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Patients with pregnancy-associated secondary brain tumors (PASBT) are challenging to manage. Because no guidelines for the management of such patients currently exist, we performed a systematic review of the literature using PRISMA guidelines with a discussion of management from a neurosurgeon’s perspective.
Systematic review of the literature using PRISMA guidelines from 1999 to 2018.
We identified 301 studies of which 16 publications (22 patients reporting 25 pregnancies, 20 deliveries, 5 early terminations) were suitable for final analysis. The most frequent primary cancers were breast (8/22, 36.36%), skin (6/22, 27.27%), and lung (5/22, 22.73%). Four patients (18.18%) had neurosurgical procedures during their pregnancies. Five patients (22.73%) received neurosurgical resection after their pregnancies. Nine patients (40.91%) received radiation therapy and seven patients (31.82%) received chemotherapy during pregnancy while seven patients (31.82%) received chemotherapy and radiation after pregnancy. There was 1 fetal death (5%) out of 20 healthy deliveries. Five pregnancies (20%) were terminated in the first trimester due to a need for urgent neurosurgical intervention.
Management of PASBT remains a challenging issue. Maternal and fetal risks associated with surgical resection and teratogenicity due to adjuvant therapy should be discussed in the context of a multidisciplinary team. Timing of surgery and the use of systemic chemoradiation depends on the gestational age (GA) of the fetus, extent, and control of the mother’s primary and metastatic disease. Guidelines need to be established to help neuro-oncology teams safely and effectively manage this group of patients.
Since the beginning of 2020, the COVID-19 pandemic has dramatically influenced almost every aspect of human life. Activities requiring human gatherings have either been postponed, cancelled, or held completely virtually. To supplement lack of in-person contact, people have increasingly turned to virtual settings on-line, advantages of which include increased inclusivity and accessibility and reduction of carbon footprint. However, emerging online technologies cannot fully replace, in-person scientific events. In-person meetings are not susceptible to poor internet connectivity problems, and they provide novel opportunities for socialization, creating new collaborations, and sharing ideas. To continue such activities, a hybrid model for scientific events could be a solution offering both in-person and virtual components. While participants can freely choose the mode of their participation, virtual meetings would most benefit those who cannot attend in-person due to the limitations. In-person portions of meetings should be organized with full consideration of prevention and safety strategies including risk assessment and mitigation, venue and environmental sanitation, participant protection and disease prevention, and promoting the hybrid model. This new way of interaction between scholars can be considered as a part of a resilience system which was neglected previously and should become a part of routine practice in scientific community.
Echinoderms make up a substantial component of Ordovician marine invertebrates, yet their speciation and dispersal history as inferred within a rigorous phylogenetic and statistical framework is lacking. We use biogeographic stochastic mapping (BSM; implemented in the R package BioGeoBEARS) to infer ancestral area relationships and the number and type of dispersal events through the Ordovician for diploporan blastozoans and related species. The BSM analysis was divided into three time slices to analyze how dispersal paths changed before and during the great Ordovician biodiversification event (GOBE) and within the Late Ordovician mass extinction intervals. The best-fit biogeographic model incorporated jump dispersal, indicating this was an important speciation strategy. Reconstructed areas within the phylogeny indicate the first diploporan blastozoans likely originated within Baltica or Gondwana. Dispersal, jump dispersal, and sympatry dominated the BSM inference through the Ordovician, while dispersal paths varied in time. Long-distance dispersal events in the Early Ordovician indicate distance was not a significant predictor of dispersal, whereas increased dispersal events between Baltica and Laurentia are apparent during the GOBE, indicating these areas were important to blastozoan speciation. During the Late Ordovician, there is an increase in dispersal events among all paleocontinents. The drivers of dispersal are attributed to oceanic and epicontinental currents. Speciation events plotted against geochemical data indicate that blastozoans may not have responded to climate cooling events and other geochemical perturbations, but additional data will continue to shed light on the drivers of early Paleozoic blastozoan speciation and dispersal patterns.
OBJECTIVES/GOALS: Lupus lesional skin has elevated interferon expression, is highly colonized with Staphylococcus aureus (50%) and has no FDA-approved treatment options. We decided to investigate the effect of topical antibiotics on lupus lesional skin to determine whether it affects inflammatory gene expression. METHODS/STUDY POPULATION: Adult Systemic Lupus Erythematosus (SLE) patients with skin inflammation were recruited for this study from the Michigan Lupus cohort. All patients gave informed consent approved by the University of Michigan IRB. Lesions were swabbed for S. aureus colonization and then skin biopsies were collected from the affected area. Patients were then randomized for either mupirocin treatment or VaselineTM as the control. Product was applied to the lesion thrice daily for 7 days and swab samples and biopsies were collected again. Biopsies were saved at −80 °C. RNA was isolated from the biopsies, checked for quality and RNA-sequencing was performed to determine transcriptomic changes. RESULTS/ANTICIPATED RESULTS: Our preliminary results indicate that a higher number of genes are differentially expressed (DEGs) following treatment with mupirocin (184) than VaselineTM (133). Interestingly the DEGs from the two treatments were almost completely independent with only a few that were DE in both treatments when the data were fitted to a scatter plot. Functional enrichment analysis of the data showed significant downregulation of cytokine and chemokine pathways in the mupirocin but not the VaselineTM treatment group. DISCUSSION/SIGNIFICANCE OF IMPACT: Our preliminary data suggests that inflammatory signaling can be reduced in lesional skin by reducing bacterial load by topical antibiotic treatment in lupus patients. This can be particularly helpful in patients who are recalcitrant to typical treatment protocols for skin inflammation. CONFLICT OF INTEREST DESCRIPTION: J.M.K. received research funding from Celgene and serves on advisory boards for AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, and Eli Lilly and J.E.G. received research funding from AbbVie, SunPharma, Celgene, and Genentech and serves on advisory boards for Novartis, AbbVie, and MiRagen. The other authors have no financial conflicts of interest.
Earlier studies examining structural brain abnormalities associated with cognitively derived subgroups were mainly cross-sectional in design and had mixed findings. Thus, we obtained cross-sectional and longitudinal data to characterize the extent and trajectory of brain structure abnormalities underlying distinct cognitive subtypes (“preserved,” “deteriorated,” and “compromised”) seen in psychotic spectrum disorders.
Data from 364 subjects (225 patients with psychotic conditions and 139 healthy controls) were first used to determine the relationship of cognitive subtypes with cross-sectional measures of subcortical volume and cortical thickness. To probe neurodevelopmental abnormalities, brain structure laterality was examined. To examine whether neuroprogressive abnormalities persist, longitudinal brain structural changes over 5 years were examined within a subset of 101 subjects. Subsequent discriminant analysis using the identified brain measures was performed on an independent subject group.
Cross-sectional comparisons showed that cortical thinning and limbic volume reductions were most widespread in “deteriorated” cognitive subtype. Laterality comparisons showed more rightward amygdala lateralization in “compromised” than “preserved” subtype. Longitudinal comparisons revealed progressive hippocampal shrinkage in “deteriorated” compared with healthy controls and “preserved” subtype, which correlated with worse negative symptoms, cognitive and psychosocial functioning. Post-hoc discrimination analysis on an independent group of 52 subjects using the identified brain structures found an overall accuracy of 71% for classification of cognitive subtypes.
These findings point toward distinct extent and trajectory of corticolimbic abnormalities associated with cognitive subtypes in psychosis, which can allow further understanding of the biological course of cognitive functioning over illness course and with treatment.
The electronic Schizophrenia Treatment Adherence Registry (e-STAR) is a prospective, observational study of patients with schizophrenia designed to evaluate long-term treatment outcomes in routine clinical practice.
Parameters were assessed at baseline and at 3 month intervals for 2 years in patients initiated on risperidone long-acting injection (RLAI) (n = 1345) or a new oral antipsychotic (AP) (n = 277; 35.7% and 36.5% on risperidone and olanzapine, respectively) in Spain. Hospitalization prior to therapy was assessed by a retrospective chart review.
At 24 months, treatment retention (81.8% for RLAI versus 63.4% for oral APs, p < 0.0001) and reduction in Clinical Global Impression Severity scores (−1.14 for RLAI versus −0.94 for APs, p = 0.0165) were significantly higher with RLAI. Compared to the pre-switch period, RLAI patients had greater reductions in the number (reduction of 0.37 stays per patient versus 0.2, p < 0.05) and days (18.74 versus 13.02, p < 0.01) of hospitalizations at 24 months than oral AP patients.
This 2 year, prospective, observational study showed that, compared to oral antipsychotics, RLAI was associated with better treatment retention, greater improvement in clinical symptoms and functioning, and greater reduction in hospital stays and days in hospital in patients with schizophrenia. Improved treatment adherence, increased efficacy and reduced hospitalization with RLAI offer the opportunity of substantial therapeutic improvement in schizophrenia.
To examine the effectiveness of an Internet Based Therapy (IBT) for Bulimia Nervosa (BN), when compared to a brief psychoeducational group therapy (PET) or a waiting list (WL).
93 female BN patients, diagnosed according to DSM-IV criteria. An experimental group (31 IBT patients) was compared to two groups (31 PET and 31 WL). PET and WL were matched to the IBT group in terms of age, disorder duration, previous treatments and severity. All patients completed assesment, prior and after treatment.
Considering IBT, mean scores were lower at the end of treatment for some EDI scales and BITE symptoms scale, while the mean BMI was higher at post-therapy. Main predictors of good IBT outcome were higher scores in EDI perfectionism and higher scores on reward dependence. Drop-out was related to higher SCL-obsessive/compulsive (p=0.045) and novelty seeking (p=0.044) scores and lower reward dependence (p=0.018). At the end of the treatment bingeing and vomiting abstinence rates (22.6% for IBT, 33.3% for PET, and 0.0% for WL; p=0.003) and drop-out rates (35.5% IBT, 12.9% PET and 0% WL; p= 0.001) differed significantly between groups. While the concrete comparison between the two treatments (IBT and PET) did not evidence significant differences for success proportions (p=0.375), statistical differences for drop-out rates (p=0.038) were obtained.
The results of this study suggest that an online self-help approach appears to be a valid treatment option for BN, especially for people who present lower severity of their eating disorder (ED) symptomatology and some specific personality traits.
Assess clinical and functioning treatment outcomes of risperidone long-acting injection (RLAI) versus oral antipsychotics for patients participating in the electronic Schizophrenia Treatment Adherence Registry (e-STAR) in Spain.
e-STAR is a 2-year, multi-national, prospective, observational study of patients with schizophrenia who were initiated on RLAI or an oral antipsychotic. Data were collected retrospectively (1-year) and prospectively every three months (2 years). Outcomes included clinical effectiveness measured by Clinical Global Impression of Illness Severity (CGI-S) and patient functioning assessed by Global Assessment of Functioning (GAF) scale. Clinical and functional outcomes are analyzed using a linear mixed model controlling for age, gender, disease duration, baseline hospitalization status and antipsychotic treatment patterns. Results presented are based on the complete e-STAR data from Spain.
1,622 patients (63.6% male, mean age 38.4±11.2 years) participated in e-STAR from Spain, 1,345 were initiated on RLAI and 277 on oral antipsychotics. RLAI treated patients had significantly longer disease duration (12.6±9.5 years vs. 10.9±9.7, p<0.01) than those treated with oral antipsychotics. During the 2-year study, clinical symptoms and functioning improved in both groups. As revealed by the mixed-model regression, RLAI patients, compared to oral patients, had significantly greater improvement on CGI-S scores (-1.10 vs. -0.88, p<0.02) and GAF scores (16.4 vs. 14.6, p<0.03). Baseline hospitalization status and disease duration were significant explanatory variables in the mixed model regression.
This 2-year, prospective, observational study showed that compared to oral antipsychotics, RLAI treatment was associated with greater improvement in clinical symptoms and functioning in patients with schizophrenia.
To evaluate patient and physician satisfaction with risperidone long-acting injection (RLAI) in patients with schizophrenia enrolled in the electronic Schizophrenia Treatment Adherence Registry (e-STAR) in Belgium.
e-STAR is an ongoing, international, prospective, observational study of patients with schizophrenia who start RLAI during their routine clinical management. Treatment satisfaction was assessed by the patient and physician on a 5-point scale from ‘very good’ to ‘very bad’.
135 patients with mean age 40.9±14 years and duration of illness 9.5±9.2 years initiated treatment with RLAI, followed-up for at least 18 months were included in this analysis. At baseline, only 29.2% of patients expressed “good” or “very good” satisfaction while 21.1% of them expressed “bad” or “very bad” with their previous treatment. Similarly at baseline, 38.2% of physicians reported “good” or “very good” level of satisfaction and 14.6% rated their satisfaction as “bad” or “very bad” at that time. After initiation of RLAI, both patient and physician satisfaction with treatment improved dramatically. At 18 months, 76.5% of patients were satisfied (‘good’ or ‘very good’) with RLAI treatment and only 2.4% felt ‘bad’ and none reported ‘very bad’. Physicians also expressed satisfaction with RLAI with 82.1% of them rated it as ‘good’ or ‘very good’. Only one physician reported satisfaction below ‘moderate’.
The low levels of patient and physician satisfaction with treatment prior to RLAI are likely to be a key decision driver to change therapy. After starting treatment with RLAI, both patient and physician satisfaction with the treatment substantially improved.
Evaluate impact of risperidone long-acting injection (RLAI) versus oral antipsychotics on hospitalization outcomes for patients in the electronic Schizophrenia Treatment Adherence Registry (e-STAR) in Spain.
e-STAR is a 2-year, multi-national, prospective, observational study of patients with schizophrenia who initiated on RLAI or an oral antipsychotic. Hospitalization outcomes including number of hospitalizations and number of days in hospital were collected retrospectively (1-year) and prospectively (2 years). Changes in hospital stays and days in hospital were compared between RLAI and oral patients using linear mixed model controlling for age, gender, disease duration, and baseline antipsychotic use patterns.
1,622 patients (63.6% male, mean age 38.4±11.2 years) participated in e-STAR from Spain, 1,345 initiated on RLAI and 277 on oral antipsychotics. RLAI patients had significantly longer disease duration (12.6±9.5 years vs. 10.9±9.7 in oral patients, p<0.01). Average hospital stay at baseline was 5 days longer for RLAI than oral patients. During the study, both treatments showed reductions in mean number of hospitalizations and mean number of days in hospital. Based on the mixed-model regression, RLAI patients, compared to oral patients, had a significantly greater reduction in mean number of hospitalizations (-0.28 vs. -0.18 in followup-year1 and -0.37 vs. -0.20 in followup-year2, p<0.05) and mean number of days in hospital (-17.23 vs. -12.96 in followup-year1 and -18.75 vs. -12.99 in followup-year2, p<0.01).
This 2-year, prospective, observational study showed that compared to oral antipsychotics, RLAI treatment was associated with greater reduction in hospital stays and days in hospital in patients with schizophrenia.
Assess illness remission in patients with schizophrenia enrolled in the electronic-Schizophrenia Treatment Adherence Registry (e-STAR) in Czech Republic and Slovakia.
e-STAR is a secure web-based, ongoing, international, long-term observational study of patients with schizophrenia who initiate RLAI during routine clinical management. Data is collected retrospectively (1 year) and prospectively (2 years). Prospectively patients are evaluated for the following symptoms: delusions, conceptual disorganization, hallucinatory behaviour, mannerisms and posturing, unusual thought content, blunted affect, passive/apathetic social withdrawal, and lack of spontaneity and flow of conversation. Patients in whom all of these symptoms are absent, minimal or mild and within normal boundaries, stable, and do not interfere with thinking, social relations, and behaviour or functioning, were considered to be in cross-sectional remission and if this persisted for at least 6 months, they were considered to be in remission.
1,068 patients have been enrolled into e-STAR in Czech Republic and Slovakia; 280 patients have been followed for at least 12-months and were included. The majority were male (57.9%) with a diagnosis of schizophrenia or schizoaffective disorder (85.7%, 14.3% respectively) with a mean age of 37±12.1 years and a mean time since diagnosis of 9.2±9 years. The proportion of patients who met the criteria for cross-sectional remission increased from 2.4% at baseline to 37.9% at 12 months. After 12-months, 20.6% of patients met the criteria for illness remission.
Based on 12-month interim results, the proportion of patients who met the criteria for illness remission increased after initiating RLAI.
The existing literature on chronic pain points to the effects anxiety sensitivity, pain hypervigilance, and pain catastrophizing on pain-related fear; however, the nature of the relationships remains unclear. The three dispositional factors may affect one another in the prediction of pain adjustment outcomes. The addition of one disposition may increase the association between another disposition and outcomes, a consequence known as suppressor effects in statistical terms.
This study examined the possible statistical suppressor effects of anxiety sensitivity, pain hypervigilance and pain catastrophizing in predicting pain-related fear and adjustment outcomes (disability and depression).
Chinese patients with chronic musculoskeletal pain (n = 401) completed a battery of assessments on pain intensity, depression, anxiety sensitivity, pain vigilance, pain catastrophizing, and pain-related fear. Multiple regression analyses assessed the mediating/moderating role of pain hypervigilance. Structural equation modeling (SEM) was used to evaluate suppression effects.
Our results evidenced pain hypervigilance mediated the effects of anxiety sensitivity (Model 1: Sobel z = 4.86) and pain catastrophizing (Model 3: Sobel z = 5.08) on pain-related fear. Net suppression effect of pain catastrophizing on anxiety sensitivity was found in SEM where both anxiety sensitivity and pain catastrophizing were included in the same full model to predict disability (Model 9: CFI = 0.95) and depression (Model 10: CFI = 0.93) (all P < 0.001) (see Figs. 3 and 4, Figs. 1 and 2).
Our findings evidenced that pain hypervigilance mediated the relationship of two dispositional factors, pain catastrophic cognition and anxiety sensitivity, with pain-related fear. The net suppression effects of pain catastrophizing suggest that anxiety sensitivity enhanced the effect of pain catastrophic cognition on pain hypervigilance.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Over 50% of adult disability claimants fail some form of SVT. While some over report psychological, affective symptoms, others may report incredible cognitive symptoms. We examined effects of different types of response bias on free recall and self-reported depression.
Participants and methods This is a single site cross-sectional study using a convenience sample (n = 224) of disability claimants in the Netherlands. The Green Word Memory Test (GWMT) was administered to all subjects. The Amsterdam Short Term Memory Test (AKTG), the Structured Inventory of Malingered. Symptomatology (SIMS), and the beck depression inventory (BDI-II) were administered in subsamples. Participant classification according to GWMT and SIMS outcomes resulted in four groups, G+/S+, G+/S−, G−/S+ and G−/S−.
Average age of the participants was 46.3 years (SD 9.9), 41.5% were female, and 43% were higher educated. GWMT was positive in 48.2% of all subjects, and 27.6% scored positive on both GWMT and SIMS. Analysis of variance of GWMT Free recall and Beck depression scores showed significant group differences [F(3, 123) = 33.21, P = .000] and [F(3, 106) = 25.17, P = .000] respectively.
Non credible test performance was prevalent in this Dutch study of disability claimants. Insufficient effort and over reporting of psychological symptoms are associated with different score profiles on regular tests and self-rating scales.
Disclosure of interest
The author receives funding for his work as a neuropsychologist in an expertise setting.
A body of evidence has accrued supporting the Fear-Avoidance Model (FAM) of chronic pain which postulated the mediating role of pain-related fear in the relationships between pain catastrophizing and pain anxiety in affecting pain-related outcomes. Yet, relatively little data points to the extent to which the FAM be extended to understand chronic pain in Chinese population and its impact on quality of life (QoL).
This study explored the relationships between FAM components and their effects on QoL in a Chinese sample.
A total of 401 Chinese patients with chronic musculoskeletal pain completed measures of three core FAM components (pain catastrophizing, pain-related fear, and pain anxiety) and QoL. Cross-sectional structural equation modeling (SEM) assessed the goodness of fit of the FAM for two QoL outcomes, Physical (Model 1) and Mental (Model 2). In both models, pain catastrophizing was hypothesized to underpin pain-related fear, thereby influencing pain anxiety and subsequently QoL outcomes.
Results of SEM evidenced adequate data-model fit (CFI30.90) for the two models tested (Model 1: CFI = 0.93; Model 2: CFI = 0.94). Specifically, pain catastrophizing significantly predicted pain-related fear (Model 1: stdb = 0.90; Model 2: stdb = 0.91), which in turn significantly predicted pain anxiety (Model 1: stdb = 0.92; Model 2: stdb = 0.929) and QoL outcomes in a negative direction (Model 1: stdb = −0.391; Model 2: stdb = −0.651) (all P < 0.001) (Table 1, Fig. 1).
Our data substantiated the existing FAM literature and offered evidence for the cross-cultural validity of the FAM in the Chinese population with chronic pain.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Valid assessments require sufficient effort from the part of the testee. Motivation may be compromised, particularly in psychiatric conditions. We examined associations between response bias on free recall and self-reported symptoms in depressed and PTSD patients.
Participants and methods
This is a cross-sectional study. Patients had depression (n = 48), or PTSD or other anxiety disorders (n = 37). A control group (n = 47%) had chronic pain disorder, fibromyalgia or chronic fatigue. The Green Word Memory Test (GWMT) was administered to all subjects. The Structured Inventory of Malingered. Symptomatology (SIMS), and the Beck Depression Inventory (BDI-II) were administered in subsamples. Study outcome was self-reported depressive symptoms in Symptom Validity Test (SVT) negative cases.
Average age of the participants was 45.1 years (SD 9.5), 48.5% were female. GWMT was positive in 52.3% of all cases, GWMT and SIMS were positive in 33.8%, and GWMT and SIMS were negative in 37.7%. No significant group effects on GWMT were found. Average BDI-II scores were 32.8 (SD 13.9) for depressed patients, 28.3 (15.5) for those with anxiety disorders, and 27.6 (14.1) for controls (P = 0.43). Seventy-eight percent of depressed GWMT negative cases reported at least moderate depressive symptoms (BDI-II > 18), and 44.4% severe symptoms (BDI-II > 29). Approximately half of the GWMT negative cases with anxiety disorders and controls scored BDI-II > 18.
Non credible test performance is prevalent in disability claimants with affective, mood disorders. However, depressive symptoms per se do not explain poor effort on cognitive tasks.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
In China, one percent of the richest population holds more than one-third of the wealth, while the poorest 25% shares no more than two percent of the total. The country’s rapid economic development has resulted in increasing socio-economic disparities, and a rapidly deteriorating environment. This puts the Chinese citizens, especially the most vulnerable and deprived socio-economic status (SES) groups, at high risks of environmental inequality (EI). In most SES-based EI studies conducted in China, household wealth has often been overlooked, though it potentially serves a good economic indicator to capture the socio-economic effect of environmental change in China. Nevertheless, existing SES databases in China are of low spatial resolution and are insufficient to support fine-grained EI studies at the intra-city level in China. The core research challenge is to develop a representative household wealth proxy in high-spatial resolution for China. This study highlights the research gaps and proposes a new household wealth proxy, which integrates both fine-grained data/features such as daytime satellite imagery and easily accessible wealth indicators such as house prices. We also capitalize on everyday economic activity data retrieved from personal mobile phones and online transaction/social platforms in the composition of our wealth proxy to achieve a higher accuracy in estimating household wealth at fine-grained resolution via machine learning. Finally, we summarize the challenges in improving both the quality and the availability of Chinese socio-economic datasets, while protecting personal privacy and information security during the data collection process for household wealth proxy development in China.
Twins Research Australia (TRA) is a community of twins and researchers working on health research to benefit everyone, including twins. TRA leads multidisciplinary research through the application of twin and family study designs, with the aim of sustaining long-term twin research that, both now and in the future, gives back to the community. This article summarizes TRA’s recent achievements and future directions, including new methodologies addressing causation, linkage to health, economic and educational administrative datasets and to geospatial data to provide insight into health and disease. We also explain how TRA’s knowledge translation and exchange activities are key to communicating the impact of twin studies to twins and the wider community. Building researcher capability, providing registry resources and partnering with all key stakeholders, particularly the participants, are important for how TRA is advancing twin research to improve health outcomes for society. TRA provides researchers with open access to its vibrant volunteer membership of twins, higher order multiples (multiples) and families who are willing to consider participation in research. Established four decades ago, this resource facilitates and supports research across multiple stages and a breadth of health domains.
Studies show that vitamin D (vit-D) (25(OH)D), the bioactive metabolite (1,25(OH)2D3) and vit-D receptors (vit-D receptor; protein disulphide isomerase, family A member 3) are expressed throughout the brain, particularly in regions pivotal to learning and memory. This has led to the paradigm that avoiding vit-D deficiency is important to preserve cognitive function. However, presently, it is not clear if the common clinical measure of serum 25(OH)D serves as a robust surrogate marker for central nervous system (CNS) homeostasis or function. Indeed, recent studies report CNS biosynthesis of endogenous 25(OH)D, the CNS expression of the CYP group of enzymes which catalyse conversion to 1,25(OH)2D3 and thereafter, deactivation. Moreover, in the periphery, there is significant ethnic/genetic heterogeneity in vit-D conversion to 1,25(OH)2D3 and there is a paucity of studies which have actually investigated vit-D kinetics across the cerebrovasculature. Compared with peripheral organs, the CNS also has differential expression of receptors that trigger cellular response to 1,25(OH)2D3 metabolites. To holistically consider the putative association of peripheral (blood) abundance of 25(OH)D on cognitive function, herein, we have reviewed population and genetic studies, pre-clinical and clinical intervention studies and moreover have considered potential confounders of vit-D analysis.
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.
Low socioeconomic status (SES) has been established as a risk factor for poor mental health; however, the relationship between SES and mental health problems can be confounded by genetic and environmental factors in standard regression analyses and observational studies of unrelated individuals. In this study, we used a within-pair twin design to control for unmeasured genetic and environmental confounders in investigating the association between SES and psychological distress. We also employed within–between pair regression analysis to assess whether the association was consistent with causality. SES was measured using the Index of Relative Socio-economic Disadvantage (IRSD), income and the Australian Socioeconomic Index 2006 (AUSEI06); psychological distress was measured using the Kessler 6 Psychological Distress Scale (K6). Data were obtained from Twins Research Australia’s Health and Lifestyle Questionnaire (2014–2017), providing a maximum sample size of 1395 pairs. Twins with higher AUSEI06 scores had significantly lower K6 scores than their co-twins after controlling for shared genetic and environmental traits (βW [within-pair regression coefficient] = −0.012 units, p = .006). Twins with higher income had significantly lower K6 scores than their co-twins after controlling for familial confounders (βW = −0.182 units, p = .002). There was no evidence of an association between the IRSD and K6 scores within pairs (βW, p = .6). Using a twin design to eliminate the effect of potential confounders, these findings further support the association between low SES and poor mental health, reinforcing the need to address social determinants of poor mental health, in addition to interventions targeted to individuals.