The way we diagnose ADHD today is gender-biased.

This paper was written by Liesl Anggijono, Neema Nelly & Sarah Jiang for the Women’s Brain Project 2020 Hackathon.

Attention-deficit hyperactivity disorder (ADHD) is considered to be one of the most common neuropsychiatric disorders of childhood (Barklet and al., 2006). ADHD was once thought of as a predominantly male disorder. While this may be true for ADHD in childhood, research suggests that the number of women with ADHD may be nearly equal to that of men with the disorder (Faraone et al., 2000) and important sex differences exist in the symptom profile. Compared to males with ADHD, females with ADHD are more prone to have difficulties with inattentive symptoms than hyperactive and impulsive symptoms, and females often receive a diagnosis of ADHD significantly later than do males (Gaub and Carlson, 1997; Gershon, 2002a, 2002b). Emerging evidence suggests differences exist in the neuropathology of ADHD, and there are hormonal factors that may play an important role in understanding ADHD in females (Nancy, 2011). Women with ADHD face an uphill battle because their symptoms are likely misdiagnosed, since ADHD looks different in girls than in boys (healthline, 2019).

The main problem in ADHD is thought to be due to the lack of cognitive functions, lack of attention, impulse control as well as excessive mobility ( Nigg, 2000). Girls with untreated ADHD are at risk for chronic low self-esteem, underachievement, anxiety, depression, teen

pregnancy, early smoking during middle school and high school. As adults, they are at risk for divorce, financial crises, single-parenting a child with ADHD, never completing college, underemployment, substance abuse, eating disorders and constant stress due to difficulty in managing the demands of daily life which overflow into the difficulties of their children (Nadeau and al., 2002).

Given the subtle but relevant differences in presentation and developmental course of ADHD, it is essential that both clinical practice and research be informed by awareness of these differences in order to better identify and promote improved quality of care to girls and women with ADHD (Nancy, 2011). Most mainstream research on attention deficit disorder (ADHD or ADD) represents that there are no significant differences on how ADHD is presented in men versus women. On the calibre, data suggest that the sexes experience the same type, number, and severity of symptoms, the same academic struggles, the same number of comorbid disorders, and the same efficacy of medication.

Research shows that ADHD exacts a greater toll on women than it does on men. Clinicians need a different set of tools for diagnosing and treating the disorder across genders — and women deserve a better understanding of how the disorder affects them. Therefore, it is important to improve methods of ADHD recognition in women and develop a diagnostic system that is specific to tackle ADHD clinical symptoms in women. The objective of our research is to develop an application for better recognition and treatment of ADHD in women through monitoring certain biomarkers, activity and eye movement. The results of these tests will help women and their doctors monitor their performance daily activities.

Women have the menstrual cycle as a biomarker where they can know and anticipate which hormones will fluctuate during different parts of the month. Hormonal fluctuations bring high levels of estrogen and progesterone, enhancing certain neurotransmitters cognitive functioning following menstruation. Estrogen and progesterone, the key female hormone, affects the brain and the levels of dopamine and norepinephrine in the brain.ADHD symptoms change along with rising and falling hormone levels. These changes directly affect their ADHD symptoms. Because

ADHD is a brain-based disorder, it is strongly impacted by hormonal fluctuations.

During the premenstrual phase, hormone levels drop and women experience an exacerbation of ADHD symptoms along with typical premenstrual changes. Low estrogen triggers greater irritability and disruptions of mood, sleep, and concentration. These observable symptoms can easily lead to a diagnosis of PMDD, without consideration of underlying ADHD. Other than that, women who are in menopause will ADHD symptoms intensify because of estrogen levels dropping. In combination with age-related cognitive changes, confusion, memory, concentration, and sleep become even more impaired.

It is important to understand how fluctuations in ADHD symptoms align with the normal hormonal fluctuations that occur during her monthly cycle. She will learn what will happen to her according to her infradian rhythm in terms of symptoms. By mapping her symptoms to the timeline of her cycle, she can work with her doctor to better manage her treatment and anticipate when symptoms rise or worsen.

Research shows that the diagnosis of ADHD could be inadequate only by performing clinical interviews, as the individual may be affected by the biased evaluation of him or herself (Meyer and al., 2001). An evaluation tool would be relevant other than psychometric tests to help individuals taking tests and of the practitioner in the diagnosis to follow-up, Electrooculogram (EOG) signals are electrical magnitudes including the movements of the eyeball in the horizontal and vertical axes with ith the designed EOG measurement system, horizontal and vertical eye movements can be recorded and displayed in real time ( Fatma and al., 2019). Vakil et al. studied the evaluation of eye movement performance with the Stroop test in adults with ADHD. The aim of that study was to compare the relationship in the eye movement between adults in the control group and adults with ADHD during the Stroop test. The results confirmed that members of the ADHD group experienced a lack of attention. When the focus times ( the time that elapsed until the eye detect the stimulus on the screen) against visual stimuli such as symbols or numbers were observed and the RTs ( the time that the first eye movement occurred after the stimulus were evaluated), it was found that the control group had a shorter time compared to the ADHD group; the study revealed the potential of using an eye tracker as a diagnostic tool for ADHD ( Vakil and al., 2019).

Genetics Analysis Overview

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders characterized by inattention, impulsivity, diminished executive functions, and hyperactivity (Mehta et al., 2020). It usually presents itself during childhood and can persist throughout adult life. Through traditional family, twin, and adoption studies, ADHD has been observed to be both familial and heritable. Genes are assumed to explain up to 76% of the variability of ADHD-related symptoms in the population (Rietveld, Hudziak, Bartels, Van Beijsterveldt, & Boomsma, 2003). Most recently, twin studies are being used to determine the phenotype of ADHD, analyze gender differences, effects on genes in comorbidity, and understand the relationship between gene and environment. Gene association studies have shown many molecular genetic findings for ADHD mostly coming from a number of pooled and meta-analyses. The data has shown a clear link between ADHD and the presence of VNTR, a dopamine D4 receptor gene, and a dopamine D5 receptor gene microsatellite marker (Bao et al., 2008). Additional studies have suggested that many of the manner and conduct struggles that ADHD patients experience can be affected by the COMT val 158/108 met variant. Thus, these results suggest the importance of examining gene-phenotype links and testing patients for these gene variants.

Family studies show that the biological relatives of probands with ADHD display higher rates of ADHD than relatives of controls. The relative risk of ADHD in first degree relatives is between 40% and 90% (Faraone et al, 2000); thus the familial risk of ADHD is higher than for rheumatoid arthritis but lower than for schizophrenia. Disorders can cluster in families because of a shared environment as well as genes. Thus twin and adoption designs are needed to separate these effects.

Through gene association studies, all this evidence has led to the investigation of DRD4, DRD5, SLC6A4 and COMT which will be discussed (Mill et al, 2005). Other genes such as those

encoding dopamine beta-hydroxylase, monoamine oxidase A, the dopamine D2 and dopamine D3 receptors have also been investigated but the results are not yet conclusive. Nearly all the published molecular genetic studies of ADHD have been based on clinical cases where ADHD has been defined according to DSM-IV diagnostic criteria. A few studies have examined ADHD defined dimensionally but the association findings here have generally been weaker.

I. Dopamine D4 Receptor Gene (DRD4)

The DRD4 gene is on chromosome 11p15.5. The D4 receptor binds both dopamine and noradrenaline. Most studies have focused on a variable number tandem repeat (VNTR) polymorphism in exon III of the gene. The number of repeats ranges from 2–11 with different populations having different alleles. This polymorphism is supposed to be functional, since the 7-repeat allele reduces the ability of the receptor to bind dopamine according to in vitro studies.

II. Dopamine D5 receptor gene (DRD5)

Another dopamine receptor gene, DRD5, on chromosome 4p15.1–15.3 also appears to be important. The associated polymorphism is a microsatellite (a dinucleotide repeat with variable number of copies) mapping 18.5 kb away from the 5′ end of the gene (Daly et al, 1999).

III. Dopamine transporter gene (SLC6A3)

The dopamine transporter gene on chromosome 5p13.3 was initially considered the most likely candidate gene for ADHD. The major reason being that it is responsible for the reuptake of dopamine in the presynaptic cleft and is the target of stimulant medication (DiMaio et al, 2003). Another reason for considering SLC6A3 an important candidate gene for ADHD is because the DAT knockout mouse model exhibits hyperactivity and deficits in inhibitory behaviour. Treating these mice with stimulants reduces symptoms (Gainetdinov et al., 2007).

IV. Catechol-O-Methyltransferase (COMT)

The gene encoding COMT, an enzyme catalyzing the degradation of dopamine, adrenaline and noradrenaline, is on chromosome 22q11.2. Interest in COMT comes from its involvement in dopaminergic pathways. The most studied polymorphism in COMT is a SNP resulting in a valine to methionine substitution. (Caspi et al, 2008).

MODEL

App mockup

Stakeholder mapping

Our results :

I . Task reminder

ADHD is characterized by neurological differences that result in difficulties meeting learning and productivity expectations. People with ADHD experience difficulties in self-managing academic, social, daily living, and health/wellness demands. This makes managing time and productivity a critical skill for academic/career success for people with ADHD. Distraction plays a big part for women with ADHD and that’s why we decided to add a task reminder to help them be aware of their activities. We use four different strategies for managing tasks :

a. Habits and Routines: This strategy promotes productive living across academic, career, daily, and social life. Key parts of habits and routines include

(1) Structured and productive morning routine : Helps patients free up both time and mental energy for the remainder of their day.

(2) Planning system : protecting personal goals

(3) Prioritization strategies : increase effectivity of the planning system

(4) reminder systems.

(2),(3) and (4) helps patients keep track of what’s in their mind and plan to stay on top of their schedules, goals, tasks, and expectations. This has been proven to reduce cognitive load and improved efficiency and/or the accuracy of task performances.

b. Reframing : Helping patients understand their temporal and productivity challenges such as challenging or frustrating experiences, like not completing tasks or not executing time as well as expected.

(1) Self-evaluation : Evaluation of personal strengths and challenges and to better understand one’s personal cognitive style of execution of tasks to bring direction of development of personal, productivity and time-management goals and strategies. This supports them to discover the style of execution and conditions that facilitated success.

(2) Reframing challenges for themselves and for others by discerning their preferences for challenge identification taking to account key factors such as cognitive style.

c. Symptom specific strategies : Helping patients cope with challenges by sustaining concentration and also by maintaining mental energy by using several techniques such as activity breaks, switching activities, using environmental cues

d. Planning according to the infradian rhythm : Planning according to a woman’s menstrual cycle or infradian rhythm because it controls our hormones that contribute to the progression and consistency of our menstrual cycle. The hypothalamus, an almond-sized brain structure, the command center of the endocrine system receives data about hormone levels throughout the body releases and inhibits hormones. These are the four main phases.

(1) Follicular: Estrogen levels rise, thus the brain’s working memory capacity is enhanced. — creativity and planning

(2) Ovulatory: Increased synaptic connections boosting mental sharpness, communication & collaboration skills.

(3) Luteal: Corpus luteum is absorbed and progesterone rises, energy begins to turn inward to focus on detail-oriented tasks — completion and detail

(4) Menstruation: Communication between both hemispheres of the brain is strongest during this time — reflection and looking inwards, analyzing your progress, and following your intuition

II. Raising awareness

Historically, research on ADHD has focused almost exclusively on hyperactive little boys, and only in the past six or seven years has any research focused on adult ADHD, there is a need to raise awareness of the needs of women with the disorder through advocacy and groundbreaking research and writing (Nadeau and al., 2002). Through our project, we will raise awareness through campaigns in-app and out-of-app posts(such as social media promotion). There are two main types of root causes content(videos, infographic,etc) we will push out. A. ADHD misconceptions

Debunking misconceptions about ADHD that has been prevalent in society such as ADHD being the cause of bad parenting, wrong diagnosis methods, bad perceptions of people’s capabilities with ADHD and ADHD being considered as a moral deficit.

B. ADHD stigma for women

Gender bias and discrimination in ADHD research and treatment and stigma surrounding ADHD for women, which delays assessment and intervention.

III. Next steps

In-app Neurocognitive training

Neurocognitive training is a potential treatment for ADHD from evidence based on supporting factors of brain plasticity from rehabilitation science and contemporary developmental neuroscience. The training is key brain networks implicated in ADHD can be strengthened, and the cognitive processes they subserve improved, through controlled exposures to information processing tasks. Cognitive training can reduce ADHD symptoms and improve functioning by targeting neuropsychological deficits thought to mediate ADHD pathophysiology. Other than that, results of the brain training can serve as a metric to track to analyze a patient’s activity.

CONCLUSION

ADHD is a condition that affects many aspects of life including: mood, cognitive abilities, behaviors, and daily tasks. Effective treatment for ADHD in adult women should be approached through a multimodal toolbox that includes genetic analysis, psychotherapy, stress management, as well as ADHD coaching and/or professional organizing.

Even those women fortunate enough to receive an accurate ADHD diagnosis often face a stigma surrounding the perception of mental health that could deter women from seeking necessary help. There is also a challenge of finding a professional who can provide appropriate treatment. Currently, there are very few clinicians experienced in treating adult ADHD and even fewer who are familiar with the unique issues faced by women with ADHD. As a result, most clinicians use standard psychotherapeutic approaches. Although these approaches can be helpful in providing insight into emotional and interpersonal issues, they do not help a woman with ADHD learn to better manage her ADHD on a daily basis or learn strategies to lead a more productive and satisfying life.

Thus, the Olivia initiative is designed to take all of these challenges into consideration when helping women best manage ADHD. Olivia utilizes a multifaceted approach including a website for the medical professional to educate on how ADHD would present differently in women. This will be useful because knowledge of ADHD in women at this time is extremely limited as few studies have been conducted on this population. Women have only recently begun to be diagnosed and treated for ADHD, and today, most of what we know about this population is based on the clinical experience of mental health professionals who have specialized in treating women. The Olivia toolbox will also include an app for the individual with ADHD. This app is designed to help women navigate struggles with stress and help instill task management skills. Another feature of this app will include eye movement recognition which will help track the user’s attentiveness. The social stigma and gender discrimination in mental health problems, especially ADHD can make challenges worse and even stop an individual from getting the help they need. Olivia aims to launch a social media campaign for this cause or partner up with an existing awareness foundation for ADHD such as ADHD Awareness Month and The Attention Deficit Disorder Association (ADDA). This is an important step in making sure that the resources that Olivia offers will be willingly utilized without stigma or discrimination.

ADHD has consequences that decrease quality of life to individuals and it manifests troubles with being over active or not paying attention. Women are less likely to

be diagnosed with ADHD compared to men even when they present the same symptoms. It is necessary to raise awareness regarding women with ADHD and to improve the diagnostic system. The deliverable results of our project are expected to develop an application for women with ADHD that would incorporate task management tools, eye movement recognition and to raise awareness. Overall, Olivia’s multifaceted approach will be able to more effectively treat and encourage women with ADHD than the traditional prescription medication approach because Olivia always puts the patient first.

ACKNOWLEDGEMENT

This paper and the research behind it would not have been possible without the exceptional support and guidance of our mentors, Piera Marongiu and Virginia Schumacher. We would also like to express appreciation for the Woman Brain Project team for coordinating this hackathon and allowing for great minds to connect worldwide.

REFERENCES

American Psychiatric Association. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, Text Revision (DSM-IV-TR). 4th ed. Washington DC, USA: American Psychiatric Publishing; 2000.

Barkley RA. Attention-deficit hyperactivity disorder: a handbook for diagnosis and treatment, 3rd ed. New York, USA: Guilford Press; 2006.

Faraone, S. V., Biederman, J., Spencer, T., Wilens, T., Seidman, L. J., Mick, E., Doyle, A. E. (2000). Attention-deficit/hyperactivity disorder in adults: An overview. Biological Psychiatry, 48, 9–20.

Fatma Latifoglu, Mustafa Yasin Esas and Esra Demirci (2019): Diagnosis of attention-deficit hyperactivity disorder using EOG signals: a new approach.

Gaub, M., Carlson, C. L. (1997). Gender differences in ADHD: A meta-analysis and critical review. Journal of the American Academy of Child & Adolescent Psychiatry, 36, 1036–1045.

Gershon, J. (2002a). A meta-analytic review of gender differences in ADHD. Journal of Attention Disorders, 5, 143–154.

Gershon, J. (2002b). An overview of research. In Quinn, P. O., Nadeau, K. G. (Eds.), Gender issues and AD/HD: Research diagnosis and treatment (pp. 23–38). Silver Spring, MD: Advantage Books.

healthline (2019). The Hidden Struggles of a Woman with ADHD.

https://www.healthline.com/health/hidden-struggles-of-a-woman-with-adhd ( Accessed 08/02/2021).

Meyer GJ, Finn SE, Eyde LD, Kay GG, Moreland KL, Dies RR, et al (2001). Psychological testing and psychological assessment: a review of evidence and issues. Am Psychol ;56:128–65.

Nadeau, K.G., & Quinn, P.O. (Eds.) (2002). Understanding women with AD/HD. Silver Spring, MD: Advantage Books.

Nadeau, K.G., & Quinn, P.O. (Eds.) (2002). Gender issues and AD/HD: Research, diagnosis, and treatment. Silver Spring, MD: Advantage Books.

Nancy L. Nussbaum (2011). ADHD and Female Specific Concerns: A Review of the Literature and Clinical Implications. Journal of Attention Disorders. Vol 16, Issue 2.

Nigg JT (2000). On inhibition/disinhibition in developmental psychopathology: views from cognitive and personality psychology and a working inhibition taxonomy. Psychol Bull; 126:220–46.

Vakil E, Mass M, Schiff R (2019). Eye movement performance on the Stroop test in adults with ADHD. J Atten Disord;10:1160–9.

Mehta, T., Mannem, N., Yarasi, N.K. et al. Biomarkers for ADHD: the Present and Future Directions. Curr Dev Disord Rep 7, 85–92 (2020). https://doi.org/10.1007/s40474-020-00196-9

Thapar, A., & Stergiakouli, E. (2008). An Overview on the Genetics of ADHD. Xin li xue bao. Acta psychologica Sinica, 40(10), 1088–1098. https://doi.org/10.3724/SP.J.1041.2008.01088

Faraone SV, Biederman J, Friedman D. Validity of DSM-IV subtypes of attention-deficit/hyperactivity disorder: a family study perspective. J Am Acad Child Adolesc Psychiatry. 2000 Mar;39(3):300–7.

Gainetdinov RR. Dopamine transporter mutant mice in experimental neuropharmacology. Naunyn Schmiedebergs Arch Pharmacol. 2007

Mill J, et al. Quantitative trait locus analysis of candidate gene alleles associated with attention deficit hyperactivity disorder (ADHD) in five genes: DRD4, DAT1, DRD5, SNAP-25, and 5HT1B. Am J Med Genet B Neuropsychiatr Genet. 2005;133B(1):68–73.

Caspi A, et al. A replicated molecular genetic basis for subtyping antisocial behavior in children with attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 2008;65(2):203–210.

Daly G, et al. Mapping susceptibility loci in attention deficit hyperactivity disorder: preferential transmission of parental alleles at DAT1, DBH and DRD5 to affected children. Mol Psychiatry.

DiMaio S, et al. Dopamine genes and attention-deficit hyperactivity disorder: a review. J Psychiatry Neurosci. 2003;28(1):27–38.

Gainetdinov RR. Dopamine transporter mutant mice in experimental neuropharmacology. Naunyn Schmiedebergs Arch Pharmacol. 2007

Kreider, Consuelo M et al. “Strategies for Coping with Time-Related and Productivity Challenges of Young People with Learning Disabilities and Attention-Deficit/Hyperactivity Disorder.” Children (Basel, Switzerland) vol. 6,2 28. 13 Feb. 2019, doi:10.3390/children6020028

student 🌐 innovator @ tks | based in jakarta,indonesia