinal Study.

Major depression is a frequent condition which variably responds to treatment. In view of its high prevalence, the presence of treatment resistance in major depression significantly impacts on quality of life. Tailoring pharmacological treatment based on genetic polymorphisms is a current trend to personalizing pharmacological treatment in patients with major depressive disorders. Current guidelines for the use of genetic tests in major depression issued by the Clinical Pharmacogenomics Implementation Consortium (CPIC) are based on CYP2D6 and CYP2C19 polymorphisms which constitute the strongest evidence for pharmacogenomic guided treatment. There is evidence of increased clinical response to pharmacological treatment in major depression although largely in non-treatment resistant patients from Western countries. In this study, well characterised participants (N = 15) with complex, largely treatment resistant unipolar major depression were investigated, and clinical improvement was measured at baseline and at week-8 after the pharmacogenomics-guided treatment with the Montgomery Åsberg Depression Rating Scale (MÅDRS). Results suggested a statistically significant improvement (p = 0.01) of 16% at endpoint in the whole group and a larger effect in case of changes in medication regime (28%, p = 0.004). This small but appreciable effect can be understood in the context of the level of treatment resistance in the group. To our knowledge, this is the first study from the Middle East demonstrating the feasibility of this approach in the treatment of complex major depressive disorders.

Can Cotard Syndrome Be Induced?: Illustration With a Rare Case of Potential Organ Transplant.

ABSTRACT: Cotard syndrome is a rare condition characterized by delusions ranging from a belief that one has lost organs to insisting that one has lost one's soul or is dead. This is the report a case of a 45-year-old man who was comatose after an attempted suicide. This was initially diagnosed as brain death and use of his organs for transplantation was actively considered. However, he awakened days later with new-onset Cotard syndrome. It remains difficult to know the link, unconscious or conscious, between this patient's delusions and the fleeting intention of doctors who intended to transplant his organs. This is the first description of a coincidence between delusional denial of an organ and the potential medico-surgical act of having an organ removed. This case is an opportunity to revisit the philosophical concepts of negation and nihilism. A multidisciplinary reflection is needed to give meaning to other clinical presentations.

AI-based dimensional neuroimaging system for characterizing heterogeneity in brain structure and function in major depressive disorder: COORDINATE-MDD consortium design and rationale.

BACKGROUND: Efforts to develop neuroimaging-based biomarkers in major depressive disorder (MDD), at the individual level, have been limited to date. As diagnostic criteria are currently symptom-based, MDD is conceptualized as a disorder rather than a disease with a known etiology; further, neural measures are often confounded by medication status and heterogeneous symptom states. METHODS: We describe a consortium to quantify neuroanatomical and neurofunctional heterogeneity via the dimensions of novel multivariate coordinate system (COORDINATE-MDD). Utilizing imaging harmonization and machine learning methods in a large cohort of medication-free, deeply phenotyped MDD participants, patterns of brain alteration are defined in replicable and neurobiologically-based dimensions and offer the potential to predict treatment response at the individual level. International datasets are being shared from multi-ethnic community populations, first episode and recurrent MDD, which are medication-free, in a current depressive episode with prospective longitudinal treatment outcomes and in remission. Neuroimaging data consist of de-identified, individual, structural MRI and resting-state functional MRI with additional positron emission tomography (PET) data at specific sites. State-of-the-art analytic methods include automated image processing for extraction of anatomical and functional imaging variables, statistical harmonization of imaging variables to account for site and scanner variations, and semi-supervised machine learning methods that identify dominant patterns associated with MDD from neural structure and function in healthy participants. RESULTS: We are applying an iterative process by defining the neural dimensions that characterise deeply phenotyped samples and then testing the dimensions in novel samples to assess specificity and reliability. Crucially, we aim to use machine learning methods to identify novel predictors of treatment response based on prospective longitudinal treatment outcome data, and we can externally validate the dimensions in fully independent sites. CONCLUSION: We describe the consortium, imaging protocols and analytics using preliminary results. Our findings thus far demonstrate how datasets across many sites can be harmonized and constructively pooled to enable execution of this large-scale project.

Effectiveness of pharmacogenomic tests including CYP2D6 and CYP2C19 genomic variants for guiding the treatment of depressive disorders: Systematic review and meta-analysis of randomised controlled trials.

Major depressive disorders are prevalent conditions with limited treatment response and remission. Pharmacogenomics tests including CYP2D6 and CYP2C19 genomic variants provide the most reliable actionable approach to guide choice and dosing of antidepressants in major depression to improve outcomes. We carried out a meta-analysis and meta-regression analyses of randomised controlled trials evaluating pharmacogenomic tests with CYP2D6 and CYP2C19 polymorphisms in major depression. A systematic review was conducted according to PRISMA and Cochrane guidelines to search several electronic databases. Logarithmically transformed odds ratios (OR) and confidence intervals (CI) for improvement, response and remission were calculated. A random-effects meta-analysis and meta-regression analyses were subsequently carried out. Twelve randomised controlled trials were included. Pharmacogenomic tests in the treatment of depression were more effective than treatment as usual for improvement (OR:1.63, CI: 1.19-2.24), response (OR: 1.46; CI: 1.16-1.85) and remission (OR: 1.85; CI: 1.23-2.76) with no evidence of publication bias. Remission was less favourable in recent studies. The results are promising but cautious use of pharmacogenomics in major depression is advisable. PROSPERO registration ID: CRD42021261143.

Intimate-partner violence and its association with symptoms of depression, perceived health, and quality of life in the Himalayan Mountain Villages of Gilgit Baltistan.

STUDY OBJECTIVES: We aimed to estimate the prevalence of intimate partner violence (IPV) and associated risk factors in married women in rural villages of Gilgit Baltistan in Pakistan. METHODS: A cross-sectional design to assess the magnitude and factors associated with IPV in a random sample of 789 married women aged 18-49 years. A World Health Organization screening instrument was used to assess the presence of IPV in the previous 12 months. A locally validated instrument was adopted to identify self-reported symptoms of major depression according to the DSM IV. Trained nurses obtained socio-demographic and reproductive history through structured interviews. Bivariate and multivariable logistic regression analyses were used to estimate prevalence and identify significant predictors of IPV. RESULTS: The mean age of the participants was 38.3 years (SD: ±12.8). The prevalence of IPV in women was 22.8% (95% Confidence Interval: 20.0-25.9), 18.5% in pregnant women (95% CI: 11.7-27.9) and significantly associated with depression in 55.1% of IPV cases. Husband education level (college/higher) (Adjusted Odds Ratio: 0.40; 95%CI: 0.22-0.70) and high household income (AOR: 0.44; 95% CI: 0.29-0.68) were protective against IPV. Increase in age (AOR;1.02; 95% CI: 1.01-1.02) and poor relationship with mother-in-law increased the risk of IPV (AOR = 2.85; 95% CI: 1.90-4.28). IPV was positively associated with symptoms of depression (AOR = 1.97; 95% CI:1.39-2.77), poor perceived quality of life (AOR = 3.54; 95% CI: 1.90-6.58) and poor health (AOR = 2.74; 95% CI: 1.92-3.92). CONCLUSION: IPV is substantial public health burden significantly associated with depressive symptoms, poor perceived health and the quality of life.

Decreased acylated and total ghrelin levels in bipolar disorder patients recovering from a manic episode.

BACKGROUND: To date, only few studies have investigated ghrelin levels in bipolar disorders, and all have exclusively measured acylated ghrelin, with none investigating total ghrelin (acylated and des-acylated). We aimed to investigate peripheral levels of acylated and total ghrelin in subjects experiencing a manic episode of bipolar disorder. METHODS: Peripheral levels of acylated and total ghrelin were measured in hospitalised medicated individuals recovering from a manic episode. Enzyme-linked immunosorbent assays (ELISA) were used to measure ghrelin levels in patients and compared with healthy controls. The relationship between ghrelin levels in bipolar disorder, self-reported hunger measures, demographic and clinical parameters was investigated with correlational analyses. RESULTS: Twenty-four subjects (15 males, 9 females) recovering from mania and 27 matched healthy controls (13 males, 14 females) were recruited for the study. Mean values of both acylated (187 vs.520 pg/mL) and total ghrelin (396 vs. 648 pg/mL) were significantly reduced in bipolar disorder (p = 0.001). Ghrelin levels correlated positively with markers of illness severity and negatively with prescribed mood stabilizers, second-generation antipsychotics, weight and body mass index. CONCLUSION: Peripheral measurements of acylated and total ghrelin were both reduced in bipolar disorder patients compared to healthy controls. Whilst illness severity promotes higher ghrelin levels, pharmacological treatment and weight gain exercise the opposite effect.

The prevalence of psychological consequences of COVID-19: A systematic review and meta-analysis of observational studies.

A systematic review and a meta-analysis were conducted to examine the overall prevalence of psychological health outcomes during COVID-19. Seven databases were systematically searched to include studies reporting on at least one psychological outcome. The pooled prevalence of primary psychological outcomes was 26% (95%CI: 21-32). Pooled prevalence for symptoms of PTSD was 33% (0-86), anxiety 28% (21-36), stress 27% (14-43), and depression 22% (13-33). The prevalence of psychological outcomes was similar in healthcare workers and in the general population (34% [24-44] and 33% [27-40] respectively). High prevalence figures support the importance of ensuring adequate provision of resources for mental health.

More than just anti-NMDAR: the many facets of autoimmune encephalitis.

This editorial expands on a Praxis article published by Beattie and colleagues in the trainees' section of this journal. The authors describe an interesting case of anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis, outline the clinical presentation and make suggestions on ways to approach this rare disorder. Here we provide an overview of autoimmune conditions that result in the production of autoantibodies targeting central nervous system proteins mediating autoimmune encephalitis and offer a perspective on approaches to diagnosis and treatment.

Structural brain correlates in major depression, anxiety disorders and post-traumatic stress disorder: A voxel-based morphometry meta-analysis.

The high comorbidity of Major Depressive Disorder (MDD), Anxiety Disorders (ANX), and Posttraumatic Stress Disorder (PTSD) has hindered the study of their structural neural correlates. The authors analyzed specific and common grey matter volume (GMV) characteristics by comparing them with healthy controls (HC). The meta-analysis of voxel-based morphometry (VBM) studies showed unique GMV diminutions for each disorder (p < 0.05, corrected) and less robust smaller GMV across diagnostics (p < 0.01, uncorrected). Pairwise comparison between the disorders showed GMV differences in MDD versus ANX and in ANX versus PTSD. These results endorse the hypothesis that unique clinical features characterizing MDD, ANX, and PTSD are also reflected by disorder specific GMV correlates.

Pattern of psychiatric in-patient admissions in Al Ain, United Arab Emirates.

An understanding of the current state of mental health services in the United Arab Emirates (UAE) from a clinical perspective is an important step in advising government and stakeholders on addressing the mental health needs of the fast-growing population. We conducted a retrospective study of data on all patients admitted to a regional psychiatric in-patient unit between June 2012 and May 2015. More Emiratis (UAE nationals) were admitted compared with expatriates. Emiratis were diagnosed more frequently with substance use disorders and expatriates with stress-related conditions. Psychotic and bipolar disorders were the most common causes for admission and had the longest in-patient stays; advancing age was associated with longer duration of in-patient stay.