GODDESS ADHD

Lotta Borg Skoglund

• Senior consultant of general medicine and psychiatry and associate professor in psychiatry, Department of Women’s and Children’s Health at Uppsala University and WOMHER, Uppsala, Sweden. Lotta’s research focus on biological sex influence specific ADHD traits, symptom severity and comorbid conditions. She holds several commissions of trust including for the Swedish Medical Product Agency (Läkemedelsverket), the National Patient Association (Attention), the Swedish National Board of Institutional Care (SiS) and the non-profit organization MIND. Lotta aims to be an active voice in the current opinion through social media, TV, press and international collaborations. She is the founder of Smart Psykiatri and Letterlife.

Helena Kopp Kallner

• Senior consultant of obstetrics and gynecology, senior lecturer and head of the clinical trials unit and research group leader at the Department of clinical Sciences Karolinska Institutet, Stockholm Sweden. Her research focus on sexual and reproductive health and safe contraceptive methods to prevent sexual transmitted diseases, abortion, and unplanned/unwanted births. Helena is the principal investigator for several international studies and a leading role in international research collaborations for reproductive health. She is president of the family planning working and reference group pf the Swedish Society of Obstetrics and Gynecology and president of the European Society for Contraception and Reproductive Health. She is a frequently engaged lecturer in abortion, contraception and gynecological treatment and a media profile advocating for equal standard of care, gender informed policy making, women’s health and women’s rights.

Lisa Thorell

• Department of Clinical Neuroscience, Karolinska Institutet, Stockholm Sweden. Lisa is head of a research group focusing on ADHD across the life span. More specifically she investigates executive function deficits and emotion dysregulation in ADHD and how this relates to daily life functioning such as academic achievement, peer problems and behavioral addictions. Lisa is frequently engaged in the societal and scientific discussion regarding potential risks and benefits with digital media and the use of digital learning tools in school. She is a member of The EUropean NETwork for HYperkinetic DISorders (EUNETHYDIS) and is the initiator or several international multicenter research collaborations.

Post Doc Darko Sarovic MD, PhD, BA and MSc. Department of Radiology, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts.

• Darko is a resident in diagnostic and interventional radiology at the Sahlgrenska University Hospital, Bachelor and Master of psychology and postdoctoral research fellow at Harvard Medical School and Massachusetts General Hospital. Darko earned his PhD in child and adolescent psychiatry and is frequently teaching medical students and supervising graduate theses at the Sahlgrenska Academy and Chalmers University of Technology. His current work involves studying the neurobiological processes underlying social communication and development of theoretical models through reconceptualization of neuropsychiatric conditions, traits, and risk factors.

Post Doc Niklas Envall PhD and Midwife Project Manager

• Senior lecturer at Dalarna University, affiliated researcher at Karolinska Institutet and Uppsala University. Niklas is a registered nurse midwife, and his research area is mainly within contraception and prevention of unwanted pregnancy. He has a focus on contraceptive counseling and leads a post-doctoral project concerning a new method for pain relief with insertion of intrauterine contraception. He is also the national principal investigator in a transregional project concerning counseling for contraceptive use postpartum. Niklas will lead the qualitative parts of the GODDESS project and co-supervise the PhD-student.

We describe associations and gender specific aspects of ADHD, comorbidity, risk-taking behaviors, and adverse psychosocial outcomes. To this end we have combined and will combine different scientific methods and used different study designs including large scale pharmacoepidemiologic studies, qualitative research, and randomized controlled trials. In addition, we contribute to the general dissemination of research findings and public awareness of ADHD and female reproductive health through popular science books, reports, and interactive social media presence.

Epidemiological research

By linking different information on individuals from a total population in for example a municipality or country we can explore different outcomes on a group level. In this way we get an overview of our research questions and the magnitude of the problem. From the large-scale population-based epidemiological studies we have performed and participated in we show that females with ADHD, (compared to unaffected females and/or same aged males) have:

• Six times higher risk for teenage deliveries Association of Attention-Deficit/Hyperactivity Disorder With Teenage Birth Among Women and Girls in Sweden – PubMed (nih.gov)
• Five times higher risk for depression using oral hormonal contraceptives Hormonal Contraceptive Use and Risk of Depression Among Young Women With Attention-Deficit/Hyperactivity Disorder – PubMed (nih.gov)
• More often are diagnosed with borderline personality disorder Familial risk and heritability of diagnosed borderline personality disorder: a register study of the Swedish population – PubMed (nih.gov) Do borderline personality disorder and attention-deficit/hyperactivity disorder co-aggregate in families? A population-based study of 2 million Swedes – PubMed (nih.gov)
• A higher rate of preterm birth (7.3% versus 5.8%) Association of maternal attention deficit hyperactivity disorder and preterm birth: a cohort study – PubMed (nih.gov)
• 17% increased risk for postpartum depression and 25 % postpartum anxiety (Andersson et al 2023) Depression and anxiety disorders during the postpartum period in women diagnosed with attention deficit hyperactivity disorder – PubMed (nih.gov)
• More likely to smoke during pregnancy Familial confounding of the association between maternal smoking during pregnancy and ADHD in offspring – PubMed (nih.gov)
• Have more comorbidity, polypharmacy, self-harm, and health care utilization (Skoglund et al. submitted for publication 2023).

Qualitative research

Semi structured interviews are a good way of exploring the needs and expectations in different target groups. From qualitative studies we get a deeper understanding of the real-life challenges and potential barriers and opportunities in the current standard of care. These studies also guide valid and relevant outcome measures in our epidemiological and clinical studies. Our qualitative studies show that:

• Young women with ADHD show risk-taking behaviors including substance abuse, sexual victimization, and fail to act on psychosocial and contraceptive counselling Knowledge, challenges, and standard of care of young women with ADHD at Swedish youth clinics – PubMed (nih.gov)
• Mothers were left with almost all extra workload for children with ADHD following school lockdowns during the Covid-19 pandemic Parental experiences of homeschooling during the COVID-19 pandemic: differences between seven European countries and between children with and without mental health conditions – PubMed (nih.gov)
• Alcohol and drugs are associated to sexual risk-taking in Swedish youths Alcohol and illicit drug consumption and the association with risky sexual behaviour among Swedish youths visiting youth health clinics – PubMed (nih.gov)
• Digital interventions targeting risk-taking behaviors can be used at youth centers Effects of an automated digital brief prevention intervention targeting adolescents and young adults with risky alcohol and other substance use: study protocol for a randomised controlled trial – PubMed (nih.gov)

Reviews

• International consensus report on ADHD in girls and women Females with ADHD: An expert consensus statement taking a lifespan approach providing guidance for the identification and treatment of attention-deficit/ hyperactivity disorder in girls and women – PubMed (nih.gov)

Public work

We aim to raise awareness, educate the public and empower girls and women beyond and outside the academic word trough:

• The popular science book “ADHD in girls and women – Connecting the dots” by Lotta Borg Skoglund published in the UK, the US, Korea, New Zeeland, Australia, and Scandinavia. Adhd – från duktig flicka till utbränd kvinna – Natur & Kultur (nok.se).
• International speeches and opinion making during 2023 include ITAKOM Edinburgh, UK 2023, Almedalen Visby, Sweden, Folkemœdet Bornholm, Denmark and ADHD World Congress Amsterdam, The Netherlands.

Equal, evidence based, and timely interventions are at the core of sustainable and effective health care. To this end we realize that we need to do more than just publish research and raise awareness. We aim to let our research inform the development of the first precision health tool for female mental health, Letterlife. Our aim is to create a platform where individualized, real-life relevant data is used to:

• Improve medical decision making in standard of care.
• Encourage safe and effective self-care for girls and women with ADHD.
• Allow sufficiently powered and adequately designed, highly granulated real-life data for research.

In essence:

• We think that by combining technology and neuroscience, we can foster self-awareness, self-efficacy and empower girls and women with ADHD to stay actively engaged, and in charge, of their bodies, minds, and hormones.
• We believe that a co-creating process involving lead patient users, patient organizations, healthcare professionals and researchers have the best potential to detect, predict and treat female specific mental health challenges across the lifespan.
• We predict that individual information, collected and validated though active and passive daily monitoring via Letterlife will generate substantial value and be critical for attaining our long-term goals of improving physical, mental, and reproductive health outcomes in girls and women with ADHD.
• We hope to contribute to the development and evaluation of the Letterlife vision of a user-friendly and holistic, digital tool to improve safety and efficacy, reduce diagnostic delay and societal costs, mitigate comorbidity and polypharmacy.
• We know that if we can improve the reproductive outcomes of female ADHD by preventing unwanted teenage births and obstetric risk factors such as substance use, support females during vulnerable periods such as puberty, preg

Epidemiological studies in pipeline

We are currently performing epidemiological studies on ADHD and:

• PREDICTIVE EPIDEMIOLOGICAL MARKERS for ADHD diagnosis
• ENDOMETRIOSIS
• MENOPAUSE
• ABORTION (contraception post abortion, re-abortions)
• SEXUAL VICTIMIZATION
• MATERNAL HEALTH CARE
• DELIVERY MODE (pain medication, complications)
• PMS/PMDS
• VULVODYNIA
• SEXUALLY TRANSMITTED DISEASES
• POSTPARTUM & LACTATION
• IVF
• CHRONIC FATIGUE, EDS, POTS, POST COVID & BURNOUT

Letterlife proof of concept studies

The proposed LETTERLIFE RESEARCH PROJECT aims to improve and tailor effective health care for girls and women with ADHD. We hypothesize that a digital tool for self-monitoring of relevant real-life individual data related to ADHD-symptoms, cognitive function, and hormonal status can increase the focus on research driven, co-created precision health. The goal is to advance knowledge and standard of care beyond the male norm, to detect female specific challenges and comorbidity and reduce long-term adverse consequences for girls and women with ADHD by:

1. Detecting how hormonal status is associated with ADHD-symptoms and lifestyle factors across the menstrual cycle.
2. Reducing the time to detection, confirmed diagnosis and treatment for girls and women with ADHD.
3. Improving the shared decision making and consequently psychiatric and reproductive outcomes in primary and specialized healthcare (psychiatry and gynecology).
4. Improving psychiatric and reproductive outcomes in females with ADHD through self-awareness and improved self-care.

The proposed project addresses the following research questions:

1. What is the knowledge and experience of gender specific challenges, barriers to current standard of care in ADHD, with regards to quality of life, pharmacotherapy, comorbidity among females with ADHD and health care professionals?

2. What are the attitudes towards sharing personal data between patients (females with ADHD)?

3. Can a digital tool for auto- and self-monitoring of ADHD-symptom, cognitive profile, hormonal status, and relevant lifestyle factors developed in collaboration with lead users:

1. Shorten time to detection, diagnosis and treatment for girls and women with ADHD?
2. Increase efficiency and precision of the clinical decision making in psychiatry and gynecology?
3. Increase compliance and inform personalized dose-regimen of ADHD-medication?
4. Increase the use and compliance of tolerable and safe contraceptives?
5. Decrease polypharmacy?
6. Improve relevant real-life outcomes (quality of life, somatic-, psychiatric-, and reproductive health, through self-care?)

Furthermore, the project address:

1. If individual cognitive profile and ADHD-symptoms are associated to quality of life, somatic-, psychiatric-, and reproductive health outcomes?
2. If hormonal fluctuation across the menstrual cycle and/or hormonal contraceptive use associated to quality of life, somatic-, psychiatric-, and reproductive health and individual cognitive profile, ADHD-symptoms, and pharmacological treatment response?

The proposed research aims focus on closing the health gaps between females and males with ADHD. Critical for attaining the long-term goals, is to decrease the diagnostic delay, mitigate multimorbidity, decrease polypharmacy and improve reproductive health through appropriate access to effective and informed health care for girl and women ADHD. The specific aims are:

1. To prevent multimorbidity and polypharmacy through early detection and improved access to health care services by:
   1. Identify barriers to access health care services and how they influence risk for multimorbidity and polypharmacy.
   2. Piloting an intervention (Letterlife) to facilitate access to healthcare and increase self-care.
2. To prevent multimorbidity through modifiable risk factors by:
   1. Understanding risk and protective factors underlying multimorbidity and polypharmacy through a mixed method design of epidemiological-, clinical-, and qualitative studies.
   2. Identifying novel prevention targets and optimizing lifestyle factors as an intervention to prevent multimorbidity and polypharmacy.
3. To move toward prevention and prediction medicine by improved clinical decision making, informed self-care and identification of individuals who may benefit from individualized pharmacological approaches (i.e., cyclic doses, tailored reproductive counselling and timely hormonal therapy).
4. To disseminate insights gained from aims 1-3 and accelerate gender informed precision health for female ADHD in patients, future research, and clinical practice by:
   1. Developing accessible, brief educational material for target groups.
   2. Developing Massive Open Online Courses for clinicians to raise awareness around hormonal and lifestyle factors and improve access to health care.
   3. Organizing events, seminar series and conferences to disseminate results.
   4. Publication of research findings in open access peer reviewed scientific journals.

The VAL-registry is a population-based data set with information on all Stockholm County healthcare between 2011 to 2021 including 85,330 with ADHD (37,591 females) and 426.626 population representatives without ADHD matched by age, sex, and socioeconomic status.

The Letterlife technology is developed by lead patient users, researchers, and health care professionals through a novel technological approach for prospectively collecting detailed, frequent, longitudinal real-life data on individual- and gender specific ADHD-symptoms, cognitive functions, and sex hormone fluctuation trough active day to day prompters and passive remote monitoring. The qualitative studies will, together with validated screening/assessment scales and diagnostic tools, inform the final decision on the most clinically relevant outcome measures.

Study 1 & 2 is semi structured interviews with healthcare professionals (physicians, nurses, midwifes and psychologists) and females with ADHD in outpatient clinics in Sweden, Norway, Finland, and Denmark.

Study 3 is a prospective observational non-randomized, non-interventional study, using Letterlife technology and smartphone sensors. Remote measurement carries out unobtrusive, real-time data collection on multiple parameters, including individual lifestyle factors, daily functioning, adverse health outcomes, and pharmacological effects over a period of 3 months, using informative periods of predictable sex hormone fluctuations.

Study 4 explore if self-recorded prospective data through Letterlife can be used to inform clinical decision making in screening and assessment before ADHD-diagnosis. The study is conducted in primary care settings where participants are randomized to Letterlife-use or treatment as usual.

Study 5 explore if self-recorded prospective data collection via Letterlife can improve clinical decision making and mitigate negative outcomes through improved standard of care and self-care for female ADHD. Primary outcomes are quality of life, everyday functioning, and life-style factors (diet, exercise, sleep, substance use, social/digital connectivity, economic decision-making) and everyday functioning (work/school attendance) depending on the outcomes of Study 1-2. All participants are blinded to self-collected data the first 3 moths when a random sample of 50 % get access to and can share graphic visualization of individual data with their health care contacts.

Studies 6 & 7 explore subjective user experience and feasibility of implementing Letterlife as part of standard of care for female ADHD in both health care professionals and girls and women with ADHD trough semi-structured interviews.

Tham Family Foundation

• Philanthropic funding of 4.000.000 SEK to Lotta Borg Skoglund and Uppsala University.

Susanne Hobohms Stiftelse

• Philanthropic donation of 900 000 SEK to Lotta Borg Skoglund and Helena Kopp Kallner.

Swedish Society of Medicine (Söderström – Königska Foundation)

• Post Doc Grant of 125.000 SEK to Lotta Borg Skoglund and the project “Sexual risk-taking, hormonal contraceptives and ADHD at Swedish youths' clinics”.

ALF Postdoc Grant

• Post Doc Grant of 700.000 SEK to Helena Kopp Kallner Karolinska Institutet and the project “Sexual risk-taking and hormonal contraceptives in youths”.

Sence & Takeda

Financial support for the statistical work by Sence AB for the study “Time After Time: Failure to identify and support females with ADHD.

Lotta Borg Skoglund is founder and owner of SMART Psykiatri (a private Swedish clinic for assessment and treatment of ADHD in children and adults) and Letterlife (a digital tool for screening and precision health for female ADHD). Advisory boards, invited speaker, scientific meetings and courses sponsored by for Shire/Takeda, Nordic Drugs, UCB Pharma, DNE Pharma, Novartis, Evolan, Lundbeck A/S and Medice. PI for research contracted by Takeda. Royalties from popular science and medical textbooks published in Sweden and internationally.

Helena Kopp Kallner receives honorariums for lectures on contraception, fibroid care, and endometriosis from: Abbvie, Actavis, Bayer, Gedeon Richter Exeltis, Nordic Pharma, Natural Cycles, Mithra, Teva, Merck, Organon, Ferring, Consilient Health. Expert opinion for: Bayer, Evolan, Gedeon Richter, Exeltis, Merck, Teva, TV4 och Natural Cycles, Pharmiva, Dynamic Code, Ellen, Estercare, Pharmiva, Gedea, Gesynta, Leia and Essity. Investigator in trials sponsored by Bayer, MSD, Mithra, Ethicon, Azanta, Gedeon Richter, Gedea, planned study for Organon, Pharmiva and Takeda. Courses sponsored by: Organon, Bayer and Gedeon Richter. Book chapters in: Guide for contraception (sponsored by Bayer) and in the Swedish medical Products agency recommendation for contraception and book chapters for 1,6 million club (Sweden's largest social club for women). President of the European Society of Contraception and Reproductive Health.