Resting-state fMRI is associated with trauma experiences, mood and psychosis in Afro-descendants with bipolar disorder and schizophrenia.

BACKGROUND: Bipolar disorder (BD) and schizophrenia (SCZ) may exhibit functional abnormalities in several brain areas, including the medial temporal and prefrontal cortex and hippocampus; however, a less explored topic is how brain connectivity is linked to premorbid trauma experiences and clinical features in non-Caucasian samples of SCZ and BD. METHODS: Sixty-two individuals with SCZ (n = 20), BD (n = 21), and healthy controls (HC, n = 21) from indigenous and African ethnicity were submitted to clinical screening (Di-PAD), traumata experiences (ETISR-SF), cognitive and functional MRI assessment. The item psychosis/hallucinations in SCZ patients showed a negative correlation with the global efficiency (GE) in the right dorsal attention network. The items mania, irritable mood, and racing thoughts in the Di-PAD scale had a significant negative correlation with the GE in the parietal right default mode network. CONCLUSIONS: Differences in the activation of specific networks were associated with earlier disease onset, history of physical abuse, and more severe psychotic and mood symptoms in SCZ and BD subjects of indigenous and black ethnicity. Findings provide further evidence on SZ and BD's brain connectivity disturbances, and their clinical significance, in non-Caucasian samples.

The definition of treatment resistance in anxiety disorders: a Delphi method-based consensus guideline.

Anxiety disorders are very prevalent and often persistent mental disorders, with a considerable rate of treatment resistance which requires regulatory clinical trials of innovative therapeutic interventions. However, an explicit definition of treatment-resistant anxiety disorders (TR-AD) informing such trials is currently lacking. We used a Delphi method-based consensus approach to provide internationally agreed, consistent and clinically useful operational criteria for TR-AD in adults. Following a summary of the current state of knowledge based on international guidelines and an available systematic review, a survey of free-text responses to a 29-item questionnaire on relevant aspects of TR-AD, and an online consensus meeting, a panel of 36 multidisciplinary international experts and stakeholders voted anonymously on written statements in three survey rounds. Consensus was defined as ≥75% of the panel agreeing with a statement. The panel agreed on a set of 14 recommendations for the definition of TR-AD, providing detailed operational criteria for resistance to pharmacological and/or psychotherapeutic treatment, as well as a potential staging model. The panel also evaluated further aspects regarding epidemiological subgroups, comorbidities and biographical factors, the terminology of TR-AD vs. "difficult-to-treat" anxiety disorders, preferences and attitudes of persons with these disorders, and future research directions. This Delphi method-based consensus on operational criteria for TR-AD is expected to serve as a systematic, consistent and practical clinical guideline to aid in designing future mechanistic studies and facilitate clinical trials for regulatory purposes. This effort could ultimately lead to the development of more effective evidence-based stepped-care treatment algorithms for patients with anxiety disorders.

Medication Non-adherence in Depression: A Systematic Review and Metanalysis.

OBJECTIVE: Medication non-adherence is frequently reported in patients with major depressive disorder (MDD). The objective of this review is to consolidate data on the prevalence of non-adherence to antidepressant in MDD. METHODS: A systematic review with meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and the protocol was registered in PROSPERO under the number CRD42021199987. Studies assessing medication adherence in MDD were searched in PubMed/Medline, Embase, CINAHL (The Cumulative Index to Nursing and Allied Health Literature) and PsycINFO. The data extraction was performed by two independents authors. Meta-analysis used random effects model and performed a subgroup analysis. RESULTS: From the articles retrieved, eleven studies were considered eligible for the final analysis. Most of them assessed non-adherence by self-report scales, followed by Pharmacy Dispensation Records, Monitoring Events Medication System (MEMS) and blood tests. The pooled proportion of non-adherence was 42% (95% IC 30%-54%), but heterogeneity was very large (I2=99%). CONCLUSION: Data from the selected studies suggests that a high number of individuals with MDD do not adequately take their medication as prescribed. The high heterogenicity of measures used for the assessment of adherence may have impacted the great variability of the results. The results suggest it is necessary that health care professionals should address this issue in order to achieve a better treatment outcome in major depression.

A resource of induced pluripotent stem cell (iPSC) lines including clinical, genomic, and cellular data from genetically isolated families with mood and psychotic disorders.

Genome-wide (GWAS) and copy number variant (CNV) association studies have reproducibly identified numerous risk alleles associated with bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ), but biological characterization of these alleles lags gene discovery, owing to the inaccessibility of live human brain cells and inadequate animal models for human psychiatric conditions. Human-derived induced pluripotent stem cells (iPSCs) provide a renewable cellular reagent that can be differentiated into living, disease-relevant cells and 3D brain organoids carrying the full complement of genetic variants present in the donor germline. Experimental studies of iPSC-derived cells allow functional characterization of risk alleles, establishment of causal relationships between genes and neurobiology, and screening for novel therapeutics. Here we report the creation and availability of an iPSC resource comprising clinical, genomic, and cellular data obtained from genetically isolated families with BD and related conditions. Results from the first 324 study participants, 61 of whom have validated pluripotent clones, show enrichment of rare single nucleotide variants and CNVs overlapping many known risk genes and pathogenic CNVs. This growing iPSC resource is available to scientists pursuing functional genomic studies of BD and related conditions.

Treatment-Resistant Depression in America Latina study: one-year follow-up of treatment resistant depression patients under standard of care reveals insights on quality of life, disability, work impairment, and depressive symptoms.

Introduction: Depressive Disorders are on the rise worldwide. This is also the case in Latin America (LatAm). Treatment-Resistant Depressive Disorder (TRD) poses additional burden to patients with depression. Impacts quality of life (QoL) and other dimensions, and standard of care (SOC) is insufficient to achieve the desired clinical outcomes. Evidence from LatAm is, however, lacking. The present study was devised as a 1-year follow-up of the SOC in TRD patients in LatAm to explore the burden of TRD. Methods: This was an observational, multinational, longitudinal study. Patients with clinical diagnosis of TRD in LatAm were included in a 1-year follow-up with SOC. Beyond the Sociodemographic characterization, outcome measures were QoL (EQ-5D-5L), disability (Sheehan Disability Scale - SDS), work productivity (Work Productivity and Activity Incapacity Questionnaire: depression - WPAI:D) and depression severity (Patient Health Questionnaire-PHQ9). Patients were assessed every 3-months and comparison was performed based on change from baseline to each visit and end of study (EOS - 12 months). Results: Patients averaged 48 (± 13.12) years, mostly female (80.9%) and married/consensual union (42.5%) or single patients (34.4%). Despite the SOC treatment, three-quarters of the patients remained symptomatic at EOS, regardless of the significant longitudinal decrease (p ≤ 0.001). Similar trends were found for disability (p ≤ 0.001) -82.2% of the patients reporting work/school disruption at EOS-, percentage of work (34%) and activity impairment (40%) at EOS (p ≤ 0.001) and only 29.2% of patients with depressive severity "none" at EOS (p ≤ 0.001). The results portray the need to improve clinical outcomes in this complex and burdensome disease in LatAm. Discussion: Here we show that the burden of TRD remains significant in essential dimensions of everyday life at EOS underlining the need for better therapeutic solutions. The improvements in most patients do not provide the desired outcome of return to the state before the condition. Further research should focus on identifying which treatments provide better outcomes in a real-world context.

Brazilian Psychiatric Association guidelines for the treatment of generalized anxiety disorder (GAD). Pharmacological and Psychotherapy approach. Perspectives.

OBJECTIVE: To combine elements of a systematic review and critical review to produce best evidence synthesis for the treatament of GAD. METHOD: There was included systematic reviews, metanalysis, and randomized controlled trials. Descriptor used was "generalized anxiety disorder", resulting in 4860 articles and 7 other studies, of which 59 were selected. RESULTS: Antidepressants and benzodiazepines are indicated, as well as pregabalin. From, atypical antipsychotics quetiapine has been studied. Cognitive behavior therapy (third wave of behavioral and cognitive therapies) as well as individual CBT proven to be effective. CONCLUSION: There is extensive literature on many effective treatments for GAD. The present work summarizes the therapeutic possibilities, emphasizing those available in the Brazil. Further studies are still needed to compare other available medications, to assess psychotherapies in more depth, new treatments and specially to assess the ideal time for maintaining therapy.

An update on the pharmacotherapeutic strategies for the treatment of dysthymic disorder: a systematic review.

INTRODUCTION: Longer treatment times, more comorbidity, more severe impairments in social, psychological, and emotional functioning, increased healthcare use, and more hospitalizations are all factors that are related to dysthymia. Given the significant prevalence of dysthymia (including persistent depressive disorder) worldwide, its comorbidity with several mental disorders, and the detrimental effects of these comorbidities, it is important to conduct a systematic review to compare the effects of pharmacological acute and maintenance treatments for dysthymia with placebo and standard care in the last 10 years, based on the publication of DSM5. AREAS COVERED: This systematic review was performed according to PRISMA guidelines. Databases, including PubMed and Cochrane Central Register of Controlled Trials, were searched to assess the effects of pharmacological acute and maintenance treatments for dysthymia in comparison with placebo and treatment as usual. EXPERT OPINION: Our review shows that SSRIs and SNRIs present efficacy for dysthymia treatment, and L-Acetylcarnitine should be investigated further for this condition in elderly patients. The comparison of antidepressant medication versus placebo showed coherent results based on three studies favoring pharmacotherapy as an effective treatment for participants with dysthymia. However, the scarcity of research on continuation and maintenance therapy in people with dysthymia highlights the need for more primary research.

Multidisciplinary contributions towards an evolutive interpretation of bipolar disorders: could it be the pathological drift of a potentially adaptive condition?

This paper tries to summarize the results of studies from different areas of knowledge supporting the idea that temperamental traits, such as "reckless/hyper-exploratory" attitudes, commonly believed to be associated with psychopathology, surprisingly turn out as adaptive under specific stress conditions. In particular, this paper analyzes an ethologic line of research on primates suggesting models for a sociobiological interpretation of mood disorders in humans; a study that found high frequencies of a genetic variance associated with bipolar disorder in people without bipolar disorder but with hyperactivity/novelty-seeking traits; the outcomes of socio-anthropological-historical surveys on the evolution of mood disorders in Western countries in the last centuries; surveys on changing societies in Africa and African migrants in Sardinia; and studies that found higher frequencies of mania and subthreshold mania among Sardinian immigrants in Latin American megacities. Although it is not unequivocally accepted that the prevalence of mood disorders has increased, it would be logical to suppose that a nonadaptive condition should have disappeared over time; mood disorders, on the contrary, persist and their prevalence might have even increased. This new interpretation could lead to counter discrimination and stigma towards people suffering from the disorder and would be a central point in psychosocial treatments in addition to pharmacological therapy. Our aim is to hypothesize that bipolar disorder, strongly characterized by these traits, may be the result of the interaction between genetic characteristics, not necessarily pathological, and specific environmental conditions rather than a mere product of an aberrant genetic profile. If mood disorders were mere nonadaptive conditions, they would have disappeared over time; however, their prevalence paradoxically persists if not even increases over time. The hypothesis that bipolar disorder may result from the interaction between genetic characteristics, not necessarily pathological, and specific environmental factors seems more credible than considering bipolar disorder as a mere product of an aberrant genetic profile.