Menopause depression: Under recognised and poorly treated.

Menopause is a biological process experienced by all people assigned female at birth. A significant number of women experience mental ill health related to the major brain gonadal hormone shifts that occur in their midlife. There is poor understanding and management of the complex mental ill health issues, with the biological brain hormone changes receiving little formal attention. The current treatment advice is to manage this special type of mental ill health in the same way that all mental ill health is managed. This leads to poor outcomes for women and their families. Many women leave the workforce earlier than expected due to menopause-related depression and anxiety, with subsequent loss of salary and superannuation. Others describe being unable to adequately parent or maintain meaningful relationships - all ending in a poor quality of life. We are a large and diverse group of national and international clinicians, lived experience and social community advocates, all working together to innovate the current approaches available for women with menopausal mental ill health. Above all, true innovation is only possible when the woman with lived experience of menopause is front and centre of this debate.

Exploring the cognitive profiles related to unimodal auditory versus multisensory hallucinations in schizophrenia-spectrum disorders.

INTRODUCTION: Hallucinations can be experienced across multiple sensory modalities, but psychiatric studies investigating the cognitive mechanisms of hallucinations have been somewhat restricted to the auditory domain. This study explored the cognitive profiles of individuals experiencing multisensory hallucinations (MH) in schizophrenia-spectrum disorders (SSD) and compared these to those experiencing unimodal auditory hallucinations (AH) or no hallucinations (NH). METHODS: Participants included SSD patients (n = 119) stratified by current hallucination status (NH, AH, MH) and nonclinical controls (NCs; n = 113). Group performance was compared across several cognitive domains: speed of processing, attention, working memory, verbal learning, visual learning, reasoning and problem-solving, social cognition, and inhibition. RESULTS: The clinical groups performed worse than NCs but differences between the clinical groups were not evident across most cognitive domains. Exploratory analyses revealed that the MH group was more impaired on the visual learning task compared to the NH (but not AH) group. CONCLUSIONS: Preliminary results suggest that impaired visual learning may be related to MH. This could be attributed to the presence of visual hallucinations (VH), or greater psychopathology, in this group. However, replication is needed, as well as the investigation of other potential cognitive mechanisms of MH.

Estrogen and psychosis - a review and future directions.

The link between sex hormones and schizophrenia has been suspected for over a century; however, scientific evidence supporting the pharmacotherapeutic effects of exogenous estrogen has only started to emerge during the past three decades. Accumulating evidence from epidemiological and basic research suggests that estrogen has a protective effect in women vulnerable to schizophrenia. Such evidence has led multiple researchers to investigate the role of estrogen in schizophrenia and its use in treatment. This narrative review provides an overview of the effects of estrogen as well as summarizes the recent work regarding estrogen as a treatment for schizophrenia, particularly the use of new-generation selective estrogen receptor modulators.

Identifying overcontrol and undercontrol personality types among young people using the five factor model, and the relationship with disordered eating behaviour, anxiety and depression.

BACKGROUND: Overcontrol and undercontrol personality types have been associated with an increase in eating pathology, depression and anxiety. The aim of the research was to explore whether latent overcontrol and undercontrol personality types could be identified using cluster analysis of the facets of the five factor model (FFM). We further aimed to understand how these personality types were associated with eating pathology, depressed mood and anxiety. METHODS: A total of 561 participants (394 women and 167 men), aged 16-30 years in Australia completed a survey designed to assess disordered eating, FFM personality traits, anxiety, depression and stress. A systematic four-step process using hierarchical, k-means, and random forest cluster analyses were used to identify a meaningful 3-cluster solution. RESULTS: The results revealed a cluster solution that represented overcontrol, undercontrol and resilient personality types, and highlighted facets of the FFM that were associated with each type. Both overcontrol and undercontrol personality types were associated with increased clinical symptoms compared to the resilient types. CONCLUSIONS: It was concluded that FFM facets may potentially be more meaningful than broad domains in identifying personality types, and that both overcontrol and undercontrol personality types are likely associated with increased clinical symptoms.

Personality has previously been found to be strongly related to eating disorders and disordered eating. A person's personality is made up by a series of personality traits. A series of traits grouped together is called a personality type. Three broad personality types have been identified consistently in previous research, being overcontrol (rigid, perfectionistic), undercontrol (impulsive, mood dependent) and resilient (flexible, low pathology). Understanding eating disorders in the context of overcontrol, undercontrol and resilient personality types has been found to be predict disordered eating behaviour and treatment course for people with eating disorders. This study aimed to identify personality types using the well known five factor model of personality among a group of Australian young people. We also aimed to understand the relationships between personality type and eating pathology. It was found that a wider range of personality traits may be more meaningful than broad domains in identifying personality types. It was further found that individuals who were overcontrol or undercontrol were more likely to experience eating pathology and disordered eating compared to resilient types. Overall, this means that that the five factor model of personality may be useful for identifying people at risk for developing an eating disorder and to consider treatment needs.

Evaluation of the Everyday Memory Questionnaire-Revised in a menopausal population: understanding the brain fog during menopause.

OBJECTIVE: Brain fog (ie, memory complaints and concentration difficulties) is frequently reported during the menopausal transition. There is lack of standardized scales available to measure brain fog across the menopausal transition. This study aimed to evaluate the factor structure of the Everyday Memory Questionnaire-Revised (EMQ-R) and to determine the most commonly reported everyday cognitive symptoms in a menopausal population. METHODS: Four hundred seventeen eligible women aged from 40 to 60 years (107 premenopausal, 149 perimenopausal, and 161 early postmenopausal) were recruited from the general community and were included in the analyses. Confirmatory factor analysis was conducted to test the model fit of the bifactor structure (ie, 4-item attentional subscale ranged 0-16, 7-item retrieval subscale ranged 0-28) of the 13-item EMQ-R (ranged 0-52) in a menopausal populations. Typical items in the retrieval subscale include "difficulty finding words," the attentional subscale include "difficulty following the thread of a story," and analysis of variance and multivariate analysis of covariance were used to investigate the group differences of individual items and two subscales. RESULTS: Confirmatory factor analysis indicated the bifactor structure of the EMQ-R has a good fit in all three groups. A significant difference was identified in the mean retrieval scores (pre: 11.8, peri: 13.6, early post: 11.7) but not in the mean attentional scores (pre: 4.53, peri: 5.01, early post: 4.65). CONCLUSIONS: The EMQ-R retrieval subscale may serve as a potential instrument to assess memory retrieval symptoms that contribute to "brain fog" in menopause. Increased memory retrieval complaints reported by the perimenopausal group suggests a transition-related memory retrieval dysfunction during menopausal transition.

Perceived Discrimination in Australia During the COVID-19 Pandemic: a Longitudinal Study.

OBJECTIVES: There have been global reports of increased discrimination during the COVID-19 pandemic relative to the pre-pandemic era, though this has not been well explored within Australia. The aim of the study was to characterise discriminatory behaviour experienced by groups previously identified as most at risk of experiencing discrimination (i.e. those of Asian descent or healthcare workers) both from pre-pandemic to pandemic and during the pandemic era in Australia. METHODS: From April 2020 to September 2021, 1479 Australian adults completed the everyday discrimination scale (EDS). Initially, participants were asked to retrospectively consider discrimination experienced pre-COVID-19 pandemic and then to consider experiences in the past month during the pandemic. Participants were invited to repeat the latter every 2 months. RESULTS: Collectively, there was a reduction in EDS scores from pre-pandemic to pandemic. Within the pandemic era, mean trajectory graphs across time revealed that changes in EDS scores in the 'non-Asian healthcare workers' and 'Asian healthcare workers' subgroups tended to mirror onto fluctuations in Australian COVID-19 case numbers. CONCLUSION: Our findings suggest social solidarity amongst the general Australian population during the pandemic, but still highlight a need to dedicate resources towards groups with heightened risk of experiencing discrimination during future public health threats.

The association between adverse events in later life and mortality in older individuals.

Background: Stress can have adverse impacts on health, particularly when it is chronic or resulting from major adverse events. Our study investigated whether relatively common adverse events in older individuals were associated with an increased risk of death, as well as cause-specific death and potential gender differences. Methods: Participants were 12896 community-dwelling Australians aged ≥70 years at enrolment into the ASPREE (ASPirin in Reducing Events in the Elderly) study and without known life-limiting disease. A questionnaire administered in the year after enrolment, collected information on ten adverse events experienced in the past year. Mortality status was verified by multiple sources including health records and the National Death Index across a maximum of 10 years. Underlying causes of death were determined using clinical information by two adjudicators. Cox-proportional hazards regression models were used to estimate mortality risk. Results: Two of the ten adverse events were associated with an increased risk of mortality in fully adjusted models. A 69% increased risk of mortality was observed in participants who reported their spouse/partner had recently died (95% CI: 1.19-2.39, P < 0.01). Cancer-related but not cardiovascular deaths also increased. Participants with a seriously ill spouse/partner also had a 23% increased risk of mortality (HR: 1.23, 95% CI: 1.02-1.48, P = 0.03). There was a tendency for these associations to be stronger among men than women. Limitations: Perceived stress and cortisol were not measured, thus limiting our understanding of the psychological and physiological impacts of adverse events. Conclusions: Experiencing adverse events in later-life, especially the death of a spouse/partner, may be a risk factor for earlier mortality. These findings may increase public health awareness and better inform initiatives for particular groups, including bereaved men.

Adverse events in older adults and the risk of dementia and cognitive decline.

Background: Increasing evidence suggests that stress could be a risk factor for dementia but this might vary by gender. This study investigated whether adverse life events were associated with cognitive decline and dementia in later-life, separately in men and women. Methods: Participants were 12,789 community-dwelling Australians aged ≥ 70 years. Ten common adverse events in later-life were self-reported. Cognitive decline was defined as a 1.5 SD decline from participants' baseline score in tests of global cognition, psychomotor speed, episodic memory, and executive functioning, which were assessed regularly over a maximum of 10.3 years. Dementia was diagnosed according to DSM-IV criteria. Results: An increased risk of dementia was observed in participants who experienced the death of a spouse/partner (HR: 1.72, 95% CI: 1.17 - 2.52) and for individuals who experienced major financial problems (HR: 1.53, 95% CI: 1.05 - 2.23). The latter also increased the risk of cognitive decline in men specifically (HR: 1.43, 95% CI: 1.10 - 1.86). In contrast, some events for women were associated with a reduced risk of dementia (e.g. close family or friends lost their job/retired (HR: 0.62, 95% CI: 0.40-0.95)). Limitations: Events including major money problems may result from prodromal dementia symptoms, thus reverse causation needs to be considered. Conclusions: Adverse life events may influence dementia risk in older adults, but associations vary depending on the nature of the event, and across genders. These findings support the need for early interventions in older people who have experienced adversities, particularly for the death of a loved one.

Impact of COVID-19 on health of menopausal women: A scoping review.

OBJECTIVE: This scoping review aims to map and summarize the direct impact of contracting COVID-19, and the indirect consequences of the pandemic on the health of peri- and postmenopausal women. METHODS: Searches for published studies were conducted in CINAHL, Cochrane, EMBASE, PubMed, Scopus, Web of Science, PsycINFO and ProQuest from inception to 26 Oct, 2022. Grey literature and reference lists of included studies were searched. Results are presented as a narrative synthesis and tables. RESULTS: Thirty-eight studies were selected in this review. Overall, a majority of studies (n = 31) suggest that menopausal women were negatively impacted, while lesser studies (n = 21) concluded that they were not and some studies (n = 14) produced both negative and neutral results. Twenty-three studies presented on the direct health impact of COVID-19 infections on menopausal women. Eleven studies focused on the indirect impact of COVID-19 in terms of contact restriction measures on menopausal health during the pandemic compared to before the pandemic. Six studies described the different indirect impact of COVID-19 on health of menopausal women with various characteristics or lifestyles. CONCLUSION: The direct and indirect impacts of COVID-19 on menopausal women on physical, mental health and social wellbeing are largely negative.

Dimensional personality pathology and disordered eating in young adults: measuring the DSM-5 alternative model using the PID-5.

Introduction: The Personality Inventory for DSM-5 (PID-5) is a self-report measure of personality pathology designed to measure pathological personality traits outlined in the DSM-5 alternative model of personality disorders. Within the extensive literature exploring the relationship between personality and disordered eating, there are few that explore the relationship between the PID-5 and disordered eating behaviours in a non-clinical sample of males and females: restrictive eating, binge eating, purging, chewing and spitting, excessive exercising and muscle building. Methods: An online survey assessed disordered eating, PID-5 traits and general psychopathology and was completed by 394 female and 167 male participants aged 16-30. Simultaneous equations path models were systematically generated for each disordered eating behaviour to identify how the PID-5 scales, body dissatisfaction and age predicted behaviour. Results: The results indicated that each of the six disordered behaviours were associated with a unique pattern of maladaptive personality traits. The statistical models differed between males and females indicating possible differences in how dimensional personality pathology and disordered eating relate. Discussion: It was concluded that understanding disordered eating behaviour in the context of personality pathology may assist formulating potentially risky behaviour.

Lifetime posttraumatic stress disorder as a predictor of mortality: a systematic review and meta-analysis.

BACKGROUND: Posttraumatic Stress Disorder (PTSD) could potentially increase the risk of mortality, and there is a need for a meta-analysis to quantify this association. This study aims to determine the extent to which PTSD is a predictor of mortality. METHODS: EMBASE, MEDLINE, and PsycINFO were searched systematically on 12th February 2020, with updated searches conducted in July 2021, and December 2022 (PROSPERO CRD42019142971). Studies involving community-dwelling participants with a diagnosis of PTSD or PTSD symptoms, and a comparator group of individuals without PTSD, and which assessed mortality risk, were included. A random-effects meta-analysis was conducted on studies reporting Odds Ratio (OR), Hazard Ratio (HR), and Risk Ratio (RR), and subgroup analysis was also performed by age, sex, type of trauma experienced, PTSD diagnosis, and cause of death. RESULTS: A total of 30 eligible studies of mostly good methodological quality were identified, with a total of more than 2.1 million participants with PTSD. The majority of studies involved male-dominated, veteran populations. PTSD was associated with a 47% (95% CI: 1.06-2.04) greater risk of mortality across six studies that reported OR/RR, and a 32% increased risk across 18 studies which reported time to death (HR: 1.32, 95% CI: 1.10-1.59). There was very high study heterogeneity (I2 > 94%) and this was not explained by the prespecified subgroup analysis. CONCLUSION: PTSD is associated with increased mortality risk, however further research is required amongst civilians, involving women, and in individuals from underdeveloped countries.

The use of first and second-generation antipsychotic drugs and the potential to develop gestational diabetes mellitus among perinatal patients with psychosis.

There is limited knowledge about the effects of antipsychotic exposure on the development of gestational diabetes mellitus (GDM) in women with mental illness. Studies have demonstrated an association between antipsychotic medications and metabolic problems such as weight gain and diabetes mellitus in non-pregnant patients with psychiatric disorders. GDM increases the risk of adverse maternal outcomes, including pregnancy-induced hypertension, antepartum and postpartum haemorrhage, and caesarean delivery. The National Register of Antipsychotic Medication in Pregnancy (NRAMP) is a prospective Australian cohort study that observed women who took antipsychotics during pregnancy. Data from 205 women were extracted for the final analysis and included women who took first or second-generation antipsychotics (FGA,SGA) during the first trimester of pregnancy (at minimum) and had a diagnosis of a psychotic disorder (n = 180). The comparison (non-exposed) group (n = 25) were women with psychosis who chose not to take any antipsychotic during the first trimester (at minimum). The comparison groups were not matched, although groups were homogenous in terms of sex, age range, diagnosis and perinatal status. The results of logistic regression analysis revealed that women who were exposed to FGAs, SGAs were seven and five times, respectively, more likely to develop GDM compared to non-exposed groups. When adjusted for confounding variables such as BMI and family history of diabetes, the potential of developing GDM decreased for women taking SGAs. In conclusion, the risk of developing GDM is lower in women taking SGAs compared with women taking FDAs. In addition, family history of diabetes and BMI adds to the risk.

Non-visual hallucinations in Parkinson's disease: a systematic review.

BACKGROUND: Non-visual hallucinations in Parkinson's disease (PD) can be prevalent and distressing. Most existing research has however, focused on visual hallucinations as well as related risk factors. The current study thus conducted a systematic review to collate existing evidence on non-visual hallucinations in PD, focusing on their prevalence, phenomenology, and clinical-cognitive correlates. METHODS: Ninety-one relevant studies were included from a systematic search across PsycINFO APA, PubMed, and Web of Science, for peer-reviewed publications in the English language, from 1970 to the present. These comprised a mix of case (30 studies; n = 56) and group design (62 studies; n = 7346) studies, divided into three somewhat overlapping collections to address our three research foci. RESULTS: Prevalence estimates for hallucinations were: auditory 1.5-72.0%, olfactory 1.6-21.0%, somatic-tactile 0.4-22.5%, gustatory 1.0-15.0%, and sensed presence 0.9-73.3%. Phenomenological inquiries revealed descriptions of vivid, consuming events replete with elaborate detail, adversely affecting PD patients in different ways. Overt experiences of multisensory hallucinations were also highly variable (0.4-80%) but exceedingly common, reported by almost half of the 45 included prevalence studies. There was some evidence for modality-specific hallucination predictors, but this was largely tentative, pending robust replication. CONCLUSIONS: Marked prevalence figures coupled with phenomenological descriptions implicating distress denote that non-visual and multisensory hallucinations in PD are of clinical significance. More direct research and clinical attention need to be devoted to the study and management of such hallucinatory experiences.

Oral contraceptives and cognition: A systematic review.

Oral contraceptives (OCs) are widely used. While the physical impacts of OCs have been well researched, there is increasing interest on potential impacts of OCs on brain, behaviour and cognition. We systematically reviewed the literature to determine the influence of OCs on cognition, including neurocognition, social cognition and emotional processing. Inclusionary criteria were: (a) premenopausal females taking OCs; (b) a control group of naturally cycling women or OCs users in their inactive (i.e. 'sugar pill') phase; and (c) at least one measure of performance on a neurocognitive or social cognitive task. The systematic review found that OC use was associated with some differences in performance on all cognitive domains examined (with the exception of basic auditory attention and psychomotor performance). Several factors were identified that are likely to modulate the way OCs influence cognition, including task related factors, OC type and control group characteristics. Directions for future research are highlighted.

One size does not fit all: Exploring how the five-factor model facets predict disordered eating behaviours among adolescent and young adult males and females.

There is a wealth of research that has highlighted the relationship between personality and eating disorders. It has been suggested that understanding how subclinical disordered eating behaviours are uniquely associated with personality can help to improve the conceptualization of individuals with eating disorders. This study aimed to explore how the facets of the Five-Factor Model (FFM) predicted restrictive eating, binge eating, purging, chewing and spitting, excessive exercising and muscle building among males and females. An online survey assessing disordered eating behaviours, FFM and general psychopathology was completed by 394 females and 167 males aged between 16 and 30 years. Simultaneous equations path models were systematically generated for each disordered eating behaviour to identify how the FFM facets, body dissatisfaction and age predicted behaviour. The results indicated that each of the six disordered behaviours were predicted by a unique pattern of thinking, feeling and behaving. Considerable differences between males and females were found for each path model, suggesting differences between males and females in the personality traits that drive disordered eating behaviours. It was concluded that it is important to take personality into account when treating males and females who engage in disordered eating behaviours.

The relationship between cognitive clusters and telomere length in bipolar-schizophrenia spectrum disorders.

BACKGROUND: Schizophrenia and bipolar disorder are complex mental illnesses that are associated with cognitive deficits. There is considerable cognitive heterogeneity that exists within both disorders. Studies that cluster schizophrenia and bipolar patients into subgroups based on their cognitive profile increasingly demonstrate that, relative to healthy controls, there is a severely compromised subgroup and a relatively intact subgroup. There is emerging evidence that telomere shortening, a marker of cellular senescence, may be associated with cognitive impairments. The aim of this study was to explore the relationship between cognitive subgroups in bipolar-schizophrenia spectrum disorders and telomere length against a healthy control sample. METHODS: Participants included a transdiagnostic group diagnosed with bipolar, schizophrenia or schizoaffective disorder (n = 73) and healthy controls (n = 113). Cognitive clusters within the transdiagnostic patient group, were determined using K-means cluster analysis based on current cognitive functioning (MATRICS Consensus Cognitive Battery scores). Telomere length was determined using quantitative PCRs genomic DNA extracted from whole blood. Emergent clusters were then compared to the healthy control group on telomere length. RESULTS: Two clusters emerged within the patient group that were deemed to reflect a relatively intact cognitive group and a cognitively impaired subgroup. Telomere length was significantly shorter in the severely impaired cognitive subgroup compared to the healthy control group. CONCLUSIONS: This study replicates previous findings of transdiagnostic cognitive subgroups and associates shorter telomere length with the severely impaired cognitive subgroup. These findings support emerging literature associating cognitive impairments in psychiatric disorders to accelerated cellular aging as indexed by telomere length.

Evidence that a working memory cognitive phenotype within schizophrenia has a unique underlying biology.

It is suggested studying phenotypes within the syndrome of schizophrenia will accelerate understanding the complex molecular pathology of the disorder. Supporting this hypothesis, we have identified a sub-group within schizophrenia with impaired working memory (WM) and have used Affymetrix™ Human Exon 1.0 ST Arrays to compare their blood RNA levels (n=16) to a group of with intact WM (n=18). Levels of 72 RNAs were higher in blood from patients with impaired WM, 11 of which have proven links to the maintenance of different aspects of working memory (cognition). Overall, changed gene expression in those with impaired WM could be linked to cognition through glutamatergic activity, olfaction, immunity, inflammation as well as energy and metabolism. Our data gives preliminary support to the hypotheses that there is a working memory deficit phenotype within the syndrome of schizophrenia with has a biological underpinning. In addition, our data raises the possibility that a larger study could show that the specific changes in gene expression we have identified could prove to be the biomarkers needed to develop a blood test to identify those with impaired WM; a significant step toward allowing the use of personalised medicine directed toward improving their impaired working memory.

Systematic review and narrative synthesis of cognition in perimenopause: The role of risk factors and menopausal symptoms.

OBJECTIVE: Many women report cognitive concerns during the menopausal transition, and cognitive testing supports objective declines in some cognitive domains for some women. Identifying risk and protective factors that mediate cognitive difficulties would help women gain better insight into how they can manage cognitive difficulties during the menopause transition. The purpose of this review was to synthesize the studies that examine the relationships between cognition, menopausal symptoms and risk/protective factors during menopause transition. METHODS: A search of the literature examining cognition and risk factors in perimenopausal women between 2010 and September 2020 was performed using Ovid MEDLINE, PsychINFO, and PubMed. The results were synthesized narratively. Studies were categorized into clusters and conceptual mapping was used to illustrate the findings. RESULTS: 33 studies were included in this review and divided into three clusters. Factors associated with cognitive and other menopausal symptoms were grouped into demographic, socio-economic, lifestyle and reproductive factors. CONCLUSION: The current review identified a broad range of demographic, reproductive, socio-economic, and lifestyle risk/protective factors that are associated with cognition and menopausal symptoms. Relationships were also observed between vasomotor, affective and sleep symptoms with cognition, suggesting a complex relationship, including direct and indirect effects of risk/protective factors on cognition during menopause.

Gaze and social functioning associations in autism spectrum disorder: A systematic review and meta-analysis.

Autism spectrum disorder (ASD) is characterized by significant social functioning impairments, including (but not limited to) emotion recognition, mentalizing, and joint attention. Despite extensive investigation into the correlates of social functioning in ASD, only recently has there been focus on the role of low-level sensory input, particularly visual processing. Extensive gaze deficits have been described in ASD, from basic saccadic function through to social attention and the processing of complex biological motion. Given that social functioning often relies on accurately processing visual information, inefficient visual processing may contribute to the emergence and sustainment of social functioning difficulties in ASD. To explore the association between measures of gaze and social functioning in ASD, a systematic review and meta-analysis was conducted. A total of 95 studies were identified from a search of CINAHL Plus, Embase, OVID Medline, and psycINFO databases in July 2021. Findings support associations between increased gaze to the face/head and eye regions with improved social functioning and reduced autism symptom severity. However, gaze allocation to the mouth appears dependent on social and emotional content of scenes and the cognitive profile of participants. This review supports the investigation of gaze variables as potential biomarkers of ASD, although future longitudinal studies are required to investigate the developmental progression of this relationship and to explore the influence of heterogeneity in ASD clinical characteristics. LAY SUMMARY: This review explored how eye gaze (e.g., where a person looks when watching a movie) is associated with social functioning in autism spectrum disorder (ASD). We found evidence that better social functioning in ASD was associated with increased eye gaze toward faces/head and eye regions. Individual characteristics (e.g., intelligence) and the complexity of the social scene also influenced eye gaze. Future research including large longitudinal studies and studies investigating the influence of differing presentations of ASD are recommended.