Examining psychotic experiences in two generations - findings from a rural household-based cohort study; the Lolland-Falster Health Study.

BACKGROUND: Psychotic disorders are highly heritable, yet the evidence is less clear for subclinical psychosis expression, such as psychotic experiences (PEs). We examined if PEs in parents were associated with PEs in offspring. METHODS: As part of the Danish general population Lolland-Falster Health Study, families with youths aged 11-17 years were included. Both children and parents reported PEs according to the Psychotic Like Experiences Questionnaire, counting only 'definite' PEs. Parents additionally reported depressive symptoms, anxiety, and mental wellbeing. The associations between parental and child PEs were estimated using generalized estimating equations with an exchangeable correlation structure to account for the clustering of observations within families, adjusting for sociodemographic characteristics. RESULTS: Altogether, 984 youths (mean age 14.3 years [s.d. 2.0]), 700 mothers, and 496 fathers from 766 households completed PEs-questionnaires. Offspring of parents with PEs were at an increased risk of reporting PEs themselves (mothers: adjusted risk ratio (aRR) 2.42, 95% CI 1.73-3.38; fathers: aRR 2.25, 95% CI 1.42-3.59). Other maternal problems (depression, anxiety, and poor mental well-being), but not paternal problems, were also associated with offspring PEs. In multivariate models adjusting for parental problems, PEs, but not other parental problems, were robustly associated with offspring PEs (mothers: aRR 2.25, 95% CI 1.60-3.19; fathers: aRR 2.44, 95% CI 1.50-3.96). CONCLUSIONS: The current findings add novel evidence suggesting that specific psychosis vulnerability in families is expressed at the lower end of the psychosis continuum, underlining the importance of assessing youths' needs based on psychosis vulnerability broadly within the family systems.

The course of borderline personality disorder from adolescence to early adulthood: A 5-year follow-up study.

BACKGROUND: Studies of the medium- to long-term clinical and functional course for treatment-seeking adolescents with borderline personality disorder (BPD) are lacking. This study aims to outline the psychopathological and functional status of participants, five years after being diagnosed with BPD during adolescence. METHODS: Participants were originally enrolled in a randomized clinical trial that compared mentalization-based group treatment with treatment as usual for adolescents with BPD. Semi-structured interview assessments at five-year follow-up included the Schedules for Clinical Assessment in Neuropsychiatry and the Structured Clinical Interview for DSM-5 Personality Disorders. Attention deficit hyperactivity disorder (ADHD), alcohol, substance and tobacco use, posttraumatic stress disorder (PTSD), complex PTSD, and general functioning were assessed using self-report instruments. RESULTS: 97 of the original sample of 111 participants (87%) participated. They were aged 19-23 years. The most prevalent disorders were ADHD (59%), any personality disorder (47%) of which half continued to meet criteria for BPD (24%), anxiety disorders (37%), depressive disorders (32%), PTSD or complex PTSD (20%), schizophrenia (16%), and eating disorders (13%). Only 16% did not meet criteria for any mental disorder. Approximately half of the sample were in psychological and/or psychopharmacological treatment at the time of follow-up. Their general functioning remained impaired, with 36% not engaged in education, employment or training (NEET), which is nearly four times the rate of NEET in the same age group in the general population. CONCLUSIONS: Although stability of the categorical BPD diagnosis is modest, adolescents meeting diagnostic criteria for BPD show a broad range of poor outcomes at five-year follow-up. BPD appears to be a marker of general maladjustment during adolescence and a harbinger of severe problems during the transition to young adulthood. Early intervention programs for adolescents diagnosed with BPD should focus upon a broad range of functional and psychopathological outcomes, especially social and vocational support, rather than the narrow BPD diagnosis.

Psychometric validation of the Danish version of the Major Depression Inventory using data from the Lolland-Falster health study (LOFUS).

PURPOSE: The Major Depression Inventory (MDI) is a widely used self-rating depression scale commonly in primary care in Denmark. It has not been subject to robust psychometric validation in a general population setting. The aim of this study was to evaluate the psychometric measurement properties of the MDI when applied in the general population. METHODS: We evaluated statistical psychometric validity using modern test theory (confirmatory factor analysis, item response theory models and Rasch measurement theory) testing local independence and differential item function across groups defined by gender, age, education, and chronic disease status. Separate analyses across different strata and across different statistical models were employed. RESULTS: Regarding structural validity we consistently identified local dependence for the item two pairs (MDI2,MDI3) and (MDI4,MDI5) across strata. This result was confirmed by bifactor CFA models and item screening. We further identified substantial differential item functioning with respect to age group and with respect to chronic disease. We identified quantified the magnitude of this lack of measurement invariance. CONCLUSION: The MDI is psychometrically valid in homogenous sub populations, but the disclosed evidence of local dependence means that published estimates of its reliability cannot be trusted. The lack of measurement invariance means that the instrument cannot be used to compare individuals or groups unless they are similar in terms of age group and chronic disease status.

Co-occurrence of borderline and schizotypal personality disorders: a scoping review.

BACKGROUND: The historical concept of borderline conditions refers to the pathology on the border between neurosis and psychosis. In DSM-III the conditions were divided into specific but also somewhat overlapping diagnostic criteria for Borderline Personality Disorder (BPD) and Schizotypal Personality Disorder (SPD). This phenomenological overlap, which results in co-occurrence of the two diagnoses, remains a clinical challenge to this day. METHODS: To address this issue we examined the co-occurrence of SPD and BPD according to the established DSM-IV/-5 diagnostic criteria. A literature search was conducted including studies that employed a structured interview with defined BPD and SPD criteria. RESULTS: Studies from 20 samples were included (i.e. 15 patients, 3 community and 2 forensic samples). For patients diagnosed primarily with BPD, 1-27% also met the criteria for SPD and for patients diagnosed primarily with SPD, 5 - 33% showed co-occurrence with BPD. In the forensic samples, co-occurrence for primary BPD was 10% and 67 - 82% for primary SPD. In the community samples, co-occurrence for primary BPD was 29% and 50% for primary SPD. The pattern of co-occurrence across community samples was particularly heterogeneous. CONCLUSION: The identified co-occurrences for BPD and SPD were considerably sample-dependent, and samples and measurements were generally too heterogeneous for a precise meta-analysis. Forensic and community samples generally showed higher co-occurrences, but these findings were characterized by potential methodological limitations.

Attachment Problems and Mentalizing Capacity Relate to Parent-Child Informant Discrepancies in Female Adolescents with Borderline Personality Disorder.

Parent-child informant discrepancies on psychopathology provide important knowledge on the parent-child relationship and the child's mental health, but mechanisms underlying parent-child informant discrepancies are largely unknown. Therefore, we investigated the relationship between attachment problems and mentalizing capacity and parent-child informant discrepancies on borderline personality disorder (BPD) severity, internalizing, and externalizing pathology in a clinical sample of 91 adolescent girls with BPD and their parents. Results showed that more attachment problems to parents and peers were related to adolescents reporting more severe BPD than parents. Adolescents who described more internalizing symptoms relative to parents, reported more parental attachment problems, but enhanced peer attachment, suggesting those adolescents who do not feel recognized by their parents might turn to their friends. When parents rated adolescents higher on externalizing behaviors, the adolescent reported more attachment problems to parents and lower mentalizing capacity, indicating that this sub-group of adolescents may reflect less about how their behavior affects others.

Childhood trauma, antipsychotic medication, and symptom remission in first-episode psychosis.

BACKGROUND: To what extent psychotic symptoms in first-episode psychosis (FEP) with a history of childhood interpersonal trauma (CIT) are less responsive to antipsychotic medication is not known. In this longitudinal study, we compare symptom trajectories and remission over the first 2 years of treatment in FEP with and without CIT and examine if differences are linked to the use of antipsychotics. METHODS: FEP (N = 191) were recruited from in- and outpatient services 1997-2000, and assessed at baseline, 3 months, 1 and 2 years. Inclusion criteria were 15-65 years, actively psychotic with a DSM-IV diagnosis of psychotic disorder and no previous adequate treatment for psychosis. Antipsychotic medication is reported as defined daily dosage (DDD). CIT (<18) was assessed with the Brief Betrayal Trauma Survey, and symptomatic remission based on scores from the Positive and Negative Syndrome Scale. RESULTS: CIT (n = 63, 33%) was not associated with symptomatic remission at 2 years follow-up (71% in remission, 14% in relapse), or time to first remission (CIT 12/ no-CIT 9 weeks, p = 0.51). Those with CIT had significantly more severe positive, depressive, and excited symptoms. FEP with physical (N = 39, 20%) or emotional abuse (N = 22, 14, 7%) had higher DDD at 1 year (p < 0.05). Mean DDD did not excerpt a significant between-group effect on symptom trajectories of positive symptoms. CONCLUSION: Results indicate that antipsychotic medication is equally beneficial in the achievement of symptomatic remission in FEP after 2 years independent of CIT. Still, FEP patients with CIT had more severe positive, depressive, and excited symptoms throughout.

Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD).

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed and treated psychiatric disorders in childhood. Typically, children and adolescents with ADHD find it difficult to pay attention and they are hyperactive and impulsive. Methylphenidate is the psychostimulant most often prescribed, but the evidence on benefits and harms is uncertain. This is an update of our comprehensive systematic review on benefits and harms published in 2015. OBJECTIVES: To assess the beneficial and harmful effects of methylphenidate for children and adolescents with ADHD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, three other databases and two trials registers up to March 2022. In addition, we checked reference lists and requested published and unpublished data from manufacturers of methylphenidate. SELECTION CRITERIA: We included all randomised clinical trials (RCTs) comparing methylphenidate versus placebo or no intervention in children and adolescents aged 18 years and younger with a diagnosis of ADHD. The search was not limited by publication year or language, but trial inclusion required that 75% or more of participants had a normal intellectual quotient (IQ > 70). We assessed two primary outcomes, ADHD symptoms and serious adverse events, and three secondary outcomes, adverse events considered non-serious, general behaviour, and quality of life. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted data extraction and risk of bias assessment for each trial. Six review authors including two review authors from the original publication participated in the update in 2022. We used standard Cochrane methodological procedures. Data from parallel-group trials and first-period data from cross-over trials formed the basis of our primary analyses. We undertook separate analyses using end-of-last period data from cross-over trials. We used Trial Sequential Analyses (TSA) to control for type I (5%) and type II (20%) errors, and we assessed and downgraded evidence according to the GRADE approach. MAIN RESULTS: We included 212 trials (16,302 participants randomised); 55 parallel-group trials (8104 participants randomised), and 156 cross-over trials (8033 participants randomised) as well as one trial with a parallel phase (114 participants randomised) and a cross-over phase (165 participants randomised). The mean age of participants was 9.8 years ranging from 3 to 18 years (two trials from 3 to 21 years). The male-female ratio was 3:1. Most trials were carried out in high-income countries, and 86/212 included trials (41%) were funded or partly funded by the pharmaceutical industry. Methylphenidate treatment duration ranged from 1 to 425 days, with a mean duration of 28.8 days. Trials compared methylphenidate with placebo (200 trials) and with no intervention (12 trials). Only 165/212 trials included usable data on one or more outcomes from 14,271 participants. Of the 212 trials, we assessed 191 at high risk of bias and 21 at low risk of bias. If, however, deblinding of methylphenidate due to typical adverse events is considered, then all 212 trials were at high risk of bias. PRIMARY OUTCOMES: methylphenidate versus placebo or no intervention may improve teacher-rated ADHD symptoms (standardised mean difference (SMD) -0.74, 95% confidence interval (CI) -0.88 to -0.61; I² = 38%; 21 trials; 1728 participants; very low-certainty evidence). This corresponds to a mean difference (MD) of -10.58 (95% CI -12.58 to -8.72) on the ADHD Rating Scale (ADHD-RS; range 0 to 72 points). The minimal clinically relevant difference is considered to be a change of 6.6 points on the ADHD-RS. Methylphenidate may not affect serious adverse events (risk ratio (RR) 0.80, 95% CI 0.39 to 1.67; I² = 0%; 26 trials, 3673 participants; very low-certainty evidence). The TSA-adjusted intervention effect was RR 0.91 (CI 0.31 to 2.68). SECONDARY OUTCOMES: methylphenidate may cause more adverse events considered non-serious versus placebo or no intervention (RR 1.23, 95% CI 1.11 to 1.37; I² = 72%; 35 trials 5342 participants; very low-certainty evidence). The TSA-adjusted intervention effect was RR 1.22 (CI 1.08 to 1.43). Methylphenidate may improve teacher-rated general behaviour versus placebo (SMD -0.62, 95% CI -0.91 to -0.33; I² = 68%; 7 trials 792 participants; very low-certainty evidence), but may not affect quality of life (SMD 0.40, 95% CI -0.03 to 0.83; I² = 81%; 4 trials, 608 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: The majority of our conclusions from the 2015 version of this review still apply. Our updated meta-analyses suggest that methylphenidate versus placebo or no-intervention may improve teacher-rated ADHD symptoms and general behaviour in children and adolescents with ADHD. There may be no effects on serious adverse events and quality of life. Methylphenidate may be associated with an increased risk of adverse events considered non-serious, such as sleep problems and decreased appetite. However, the certainty of the evidence for all outcomes is very low and therefore the true magnitude of effects remain unclear. Due to the frequency of non-serious adverse events associated with methylphenidate, the blinding of participants and outcome assessors is particularly challenging. To accommodate this challenge, an active placebo should be sought and utilised. It may be difficult to find such a drug, but identifying a substance that could mimic the easily recognised adverse effects of methylphenidate would avert the unblinding that detrimentally affects current randomised trials. Future systematic reviews should investigate the subgroups of patients with ADHD that may benefit most and least from methylphenidate. This could be done with individual participant data to investigate predictors and modifiers like age, comorbidity, and ADHD subtypes.

Prevalence and incidence of personality disorders among children and adolescents in Danish mental health services: a nationwide register study.

A few epidemiological studies have examined personality disorders (PDs) among children and adolescents in secondary mental health services. This study aims to describe the prevalence and incidence of PDs among children and adolescents who have attended Danish child and adolescent psychiatric services (CAPS). Using register-based data, we studied all patients under the age of 18 years who were admitted to in- and outpatient CAPS (N = 115,121) in Denmark from 2007 to 2017. A total of 4952 patients were diagnosed with a PD during the study period. The mean prevalence was 859 patients per year, and the mean incidence was 274 patients per year, including an increased incidence and prevalence of borderline, anxious, and unspecified PDs over the decade. The number of patients diagnosed with PDs increased from 700 to 851 per year, but the proportion of patients with PDs compared to all psychiatric diagnoses decreased from 4.2% to 2.8% over the study period. The PD population had an older age (14.8 years vs. 11.3 years; p < 0.001), a higher likelihood of being female (74% vs. 44%; p < 0.001), and four times more contacts with the psychiatric emergency departments than other patients with a psychiatric diagnosis. Future studies should focus on (a) implementing further epidemiological studies in different countries; (b) tracking diagnostic practices to facilitate comparisons and provide feedback for training clinicians and raising awareness; and (c) estimating trajectories of PDs, including costs within the CAPS, to facilitate informed decision-making regarding the future organization and provision of services to these children, adolescents, and their families.

Concurrent validity of the anxiety symptom-scale compared to two well-being scales: results from the Lolland-Falster health study.

OBJECTIVE: To examine the concurrent validity of the Anxiety Symptom-scale against two well-being scales, the Cantril Ladder (CL) and World Health Organization Well-Being Index (WHO-5), to test the algorithm defining anxiety against these scales, and identify cut-off points for the Anxiety Symptom-scale sum score. SUBJECTS: 14,405 adult respondents completing all psychometric questions in the Lolland Falster Health Study. METHOD: Receiver operating characteristic analyses comparing Anxiety Symptom-scale WHO-5 and CL. RESULTS: 2.5% of respondents had an anxiety disorder (3% female and 2% male) according to the Anxiety Symptom-scale algorithm. The area under the curve (AUC) was 0.87 for CL and 0.90 for WHO-5 (using inverse scores), indicating high concordance with anxiety disorder as identified by the scale. A score solely ≥2 on item 10 is a relevant cut off to low wellbeing. Anxiety disorder covers a broad range on the scale's sum score, with 3 to 4 indicating low well-being in this population sample and a sensitivity of 0.85 - 0.99 against CL and WHO-5. CONCLUSION: The Anxiety Symptom-scale is a sensitive and valid instrument for the identification of patients in low well-being with symptoms of anxiety. A score ≥2 on the functional impact (Item 10) of all symptoms is a relevant indicator of anxiety associated with low well-being in this sample. A higher Anxiety Symptom-scale sum score is coherent with lower well-being, though without specific cut-off points. Further validation of the Anxiety Symptom-scale in a clinical setting is recommended.

Prevalence of anxiety disorders and association to socioeconomic position. Results from the Lolland Falster Health Study.

PURPOSE: The purpose of this study is to describe the prevalence of anxiety disorders in a general population and the association to socioeconomic position (SEP), which has not been described in a Danish context before. MATERIAL AND METHODS: We present data on anxiety symptoms from respondents in the rural-provincial Lolland-Falster population Health Study (LOFUS). Analyses of the questionnaire responses to the Anxiety Symptom Scale were done by descriptive statistics and logistic regression analyses adjusted for sex and age. RESULTS: 14,834 LOFUS respondents who completed the Anxiety Symptom Scale were included; According to the original algorithm 371 (2.5%) had an anxiety disorder. The adjusted odds ratios (aOR) for anxiety disorder were strongly associated to SEP. We found aOR for anxiety to be: 3.8 (confidence interval (CI 95%) 2.54 - 5.92) for respondents with no postsecondary education compared to those with 3+ years of postsecondary education; 11.9 (CI 8.89 - 16.01) for respondents temporarily out of a job compared to those working; 9.4 (CI 6.06 - 14.51) for those experiencing constant financial strain compared to those not experiencing financial strain. Relaxing the criteria for anxiety to item 10 > 1, the prevalence raised to 3.9%. The association was unchanged related to education; however, the aOR dropped to 9 and 8 respectively, for being temporally out of job, or in financial strain every month- when doing same comparisons. CONCLUSIONS: The 14-day prevalence of anxiety disorder seems low but strongly associated to SEP especially for individuals temporarily out of a job or experiencing financial strain.

Antipsychotic prescribing practices for outpatients with schizophrenia and reasons for non-clozapine treatment - Data from a Danish quality assessment audit.

BACKGROUND: Clozapine is the gold standard for treating treatment-resistant schizophrenia (TRS) although widely underutilised. Both organisational, patient- and clinician related reasons for the underutilisation have been reported, however, the clinical impact of either in real-world settings is not fully elucidated. AIM: This audit aimed to evaluate the local antipsychotic (AP) prescribing practices for outpatients with schizophrenia and to assess the spectrum and prevalence of journalised reasons for non-clozapine treatment amongst eligible outpatients. METHODS: Data on demographics, current and former AP treatments, as well as documented reasons for non-clozapine treatment, was extracted through chart audit. RESULTS: Of the 668 affiliated outpatients with schizophrenia, 43% were treated with AP polytherapy (APP) and 19.6% with clozapine. The most prevalent reason for clozapine discontinuation was related to side effects whereas the most prevalent reason for refusal or omission of clozapine treatment was related to the associated monitoring regimen. CONCLUSIONS: This audit showed that APP prescribing is a highly prevalent practice in our services when treating outpatients with schizophrenia and that clozapine is underutilised in a 'last resort' manner. The blood-monitoring regimen associated with clozapine treatment was found to be an important factor in the underutilisation. It seemed, however, that the monitoring constituted a barrier for different reasons, requiring different approaches to remedy. Future studies, directly involving both patients and clinicians in the identification and management of the most clinically relevant barriers and their corresponding facilitators, are warranted.

Mentalizing in Adolescents With and Without Prominent Borderline Features: Validation of the Reflective Functioning Questionnaire for Youths (RFQY) and an Investigation of the Factor Structure of Hypo- and Hypermentalizing.

The Reflective Functioning Questionnaire for Youths (RFQY) is a self-report measure of reflective functioning (RF) also referred to as mentalizing. Lower levels of RF are characteristic of a wide range of mental disorders and are especially relevant in the assessment of personality pathology. The goal of the current study is to examine the psychometric properties of a Danish translation of the RFQY and to corroborate previous research on the measure's ability to differentiate between adolescents with and without borderline personality disorder (BPD) features. 889 adolescents were administered the RFQY and divided into three subsamples: a community sample (n = 644), a clinical non-personality disorder sample (n = 64), and a BPD sample (n = 181). Construct validity was examined through bivariate correlations between RFQY and a dimensional assessment of borderline personality features. Analysis of variance (ANOVA) supported the utility of the RFQY to discriminate between adolescents with and without BPD features. Moreover, a two-factor structure based on previous research of the adult version of the RFQ was examined. A series of exploratory and confirmatory factor analyses yielded a two-factor structure corroborating previous research. Implications for prevention, assessment, and treatment are discussed along with methodological limitations and suggestions for future research.

Psychotherapies for borderline personality disorder: a focused systematic review and meta-analysis.

BACKGROUND: A recently updated Cochrane review supports the efficacy of psychotherapy for borderline personality disorder (BPD). AIMS: To evaluate the effects of standalone and add-on psychotherapeutic treatments more concisely. METHOD: We applied the same methods as the 2020 Cochrane review, but focused on adult samples and comparisons of active treatments and unspecific control conditions. Standalone treatments (i.e. necessarily including individual psychotherapy as either the sole or one of several treatment components) and add-on interventions (i.e. complementing any ongoing individual BPD treatment) were analysed separately. Primary outcomes were BPD severity, self-harm, suicide-related outcomes and psychosocial functioning. Secondary outcomes were remaining BPD diagnostic criteria, depression and attrition. RESULTS: Thirty-one randomised controlled trials totalling 1870 participants were identified. Among standalone treatments, statistically significant effects of low overall certainty were observed for dialectical behaviour therapy (self-harm: standardised mean difference (SMD) -0.54, P = 0.006; psychosocial functioning: SMD -0.51, P = 0.01) and mentalisation-based treatment (self-harm: risk ratio 0.51, P < 0.0007; suicide-related outcomes: risk ratio 0.10, P < 0.0001). For adjunctive interventions, moderate-quality evidence of beneficial effects was observed for DBT skills training (BPD severity: SMD -0.66, P = 0.002; psychosocial functioning: SMD -0.45, P = 0.002), and statistically significant low-certainty evidence was observed for the emotion regulation group (BPD severity: mean difference -8.49, P < 0.00001), manual-assisted cognitive therapy (self-harm: mean difference -3.03, P = 0.03; suicide-related outcomes: SMD -0.96, P = 0.005) and the systems training for emotional predictability and problem-solving (BPD severity: SMD -0.48, P = 0.002). CONCLUSIONS: There is reasonable evidence to conclude that psychotherapeutic interventions are helpful for individuals with BPD. Replication studies are needed to enhance the certainty of findings.

Control interventions in randomised trials among people with mental health disorders.

BACKGROUND: Control interventions in randomised trials provide a frame of reference for the experimental interventions and enable estimations of causality. In the case of randomised trials assessing patients with mental health disorders, many different control interventions are used, and the choice of control intervention may have considerable impact on the estimated effects of the treatments being evaluated. OBJECTIVES: To assess the benefits and harms of typical control interventions in randomised trials with patients with mental health disorders. The difference in effects between control interventions translates directly to the impact a control group has on the estimated effect of an experimental intervention. We aimed primarily to assess the difference in effects between (i) wait-list versus no-treatment, (ii) usual care versus wait-list or no-treatment, and (iii) placebo interventions (all placebo interventions combined or psychological, pharmacological, and physical placebos individually) versus wait-list or no-treatment. Wait-list patients are offered the experimental intervention by the researchers after the trial has been finalised if it offers more benefits than harms, while no-treatment participants are not offered the experimental intervention by the researchers. SEARCH METHODS: In March 2018, we searched MEDLINE, PsycInfo, Embase, CENTRAL, and seven other databases and six trials registers. SELECTION CRITERIA: We included randomised trials assessing patients with a mental health disorder that compared wait-list, usual care, or placebo interventions with wait-list or no-treatment . DATA COLLECTION AND ANALYSIS: Titles, abstracts, and full texts were reviewed for eligibility. Review authors independently extracted data and assessed risk of bias using Cochrane's risk of bias tool. GRADE was used to assess the quality of the evidence. We contacted researchers working in the field to ask for data from additional published and unpublished trials. A pre-planned decision hierarchy was used to select one benefit and one harm outcome from each trial. For the assessment of benefits, we summarised continuous data as standardised mean differences (SMDs) and dichotomous data as risk ratios (RRs). We used risk differences (RDs) for the assessment of adverse events. We used random-effects models for all statistical analyses. We used subgroup analysis to explore potential causes for heterogeneity (e.g. type of placebo) and sensitivity analyses to explore the robustness of the primary analyses (e.g. fixed-effect model). MAIN RESULTS: We included 96 randomised trials (4200 participants), ranging from 8 to 393 participants in each trial. 83 trials (3614 participants) provided usable data. The trials included 15 different mental health disorders, the most common being anxiety (25 trials), depression (16 trials), and sleep-wake disorders (11 trials). All 96 trials were assessed as high risk of bias partly because of the inability to blind participants and personnel in trials with two control interventions. The quality of evidence was rated low to very low, mostly due to risk of bias, imprecision in estimates, and heterogeneity. Only one trial compared wait-list versus no-treatment directly but the authors were not able to provide us with any usable data on the comparison. Five trials compared usual care versus wait-list or no-treatment and found a SMD -0.33 (95% CI -0.83 to 0.16, I² = 86%, 523 participants) on benefits. The difference between all placebo interventions combined versus wait-list or no-treatment was SMD -0.37 (95% CI -0.49 to -0.25, I² = 41%, 65 trials, 2446 participants) on benefits. There was evidence of some asymmetry in the funnel plot (Egger's test P value of 0.087). Almost all the trials were small. Subgroup analysis found a moderate effect in favour of psychological placebos SMD -0.49 (95% CI -0.64 to -0.30; I² = 53%, 39 trials, 1656 participants). The effect of pharmacological placebos versus wait-list or no-treatment on benefits was SMD -0.14 (95% CI -0.39 to 0.11, 9 trials, 279 participants) and the effect of physical placebos was SMD -0.21 (95% CI -0.35 to -0.08, I² = 0%, 17 trials, 896 participants). We found large variations in effect sizes in the psychological and pharmacological placebo comparisons. For specific mental health disorders, we found significant differences in favour of all placebos for sleep-wake disorders, major depressive disorder, and anxiety disorders, but the analyses were imprecise due to sparse data. We found no significant differences in harms for any of the comparisons but the analyses suffered from sparse data. When using a fixed-effect model in a sensitivity analysis on the comparison for usual care versus wait-list and no-treatment, the results were significant with an SMD of -0.46 (95 % CI -0.64 to -0.28). We reported an alternative risk of bias model where we excluded the blinding domains seeing how issues with blinding may be seen as part of the review investigation itself. However, this did not markedly change the overall risk of bias profile as most of the trials still included one or more unclear bias domains. AUTHORS' CONCLUSIONS: We found marked variations in effects between placebo versus no-treatment and wait-list and between subtypes of placebo with the same comparisons. Almost all the trials were small with considerable methodological and clinical variability in factors such as mental health population, contents of the included control interventions, and outcome domains. All trials were assessed as high risk of bias and the evidence quality was low to very low. When researchers decide to use placebos or usual care control interventions in trials with people with mental health disorders it will often lead to lower estimated effects of the experimental intervention than when using wait-list or no-treatment controls. The choice of a control intervention therefore has considerable impact on how effective a mental health treatment appears to be. Methodological guideline development is needed to reach a consensus on future standards for the design and reporting of control interventions in mental health intervention research.

Pharmacological interventions for people with borderline personality disorder.

BACKGROUND: Among people with a diagnosis of borderline personality disorder (BPD) who are engaged in clinical care, prescription rates of psychotropic medications are high, despite the fact that medication use is off-label as a treatment for BPD. Nevertheless, people with BPD often receive several psychotropic drugs at a time for sustained periods. OBJECTIVES: To assess the effects of pharmacological treatment for people with BPD. SEARCH METHODS: For this update, we searched CENTRAL, MEDLINE, Embase, 14 other databases and four trials registers up to February 2022. We contacted researchers working in the field to ask for additional data from published and unpublished trials, and handsearched relevant journals. We did not restrict the search by year of publication, language or type of publication. SELECTION CRITERIA: Randomised controlled trials comparing pharmacological treatment to placebo, other pharmacologic treatments or a combination of pharmacologic treatments in people of all ages with a formal diagnosis of BPD. The primary outcomes were BPD symptom severity, self-harm, suicide-related outcomes, and psychosocial functioning. Secondary outcomes were individual BPD symptoms, depression, attrition and adverse events. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials, extracted data, assessed risk of bias using Cochrane's risk of bias tool and assessed the certainty of the evidence using the GRADE approach. We performed data analysis using Review Manager 5 and quantified the statistical reliability of the data using Trial Sequential Analysis. MAIN RESULTS: We included 46 randomised controlled trials (2769 participants) in this review, 45 of which were eligible for quantitative analysis and comprised 2752 participants with BPD in total. This is 18 more trials than the 2010 review on this topic. Participants were predominantly female except for one trial that included men only. The mean age ranged from 16.2 to 39.7 years across the included trials. Twenty-nine different types of medications compared to placebo or other medications were included in the analyses. Seventeen trials were funded or partially funded by the pharmaceutical industry, 10 were funded by universities or research foundations, eight received no funding, and 11 had unclear funding. For all reported effect sizes, negative effect estimates indicate beneficial effects by active medication. Compared with placebo, no difference in effects were observed on any of the primary outcomes at the end of treatment for any medication. Compared with placebo, medication may have little to no effect on BPD symptom severity, although the evidence is of very low certainty (antipsychotics: SMD -0.18, 95% confidence interval (CI) -0.45 to 0.08; 8 trials, 951 participants; antidepressants: SMD -0.27, 95% CI -0.65 to 1.18; 2 trials, 87 participants; mood stabilisers: SMD -0.07, 95% CI -0.43 to 0.57; 4 trials, 265 participants). The evidence is very uncertain about the effect of medication compared with placebo on self-harm, indicating little to no effect (antipsychotics: RR 0.66, 95% CI 0.15 to 2.84; 2 trials, 76 participants; antidepressants: MD 0.45 points on the Overt Aggression Scale-Modified-Self-Injury item (0-5 points), 95% CI -10.55 to 11.45; 1 trial, 20 participants; mood stabilisers: RR 1.08, 95% CI 0.79 to 1.48; 1 trial, 276 participants). The evidence is also very uncertain about the effect of medication compared with placebo on suicide-related outcomes, with little to no effect (antipsychotics: SMD 0.05, 95 % CI -0.18 to 0.29; 7 trials, 854 participants; antidepressants: SMD -0.26, 95% CI -1.62 to 1.09; 2 trials, 45 participants; mood stabilisers: SMD -0.36, 95% CI -1.96 to 1.25; 2 trials, 44 participants). Very low-certainty evidence shows little to no difference between medication and placebo on psychosocial functioning (antipsychotics: SMD -0.16, 95% CI -0.33 to 0.00; 7 trials, 904 participants; antidepressants: SMD -0.25, 95% CI -0.57 to 0.06; 4 trials, 161 participants; mood stabilisers: SMD -0.01, 95% CI -0.28 to 0.26; 2 trials, 214 participants). Low-certainty evidence suggests that antipsychotics may slightly reduce interpersonal problems (SMD -0.21, 95% CI -0.34 to -0.08; 8 trials, 907 participants), and that mood stabilisers may result in a reduction in this outcome (SMD -0.58, 95% CI -1.14 to -0.02; 4 trials, 300 participants). Antidepressants may have little to no effect on interpersonal problems, but the corresponding evidence is very uncertain (SMD -0.07, 95% CI -0.69 to 0.55; 2 trials, 119 participants). The evidence is very uncertain about dropout rates compared with placebo by antipsychotics (RR 1.11, 95% CI 0.89 to 1.38; 13 trials, 1216 participants). Low-certainty evidence suggests there may be no difference in dropout rates between antidepressants (RR 1.07, 95% CI 0.65 to 1.76; 6 trials, 289 participants) and mood stabilisers (RR 0.89, 95% CI 0.69 to 1.15; 9 trials, 530 participants), compared to placebo. Reporting on adverse events was poor and mostly non-standardised. The available evidence on non-serious adverse events was of very low certainty for antipsychotics (RR 1.07, 95% CI 0.90 to 1.29; 5 trials, 814 participants) and mood stabilisers (RR 0.84, 95% CI 0.70 to 1.01; 1 trial, 276 participants). For antidepressants, no data on adverse events were identified. AUTHORS' CONCLUSIONS: This review included 18 more trials than the 2010 version, so larger meta-analyses with more statistical power were feasible. We found mostly very low-certainty evidence that medication may result in no difference in any primary outcome. The rest of the secondary outcomes were inconclusive. Very limited data were available for serious adverse events. The review supports the continued understanding that no pharmacological therapy seems effective in specifically treating BPD pathology. More research is needed to understand the underlying pathophysiologic mechanisms of BPD better. Also, more trials including comorbidities such as trauma-related disorders, major depression, substance use disorders, or eating disorders are needed. Additionally, more focus should be put on male and adolescent samples.

Welfare consequences of early-onset Borderline Personality Disorder: a nationwide register-based case-control study.

Information regarding welfare consequences of early onset of Borderline Personality Disorder (BPD) is limited. This nationwide study aimed to estimate the educational and employment outcome and health care costs of patients with early-onset BPD compared with matched controls. All patients (< 19 years) with first diagnosis of BPD in the Danish Patient Register (NPR) during the period 1983-2015 were included. Health care costs and socioeconomic variables were extracted from national registers. A total of 171 patients was compared with 677 controls. At the age of 20 years, BPD patients had reached a statistically significantly lower educational level (including lower primary school grades) and employment status compared with the controls. When adjusting for the parents' educational level, BPD patients were nearly 22 times more likely to be unemployed (OR = 21.7, 95% CI 11.9, 39.6), and nearly 15 times more likely to be on disability pension (OR = 14.8, 95% CI 5.0, 43.9) than controls. Furthermore, the total health care costs were more than 8 times higher in the BPD group. Early onset of BPD was associated with lower educational and vocational outcome and increased health care costs as early as at the age of 20 years. Even after controlling for parents' lower socioeconomic status, the patients have poorer outcome than the control group. This underlines that initiatives to support patients in finishing school and secondary education is highly needed. Future prevention and early intervention programs should target patients with early-onset BPD and their families.

Maladaptive personality traits may link childhood trauma history to current internalizing symptoms.

Research supports a strong relationship between childhood maltreatment and internalizing psychopathology (e.g., anxiety and depression), and features of personality are assumed to explain some of this relationship. In this study, we proposed a model in which maladaptive traits mediate the effect of childhood trauma history on internalizing symptoms in adult individuals. A mixed sample (N = 462) composed of 142 psychiatric patients and 320 community-dwelling individuals completed the Childhood Trauma Questionnaire (CTQ), the Personality Inventory for DSM-5 (PID-5), and the Symptom Checklist (SCL-27) for internalizing psychopathology. The effect of childhood traumas explained 34% of the variance in internalizing symptoms while controlling for the influence of age and gender. The traits accounted for 78% of this effect, which was predominantly exerted through the domains of Negative Affectivity, Detachment, and Psychoticism, and specifically through the facets of Depressivity, Suspiciousness, Anxiousness, Perceptual Dysregulation, and Distractibility. This finding provides preliminary support for the proposed model indicating that the aforementioned maladaptive trait domains potentially function as mediating links by which childhood traumas are translated into internalizing symptoms in adulthood. However, these findings must be interpreted with caution due to the cross-sectional and retrospective mono-method design of this study. Clinical implications are discussed in relation to transdiagnostic treatment and the potential value of specifying trait domain specifiers in ICD-11 and DSM-5 models of personality disorders.

Costs of schizotypal disorder: A matched-controlled nationwide register-based study of patients and spouses.

OBJECTIVE: Information on societal cost of patients with schizotypal disorder is limited. The aim was to investigate the societal costs of schizotypal disorder before and after initial diagnosis including both patients and their spouses. METHODS: A register-based cohort study of 762 patients with incident schizotypal disorder (ICD-10; F21) including their spouses and 3048 matched controls, during 2002 to 2016. Total healthcare costs, home care costs, and costs of lost productivity of patients and spouses were included in the analysis. RESULTS: Total costs amounted €47,215 per year for patients with schizotypal disorder, which was fifteen times higher than the matched controls. Of these, 41% were healthcare and home care costs and 59% were costs of lost productivity. Healthcare costs and costs of lost productivity were increased during five years before initial diagnosis of schizotypal disorder. Total costs of spouses to patients were €21,384 compared with € 2519 among spouses of controls. 75% of the total costs of spouses to patients were related to lost productivity. The total costs were higher than the costs of borderline personality disorder, but on the same level as the costs of schizophrenia identified in earlier comparable studies. CONCLUSIONS: The total societal costs of patients with schizotypal disorder drawn from national registers differed substantially from the controls representing the general population. As evidence-based recommendations for diagnoses and treatment of patients with schizotypal disorder do not exist, future research should focus on developing effective treatment for this group of patients to reduce cost of illness.

Socioeconomic position and mental health care use before and after first redeemed antidepressant and time until subsequent contact to psychologist or psychiatrists: a nationwide Danish follow-up study.

PURPOSE: The purpose was to investigate inequalities in access to care among people with possible depression. METHOD: In this nationwide register-based cohort study of 30,593 persons, we observed the association between socioeconomic position (SEP, education/income) and mental health care use (MHCU) four months before the date of first redeemed antidepressant (Index Date/ID) and 12 months afterwards-and time to contact to psychologist/psychiatrist (PP). Logistic, Poisson, and Cox regression models were used, adjusted for sex, age, cohabitation, and psychiatric comorbidity. RESULTS: Before ID, high SEP was associated with less GP contact (general practitioner), higher odds ratios for GP-Mental Health Counseling (GP-MHC), psychologist contact, and admissions to hospital. This disparity decreased the following 12 months for GP-MHC but increased for contact to psychologist; same pattern was seen for rate of visits. However, the low-income group had more contact to private psychiatrist. For the 25,217 individuals with no MHCU before ID, higher educational level was associated with almost twice the rate of contact to PP the following 12 months; for the high-income group, the rate was 40% higher. 10% had contact to PP within 40 days after ID in the group with higher education; whereas, 10% of those with a short education would reach PP by day 120. High-income group had faster access as well. CONCLUSION: Being in high SEP was positively associated with MHCU, before and after ID, and more rapid PP contact, most explicit when measured by education. Co-payment for psychologist may divert care towards private psychiatrist for low-income groups.

Exploring Identity Disturbance and Psychotic Spectrum Symptoms as Predictors of Borderline and Schizotypal Personality Disorders.

INTRODUCTION: Borderline personality disorder (BPD) and schizotypal personality disorder (SPD) were introduced in DSM-III and retained in DSM-5 Section II. They often co-occur and some aspects of the clinical differentiation between the 2 diagnoses remain unclear (e.g., psychotic-like features and identity disturbance). METHODS: The present study explored if self-reported identity disturbance and psychosis proneness could discriminate between the BPD and SPD DSM-5 diagnoses. All patients were interviewed with the Schedules for Clinical Assessment in Neuropsychiatry and the Structured Clinical Interview for DSM-5 Personality Disorders, and administered the Inventory of Personality Organization, Self-Concept and Identity Measure, Schizotypal Personality Questionnaire, Perceptual Aberration Scale, and the Magical Ideation Scale. RESULTS: A total of 105 patients were initially assessed, 26 were excluded, and the final sample (N = 79) was composed of 34 BPD patients, 25 SPD patients, and 20 patients with co-occurring SPD and BPD. The BPD group (n = 34) was first compared with the pure SPD group (n = 25), and secondly with the total group of patients diagnosed with SPD (n = 25 + 20). Logistic regression analyses indicated that primitive defenses and disorganization best differentiated the BPD and the pure SPD group, while primitive defenses and interpersonal factor along with perceptual aberrations best differentiated the BPD and the total SPD group. CONCLUSION: Identity disturbance did not predict the diagnostic groups, but BPD patients were characterized by primitive defenses, which are closely related to identity disturbance. Pure SPD was characterized by oddness/eccentricity, while the lack of specificity for cognitive-perceptual symptoms suggests that the positive symptoms do not differentiate BPD from SPD.