Prospective and Retrospective Measures of Child Maltreatment and Their Association With Psychopathology: A Systematic Review and Meta-Analysis.

Importance: Prospective and retrospective measures of childhood maltreatment identify largely different groups of individuals. However, it is unclear if these measures are differentially associated with psychopathology. Objective: To analyze the associations of prospective and retrospective measures of childhood maltreatment with psychopathology. Data Sources: Based on a preregistered protocol, Embase, PsycInfo, and MEDLINE were searched for peer-reviewed studies published by January 1, 2023, that measured the associations of prospective and retrospective measures of child maltreatment with psychopathology. Study Selection: Titles and abstracts of all articles captured by the search and full texts of potentially eligible studies were independently screened by 2 authors. Observational studies with measures of the association of prospective and retrospective measures of childhood maltreatment with psychopathology were included. Data Extraction and Synthesis: Multiple investigators independently extracted data. Multilevel random-effects meta-analyses were used to pool the results and test predictors of heterogeneity. Main Outcome and Measures: Associations between prospective or retrospective measures of child maltreatment and psychopathology, both unadjusted and adjusted (ie, the association between prospective measures of maltreatment and psychopathology adjusted for retrospective measures, and vice versa), and moderation of these associations by preselected variables. Results: The meta-analyses were based on 24 studies including 15 485 individuals (51.0% female; mean age, 21.3 years at retrospective report). Retrospective measures of childhood maltreatment showed stronger associations with psychopathology relative to prospective measures in both unadjusted analyses (retrospective measures: odds ratio [OR], 2.21; 95%, 1.94-2.42 vs prospective measures: OR, 1.56; 95% CI, 1.39-1.76) and adjusted analyses (retrospective measures: OR, 2.14; 95% CI, 1.90-2.42 vs prospective measures: OR, 1.27; 95% CI, 1.13-1.41). There was no statistically significant moderation of the unadjusted or adjusted associations between prospective measures of child maltreatment and psychopathology. The associations between retrospective measures and psychopathology were stronger when the assessment of psychopathology was based on self-reports and was focused on internalizing or emotional disorders. Conclusions and Relevance: Psychopathology is more strongly associated with retrospective measures-which capture the first-person, subjective appraisal of childhood events reflected in memory recall-compared to prospective measures-which essentially capture third-person accounts of such events. Maltreatment-related psychopathology may be driven by subjective interpretations of experiences, distressing memories, and associated schemas, which could be targeted by cognitive interventions.

Mental health in Europe during the COVID-19 pandemic: a systematic review.

The COVID-19 pandemic caused immediate and far-reaching disruption to society, the economy, and health-care services. We synthesised evidence on the effect of the pandemic on mental health and mental health care in high-income European countries. We included 177 longitudinal and repeated cross-sectional studies comparing prevalence or incidence of mental health problems, mental health symptom severity in people with pre-existing mental health conditions, or mental health service use before versus during the pandemic, or between different timepoints of the pandemic. We found that epidemiological studies reported higher prevalence of some mental health problems during the pandemic compared with before it, but that in most cases this increase reduced over time. Conversely, studies of health records showed reduced incidence of new diagnoses at the start of the pandemic, which further declined during 2020. Mental health service use also declined at the onset of the pandemic but increased later in 2020 and through 2021, although rates of use did not return to pre-pandemic levels for some services. We found mixed patterns of effects of the pandemic on mental health and social outcome for adults already living with mental health conditions.

Subjective and objective experiences of childhood adversity: a meta-analysis of their agreement and relationships with psychopathology.

BACKGROUND: Researchers use both subjective self-report and objective measures, such as official records, to investigate the impact of childhood adversity on psychopathology. However, it is unclear whether subjective and objective measures of childhood adversity (a) show agreement, and (b) differentially predict psychopathology. METHOD: To address this, we conducted a pre-registered meta-analysis to examine the agreement between subjective and objective measures of childhood adversity, and their prediction of psychopathology. We searched in PubMed, PsycINFO and Embase for articles with both subjective measures (self-reports) and objective measures of childhood adversity (comprising official records, or reports from multiple informants unrelated to the target individual), and measures of psychopathology. RESULTS: We identified 22 studies (n = 18,163) with data on agreement between subjective and objective measures of childhood adversities, and 17 studies (n = 14,789) with data on the associations between subjective and objective measures with psychopathology. First, we found that subjective and objective measures of childhood adversities were only moderately correlated (e.g. for maltreatment, r = .32, 95% CI = 0.23-0.41). Second, subjective measures of childhood adversities were associated with psychopathology, independent of objective measures (e.g. for maltreatment, r = .16, 95% CI = 0.09-0.22). In contrast, objective measures of childhood adversities had null or minimal associations with psychopathology, independent of subjective measures (e.g. r for maltreatment = .06, 95% CI = -0.02-0.13). CONCLUSIONS: Our findings suggest that the effects of childhood adversity on psychopathology are primarily driven by a person's subjective experience. If this is the case, clinical interventions targeting memories and cognitive processes surrounding childhood adversity may reduce the risk of psychopathology in exposed individuals.

Clinical correlates of early onset antipsychotic treatment resistance.

BACKGROUND: There is evidence of heterogeneity within treatment-resistant schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and others becoming treatment-resistant after an initial response period. These groups may have different aetiologies. AIM: This study investigates sociodemographic and clinical correlates of early onset of TRS. METHOD: Employing a retrospective cohort design, we do a secondary analysis of data from a cohort of people with TRS attending the South London and Maudsley. Regression analyses were conducted to identify the correlates of the length of treatment to TRS. Predictors included the following: gender, age, ethnicity, problems with positive symptoms, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics. RESULTS: In a cohort of 164 people with TRS (60% were men), the median length of treatment to TRS was 3 years and 8 months. We observed no cut-off on the length of treatment until TRS presentation differentiating between early and late TRS (i.e. no bimodal distribution). Having mild to very severe problems with hallucinations and delusions at the treatment start was associated with earlier TRS (~19 months earlier). In sensitivity analyses, including only complete cases (subject to selection bias), treatment with a long-acting injectable antipsychotic was additionally associated with later TRS (~15 months later). CONCLUSION: Our findings do not support a clear separation between early and late TRS but rather a continuum of the length of treatment before TRS onset. Having mild to very severe problems with positive symptoms at treatment start predicts earlier onset of TRS.

A predictor model of treatment resistance in schizophrenia using data from electronic health records.

OBJECTIVES: To develop a prognostic tool of treatment resistant schizophrenia (TRS) in a large and diverse clinical cohort, with comprehensive coverage of patients using mental health services in four London boroughs. METHODS: We used the Least Absolute Shrinkage and Selection Operator (LASSO) for time-to-event data, to develop a risk prediction model from the first antipsychotic prescription to the development of TRS, using data from electronic health records. RESULTS: We reviewed the clinical records of 1,515 patients with a schizophrenia spectrum disorder and observed that 253 (17%) developed TRS. The Cox LASSO survival model produced an internally validated Harrel's C index of 0.60. A Kaplan-Meier curve indicated that the hazard of developing TRS remained constant over the observation period. Predictors of TRS were: having more inpatient days in the three months before and after the first antipsychotic, more community face-to-face clinical contact in the three months before the first antipsychotic, minor cognitive problems, and younger age at the time of the first antipsychotic. CONCLUSIONS: Routinely collected information, readily available at the start of treatment, gives some indication of TRS but is unlikely to be adequate alone. These results provide further evidence that earlier onset is a risk factor for TRS.

Using a statistical learning approach to identify sociodemographic and clinical predictors of response to clozapine.

BACKGROUND: A proportion of people with treatment-resistant schizophrenia fail to show improvement on clozapine treatment. Knowledge of the sociodemographic and clinical factors predicting clozapine response may be useful in developing personalised approaches to treatment. METHODS: This retrospective cohort study used data from the electronic health records of the South London and Maudsley (SLaM) hospital between 2007 and 2011. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression statistical learning approach, we examined 35 sociodemographic and clinical factors' predictive ability of response to clozapine at 3 months of treatment. Response was assessed by the level of change in the severity of the symptoms using the Clinical Global Impression (CGI) scale. RESULTS: We identified 242 service-users with a treatment-resistant psychotic disorder who had their first trial of clozapine and continued the treatment for at least 3 months. The LASSO regression identified three predictors of response to clozapine: higher severity of illness at baseline, female gender and having a comorbid mood disorder. These factors are estimated to explain 18% of the variance in clozapine response. The model's optimism-corrected calibration slope was 1.37, suggesting that the model will underfit when applied to new data. CONCLUSIONS: These findings suggest that women, people with a comorbid mood disorder and those who are most ill at baseline respond better to clozapine. However, the accuracy of the internally validated and recalibrated model was low. Therefore, future research should indicate whether a prediction model developed by including routinely collected data, in combination with biological information, presents adequate predictive ability to be applied in clinical settings.

Interplay between polygenic propensity for ageing-related traits and the consumption of fruits and vegetables on future dementia diagnosis.

BACKGROUND: Understanding how polygenic scores for ageing-related traits interact with diet in determining a future dementia including Alzheimer's diagnosis (AD) would increase our understanding of mechanisms underlying dementia onset. METHODS: Using 6784 population representative adults aged ≥50 years from the English Longitudinal Study of Ageing, we employed accelerated failure time survival model to investigate interactions between polygenic scores for AD (AD-PGS), schizophrenia (SZ-PGS) and general cognition (GC-PGS) and the baseline daily fruit and vegetable intake in association with dementia diagnosis during a 10-year follow-up. The baseline sample was obtained from waves 3-4 (2006-2009); follow-up data came from wave 5 (2010-2011) to wave 8 (2016-2017). RESULTS: Consuming < 5 portions of fruit and vegetables a day was associated with 33-37% greater risk for dementia in the following 10 years depending on an individual polygenic propensity. One standard deviation (1-SD) increase in AD-PGS was associated with 24% higher risk of dementia and 47% higher risk for AD diagnosis. 1-SD increase in SZ-PGS was associated with an increased risk of AD diagnosis by 66%(95%CI = 1.05-2.64) in participants who consumed < 5 portions of fruit or vegetables. There was a significant additive interaction between GC-PGS and < 5 portions of the baseline daily intake of fruit and vegetables in association with AD diagnosis during the 10-year follow-up (RERI = 0.70, 95%CI = 0.09-4.82; AP = 0.36, 95%CI = 0.17-0.66). CONCLUSION: A diet rich in fruit and vegetables is an important factor influencing the subsequent risk of dementia in the 10 years follow-up, especially in the context of polygenetic predisposition to AD, schizophrenia, and general cognition.

Employment and relationship outcomes in first-episode psychosis: A systematic review and meta-analysis of longitudinal studies.

As employment and relationship status are important long-term outcomes in individuals with a diagnosis of first episode psychosis (FEP) disorders, there is a need to elucidate more accurately the extent of these social deficits in people with FEP. This in turn can aid treatment planning and policy development ultimately ensuring more complete and sustainable recoveries. We carried out a systematic review and meta-analysis of longitudinal studies in FEP reporting on employment and relationship status during the illness course. Random effects meta-analyses and meta-regression analyses were employed. Seventy-four studies were included with a sample totalling 15,272 (range = 20-1724) FEP cases with an average follow-up duration of 8.3 years (SD = 7.2). 32.5% (95%CI = 28.5-36.9) of people with a diagnosis of FEP disorders were employed and 21.3% (95%CI = 16.5-27.1) were in a relationship at the end of follow-up. Studies from high-income countries and Europe had a higher proportion of people in employment at the end of follow-up compared to middle-income nations and non-European countries. The inverse was found for relationship status. The proportion of people with a diagnosis of FEP in employment decreased significantly with longer follow-up. Living with family, being in a relationship at first contact and Black and White ethnicities were identified as significant moderators of these outcomes. These findings highlight marked functional recovery deficits for people with FEP, although cultural factors need to be considered. They support the need for interventions to improve employment opportunities, and social functioning, both in early psychosis and during the longitudinal illness course.

Prediction of individuals at high risk of chronic kidney disease during treatment with lithium for bipolar disorder.

BACKGROUND: Lithium is the most effective treatment in bipolar disorder. Its use is limited by concerns about risk of chronic kidney disease (CKD). We aimed to develop a model to predict risk of CKD following lithium treatment initiation, by identifying individuals with a high-risk trajectory of kidney function. METHODS: We used United Kingdom Clinical Practice Research Datalink (CPRD) electronic health records (EHRs) from 2000 to 2018. CPRD Aurum for prediction model development and CPRD Gold for external validation. We used elastic net regularised regression to generate a prediction model from potential features. We performed discrimination and calibration assessments in an external validation data set. We included all patients aged ≥ 16 with bipolar disorder prescribed lithium. To be included patients had to have ≥ 1 year of follow-up before lithium initiation, ≥ 3 estimated glomerular filtration rate (eGFR) measures after lithium initiation (to be able to determine a trajectory) and a normal (≥ 60 mL/min/1.73 m2) eGFR at lithium initiation (baseline). In the Aurum development cohort, 1609 fulfilled these criteria. The Gold external validation cohort included 934 patients. We included 44 potential baseline features in the prediction model, including sociodemographic, mental and physical health and drug treatment characteristics. We compared a full model with the 3-variable 5-year kidney failure risk equation (KFRE) and a 3-variable elastic net model. We used group-based trajectory modelling to identify latent trajectory groups for eGFR. We were interested in the group with deteriorating kidney function (the high-risk group). RESULTS: The high risk of deteriorating eGFR group included 191 (11.87%) of the Aurum cohort and 137 (14.67%) of the Gold cohort. Of these, 168 (87.96%) and 117 (85.40%) respectively developed CKD 3a or more severe during follow-up. The model, developed in Aurum, had a ROC area of 0.879 (95%CI 0.853-0.904) in the Gold external validation data set. At the empirical optimal cut-point defined in the development dataset, the model had a sensitivity of 0.91 (95%CI 0.84-0.97) and a specificity of 0.74 (95% CI 0.67-0.82). However, a 3-variable elastic net model (including only age, sex and baseline eGFR) performed similarly well (ROC area 0.888; 95%CI 0.864-0.912), as did the KFRE (ROC area 0.870; 95%CI 0.841-0.898). CONCLUSIONS: Individuals at high risk of a poor eGFR trajectory can be identified before initiation of lithium treatment by a simple equation including age, sex and baseline eGFR. Risk was increased in individuals who were younger at commencement of lithium, female and had a lower baseline eGFR. We did not identify strong predicters of eGFR decline specific to lithium-treated patients. Notably, lithium duration and toxicity were not associated with high-risk trajectory.

Prevalence and characteristics of antidepressant prescribing in adults with comorbid depression and type 2 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Treatment guidelines do not provide specific recommendations for antidepressant prescribing in people with type 2 diabetes mellitus (T2DM). It is important to understand the prevalence of antidepressant prescribing and associated patient characteristics, to recognise safety issues or inequalities related to treatment access. METHODS AND RESULTS: Seven databases were searched using terms related to depression, T2DM and antidepressant medication. From 14,389 reports retrieved, 9 met inclusion criteria. The prevalence of antidepressant prescribing varied considerably between studies from 18% to 87%. Where meta-analyses were possible, the pooled odds ratio for receiving an antidepressant were 1.52 (95% confidence intervals (CIs) 1.28 - 1.82) in women compared to men, 0.53 (95% CIs 0.23-1.20%) in Black and Ethnic Minorities compared to White ethnicity and 1.29 (95% CIs 0.92-1.80) in insulin users compared to individuals with non-insulin controlled T2DM. CONCLUSIONS: Antidepressant prescribing is more common in women with T2DM compared to men, however, the difference is less than in the general population. Insulin users, representing individuals with more advanced T2DM, were as likely to be prescribed antidepressants as those who did not use insulin. There is a gap in the literature concerning which antidepressant agents are being prescribed, and alongside which concurrent medications and comorbidities.

Hospitalisation and length of hospital stay following first-episode psychosis: systematic review and meta-analysis of longitudinal studies.

BACKGROUND: Reducing hospitalisation and length of stay (LOS) in hospital following first episode psychosis (FEP) is important, yet reliable measures of these outcomes and their moderators are lacking. We conducted a systematic review and meta-analysis to investigate the proportion of FEP cases who were hospitalised after their first contact with services and the LOS in a hospital during follow-up. METHODS: Studies were identified from a systematic search across major electronic databases from inception to October 2017. Random effects meta-analyses and meta-regression analyses were conducted. RESULTS: 81 longitudinal studies encompassing data for 23 280 FEP patients with an average follow-up length of 7 years were included. 55% (95% CI 50.3-60.5%) of FEP cases were hospitalised at least once during follow-up with the pooled average LOS of 116.7 days (95% CI 95.1-138.3). Older age of illness onset and being in a stable relationship were associated with a lower proportion of people who were hospitalised. While the proportion of hospitalised patients has not decreased over time, LOS has, with the sharpest reduction in the latest time period. The proportion of patients hospitalised during follow-up was highest in Australia and New Zealand (78.4%) compared to Europe (58.1%) and North America (48.0%); and lowest in Asia (32.5%). Black ethnicity and longer duration of untreated psychosis were associated with longer LOS; while less severe psychotic symptoms at baseline were associated with shorter LOS. CONCLUSION: One in two FEP cases required hospitalisation at least once during a 7-year follow-up with an average length of hospitalisation of 4 months during this period. LOS has declined over time, particularly in those countries in which it was previously longest.

Biographical films as a person-centered approach to reduce neuropsychiatric symptoms of dementia in residential care: A feasibility study.

OBJECTIVE: Neuropsychiatric symptoms are a major component of dementia irrespective of severity or subtype. We aimed to determine the feasibility of biographical films to reduce neuropsychiatric symptoms in people with moderate to severe dementia over a 32-week period. METHOD: A total of 11 people with dementia situated in a residential care home took part in this mixed-method feasibility study. Carers reported neuropsychiatric symptoms of residents at three time-points, and their experience of the study was obtained at a feedback session. RESULTS: There was a significant reduction in neuropsychiatric symptoms in residents with neuropsychiatric impairment from baseline to the end of study (p = .042; d = .98). Thematic analysis identified three major themes: Triggered memories, knowledge gained to support care, and perceived changes in the resident. CONCLUSION: The findings suggest that it is feasible to use biographical films long-term to reduce neuropsychiatric symptoms of dementia, alongside routine care.

The effectiveness of two types of MADS for OSA therapy.

OBJECTIVES: The purpose of this study was to determine differences in effectiveness between two types of mandibular advancement device (MAD). MATERIAL AND METHODS: In this retrospective, cohort study, the two devices used were MAD type "Somnodent-Flex" (MAD 1) and MAD type "Herbst" (MAD 2). One hundred thirty-seven patients participated in this study, 67 patients were treated with MAD 1, and 70 patients with MAD 2. The indication MAD with obstructive sleep apnea (OSA) is based on a polysomnography test, in accordance with the CBO guidelines. The effectiveness of MAD therapy can be determined by a second polysomnography test (with the MAD in situ). The apnea-hypopnea index (AHI) is registered during the first and the second polysomnography test. Changes in these values determine the effectiveness. RESULTS: A significant decrease in AHI was found regarding T1 and T2 for both the MADs: F (1, 134) = 140,850, p < 0,001. The mean differences of both the MADs turned out to correlate to T1. After correcting for this covariance, there was no significant difference between the two MAD devices regarding the AHI value: F (1, 134) = 1160, p = 0,283. CONCLUSIONS: The results of the present study show no significant difference in effectiveness between MAD 1 and MAD 2 in respect to the AHI value. CLINICAL RELEVANCE: Since 2012, healthcare insurance companies in the Netherlands refunds MAD type "Somnodent" used for treatment of sleep apnea. It is important to investigate if this type of MAD is as more effective or less effective as other types of MADs. If research points out that other MADs are more effective in reducing the sleep apnea, refund policies have to be adapted.

Pharmacokinetics and tolerability of lamotrigine and olanzapine coadministered to healthy subjects.

AIM: To assess the pharmacokinetic effect and tolerability of lamotrigine 200 mg day(-1) and olanzapine 15 mg day(-1) coadministration in healthy male volunteers. METHODS: Subjects were randomized to receive either lamotrigine titrated on days 1-42 with olanzapine added on days 43-56 (LTG + OLZ group; N = 16), lamotrigine titration with placebo added on days 43-56 (LTG group; N = 12), or placebo on days 1-42 with olanzapine added on days 43-56 (OLZ group; N = 16). Steady state (0-24 h) pharmacokinetic profiles were determined on day 56 in each group. RESULTS: The average (90% confidence interval) ratios of lamotrigine area under the concentration-time curve from 0 to 24 h and maximum observed concentration for the comparison of LTG + OLZ:LTG were 0.76 (0.65, 0.90) and 0.80 (0.71, 0.90), respectively. Olanzapine pharmacokinetics were essentially unaffected by lamotrigine. The most frequently reported adverse events (AEs) during combination therapy were fatigue, dizziness and mild transaminase elevations. These AEs occurred at similar frequencies in the LTG + OLZ and OLZ cohorts, while being less frequent or absent in the LTG group. CONCLUSIONS: Lamotrigine and olanzapine coadministration in patients who may benefit from the combination was supported by this study. Lamotrigine dosing schedules are recommended to remain unchanged when combined with olanzapine therapy. However, the possibility exists that the lamotrigine dose for some patients may need adjustment to optimize treatment when olanzapine is added to or withdrawn from a regimen including lamotrigine.

The effect of a fracture protocol on hospital prescriptions after minimal trauma fractured neck of the femur: a retrospective audit.

Effective therapies for the treatment of osteoporosis and fracture have been available for a number of years. Despite this, there are numerous reports indicating very low uptake rates in those admitted to hospital with fracture. The aim of this retrospective audit was to assess the impact of a fracture protocol on inpatient prescriptions of osteoporosis therapy. A fracture protocol was arrived at by consensus and was based on recommendations from the Australian Fracture Prevention Summit, which included specific advice on the commencement in hospital of calcium, vitamin D, synthetic estrogen receptor modulators (SERMs) and bisphosphonates. We studied subjects who were treated for fractured neck of the femur at Royal Hobart Hospital from March 2002 to March 2004 and included 161 prior to the start of the protocol and 93 after. As compared to the baseline period, subjects after the introduction of the protocol had higher rates of in-hospital prescription for any treatment (58 vs. 36%, P <0.01), calcium (51 vs. 26%, P <0.01), vitamin D (48 vs. 29%, P <0.01) and oral bisphosphonates (24 vs. 5%, P <0.01), but not SERMs as expected (1 vs. 1%, P =0.70). Additional factors affecting the decision to start any treatment included in-hospital death (OR 0.16, 95% CI 0.05-0.49), dementia (OR 0.39, 95% CI 0.21-0.74), a trend for female sex (OR 1.79, 95%CI 0.96-3.36), but not age. In conclusion, a structural approach to changing hospital policy from the top down is effective at substantially increasing the usage of effective therapy after fractured neck of the femur.