Publications by authors named "Mary V Seeman"

122 Publications

Disparities in Screening and Treatment of Cardiovascular Diseases in Patients With Mental Disorders Across the World: Systematic Review and Meta-Analysis of 47 Observational Studies.

Am J Psychiatry 2021 Jul 14:appiajp202121010031. Epub 2021 Jul 14.

Neurosciences Department (Solmi, Miola), Padua Neuroscience Center (Solmi), Department of General Psychology (Poddighe), and Department of Philosophy, Sociology, Education, and Applied Psychology (Delogu), University of Padua, Italy; Early Psychosis: Interventions and Clinical Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London (Solmi, Fusar-Poli); Psychiatry Department, University of Ottawa, Ottawa (Fiedorowicz); Department of Clinical Medicine, Faculty of Health Sciences, UiT-Arctic University of Norway, Tromsø (Høye); Division of Mental Health and Substance Abuse, University Hospital of North Norway, Tromsø (Høye); Center for Clinical Documentation and Evaluation (SKDE), Tromsø (Høye, Heiberg); Physiotherapy Department, South London and Maudsley NHS Foundation Trust, and Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King's College London (Stubbs); Cambridge Centre for Sport and Exercise Science, Anglia Ruskin University, Cambridge, U.K. (Smith); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, and School of Medical Sciences, Örebro University, Örebro, Sweden (Larsson); Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark, and Department of Clinical Sciences, Lund University, Lund, Sweden (Attar); Department of Psychiatry, Aalborg University Hospital, and Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (Nielsen); Centre for Innovation in Mental Health-Developmental Lab, School of Psychology, University of Southampton, and NHS Trust, Southampton, U.K. (Cortese); Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York (Cortese); Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, U.K. (Cortese); Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea (Shin); National Institute for Health Research, Maudsley Biomedical Research Centre, and OASIS Service, South London and Maudsley NHS Foundation Trust, London (Fusar-Poli); Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy (Fusar-Poli); Division of Psychology and Mental Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, U.K. (Firth); NICM Health Research Institute, Western Sydney University, Westmead, Australia (Firth); Department of Psychiatry, University of British Columbia, Vancouver (Yatham); Department of Psychiatry, University of Toronto, and Centre for Addiction and Mental Health, Toronto (Castle, Seeman); IMPACT (Innovation in Mental and Physical Health and Clinical Treatment) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, Australia (Carvalho); Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Charité University Medicine Berlin, Berlin (Correll); Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, N.Y. (Correll); and Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, N.Y. (Correll).

Objective: This study used meta-analysis to assess disparities in cardiovascular disease (CVD) screening and treatment in people with mental disorders, a group that has elevated CVD incidence and mortality.

Methods: The authors searched PubMed and PsycInfo through July 31, 2020, and conducted a random-effect meta-analysis of observational studies comparing CVD screening and treatment in people with and without mental disorders. The primary outcome was odds ratios for CVD screening and treatment. Sensitivity analyses on screening and treatment separately and on specific procedures, subgroup analyses by country, and by controlling for confounding by indication, as well as meta-regressions, were also run, and publication bias and quality were assessed.

Results: Forty-seven studies (N=24,400,452 patients, of whom 1,283,602 had mental disorders) from North America (k=26), Europe (k=16), Asia (k=4), and Australia (k=1) were meta-analyzed. Lower rates of screening or treatment in patients with mental disorders emerged for any CVD (k=47, odds ratio=0.773, 95% CI=0.742, 0.804), coronary artery disease (k=34, odds ratio=0.734, 95% CI=0.690, 0.781), cerebrovascular disease (k=8, odds ratio=0.810, 95% CI=0.779, 0.842), and other mixed CVDs (k=11, odds ratio=0.839, 95% CI=0.761, 0.924). Significant disparities emerged for any screening, any intervention, catheterization or revascularization in coronary artery disease, intravenous thrombolysis for stroke, and treatment with any and with specific medications for CVD across all mental disorders (except for CVD medications in mood disorders). Disparities were largest for schizophrenia, and they differed across countries. Median study quality was high (Newcastle-Ottawa Scale score, 8); higher-quality studies found larger disparities, and publication bias did not affect results.

Conclusions: People with mental disorders, and those with schizophrenia in particular, receive less screening and lower-quality treatment for CVD. It is of paramount importance to address underprescribing of CVD medications and underutilization of diagnostic and therapeutic procedures across all mental disorders.
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http://dx.doi.org/10.1176/appi.ajp.2021.21010031DOI Listing
July 2021

Age at onset of mental disorders worldwide: large-scale meta-analysis of 192 epidemiological studies.

Mol Psychiatry 2021 Jun 2. Epub 2021 Jun 2.

Department of Psychosis Studies, Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11-34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7-16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9-25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14-29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15-23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17-48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20-41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20-34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20-33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21-46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.
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http://dx.doi.org/10.1038/s41380-021-01161-7DOI Listing
June 2021

'Distant socializing,' not 'social distancing' as a public health strategy for COVID-19.

Pathog Glob Health 2021 May 30:1-8. Epub 2021 May 30.

Centre for Depression and Suicide Studies, St. Michael's Hospital, Toronto, Canada.

Social distancing, also referred to as physical distancing, means creating a safe distance of at least two meters (six feet) between yourself and others. This is a term popularized during the COVID-19 pandemic, as it is one of the most important measures to prevent the spread of this virus. However, the term 'social distancing' can be misleading, as it may imply that individuals should stop socializing. However, socializing in a safe context (i.e. over the phone, video-chat, etc.) is especially important during this time of crisis. Therefore, in this narrative review, we suggest the term 'distant socializing' as more apt expression, to promote physical distancing measures while also highlighting the importance of maintaining social bonds. Further, articles discussing the practice, implementation, measurement, and mental health effects of physical distancing are reviewed. Physical distancing is associated with psychiatric symptoms (such as anxiety and depression), suicidal ideation, and domestic violence. Further, unemployment and job insecurity have significantly increased during COVID-19, which may exacerbate these negative mental health effects. Governments, medical institutions, and public health bodies should therefore consider increasing mental health resources both during and after the pandemic, with a specific focus on frontline workers, COVID-19 survivors, and marginalized communities.
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http://dx.doi.org/10.1080/20477724.2021.1930713DOI Listing
May 2021

The Pharmacodynamics of Antipsychotic Drugs in Women and Men.

Authors:
Mary V Seeman

Front Psychiatry 2021 9;12:650904. Epub 2021 Apr 9.

Department of Psychiatry, University of Toronto, Toronto, ON, Canada.

Animal and human experiments have confirmed sex differences in the expression of hepatic enzymes that metabolize antipsychotic drugs and that may, in this way, be partly responsible for the clinical sex/gender differences observed in the efficacy and tolerability of antipsychotic treatment. The aim of this mini review is to synthesize the literature on the pharmacodynamics of male/female differential response to antipsychotic drugs. Relevant search terms were used to search for pre-clinical and human trials and analysis of antipsychotic differential drug response and occurrence/severity of adverse effects in women and men. The search found that sex influences drug response the amount of a given drug that enters the brain and the number of neurotransmitter receptors to which it can bind. Consequently, sex partly determines the efficacy of a specific drug and its liability to induce unwanted effects. There are other factors that can overshadow or enhance the dimorphic effect of sex, for instance, the host's age, hormonal status, diet and life style as well as the molecular structure of the drug and its dose, and the method of its administration. Most of all, the host's individual genetics affects each step of a drug's pharmacodynamics. On average, women's psychotic symptoms respond to antipsychotic drugs at doses lower than men's. This means that many women may be overdosed and, thus, experience unnecessary adverse effects. That being said, factors such as genetics and age probably determine drug response and tolerability to a greater degree than do biological sex or gender social roles.
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http://dx.doi.org/10.3389/fpsyt.2021.650904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062799PMC
April 2021

Sex differences in schizophrenia relevant to clinical care.

Authors:
Mary V Seeman

Expert Rev Neurother 2021 Apr 16;21(4):443-453. Epub 2021 Mar 16.

Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

: Most medical diagnoses present somewhat differently in men and women, more so at specific periods of life. Treatment effects may also differ. This is true for schizophrenia, where premorbid effects are experienced earlier in life in boys than in girls, and where symptoms and outcomes differ.: This review does not cover all the differences that have been reported between men and women but, instead, focuses on the ones that carry important implications for clinical care: effective antipsychotic doses, medication side effects, symptom fluctuation due to hormonal levels, comorbidities, and women's requirements for prenatal, obstetric, postpartum, and parenting support.: Of consequence to schizophrenia, sex-biased genes, epigenetic modifications, and sex steroids all impact the structure and function of the brain. Furthermore, life experiences and social roles exert major sex-specific influences. The co-morbidities that accompany schizophrenia also affect men and women to different degrees. This review offers several examples of sex-specific intervention and concludes that gold standard treatment must look beyond symptoms and address all the physiologic, psychologic, and social role needs of men and women suffering from this psychiatric disorder.
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http://dx.doi.org/10.1080/14737175.2021.1898947DOI Listing
April 2021

Editorial: Psychoneuroendocrinology of Psychosis Disorders.

Front Psychiatry 2020 9;11:607590. Epub 2020 Nov 9.

Department of Psychiatry, University of Toronto, Toronto, ON, Canada.

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http://dx.doi.org/10.3389/fpsyt.2020.607590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7680761PMC
November 2020

Sleep Disturbances in Patients with Persistent Delusions: Prevalence, Clinical Associations, and Therapeutic Strategies.

Clocks Sleep 2020 Oct 16;2(4):399-415. Epub 2020 Oct 16.

Department of Psychiatry, University of Toronto, #605 260 Heath St. West, Toronto, ON M5T 1R8, Canada.

Sleep disturbances accompany almost all mental illnesses, either because sound sleep and mental well-being share similar requisites, or because mental problems lead to sleep problems, or vice versa. The aim of this narrative review was to examine sleep in patients with delusions, particularly in those diagnosed with delusional disorder. We did this in sequence, first for psychiatric illness in general, then for psychotic illnesses where delusions are prevalent symptoms, and then for delusional disorder. The review also looked at the effect on sleep parameters of individual symptoms commonly seen in delusional disorder (paranoia, cognitive distortions, suicidal thoughts) and searched the evidence base for indications of antipsychotic drug effects on sleep. It subsequently evaluated the influence of sleep therapies on psychotic symptoms, particularly delusions. The review's findings are clinically important. Delusional symptoms and sleep quality influence one another reciprocally. Effective treatment of sleep problems is of potential benefit to patients with persistent delusions, but may be difficult to implement in the absence of an established therapeutic relationship and an appropriate pharmacologic regimen. As one symptom can aggravate another, comorbidities in patients with serious mental illness all need to be treated, a task that requires close liaison among medical specialties.
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http://dx.doi.org/10.3390/clockssleep2040030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711969PMC
October 2020

Aripiprazole monotherapy as transdiagnostic intervention for the treatment of mental disorders: An umbrella review according to TRANSD criteria.

Eur Neuropsychopharmacol 2020 12 16;41:16-27. Epub 2020 Oct 16.

Early Psychosis: Interventions and Clinical-Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy; OASIS Service, South London and Maudsley NHS Foundation Trust, London, UK; National Institute for Health Research, Maudsley Biomedical Research Centre, London, UK.

Aripiprazole is approved in different countries as treatment for several mental disorders, but its transdiagnostic potential has not yet been assessed according to established criteria such as the recently proposed TRANSD criteria. The present work aims to test whether aripiprazole monotherapy could be considered a transdiagnostic intervention. An umbrella review of meta-analyses of randomized controlled trials (RCTs) of aripiprazole monotherapy vs placebo was conducted for any disorder defined according to standard diagnostic criteria. Primary outcomes were levels of psychiatric disease-specific symptoms. TRANSD criteria were applied to assess transdiagnosticity, while the AMSTAR -2 tool was used to assess the quality of eligible meta-analyses. Four pairwise meta-analyses and three network meta-analyses were included, consisting of 25 RCTs of aripiprazole monotherapy vs. placebo (N=5469). Aripiprazole outperformed placebo on primary outcomes in Alzheimer's disease with behavioral disturbance (AD) (neuropsychiatric symptoms SMD 0.20, 95%CI 0.05-0.35, max 15 mg/day), autism spectrum disorder (ASD) (severity of symptoms SMD 0.39, 95%CI 0.30-0.48, max 15 mg/day), bipolar I disorder (BD) (severity of manic symptoms SMD 0.30, 95%CI 0.12-0.47, max 30 mg/day), and schizophrenia/schizoaffective disorder (response rate RR 0.84, 95%CI 0.78-0.92, max 30 mg/day). TRANSD criteria were met (pooled SMD 0.25, 95%CI 0.09-0.41) across these disorders Quality was high in all the included meta-analyses according to AMSTAR-2. According to TRANSD criteria, aripiprazole monotherapy is a (dose-specific) transdiagnostic intervention to treat psychiatric disease-specific symptoms across 5 diagnoses (AD, ASD, BD (mania), schizophrenia/schizoaffective disorder), across four DSM-5 diagnostic groups (neurocognitive disorders, neurodevelopmental disorders, bipolar and related disorders, schizophrenia spectrum and other psychotic disorders).
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http://dx.doi.org/10.1016/j.euroneuro.2020.09.635DOI Listing
December 2020

Targeting Gender and Age in First-Episode Psychosis Services: A Commentary on Ferrara and Srihari.

Authors:
Mary V Seeman

Psychiatr Serv 2021 01 23;72(1):94-95. Epub 2020 Sep 23.

Department of Psychiatry, University of Toronto, Ontario.

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http://dx.doi.org/10.1176/appi.ps.202000478DOI Listing
January 2021

The gut microbiome and antipsychotic treatment response.

Authors:
Mary V Seeman

Behav Brain Res 2021 01 2;396:112886. Epub 2020 Sep 2.

Department of Psychiatry, University pf Toronto, Suite #605 260 Heath St. West, Toronto, Ontario, M5P 3L6, Canada. Electronic address:

Patients with psychosis usually respond to one antipsychotic drug and not to another; one third fail to respond to any. Some patients, who initially do well, stop responding. Some develop serious side effects even at low doses. While several of the reasons for this variability are known, many are not. The aim of this review is to explore the potential role of intestinal organisms in response/non-response to antipsychotics. Much of the literature in this field is relatively new and still, for the most part, theoretical. A growing number of animal experiments and clinical trials are starting to point, however, to substantial effects of antipsychotics on the composition of gut bacteria and, reciprocally, to the effects of microbiota on the pharmacokinetics of antipsychotic medication. Because so many factors influence the constituents of the human intestine, it is difficult, at present, to sort out how much one or more either enhance or dampen the benefits of antipsychotics or the character/severity of the adverse effects they induce. Dietary and other therapies are being devised to reverse dysbiosis. If successful, such therapies plus the modification of factors that, together, are known to determine the composition of microbiota could help to maximize the effectiveness of currently available antipsychotic therapy.
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http://dx.doi.org/10.1016/j.bbr.2020.112886DOI Listing
January 2021

Portrait of an Exhibitionist.

Authors:
Mary V Seeman

Psychiatr Q 2020 12;91(4):1249-1263

Department of Psychiatry, University of Toronto, 260 Heath St. W. Suite #605, Toronto, ON, M5P 3L6, Canada.

Exhibitionism has been viewed through many lenses, from the perspectives of sexual deviance, forensic psychiatry, psychopathology, psychological dynamics, feminism, behaviorism, and psychopharmacology. Starting from the description of one psychotherapy patient, the aim of this paper is to synthesize this disparate literature. The findings of the synthesis include an estimate of the lifetime male prevalence of exhibitionism, 2-4%, peaking in late adolescence. Insecure attachment, sexual abuse in childhood, substance abuse, and sexual dysfunction are acknowledged risk factors. Motives behind the act of genital exposure remain obscure, constructed of both sexual and non-sexual impulses. The usual response of women victims is alarm and disgust. Successful treatment relies on a strong therapeutic alliance with specific psychological and psychopharmacological interventions - comparative effectiveness not yet determined. In conclusion, precedents for exhibitionism vary. The frequency of the behavior usually wanes with age and, while exhibitionists may pose a risk to others, they usually do not. There is, as yet, no gold standard treatment; the recommendation for therapists is to respond to individual facets of the patient's circumstances and history.
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http://dx.doi.org/10.1007/s11126-020-09810-wDOI Listing
December 2020

Coping Well.

Authors:
Mary V Seeman

J Psychosoc Rehabil Ment Health 2020 Jun 21:1-2. Epub 2020 Jun 21.

University of Toronto, Toronto, Canada.

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http://dx.doi.org/10.1007/s40737-020-00172-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306184PMC
June 2020

The ethical, social, and cultural dimensions of screening for mental health in children and adolescents of the developing world.

PLoS One 2020 24;15(8):e0237853. Epub 2020 Aug 24.

Division of Clinical Public Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

Despite their burden and high prevalence, mental health disorders of children and adolescents remain neglected in many parts of the world. In developing countries, where half of the population is younger than 18 years old, one of every five children and adolescents is estimated to suffer from a mental health disorder. It is then essential to detect these conditions through screening in a timely and accurate manner. But such screening is fraught with considerable ethical, social, and cultural challenges. This study systematically identifies, for the first time, these challenges, along with potential solutions to address them. We report on the results of an international multi- and inter-disciplinary three-round Delphi survey completed by 135 mental health experts from 37 countries. We asked these experts to identify and rank the main ethical, social, and cultural challenges of screening for child and adolescent mental health problems in developing nations, and to propose solutions for each challenge. Thirty-nine significant challenges emerged around eight themes, along with 32 potential solutions organized into seven themes. There was a high degree of consensus among the experts, but a few interesting disagreements arose between members of the panel from high-income countries and those from low- and middle-income nations. The panelists overwhelmingly supported mental health screening for children and adolescents. They recommended ensuring local acceptance and support for screening prior to program initiation, along with careful and comprehensive protection of human rights; integrating screening procedures into primary care; designing and implementing culturally appropriate screening tools, programs, and follow-up; securing long-term funding; expanding capacity building; and task-shifting screening to local non-specialists. These recommendations can serve as a guide for policy and decision-making, resource allocation, and international cooperation. They also offer a novel approach to reduce the burden of these disorders by encouraging their timely and context-sensitive prevention and management.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237853PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446846PMC
October 2020

The ethical, social, and cultural dimensions of screening for mental health in children and adolescents of the developing world.

PLoS One 2020 24;15(8):e0237853. Epub 2020 Aug 24.

Division of Clinical Public Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

Despite their burden and high prevalence, mental health disorders of children and adolescents remain neglected in many parts of the world. In developing countries, where half of the population is younger than 18 years old, one of every five children and adolescents is estimated to suffer from a mental health disorder. It is then essential to detect these conditions through screening in a timely and accurate manner. But such screening is fraught with considerable ethical, social, and cultural challenges. This study systematically identifies, for the first time, these challenges, along with potential solutions to address them. We report on the results of an international multi- and inter-disciplinary three-round Delphi survey completed by 135 mental health experts from 37 countries. We asked these experts to identify and rank the main ethical, social, and cultural challenges of screening for child and adolescent mental health problems in developing nations, and to propose solutions for each challenge. Thirty-nine significant challenges emerged around eight themes, along with 32 potential solutions organized into seven themes. There was a high degree of consensus among the experts, but a few interesting disagreements arose between members of the panel from high-income countries and those from low- and middle-income nations. The panelists overwhelmingly supported mental health screening for children and adolescents. They recommended ensuring local acceptance and support for screening prior to program initiation, along with careful and comprehensive protection of human rights; integrating screening procedures into primary care; designing and implementing culturally appropriate screening tools, programs, and follow-up; securing long-term funding; expanding capacity building; and task-shifting screening to local non-specialists. These recommendations can serve as a guide for policy and decision-making, resource allocation, and international cooperation. They also offer a novel approach to reduce the burden of these disorders by encouraging their timely and context-sensitive prevention and management.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237853PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7446846PMC
October 2020

Women with Schizophrenia over the Life Span: Health Promotion, Treatment and Outcomes.

Int J Environ Res Public Health 2020 08 3;17(15). Epub 2020 Aug 3.

Department of Mental Health, Parc Taulí University Hospital, Institut d'Investigació i Innovació Parc Taulí (I3PT), Autonomous University of Barcelona (UAB), 08280 Sabadell, Barcelona, Spain.

Women with schizophrenia show sex-specific health needs that differ according to stage of life. The aim of this narrative review is to resolve important questions concerning the treatment of women with schizophrenia at different periods of their life-paying special attention to reproductive and post-reproductive stages. Review results suggest that menstrual cycle-dependent treatments may be a useful option for many women and that recommendations re contraceptive options need always to be part of care provision. The pregnancy and the postpartum periods-while constituting vulnerable time periods for the mother-require special attention to antipsychotic effects on the fetus and neonate. Menopause and aging are further vulnerable times, with extra challenges posed by associated health risks. Pregnancy complications, neurodevelopmental difficulties of offspring, cancer risk and cognitive defects are indirect results of the interplay of hormones and antipsychotic treatment of women over the course of the lifespan. The literature recommends that health promotion strategies need to be directed at lifestyle modifications, prevention of medical comorbidities and increased psychosocial support. Careful monitoring of pharmacological treatment has been shown to be critical during periods of hormonal transition. Not only does treatment of women with schizophrenia often need to be different than that of their male peers, but it also needs to vary over the course of life.
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http://dx.doi.org/10.3390/ijerph17155594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432627PMC
August 2020

Schizophrenia and cancer.

Curr Opin Support Palliat Care 2020 09;14(3):232-238

Department of Psychiatry. University of Toronto. Toronto, Canada.

Purpose Of Review: The cancer mortality rate in persons with schizophrenia is higher than it is in the general population. The purpose of this review is to determine why, and to identify solutions.

Recent Findings: The recent literature points to three groups of reasons why mortality is high: patient reasons such as nonadherence to treatment, provider reasons such as diagnostic overshadowing, and health system reasons such as a relative lack of collaboration between medicine and psychiatry. Strategies for cancer prevention, early detection, and effective treatment are available but difficult to put into practice because of significant barriers to change, namely poverty, cognitive and volitional deficits, heightened stress, stigma, and side effects of antipsychotic medication. The literature makes recommendations about surmounting these barriers and also offers suggestions with respect to support and palliative care in advanced stages of cancer. Importantly, it offers examples of effective collaboration between mental health and cancer care specialists.

Summary: The high mortality rate from cancer in the schizophrenia population is a matter of urgent concern. Although reasons are identifiable, solutions remain difficult to implement. As we work toward solutions, quality palliative care at the end of life is required for patients with severe mental illness. VIDEO ABSTRACT.
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http://dx.doi.org/10.1097/SPC.0000000000000512DOI Listing
September 2020

Addressing Delusions in Women and Men with Delusional Disorder: Key Points for Clinical Management.

Int J Environ Res Public Health 2020 06 25;17(12). Epub 2020 Jun 25.

Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada.

Delusional disorders (DD) are difficult conditions for health professionals to treat successfully. They are also difficult for family members to bear. The aim of this narrative review is to select from the clinical literature the psychosocial interventions that appear to work best for these conditions and to see whether similar strategies can be modeled or taught to family members so that tensions at home are reduced. Because the content of men's and women's delusions sometimes differ, it has been suggested that optimal interventions for the two sexes may also differ. This review explores three areas: (a) specific treatments for men and women; (b) recommended psychological approaches by health professionals, especially in early encounters with patients with DD; and (c) recommended psychoeducation for families. Findings are that there is no evidence for differentiated psychosocial treatment for men and women with delusional disorder. What is recommended in the literature is to empathically elicit the details of the content of delusions, to address the accompanying emotions rather than the logic of the presented argument, to teach self-soothing techniques, and to monitor behavior with respect to its safety. These recommendations have only been validated in individual patients and families. More rigorous clinical trials need to be conducted.
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http://dx.doi.org/10.3390/ijerph17124583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344970PMC
June 2020

Moderators and mediators of antipsychotic response in delusional disorder: Further steps are needed.

World J Psychiatry 2020 Apr 19;10(4):34-45. Epub 2020 Apr 19.

Department of Psychiatry, University of Toronto, Toronto, ON M5P 3L6, Canada.

Delusional disorder (DD) has been traditionally considered a relatively rare and treatment-resistant psychotic disorder. In the last decade, increasing attention has focused on therapeutic outcomes of individuals affected by this disorder. The aim of this paper is to provide a synthesis of the literature addressing two very important questions arising from DD research: (1) For which patients with DD do antipsychotic medications work best (the moderators of response); and (2) What variables best explain the relationship between such treatments and their effectiveness (the mediators of response). We searched PubMed and Google Scholar databases for English, German, French and Spanish language papers published since 2000. We also included a few classic earlier papers addressing this topic. Variables potentially moderating antipsychotic response in DD are gender, reproductive status, age, duration of illness, the presence of comorbidity (especially psychiatric comorbidity) and its treatment, brain structure, and genetics of neurochemical receptors and drug metabolizing enzymes. Antipsychotic and hormonal blood levels during treatment, as well as functional brain changes, are potential mediating variables. Some, but not all, patients with DD benefit from antipsychotic treatment. Understanding the circumstances under which treatment works best can serve to guide optimal management.
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http://dx.doi.org/10.5498/wjp.v10.i4.34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203082PMC
April 2020

Antipsychotic-induced Hyperprolactinemia in aging populations: Prevalence, implications, prevention and management.

Prog Neuropsychopharmacol Biol Psychiatry 2020 07 31;101:109941. Epub 2020 Mar 31.

Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada, M5P 3L6.

This paper reviews the prevalence, implications, prevention and management of antipsychotic-induced hyperprolactinemia in aging populations. Antipsychotics are indicated mainly for the treatment of psychotic illness but are also used in other conditions. Complications induced by antipsychotics increase with age, due to age-related changes in drug metabolism and excretion. Almost all antipsychotics lead to hyperprolactinemia by blocking dopamine D2 receptors in the anterior pituitary gland, which counteracts dopamine's inhibitory action on prolactin secretion. The main findings of this narrative review are that, though many of the known side effects of high prolactin levels lose their salience with age, the risk of exacerbating osteoporosis remains critical. Methods of preventing antipsychotic-induced hyperprolactinemia in older individuals include using antipsychotic medication (AP) as sparingly as possible and monitoring AP serum levels, regularly measuring prolactin levels, closely monitoring bone density, treating substance abuse, and teaching patients stress management techniques. When hyperprolactinemia symptoms cannot be otherwise managed, adjunctive drugs are available. Potential helpful adjuncts are: dopamine agonists, antipsychotics with partial agonist properties (e.g. aripiprazole), selective estrogen receptor modulators, and metformin. Because a gold standard for prevention/treatment has not been established, clinical decisions need to be made based on safety and individual circumstance.
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http://dx.doi.org/10.1016/j.pnpbp.2020.109941DOI Listing
July 2020

Similar psychosis risks in adoptees and immigrants.

Authors:
Mary V Seeman

Int J Soc Psychiatry 2020 05 5;66(3):292-299. Epub 2020 Feb 5.

Department of Psychiatry, University of Toronto, Toronto, ON, Canada.

Background: There is a consensus that adoptees and immigrants both experience more mental health problems than their peers. The two groups share many risk factors for psychosis, but an increased risk for psychotic illness has only been demonstrated for immigrants.

Aims: The aim of this review is to describe psychosis risk factors in adoptees, with a focus on difficulties with identity formation, identification with in-groups, attachment to parents, and coping with loss and with discrimination.

Method: The literature in these five areas is reviewed as it pertains to adoption and psychosis.

Results: There are no clear findings because the relevant studies have not been done, but the literature suggests that adopted children face challenges very similar to those of immigrants to a new country.

Conclusion: The immigration field and the adoption field have much to learn from each other. It is recommended that a prevention strategy analogous to increased neighbourhood ethnic density be implemented with adoptees - that they be intentionally exposed from early childhood and throughout adolescence to age peers who share a similar background and with whom they can readily identify. It is also recommended that immigrants be welcomed into their host country with the same open arms as adoptive parents welcome their new children.
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http://dx.doi.org/10.1177/0020764020903324DOI Listing
May 2020

Why Are Women Prone to Restless Legs Syndrome?

Authors:
Mary V Seeman

Int J Environ Res Public Health 2020 01 6;17(1). Epub 2020 Jan 6.

Department of Psychiatry, University of Toronto, Toronto, ON M5G 1L7, Canada.

Restless legs syndrome is a relatively common neurologic disorder considerably more prevalent in women than in men. It is characterized by an inactivity-induced, mostly nocturnal, uncomfortable sensation in the legs and an urge to move them to make the disagreeable sensation disappear. Some known genes contribute to this disorder and the same genes contribute to an overlapping condition-periodic leg movements that occur during sleep and result in insomnia. Dopamine and glutamate transmission in the central nervous system are involved in the pathophysiology, and an iron deficiency has been shown in region-specific areas of the brain. A review of the literature shows that pregnant women are at particular risk and that increased parity is a predisposing factor. Paradoxically, menopause increases the prevalence and severity of symptoms. This implies a complex role for reproductive hormones. It suggests that rather than absolute levels of estrogen may be responsible for the initiation of symptoms. Both iron (at relatively low levels in women) and estrogen (at relatively high oscillating levels in women) influence dopamine and glutamate transmission, which may help to explain women's vulnerability to this condition. The syndrome is comorbid with several disorders (such as migraine, depression, and anxiety) to which women are particularly prone. This implies that the comorbid condition or its treatment, or both, contribute to the much higher prevalence in women than in men of restless legs syndrome.
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http://dx.doi.org/10.3390/ijerph17010368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981604PMC
January 2020

The Gut Microbiome and Treatment-Resistance in Schizophrenia.

Authors:
Mary V Seeman

Psychiatr Q 2020 03;91(1):127-136

Department of Psychiatry, University of Toronto, 260 Heath St. West Suite #605, Toronto, Ontario, M5P 3L6, Canada.

The effect of antipsychotic medication is poor in 30-40% of patients with schizophrenia; treatment resistance is usually met with shifts to new drugs or drug augmentation strategies or a trial of clozapine. The purpose of this review was to examine the potential role of intestinal bacteria in the bioavailability of antipsychotic medication and the possibility that parenterally administered antipsychotics might be able to overcome treatment resistance. Databases were searched with appropriate terms to locate relevant papers dealing with the effect of antipsychotic drugs on the gut microbiome and the effect of bacterial metabolizing enzymes on antipsychotic drugs. Also searched were papers addressing the various current parenteral formulations of antipsychotic drugs. Sixty-five recent pertinent papers were reviewed and the results are suggestive of the premise that there is a drug refractory form of psychosis for which the composition of gut bacteria is responsible, and that parenteral drug administration could overcome the problem.
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http://dx.doi.org/10.1007/s11126-019-09695-4DOI Listing
March 2020

Geriatric pharmacotherapy: Appraising new drugs for neurologic disorders in older patients.

Handb Clin Neurol 2019 ;167:3-18

Drug Design and Development Section, Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States. Electronic address:

New drug development for neurologic disorders has one of the highest attrition rates of all clinical drug developments. This is problematic when, with innovative technology available in so many aspects of life, modern societies expect to have effective treatments for neurodegenerative disorders and mental health conditions that provide something beyond simple symptomatic relief-the expectation is treatment that impacts and mitigates fundamental mechanisms that drive these disorders. The disease burden of neurologic disorders remains extremely high, whereas the proportion of patients receiving effective therapy is relatively low, demonstrating a sizeable unmet medical need. Whether for novel breakthrough therapies or for drugs considered successful, deciding on the basis of clinical trial data whether a particular treatment will be effective for a specific patient is always a leap of faith. However, expertise at reading trial results combined with knowledge of the patient and of his or her disease, together with an understanding of the effect of age on drug pharmacokinetics and pharmacodynamics, the effect of age on the patient's condition, and the effect of age on the patient's life and outlook will ensure the landing is safe. The focus of this article is to provide such knowledge and thereby optimize this expertise.
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http://dx.doi.org/10.1016/B978-0-12-804766-8.00001-7DOI Listing
April 2020

Sex influences in the preventive effects of N-acetylcysteine in a two-hit animal model of schizophrenia.

J Psychopharmacol 2020 01 26;34(1):125-136. Epub 2019 Sep 26.

Drug Research and Development Center, Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceara, Fortaleza, CE, Brazil.

Background: Schizophrenia (SCZ) is a neurodevelopmental disorder influenced by patient sex. Mechanisms underlying sex differences in SCZ remain unknown. A two-hit model of SCZ combines the exposure to perinatal infection (first-hit) with peripubertal unpredictable stress (PUS, second-hit). N-acetylcysteine (NAC) has been tested in SCZ because of the involvement of glutathione mechanisms in its neurobiology.

Aims: We aim to investigate whether NAC administration to peripubertal rats of both sexes could prevent behavioral and neurochemical changes induced by the two-hit model.

Methods: Wistar rats were exposed to polyinosinic:polycytidylic acid (a viral mimetic) or saline on postnatal days (PND) 5-7. On PND30-59 they received saline or NAC 220 mg/kg and between PND40-48 were subjected to PUS or left undisturbed. On PND60 behavioral and oxidative alterations were evaluated in the prefrontal cortex (PFC) and striatum. Mechanisms of hippocampal memory regulation such as immune expression of G protein-coupled estrogen receptor 1 (GPER), α7-nAChR and parvalbumin were also evaluated.

Results: NAC prevented sensorimotor gating deficits only in females, while it prevented alterations in social interaction, working memory and locomotor activity in both sexes. Again, in rats of both sexes, NAC prevented the following neurochemical alterations: glutathione (GSH) and nitrite levels in the PFC and lipid peroxidation in the PFC and striatum. Striatal oxidative alterations in GSH and nitrite were observed in females and prevented by NAC. Two-hit induced hippocampal alterations in females, namely expression of GPER-1, α7-nAChR and parvalbumin, were prevented by NAC.

Conclusion: Our results highlights the influences of sex in NAC preventive effects in rats exposed to a two-hit schizophrenia model.
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http://dx.doi.org/10.1177/0269881119875979DOI Listing
January 2020

The association between hormones and antipsychotic use: a focus on postpartum and menopausal women.

Ther Adv Psychopharmacol 2019 3;9:2045125319859973. Epub 2019 Jul 3.

Department of Psychiatry, University of Toronto, 260 Heath Street West, Suite 605, Toronto, Ontario M5P 3L6, Canada.

During the postpartum and menopausal periods of women's lives, there is a well-established and significant drop of circulating estrogens. This may be the reason why both these periods are associated with an increased risk for onset or exacerbation of psychiatric disorders. Whether symptoms are mainly affective or mainly psychotic, these disorders are frequently treated with antipsychotic medications, which calls for an examination of the relationship between hormone replacement and antipsychotic agents at these time periods. The aim of this narrative review is to summarize what is known about the association of hormones and antipsychotics in the postnatal period and at menopause. In the review, we focus on estrogen and oxytocin hormones and include, for the most part, only papers published within the last 10 years. Both estradiol and oxytocin have at various times been implicated in the etiology of postpartum disorders, and estrogens, sometimes combined with progesterone, have been tested as potential treatments for these conditions. The role of estradiol as an adjunct to antipsychotics in the prevention of postpartum relapses is currently controversial. With respect to oxytocin, studies are lacking. Psychosis in menopausal and postmenopausal women has been successfully treated with estrogens and selective estrogen-receptor modulators, mainly raloxifene, in addition to antipsychotics. Some symptoms appear to respond better than others. No oxytocin study has specifically targeted postmenopausal women. Because of feedback mechanisms, there is a theoretical danger of therapy with exogenous hormones interfering with endogenous secretion and disturbing the balance among inter-related hormones. When used with antipsychotics, hormones may also affect the metabolism and, hence, the brain level of specific antipsychotics. This makes treatment with antipsychotics plus hormones complicated. Dose, timing and route of intervention may all prove critical to efficacy. While much remains unknown, this literature review indicates that, within standard dose ranges, the combination of hormones and antipsychotics for postnatal and menopausal women suffering severe mental distress can be beneficial, and is safe.
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http://dx.doi.org/10.1177/2045125319859973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610461PMC
July 2019

Schizophrenia Mortality: Barriers to Progress.

Authors:
Mary V Seeman

Psychiatr Q 2019 09;90(3):553-563

Department of Psychiatry, University of Toronto, 260 Heath St. West, Suite #605, Toronto, Ontario, M5P 3L6, Canada.

Individuals with schizophrenia die, on average, 20 years before their peers, with 'natural causes' accounting for 80% of premature deaths. The aim of this narrative review is to address this phenomenon from the perspective of known factors that contribute to long life. The relevant literature from the last decade was searched in PubMed and Google Scholar databases. Four factors have been shown to be common to centarians, people who live to be a hundred: genes, life style behaviors that favor a healthy heart, social support, and a subjective purpose in life. The latter three factors are potentially modifiable but, in the context of schizophrenia, there are barriers to change, namely poverty, illness symptoms, stress, stigma, and side effects of antipsychotic medication. Barriers to change need to be addressed before substantial progress can be made in increasing the health and mortality risk of people with schizophrenia.
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http://dx.doi.org/10.1007/s11126-019-09645-0DOI Listing
September 2019

Schizophrenia Mortality: Barriers to Progress.

Authors:
Mary V Seeman

Psychiatr Q 2019 09;90(3):553-563

Department of Psychiatry, University of Toronto, 260 Heath St. West, Suite #605, Toronto, Ontario, M5P 3L6, Canada.

Individuals with schizophrenia die, on average, 20 years before their peers, with 'natural causes' accounting for 80% of premature deaths. The aim of this narrative review is to address this phenomenon from the perspective of known factors that contribute to long life. The relevant literature from the last decade was searched in PubMed and Google Scholar databases. Four factors have been shown to be common to centarians, people who live to be a hundred: genes, life style behaviors that favor a healthy heart, social support, and a subjective purpose in life. The latter three factors are potentially modifiable but, in the context of schizophrenia, there are barriers to change, namely poverty, illness symptoms, stress, stigma, and side effects of antipsychotic medication. Barriers to change need to be addressed before substantial progress can be made in increasing the health and mortality risk of people with schizophrenia.
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http://dx.doi.org/10.1007/s11126-019-09645-0DOI Listing
September 2019

Does Gender Influence Outcome in Schizophrenia?

Authors:
Mary V Seeman

Psychiatr Q 2019 03;90(1):173-184

Department of Psychiatry, University of Toronto, # 605 260 Heath St. West, Toronto, ON, M5P 3L6, Canada.

Good outcome of schizophrenia has several meanings and most of these meanings carry both positive and negative undertones depending on perspective. Currently, a person's subjective sense that illness has been partly overcome and that life is meaningful has come to be viewed as the most valid signpost of a good outcome. A review of the literature shows that women have certain advantages over men in that their illness starts at a later age and that their symptoms respond more quickly and more completely to available treatments. These advantages serve women well at the outset of illness but benefits appear to dissipate over time. Gender differences in outcome thus vary depending on the age of the patient. They also vary with the social and cultural background of the study population. Neither sex, therefore, has a monopoly on good outcome. The hope is that studying gender differences will uncover critical elements of good outcome that lead to interventions that will benefit both women and men.
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http://dx.doi.org/10.1007/s11126-018-9619-yDOI Listing
March 2019

Women who suffer from schizophrenia: Critical issues.

Authors:
Mary V Seeman

World J Psychiatry 2018 Nov 9;8(5):125-136. Epub 2018 Nov 9.

Department of Psychiatry, University of Toronto, Institute of Medical Science, Toronto, ON M5P 3L6, Canada.

Many brain diseases, including schizophrenia, affect men and women unequally - either more or less frequently, or at different times in the life cycle, or to varied degrees of severity. With updates from recent findings, this paper reviews the work of my research group over the last 40 years and underscores issues that remain critical to the optimal care of women with schizophrenia, issues that overlap with, but are not identical to, the cares and concerns of men with the same diagnosis. Clinicians need to be alert not only to the overarching needs of diagnostic groups, but also to the often unique needs of women and men.
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http://dx.doi.org/10.5498/wjp.v8.i5.125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230925PMC
November 2018

Single men seeking adoption.

Authors:
Mary V Seeman

World J Psychiatry 2018 Sep 20;8(3):83-87. Epub 2018 Sep 20.

Department of Psychiatry, University of Toronto, Toronto, ON M5P 3L6, Canada.

It was once impossible anywhere in the world for single adults to adopt children, and this is still the case in many jurisdictions. Elsewhere, however, single adults are now being actively recruited primarily because they are more willing than are married couples to adopt older or disabled children or to adopt across racial or other barriers. This is true for single men as well as for single women, but single men seeking to adopt continue to be widely viewed with skepticism and are reportedly often judged to be inappropriate parents. This paper reviews the sparse fostering and adoption literature on single heterosexual males and addresses the evident ambivalence with which parenting by single men is held among both child and adult mental health professionals. The paper also discusses the parenting styles of mothers and fathers, the ways that the central nervous system in both sexes has been found to respond to parenthood, the similarity of outcomes between single male and single female parenting, and the availability in North America of support and training for foster and adoptive single parents. The paper concludes that, in general, single men have as much to offer an adopted child as do single women and that seeming discrimination against them by childcare agencies requires investigation.
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http://dx.doi.org/10.5498/wjp.v8.i3.83DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6147772PMC
September 2018