Efficacy and safety of a mineral and vitamin treatment on symptoms of antenatal depression: 12-week fully blinded randomised placebo-controlled trial (NUTRIMUM).

BACKGROUND: Broad-spectrum micronutrients (minerals and vitamins) have shown benefit for treatment of depressive symptoms. AIMS: To determine whether additional micronutrients reduce symptoms of antenatal depression. METHOD: Eighty-eight medication-free pregnant women at 12-24 weeks gestation, who scored ≥13 on the Edinburgh Postnatal Depression Scale (EPDS), were randomised 1:1 to micronutrients or active placebo (containing iodine and riboflavin), for 12 weeks. Micronutrient doses were generally between recommended dietary allowance and tolerable upper level. Primary outcomes (EPDS and Clinical Global Impression - Improvement Scale (CGI-I)) were analysed with constrained longitudinal data analysis. RESULTS: Seventeen (19%) women dropped out, with no group differences, and four (4.5%) gave birth before trial completion. Both groups improved on the EPDS, with no group differences (P = 0.1018); 77.3% taking micronutrients and 72.7% taking placebos were considered recovered. However, the micronutrient group demonstrated significantly greater improvement, based on CGI-I clinician ratings, over time (P = 0.0196). The micronutrient group had significantly greater improvement on sleep and global assessment of functioning, and were more likely to identify themselves as 'much' to 'very much' improved (68.8%) compared with placebo (38.5%) (odds ratio 3.52, P = 0.011; number needed to treat: 3). There were no significant group differences on treatment-emergent adverse events, including suicidal ideation. Homocysteine decreased significantly more in the micronutrient group. Presence of personality difficulties, history of psychiatric medication use and higher social support tended to increase micronutrient response compared with placebo. CONCLUSIONS: This study highlights the benefits of active monitoring on antenatal depression, with added efficacy for overall functioning when taking micronutrients, with no evidence of harm. Trial replication with larger samples and clinically diagnosed depression are needed.

The impact of antidepressants and human development measures on the prevalence of sadness, worry and unhappiness: cross-national comparison.

Depression is a major public health concern. Depressed individuals have received increasing treatment with antidepressants in Western countries. In this study, we examine the relationship among individual symptoms (sadness, worry and unhappiness), human development factors and antidepressant use in 29 OECD countries. We report that increased antidepressant prescribing is not associated with decreased prevalence of sadness, worry or unhappiness. However, income, education and life expectancy (measured using the Human Development Index) are associated with lower prevalence of all these symptoms. This suggests that increasing spending on depression treatment may not be as effective as general public health interventions at reducing depression in communities.

Childhood anxious/withdrawn behaviour and later anxiety disorder: a network outcome analysis of a population cohort.

BACKGROUND: Several previous studies have identified a continuity between childhood anxiety/withdrawal and anxiety disorder (AD) in later life. However, not all children with anxiety/withdrawal problems will experience an AD in later life. Previous studies have shown that the severity of childhood anxiety/withdrawal accounts for some of the variability in AD outcomes. However, no studies to date have investigated how variation in features of anxiety/withdrawal may relate to continuity prognoses. The present research addresses this gap. METHODS: Data were gathered as part of the Christchurch Health and Development Study, a 40-year population birth cohort of 1265 children born in Christchurch, New Zealand. Fifteen childhood anxiety/withdrawal items were measured at 7-9 years and AD outcomes were measured at various interviews from 15 to 40 years. Six network models were estimated. Two models estimated the network structure of childhood anxiety/withdrawal items independently for males and females. Four models estimated childhood anxiety/withdrawal items predicting adolescent AD (14-21 years) and adult AD (21-40 years) in both males and females. RESULTS: Approximately 40% of participants met the diagnostic criteria for an AD during both the adolescent (14-21 years) and adult (21-40 years) outcome periods. Outcome networks showed that items measuring social and emotional anxious/withdrawn behaviours most frequently predicted AD outcomes. Items measuring situation-based fears and authority figure-specific anxious/withdrawn behaviour did not consistently predict AD outcomes. This applied across both the male and female subsamples. CONCLUSIONS: Social and emotional anxious/withdrawn behaviours in middle childhood appear to carry increased risk for AD outcomes in both adolescence and adulthood.

The long-term impacts of the Canterbury earthquakes on the mental health of the Christchurch Health and Development Study cohort.

OBJECTIVE: Long-term studies following disasters are rare. It is important to quantify long-term effects of disasters to determine impacts on populations over time. We therefore aim to report the long-term associations between exposure to the Canterbury earthquakes and common mental disorders, taking into account potential confounding factors. METHODS: The Christchurch Health and Development Study is a 40-year longitudinal study of a birth cohort of New Zealand children (635 males and 630 females). The Christchurch Health and Development Study includes 884 participants with data on earthquake exposure and mental health outcomes at ages 34 and 40 years. Rates of Diagnostic and Statistical Manual of Mental Disorders (4th ed.) disorders were measured categorically and using an expanded definition that included sub-syndromal symptoms. The current impact of the earthquakes is reported using 12-month prevalence data 7 years after the earthquakes. The cumulative impact of the earthquakes over the 7 years since onset is also reported. RESULTS: There was a linear trend towards increasing rates of disorder with increasing exposure to the earthquakes. After adjusting for covariates, the 12-month prevalence of anxiety disorder symptoms was significantly increased (p = 0.003). The earthquakes were also associated with cumulative increases in symptoms of post-traumatic stress disorder (p < 0.001), anxiety disorder (p = 0.016), nicotine dependence (p = 0.012), and the total number of disorders (p = 0.039). CONCLUSION: The Canterbury earthquakes were associated with persistent increases in Anxiety Disorder symptoms 7 years after their onset. The earthquakes were also associated with cumulative increases in symptoms of common psychiatric disorders. The magnitude of these effects is small, may no longer be clinically significant and has decreased over time.

Protocol for a randomised placebo-controlled trial investigating the efficacy and safety of a vitamin-mineral formula targeting dysregulated emotions in teenagers: The balancing emotions of adolescents with micronutrients (BEAM) study.

Background: Emotional dysregulation (ED) is a significant contributing factor to psychological distress in young people. ED is a transdiagnostic dimension characterized by an excessive reactivity to negative emotional stimuli with affective (anger) and behavioral (aggression) components, and is present across anxiety, mood and behavioral disorders. Due to early onset, high prevalence and persistence, ED in childhood is one of the most psychosocially impairing and cost-intensive mental health conditions, with not enough children improving with conventional treatments. Clinical trials have established preliminary efficacy of micronutrients (vitamins and minerals) in the treatment of ED. This project expands the research to examine micronutrient efficacy for teenagers with ED. Methods: This study is the first double-blind (participant and investigators) 8 week randomized controlled trial (with 8 week open-label extension and one year follow-up) designed to explore the efficacy and safety of micronutrients compared with placebo in 150 medication-free emotionally dysregulated youth (12-17 years), referred via self-referral, delivered remotely throughout New Zealand, using a website for monitoring symptoms, with a psychologist available online via text, email and video for assessment and monitoring. The primary outcome measures will be the Clinical Global Impression (CGI-I), the reactivity subscale of the Emotion Dysregulation Inventory (EDI) and the Clinician Rated Temper and Irritability Scale (CL-ARI). Discussion: Micronutrient intervention delivered alongside online assessment and monitoring has the potential to transform delivery of mental health care to young people who may not be willing or able to access traditional therapies. We also hope that this intervention shows acceptability across different ethnicities.

Multisite sentinel surveillance of self-harm in New Zealand: protocol for an observational study.

INTRODUCTION: New Zealand (NZ) has a persistently high rate of suicide, particularly among young people. Hospital presentation for self-harm (SH) is one of the strongest predictors of death by suicide. Improving the monitoring of SH and suicide is a key recommendation for suicide prevention by WHO. This study will establish the first ever sentinel surveillance for SH at several large hospitals and a monthly survey of all practicing paediatricians in NZ. The study will provide robust information about the epidemiology of SH, factors associated with SH and the types of interventions required for those presenting to hospital with SH. METHOD AND ANALYSIS: This observational study will establish SH surveillance in the emergency departments of three public hospitals for the first time in NZ, where study population will include individuals of all ages who present with SH or suicidal ideation. The study methodology is in line with the WHO Best Practice guidelines and international collaborators in Australia and Europe. Electronic triage records will be reviewed manually by the research team to identify potential cases that meet inclusion criteria. For all eligible cases, variables of interest will be extracted from routine clinical records by the research team and recorded on a secure web-based survey application. Additionally, SH surveillance data for the national paediatric population (<15 years) will be obtained via the New Zealand Paediatric Surveillance Unit (NZPSU); paediatricians will report on included cases using the same variables using a secure survey application. A deidentified dataset will be produced for aggregated statistical analysis. ETHICS AND DISSEMINATION: The University of Otago Health Ethics Committee granted ethical approval for this study in addition to local ethics approval at participating hospital sites. The study findings will be disseminated to relevant stakeholders in NZ, in addition to international audiences through publications in peer-reviewed scientific journals and conference presentations.

Expanding the system: A brief psychosocial complex systems model of internalising disorder.

BACKGROUND: The aetiology of internalising disorders remains poorly understood. Recently, a bottom-up network perspective has suggested mental disorders are best conceptualised as emergent systems, and may be explained by mapping systems of symptoms embedded within a complex biopsychosocial environment. Under this framework, the complex system in which internalising disorders are embedded remains poorly understood. The present research outlines a brief psychosocial system of internalising disorders as a basis for future research. METHODS: A Mixed Graphical Model was fitted on 15 psychosocial variables (including depression and anxiety) collected during the Christchurch Health and Development Study, a representative population birth cohort of 1265 people born in 1977 in Christchurch, New Zealand. RESULTS: The model demonstrates that psychosocial risk factors for internalising disorders tend to be inter-related. The psychosocial system accounted for 19.9% of the variance in the diagnostic depression variable, and 5.0% of the variance in diagnostic anxiety. Most variables (10/13) were associated with depression and anxiety either directly or indirectly. LIMITATIONS: First, the estimated model is undirected, so causal directions are unspecified except for longitudinal relationships. Second, binary diagnostic variables were used for depression and anxiety, meaning the model does include symptom-level complexity. Third, the model does not account for within-person effects. CONCLUSIONS: This exploratory model may serve as a basis for the mapping of greater (bio) psychosocial complexity around internalising disorders. The model concisely demonstrates the need for researchers to "embrace complexity", but also underscores the conceptual scope that is required to do so on a broader (bio) psychosocial level.

Long-term efficacy of metacognitive therapy and cognitive behaviour therapy for depression.

OBJECTIVE: To examine the two-year outcomes for depression, anxiety, cognitive and global social functioning after cognitive behavioural therapy (CBT) and metacognitive therapy (MCT) for depression. METHOD: Participants were 31 adults with a diagnosis of major depressive disorder in a randomised pilot study comparing MCT and CBT. Therapy modality differences in change in depression and anxiety symptoms, dysfunctional attitudes, metacognitions, rumination, worry and global social functioning were examined at the two-year follow-up for those who completed therapy. RESULTS: Significant improvements, with large effect sizes, were evident for all outcome variables. There were no significant differences in outcome between CBT and MCT. The greatest change over time occurred for depression and anxiety. Large changes were evident for metacognitions, rumination, dysfunctional attitudes, worry and global social functioning. Sixty-seven percent had not experienced a major depression and had been well during all of the past year, prior to the follow-up assessment. CONCLUSION: The finding at end treatment, of no modality specific differences, was also evident at two-year follow-up. Although CBT and MCT targeted depression, improvements were much wider, and although CBT and MCT take different approaches, both therapies produced positive change over time across all cognitive variables. CBT and MCT provide treatment options, that not only improve the longer-term outcome of depression, but also result in improvements in anxiety, global social functioning and cognitive status.

National characteristics associated with prevalence of depression and anxiety symptoms: a cross-sectional ecological study.

Background: Cross-national comparisons of the prevalence of mental disorders have relied on lay-administered interviews scored using complex diagnostic algorithms. However, this approach has led to some paradoxical findings, with more vulnerable countries showing lower prevalence, and its appropriateness for cross-national comparisons has been questioned. This study used an alternative method involving simple questions from social surveys to assess the prevalence of specific depression and anxiety symptoms, and investigated their association with national indicators of human development, quality of government, mental health resources, and mental health governance. Methods: The study used data on the prevalence of three symptoms indicating depression or anxiety: sadness, worry, and unhappiness. These data were taken from the Gallup World Poll (142 countries) and the World Values Survey (77 countries). National characteristics examined covered indicators of human development (income, life span, education, gender equality), quality of government (human freedom, perceptions of corruption), mental health resources (per capita numbers of psychiatrists, mental health nurses, psychologists, and social workers), and mental health governance (whether there is a national mental health plan and a mental health law). Results: All the human development and quality of government indicators, and some of the mental health resource indicators, were strongly associated with a lower prevalence of symptoms. Conclusion: Populations of nations with higher human development, quality of government, and mental health resources have better mental health when measured by the prevalence of specific symptoms.

The five year outcome of major depression: Effects of baseline variables and type of treatment.

BACKGROUND: Depression is commonly a relapsing or chronic disorder. Long-term outcome is therefore important. We report on the outcome of major depression five years after receiving treatment with medication or psychotherapy. METHODS: 472 patients were treated in three consecutive randomised controlled trials in one clinical research centre. 298 were followed up at five years. Of these, 106 patients were treated with medications, while the remaining 192 were given psychotherapy. The a priori outcome measure was mood symptoms in the two years prior to the assessment. RESULTS: The majority (56%) of patients had no depressive symptoms in the prior two years. One third (32%) had fluctuating depression, while 12% were chronic depressed. Predictors of outcome were few; baseline severity, suicidality, personality pathology, and type of treatment. Those receiving medication did somewhat worse, even when adjusted for this group's higher depression severity, suicidality and personality pathology at baseline. CONCLUSIONS: Long-term depressive symptoms are common after evidence-based treatment, although over half the patients appear to recover. Psychotherapy may be superior to medication in reducing the level of symptoms in the longer term. Personality remains one of the few baseline predictors of long-term outcome.

Is mandatory prospective trial registration working? An update on the adherence to the International Committee of Medical Journal Editors guidelines across five psychiatry journals: 2015-2020.

OBJECTIVE: Previous research indicated that the International Committee of Medical Journal Editors guidelines of prospective trial registration with clearly identified primary and secondary outcome measures are only adhered to in 14.4% of studies published in the top five psychiatry journals between 1 January 2009 and 31 July 2013. This study examined if adherence has improved. METHODS: The registration information, article information, primary outcome measures (POMs), participant numbers and funding source were extracted from studies published in the same five psychiatry journals between 1 January 2015 and 31 December 2019. Discrepancies between POMs in the articles and registry were tracked. RESULTS: Of the 7268 publications, 268 studies required registration. Three (1.1%) were unregistered, 107 (39.9%) were retrospectively registered, and 158 (58.9%) were prospectively registered. Of the 158 prospectively registered studies, 16 (10.1%) had unclear POMs in the article or registration, 22 (13.9%) had discrepancies between registered and published POMs, and 33 (20.9%) had no POM discrepancies but had retrospectively updated POMs in the registry. Of the 22 studies with discrepancies, nine (40.9%) were determined to favour statistically significant results. Overall, 87 (32.5%) of the 268 studies were prospectively registered with no discrepancies between registered and published POMs and no changes to registered POMs or timeframes. CONCLUSION: Although this rate of one third of published articles fully adhering to the guidelines is an improvement compared to previous research, further efforts still need to be made by both authors and journals to ensure full transparency in the reporting of studies in psychiatry.

ICD-11 Personality Disorders: Utility and Implications of the New Model.

The ICD-11 classification of personality disorders represents a paradigm shift in diagnosis. This was felt necessary because previous personality disorder classifications had major problems. These included unnecessary complexity, inconsistency with data on normal personality traits, and minimal consideration of severity despite this being shown to be the major predictor of outcome. The ICD-11 classification abolishes all categories of personality disorder except for a general description of personality disorder. This diagnosis can be further specified as "mild," "moderate," or "severe." Patient behavior can be described using one or more of five personality trait domains; negative affectivity, dissociality, anankastia, detachment, and disinhibition. Clinicians may also specify a borderline pattern qualifier. The ICD-11 shows considerable alignment with the DSM-5 Alternative Model for Personality Disorders. Early evidence around the reliability and validity of the new model appear promising, although at present there is still limited specific evidence due to the model being so recently finalized. However, for the model to be successful, it needs to be embraced by clinicians and used widely in normal clinical practice.

Development and initial evaluation of the ICD-11 personality disorder severity scale: PDS-ICD-11.

AIM: No measure has formally been developed to assess the published ICD-11 model of Personality Disorder (PD) severity. We therefore set out to develop and evaluate the 14-item Personality Disorder Severity ICD-11 (PDS-ICD-11) scale. METHOD: A representative U.S. community sample (N = 428; 50.9% women) and a New Zealand mental health sample (N = 87; 61.5% women) completed the PDS-ICD-11 scale along with a series of established PD and impairment measures. RESULTS: Item response theory supported the unidimensionality of PDS-ICD-11 (median item loading of 0.68) and indicated that a PDS-ICD-11 score of 17.5 may serve as a benchmark for pronounced dysfunction. Correlation and regression analyses supported both criterion validity and incremental validity in predicting impairment and PD symptoms. The PDS-ICD-11 was particularly associated with measures of Level of Personality Functioning Scale (LPFS), Global PD severity, and Borderline PD symptom score. A comparison between clinical individuals diagnosed with an ICD-11 PD vs. no PD supported diagnostic validity. CONCLUSION: This initial construction study suggests that the PDS-ICD-11 constitutes a promising instrument that provides a quick impression of the severity of personality dysfunction according to the official ICD-11 PD guidelines. Clearly, more research is needed to corroborate its validity and utility. The PDS-ICD-11 scale is provided as online supporting information.

Pyroluria: Fact or Fiction?

Objective: The term "Mauve factor" (pyrroluria) dates back to 1958 when Dr. Abram Hoffer defined the condition as elevated levels of pyrroles in the urine, currently called hydroxyhemepyrrolin-2-one (HPL). It was suggested that the raised pyrrole levels lead to depletions in zinc and vitamin B6, which, in turn, were hypothesized to result in a range of psychiatric disorders, such as schizophrenia, anxiety, and depression. Treatment implications are supplementation with zinc and B6. This article aimed to review the scientific literature associating pyrroluria with psychiatric symptoms, explore the validity of HPL testing, explore the role of nutrients as treatment options for pyrroluria, and discuss future research directions. Methods: A PRISMA review was conducted using search results from electronic databases PubMed, MEDLINE, PsycINFO, EMBASE from inception to February 2020 using the following keywords: hydroxyhemepyryrrolin (HPL), kryptopyrrole (KP), mauve factor, pyroluria, pyrroluria, monopyrroles. Article reference lists were also scanned and included where relevant. Results: Seventy-three articles were identified of which only three studies identified significantly higher HPL levels in a psychiatric population compared with controls, and there were no placebo-controlled treatment trials directed at pyrroluria. The other 13 clinical studies either showed no association or did not provide adequate data to show group differences in HPL levels. Despite an extensive history of practitioners diagnosing and treating a wide variety of mental health conditions associated with pyrroluria as well as clinical observations of elevated HPL being associated with psychiatric disorders, there was no clear research that showed the following: (1) elevated HPL is robustly associated with increased mental health symptoms, (2) elevated HPL in urine is associated with increased urine excretion of zinc and B6, and (3) high-dose zinc and B6 are an efficacious treatment for mental health problems associated with elevated HPL. Conclusions: Elevated HPL is a clinically observed, but poorly researched biomarker with unclear associations with mental disorders. Based on current evidence, HPL testing is not recommended as a screening or treatment tool. Further research is required in the following areas: establishment of which specific clinical populations exhibit elevated HPL, validation of the chemistry and validity of testing, and controlled trials to establish efficacy of high-dose zinc and B6 as treatment of elevated pyrroles.

Cross-national differences in the prevalence of mental illness symptoms: Evidence against the vulnerability paradox.

OBJECTIVES: The vulnerability paradox refers to the observation that greater vulnerability is associated with higher prevalence of mental disorder at the individual level, but lower prevalence at the country level. The paradox is supported by studies estimating prevalence using the Composite International Diagnostic Interview and by suicide mortality data. However, cross-national studies using single-item measures of subjective well-being find no evidence of a paradox, with vulnerability being associated with lower well-being at both the individual and country levels. These findings suggest the potential usefulness of simple indicators for studying cross-national differences. In this study, we investigated the vulnerability paradox using cross-national data on the prevalence of three symptoms that indicate depression or anxiety: unhappiness, sadness and worry. METHODS: The data on prevalence of unhappiness were taken from 77 countries in the World Values Survey 2017-2020 and data on prevalence of sadness and worry from 142 countries in the Gallup World Poll in 2018. Country vulnerability was measured by the Vulnerability Index and gross domestic product per capita. The data were analyzed using random-effects meta-analysis, with vulnerability measures as moderator variables. RESULTS: For all three symptoms, prevalence was associated with higher Vulnerability Index and lower gross domestic product per capita. When both moderators were entered in meta-regressions, there were significant associations for the Vulnerability Index, but not for gross domestic product per capita. CONCLUSION: These findings are inconsistent with the vulnerability paradox. They underscore that reducing mental disorders should be a priority in poorer nations and that further economic and social development may be an important contributor to achieving this.

The borderline pattern descriptor in the International Classification of Diseases, 11th Revision: A redundant addition to classification.

OBJECTIVE: The International Classification of Diseases, 11th Revision classification of personality disorder removes all categories of disorder in favour of a single diagnostic spectrum extending from no personality dysfunction to severe personality disorder. Following concerns from some clinicians and Personality Disorder Societies, it was subsequently agreed to include a borderline pattern descriptor as a qualifier of the main diagnosis. We explore the value of this additional descriptor by examining personality data in patients with major depression. METHOD: We examined personality data obtained using the Structured Clinical Interview for Personality Disorder-II in 606 patients enrolled in five randomised controlled trials of depression. The Structured Clinical Interview for Personality Disorder-II uses the Diagnostic and Statistical Manual of Mental Disorders categorical system, which includes borderline personality disorder. The International Classification of Diseases, 11th Revision classification has five domain traits. Each of the Diagnostic and Statistical Manual of Mental Disorders personality disorder symptoms or behaviours from Structured Clinical Interview for Personality Disorder-II was reordered into the five domains independently by two assessors. The relationship between the two systems was examined by tabular and correlational analysis. RESULTS: The findings showed that the symptoms of borderline personality disorder were associated with greater severity of personality disturbance in the International Classification of Diseases, 11th Revision classification (p < 0.0001) and were associated primarily with the Negative Affective, Dissocial and Disinhibited domains. There was only a weak association with the other two domains, Anankastia and Detachment. CONCLUSION: The addition of a borderline pattern descriptor is likely to add little to the International Classification of Diseases, 11th Revision classification of personality disorder. Its features are well represented within the severity/domain structure, which allows for more fine-grained description of the personality features that constitute the borderline concept.