The gender imbalance in ADHD
Wednesday, December 2nd, 2015
Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent neuropsychiatric condition placing a considerable burden of disease on our population. ADHD primarily manifests in childhood with symptoms of inattention, hyperactivity and/or impulsivity that affect normal function.  Though ADHD affects both children and adults, current literature has focused greatly on the disorder in children and this paper will focus mainly on the paediatric population. Australian statistics reported ADHD as the leading mental and behavioural condition amongst children 0-14 years of age, accounting for 12% of children with a disability in 2004.  Furthermore, the diagnosis of ADHD in paediatric consultations has increased in frequency to almost 18% of the referred population.  Unfortunately, the prevalence of ADHD has been difficult to assess due to its heterogeneous nature and dependence on diagnostic criteria and classification.  Despite these obstacles, the reported demographic of ADHD has illustrated a skewed gender distribution towards males worldwide, creating a scope for exploring the gender differences in ADHD. [5-7] Current research has focused on theories supporting changing diagnostic criteria, phenotypic differences and biological differences to explain this gender difference in the prevalence of ADHD. However, to better understand this gender distribution, it is important to understand the terminology utilised in ADHD and how this has influenced current prevalence estimates for the disorder.
Definition of ADHD
The terminology and criteria surrounding ADHD have undergone significant revision over time. On the whole, it should be emphasised that normal childhood development displays active, impulsive and inattentive behavior and diagnosing ADHD should be based on a comprehensive subjective and objective assessment of the individual.  The American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM) provides specific criteria for diagnosing ADHD, but is also a prime example of the changing definition of the disorder.  ADHD was initially defined as a hyperkinetic reaction of childhood in the DSM-II, followed by Attention Deficit Disorder, with or without hyperactivity, in DSM-III, and finally ADHD with subtypes presented in DSM-IV.  The DSM-V now defines ADHD as pattern of inattention and/or hyperactivity-impulsivity that is persistent, interferes with development, has symptoms presenting in two or more settings, and directly impacts on the individual’s functional capabilities.  The core symptoms of inattention and hyperactivity-impulsivity each contain their own set of symptoms, of which six or more must be present in children and five or more in adults for at least 6 months prior to assessment.  The DSM-V has also reframed subtypes of ADHD from the DSM-IV to presentations including combined presentation, predominantly inattentive presentation and predominantly hyperactivity-impulsivity presentation. This evolving terminology has been implicated in many studies attempting to explain the differing prevalence of ADHD across the world, which, in turn, influences the gender distribution of ADHD.
Prevalence of ADHD
ADHD is a heterogeneous disorder with symptoms requiring both temporal and spatial conditions and the lack of definite diagnostic tools has prevented an accurate representation of the disorder worldwide. [4,8,10] Firstly, there are variations in methodology, including the diagnostic criteria used and evaluation of clinical impairment.  For example, studies may illustrate increased rates of childhood ADHD classified using the DSM-IV criteria but decreased rates in those who undergo further assessment, suggesting diagnostic inaccuracy.  Furthermore, a recent community-based study in America illustrated increasing prevalence estimates with the new DSM-V criteria for age of onset and symptom count, but decreasing prevalence with the new criteria requiring a degree of impairment due to the disorder, based on changing case definitions of ADHD.  Overall, there are strengths to having accepted diagnostic criteria in the DSM, however the lack of tools to identify and quantify these symptoms continues to be an obstacle in current prevalence estimates for ADHD.
In addition, the population sample (e.g. community or clinic) contributes greatly to varying prevalence estimates.  For example, an Australian study based on participants identified in a parental-reported survey illustrated an ADHD prevalence of 13.6% with a male: female prevalence ratio of 2:1.  Conversely, an Australian clinical study showed a greater gender difference with a male to female ratio of 4:1.  This illustrates a well-recognised pattern in the prevalence of ADHD where male to female ratios are higher in referred populations than in community-based samples. [4,7,11] The main explanation for this evident gender distribution between the population samples has widely been accepted as referral bias, whereby a myriad of factors has resulted in a greater number of males reaching clinics for diagnosis and management of ADHD.  There have been many factors found contributing to this referral bias including phenotypic differences, recognition of comorbidities and symptom reporting amongst the ADHD patient population.  Overall, the skewed gender distribution in ADHD prevalence is influenced by both methodology and population variables and these need to be carefully considered when analysing the role of gender in ADHD.
Phenotypic differences in ADHD
ADHD presents with a myriad of manifestations that share the underlying characteristics of inattention and/or hyperactivity. In general, the main differences in symptom recognition for ADHD differs with males being more likely to be recognised for externalising symptoms in contrast to females exhibiting internalising features. [5,7,12] These symptoms can be further described as males more likely to present with disruptive behaviours that correspond to the hyperactive-impulsive core symptoms whereas females are more likely to present with symptoms correlating to inattention. [6,7,10,12] Multiple studies have also shown that females are more likely to exhibit physiological anxiety, whereas males were reported for rule breaking and risk taking actions. [6,12] Females were also more likely to present with somatic complaints, which have been considered a marker for anxiety proneness across the literature. [7,12]
Furthermore, the recent inclusion of ADHD subtypes has added to the gender differences in ADHD, where females are found more likely to be diagnosed with predominantly inattentive ADHD whereas males are more commonly diagnosed with predominantly hyperactivity-impulsivity or combined presentations. [12,13] This, in turn, has consequences on the aforementioned referral bias, where females who are identified to have symptoms of ADHD were not considered impaired if exhibiting inattenttive ADHD, but considered severely impaired when exhibiting hyperactive-impulsive ADHD. [11,13] Another implication of these subtypes is the tendency for hyperactive and/or impulsive behaviour to lessen over time whereas inattentive behaviour tends to persist.  This, in turn, may lead to more males being recognised for their ADHD in childhood due to an increased tendency to express hyperactive/impulsive behaviour and for female patients to be under-recognised.  Phenotypic differences in ADHD play an important role in ascertaining the gender distribution of this disoder as these differences may result in referral bias and therefore account for the greater number of males recognised with the disorder. [11,13]
Comorbidities in ADHD
Comorbidity in childhood psychiatry is an expected phenomenon, with ADHD commonly presenting with common concurrent neuropsychiatric conditions.  For example, disruptive behavioural disorders such as oppositional defiant disorder have a high rate of comorbidity with ADHD, sharing particular symptoms with the hyperactive or impulsive subtype.  Similarly, anxiety disorders are also commonly diagnosed in patients with ADHD, usually with a more severe and distinctly inattentive clinical presentation.  Furthermore, these childhood psychiatric disorders appear to illustrate a similar gender distribution to that of ADHD, with disorders such as autism spectrum disorder being widely accepted to have a male predominance in childhood.  However, reports of comorbidity in ADHD is subject to the same limitations of referral bias, phenotypic differences and diagnostic criteria that influence the prevalence and gender distribution across childhood psychiatry. 
Furthermore, both males and females have been found more likely to have comorbid ADHD, in comparison to a solitary diagnosis of ADHD  Some studies have shown parents and teachers to report more difficulties with oppositional behaviours, social difficulties, depression and anxiety in females, compared to their male counterparts.  However others have illustrated an equal increase in presentation of comorbid conditions in the hyperactivity-impulsivity subtypes, with the gender difference being higher levels of comorbidity for females in the inattentive subtype through comorbid social and generalised anxiety disorders.  Another study found the only statistically significant gender difference to be a higher rate of substance use disorders in females with ADHD, particularly in early adolescence.  Overall, comorbidity in ADHD is an important consideration in studying the prevalence of the disease and how the gender distribution of these disorders can influence the gender distribution of ADHD.
Symptom reporting in ADHD
Firstly, many studies have commented on symptoms reported by patients, parents, teachers and clinicians – all of which provide different criteria for diagnosis of ADHD. Studies have shown self-reported symptoms to be highest in the clinical setting, whereas community-based research focuses heavily on parent- and teacher-reported symptoms.  A review of variations in ADHD prevalence mentioned that multiple studies have shown different rates of symptom reporting between parent and teacher.  Teachers’ contributions are substantial as they can provide daily observations of patients in comparison to unaffected individuals of the same age, environment and developmental level.  Parents are also valuable as they provide a change in an individual’s behaviour over time. However, both groups lend themselves to symptom recognition biased towards hyperactivity and impulsivity, as these tend to be more disruptive in both the school and home environment. This results in under-recognition of internalising symptoms such as depression and inattention, which, in turn, influence the rates of symptom reporting for ADHD. [4,12]
Furthermore, the culture surrounding ADHD has resulted in it being considered a male disorder. [5,10] This has multiple implications, from a greater tendency to recognise symptoms in the community to specialist referral for ADHD symptoms, with the social and cultural constructs of ADHD making males more likely to be subject to symptom reporting. [7,10] The lower prevalence rates have also been attributed to the higher likelihood of referral for disruptive behaviour, more commonly seen in the hyperactivity-impulsivity presentation or combined presentation of ADHD . This, in itself, creates a skewed gender distribution as these have been illustrated at higher rates in the male population.  On average, there are more similarities than differences in the symptomatology of ADHD across genders, and symptoms are not sex-specific, but rather show trends as discussed above. [5,13] However, it is important to be aware of the gender differences when applied to ADHD subtypes, comorbid psychological conditions and the sources of symptom reporting for accurate diagnosis and management of ADHD in our population.
Biological Differences in ADHD
Biological factors have also been shown to influence gender differences in ADHD prevalence in our population. However, the majority of research conducted in this field has been underpowered due to the disproportionate number of males diagnosed with the disease, and the lack of drive to characterise any prospective sex differences.  A recent review discussed the evidence for neurogenetic and endocrine mechanisms, where differences in chromosomal composition, sex-linked genes and early exposure to hormones can interact to affect the manifestation of ADHD between sexes.  For example, there is an inherent sex difference in the male-limited expression of the Y chromosome and the presence of only one X chromosome, which leads to the presence of different genes and mutations that may influence neurodevelopment and susceptibility to ADHD between genders. 
Furthermore, there is increasing research into the anatomy and physiology of the neurological aspects of ADHD. This has illustrated a complex network of brain regions that are structurally modified to produce a developmental deviation in response to immature cortical under-arousal.  This has also produced gender differences whereby electroencephalography (EEG) studies have shown different patterns between males and females, and further differentiation between ADHD subtypes.  Overall, the current literature has emphasised a need for more focused research on the biological differences in ADHD to better characterise the profile of ADHD in males and females.
Management of ADHD
The implications of gender differences on the diagnosis and identification of ADHD have been discussed, however it is important to also consider the impact of gender on the management of ADHD. Pharmacological management in the form of stimulant medication has recently been gaining traction in current treatment practices for ADHD. [3,21] In general, current trends have shown that males with ADHD are more likely to receive pharmacotherapy and psychotherapy than females.  For example, in Western Australia, the prescription rates for stimulant medication were greater in males than females.  NSW Public Health illustrated a similar pattern, with males four times more likely to be on stimulant medication than females, though there has been an increase in the prescription patterns for females over the last two decades.  These statistics elucidate gender differences in practitioner trends and management of ADHD, however further investigation would be required to explain these trends in correlation to the disease recognition and prevalence as discussed earlier. In addition, it is also important to consider the possibility of gender differences in the treatment response for ADHD, though a recent population-based study has shown the response was favourable and did not differ between genders. 
In addition to pharmacological management, there is an increased role of behavioural intervention in the management of ADHD. Behavioural therapy represents a collection of specific interventions that modify the physical and social environment in order to change behaviour.  These interventions can be delivered through parental, classroom or peer interventions that reward desired behavioural traits and discourage undesirable behaviours through techniques such as planned ignoring, appropriate consequences and/or punishment.  When considering individual behavioural intervention in ADHD management, females are said to benefit from management of comorbid conditions such as mood and/or anxiety disorders that may exacerbate the expression of ADHD in combination with pharmacotherapy.  Mixed-gender treatment is another option for behavioural intervention in ADHD, which involves group-based behavioural interventions with both male and female patients. However, studies have shown gender differences to influence this management strategy as the mixed-gender setting may suppress treatment effect in females and fail to address gender-specific social impairments.  A recent American study investigated the effects of single- versus mixed-gender treatment for adolescent females and found females were more likely to benefit from single-gender treatment with more assertiveness, self-management and compliance.  Conversely, males exhibited lower levels of physical and relational aggression and better self-management and compliance in the mixed-gender setting.  Overall, behavioural intervention is important in the management of ADHD and needs to account for gender differences in disease presentation and response to treatment.
Future directions in ADHD
ADHD is rapidly gaining awareness for its burden of disease in our paediatric population. However, current literature has lacked focus in characterising important epidemiological trends in ADHD, such as the distribution between genders. Firstly, most of the discussion above has been based on studies using the DSM-IV criteria for diagnosis and therefore further studies based on the DSM-V criteria may again alter the gender prevalence of the disorder. Secondly, study design needs to account for population sample bias, especially between community- and clinic-based samples, in order to better estimate the disease and gender prevalence across the world. Studies also need to be designed with the aim of defining the phenotypic differences and the direct impact of these on symptom reporting in order to tailor future practice and better recognise ADHD throughout the population. The same should apply to biological differences and response to management, both pharmacological and behavioural as the main examples, for more effective clinical practice. It should also be noted this discussion focused mainly on paediatric ADHD, however current literature has seen rapid growth in research into adults with ADHD, though it is limited with regards to the gender distribution in these populations. Similar to the evidence discussed above, it is reasonable to expect the gender ratios in ADHD prevalence to be similarly affected by referral or identification bias, poorly defined diagnostic criteria and biological differences.  On the whole, the consensus across current literature is a need for further investigation that can better define the prevalence of ADHD in our population and the influence, if any, of gender.
ADHD is an increasing burden of psychiatric disease for our paediatric population with a reported greater prevalence amongst male patients. The skewed gender distribution of the disorder has been widely varied due to differing diagnostic criteria, terminology and research methodology. The differences found illustrated variation in disease presentation and psychological comorbidities, as well as biological differences that may account for the variation in disease presentation between genders. Furthermore, there were differences in reporting of ADHD symptomatology between patient, parent, teacher and clinician as well as differing trends in management that may influence the recognition and treatment of ADHD across our population. Overall, these differences warrant further research to better understand ADHD and characterise the disease profiles between males and females for increased accuracy in identification, diagnosis and treatment in our population.
Many thanks to Associate Professor Christine Phillips for introducing students to the social foundations of medicine and promoting discussion on a gender perspective.
Conflicts of interest
M Bokil: firstname.lastname@example.org
 National Health and Medical Research Council. Clinical Practice Points on the diagnosis, assessment and management of Attention Deficit Hyperactivity Disorder in children and adolescents. Commonwealth of Australia; 2012.
 Australian Institute of Health and Welfare (AIHW). Children with disabilities in Australia. AIHW cat. no. DIS 38. Canberra: AIHW; 2004.
 Efron D, Davies S, Sciberras E. Current Australian Pediatric Practice in the Assessment and Treatment of ADHD. Acad Pediatr. 2013;13(4):328-33.
 Skounti M, Philalithis A, Galanakis E. Variations in prevalence of attention deficit hyperactivity disorder worldwide. Eur J Pediatr. 2007;116(2):117-23.
 Ramtekkar UP, Reiersen AM, Todorov AA, Todd RD. Sex and age differences in Attention-Deficit/Hyperactivity Disorder symptoms and diagnoses: Implications for DSM-V and ICD-11. J Am Acad Child Adolesc Psychiatry. 2010;49(3):217-28.
 Graetz BW, Sawyer MG, Baghurst P. Gender Differences Among Children with DSM-IV ADHD in Australia. J Am Acad Child Adolesc Psychiatry. 2005;44(2):159-68.
 Rucklidge JJ. Gender differences in attention-deficit/hyperactivity disorder. Psychiatr Clin North Am. 2010;33(2):357-73.
 McKeown RE, Holbrook JR, Danielson ML, Cuffe SP, Wolraich ML, Visser SN. The Impact of Case Definition on Attention-Deficit/Hyperactivity Disorder Prevalence Estimates in Community-Based Samples of School-Aged Children. J Am Acad Child Adolesc Psychiatry. 2015;54(1):53-61.
 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th edition. Arlington, VA: American Psychiatric Association; 2013.
 Sciutto MJ, Eisenberg M. Evaluating the Evidence For and Against the Overdiagnosis of ADHD. J Atten Disord. 2007;11(2):106-13.
 Coles EK, Slavec J, Bernstein M, Baroni E. Exploring the Gender Gap in Referrals for Children with ADHD and Other Disruptive Behaviour Disorders. J Atten Disord. 2012;12(2):101-8.
 Skogli EW, Teicher MH, Andersen PN, Hovik KT, Oie M. ADHD in girls and boys – gender differences in co-existing symptoms and executive function measures. BMC Psychiatry. 2013;13:298-309.
 Biederman J, Mick E, Faraone SV, Braaten E, Doyle A, Spencer T, et al. Influence of Gender on Attention Deficit Hyperactivity Disorder in Children Referred to a Psychiatric Clinic. Am J Psychiatry. 2002;159(1):36-42.
 Elia J, Ambrosini P, Berrettini W. ADHD Characteristics: I. Concurrent co-morbidity patterns in children and adolescents. Child Adolesc Psychiatry Ment Health. 2008;2(1):15-23.
 Halldorsdottir T, Ollendick TH. Comorbid ADHD: Implication for the Treatment of Anxiety Disorders in Children and Adolescents. Cogn Behav Pract. 2014;21(3):310-22.
 Werling DM, Geschwind DH. Sex differences in autism spectrum disorders. Curr Opin Neurol. 2013;26(2):146-53.
 Levy F, Hay DA, Bennett KS, McStephen M. Gender differences in ADHD subtype comorbidity. J Am Acad Child Adolesc Psychiatry. 2005;44(4):368-76.
 Cortese S. The neurobiology and genetics of Attention-Deficit/Hyperactivity Disorder (ADHD): What every clinician should know. Eur J Paediatr Neurol. 2012;16(5):422-33.
 Davies W. Sex differences in Attention Deficit Hyperactivity Disorder: Candidate genetic and endocrine mechanisms. Frontiers of Neuroendocrinology. 2014;35(3):331-46.
 Dupuy FE, Barry RJ, Clarke AR, McCarthy R, Selikowitz M. Sex differences between the combined and inattentive types of attention-deficit/hyperactivity disorder: An EEG perspective. Int J Psychophysiol. 2013;89(3):320-7.
 Subcommittee on Attention-Deficit/Hyperactivity Disorder, Steering Committee on Quality Improvement and Management, Wolraich M, Brown L, Brown RT, DuPaul G, et al. ADHD: Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. American Academy of Pediatrics. 2011;128(5):1007-22.
 Preen DB, Calver J, Sanfilippo FM, Bulsara M, Holman CDAJ. Patterns of psychostimulant prescribing to children with ADHD in Western Australia: variations in age, gender, medication type and dose prescribed. Aust N Z J Public Health. 2007;31(2):120-6.
 Salmelainen P. Trends in the prescribing of stimulant medication for the treatment of Attention Deficit Hyperactivity Disorder in children and adolescents in NSW. Sydney, NSW: Department of Health; 2002.
 Barbaresi WJ, Katusic SK, Colligan RC, Weaver A, Leibson CL, Jacobsen SJ. Long-Term Stimulant Medication Treatment of Attention-Deficit Hyperactivity Disorder: Results from a Population-Based Study. J Dev Behav Pediatr. 2006;27(1):1-10.
 Quinn PO. Treating adolescent girls and women with ADHD: gender-specific issues. J Clin Psychol. 2005;61(5):579-87.
 Babinski DE, Sibley MH, Ross JM, Pelham WE. The Effects of Single Versus Mixed Gender Treatment for Adolescent Girls with ADHD. J Clin Child Adolesc Psychol. 2014;42(2):243-50.
 Williamson D, Johnston C. Gender differences in adults with attention-deficit/hyperactivity disorder: A narrative review. Clin Psychol Rev. 2015;40:15-27.