The one and the many: a case highlighting comorbidity and complexity in psychiatry

Diagnostic categorisation is a typical stage of the medical model. Nevertheless, it is important to consider what is helpful to both the clinician and the patient when symptoms, experiences and perceptions are categorised. In this case report, we address the problem of comorbidity and complexity in psychiatry. Research and clinical experience point to significant overlap between personality disorders, mood disorders, and developmental disorders such as attention-deficit hyperactivity disorder. In the face of such complexity, we discuss ways of addressing and managing multiple diagnoses in clinical practice. We synthesise the perspectives and views of a general practice trainee, two consultant psychiatrists and a person with lived experience

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

© The Author(s) 2020. 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

Regional default mode network connectivity in major depressive disorder

The relationship between altered default mode network (DMN) connectivity and abnormal serotonin function in major depressive disorder (MDD) has not been investigated. Using intravenous citalopram and resting-state fMRI, we investigated DMN intra-network connectivity and serotonin function in 77 healthy controls and patients with MDD. There were no significant main effects of MDD or citalopram on DMN intra-network connectivity; however, significant interactions indicated that group differences under saline were modified by citalopram. In MDD patients during saline infusion, in contrast with controls, the DMN (i) did not include the precuneus that was instead part of an anti-correlated network but (ii) did include amygdala that was part of the anti-correlated network in controls. Citalopram infusion in MDD patients restored the pattern seen in controls under saline. In healthy controls, citalopram infusion disengaged the precuneus from the DMN and engaged the amygdala, partially reproducing the abnormalities seen under saline in MDD. In exploratory analyses within the MDD group, greater rumination self-ratings were associated with greater intra-network connectivity of the anterior cingulate cortex with the DMN. We hypothesise that, in MDD, disengagement of the precuneus from the DMN relates to overgeneral memory bias in rumination. The opposite effect, with greater engagement of the amygdala in the DMN, reflects the negative valence of rumination. Reversal of these abnormalities by citalopram suggests that they may be related to impaired serotonin function. That citalopram engaged the amygdala in the DMN in controls may relate to the paradoxical effects on aversive processing seen with acute SSRIs in healthy subjects

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

Child maltreatment and neglect in the United Arab Emirates and relationship with low self-esteem and symptoms of depression

Objectives: To our knowledge, this study is the first in the United Arab Emirates (UAE) to investigate the prevalence of child maltreatment in relation to depressive symptoms and self-esteem.Study design: Exposure to physical maltreatment, emotional abuse and neglect was evaluated in 518 adolescents (86% response rate) randomly selected from schools in Al Ain in the Emirate of Abu Dhabi. The Rosenberg self-esteem scale and the Beck Depression Inventory were used to measure self-esteem and depressive symptoms by using multivariate logistic regression analyses.Results: The mean age of study participants was 14.3 years. Emotional abuse was the most frequent form of maltreatment (33.9%), physical abuse (12.6%) and neglect (12.1%) followed. Male sex was a positive predictor of physical abuse (OR = 2.12; 95% CI 1.18-3.77), whilst higher maternal level of education was protective (OR = 0.40; 95% CI 0.19-0.86). Daily screen time (OR = 2.77; 95% CI 1.17-6.56) and tobacco smoking (OR = 1.86; 95% CI 1.09-3.18) positively predicted emotional abuse. Emotionally maltreated and neglected participants were less likely to report high level of self-esteem and more likely to report symptoms of depression.Conclusions: Child maltreatment in the UAE is of a similar magnitude to what reported in other countries around the world and significantly associated with low self-esteem and depressive symptoms

Meta-analysis of regional white matter volume in bipolar disorder with replication in an independent sample using coordinates, T-maps, and individual MRI data

Converging evidence suggests that bipolar disorder (BD) is associated with white matter (WM) abnormalities. Meta-analyses of voxel based morphometry (VBM) data is commonly performed using published coordinates, however this method is limited since it ignores non-significant data. Obtaining statistical maps from studies (T-maps) as well as raw MRI datasets increases accuracy and allows for a comprehensive analysis of clinical variables. We obtained coordinate data (5-studies), T-Maps (12-studies, including unpublished data) and raw MRI datasets (5-studies) and analysed the 24 studies using Seed-based d Mapping (SDM). A VBM analysis was conducted to verify the results in an independent sample. The meta-analysis revealed decreased WM volume in the posterior corpus callosum extending to WM in the posterior cingulate cortex. This region was significantly reduced in volume in BD patients in the independent dataset (p=0.003) but there was no association with clinical variables. We identified a robust WM volume abnormality in BD patients that may represent a trait marker of the disease and used a novel methodology to validate the findings

Focusing on Comorbidity A Novel Meta-Analytic Approach and Protocol to Disentangle the Specific Neuroanatomy of Co-occurring Mental Disorders

Background: In mental health, comorbidities are the norm rather than the exception. However, current meta-analytic methods for summarizing the neural correlates of mental disorders do not consider comorbidities, reducing them to a source of noise and bias rather than benefitting from their valuable information. Objectives: We describe and validate a novel neuroimaging meta-analytic approach that focuses on comorbidities. In addition, we present the protocol for a meta-analysis of all major mental disorders and their comorbidities. Methods: The novel approach consists of a modification of Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) in which the linear models have no intercept. As in previous SDM meta-analyses, the dependent variable is the brain anatomical difference between patients and controls in a voxel. However, there is no primary disorder, and the independent variables are the percentages of patients with each disorder and each pair of potentially comorbid disorders. We use simulations to validate and provide an example of this novel approach, which correctly disentangled the abnormalities associated with each disorder and comorbidity. We then describe a protocol for conducting the new meta-analysis of all major mental disorders and their comorbidities. Specifically, we will include all voxel-based morphometry (VBM) studies of mental disorders for which a meta-analysis has already been published, including at least 10 studies. We will use the novel approach to analyze all included studies in two separate single linear models, one for children/adolescents and one for adults. Discussion: The novel approach is a valid method to focus on comorbidities. The meta-analysis will yield a comprehensive atlas of the neuroanatomy of all major mental disorders and their comorbidities, which we hope might help develop potential diagnostic and therapeutic tools

A leaky umbrella has little value: evidence clearly indicates the serotonin system is implicated in depression.

A recent “umbrella” review examined various biomarkers relating to the serotonin system, and concluded there was no consistent evidence implicating serotonin in the pathophysiology of depression. We present reasons for why this conclusion is overstated, including methodological weaknesses in the review process, selective reporting of data, over-simplification, and errors in the interpretation of neuropsychopharmacological findings. We use the examples of tryptophan depletion and serotonergic molecular imaging, the two research areas most relevant to the investigation of serotonin, to illustrate this