New developments and potential future research directions in adult ADHD

The review produced by S. Cortese and nineteen other worldwide renowned scientists ¹ provides a comprehensive update on the current position of our knowledge and understanding of attention‐deficit/hyperactivity disorder (ADHD) in adults. The first conclusion is that, although a lot of progress has been made by research and in clinical practice, the science of adult ADHD lags behind compared to childhood ADHD and to other psychiatric disorders in adulthood. Key unmet needs according to individuals with lived experience may lead the way to better understanding and treatment of ADHD in adulthood. Here I highlight some new developments and potential future research directions.

Regarding the decision about whether impairment is severe enough in adults with mild symptoms, I would like to challenge the notion of “negligible impairment” in adults who suffer from low self‐esteem, inner distress and self‐blame. A recent paper compared the endorsement of DSM‐5 criteria for ADHD between genders, using the Diagnostic Interview for ADHD in Adults (DIVA‐5) in 2,257 adults. Of the five potential domains of impairment, particularly self‐esteem issues were highly common (in 89% of women and 81% of men) ² . The high recognition of self‐esteem problems in adults with ADHD may be interpreted as a plea to reconsider this impairment as important, having high impact in both genders.

Sleep loss is present in around 80% of both children and adults with ADHD, even before the start of any stimulant treatment. The most common comorbid sleep disorder is the circadian rhythm sleep‐wake disorder, delayed sleep phase type, leading to chronic late and short sleep ³ . Melatonin onset in the evening has been shown to be 1.5 hrs delayed in adults with ADHD, which may point to a dysregulation of the circadian clock ⁴ . This understudied area needs more attention in ADHD.

Recently, an alarmingly high number of health conditions have been found to be more common in adults with ADHD, including obesity, diabetes type 1 and 2, cardiovascular diseases, dementia and Parkinson's disease, migraine, asthma, allergies, irritable bowel syndrome and ulcerative colitis, arthritis, many autoimmune disorders, epilepsy, early menopause, and chronic obstructive pulmonary disease. It may be time to consider ADHD as a systemic disease, including both mental and physical manifestations, and start rethinking from there. We know that ADHD is a heritable condition, but what the 76 genes currently identified exactly do is still subject of investigation ⁵ . All these comorbidities may help to find the key(s) to more general factors involved in both mental and physical diseases.

The high rate of autoimmune disorders and inflammatory diseases with a strong genetic load may point in this direction. ADHD has been found to be associated with weak connective tissue, manifesting in a variety of hypermobility syndromes, Ehlers‐Danlos syndrome, musculoskeletal pain syndromes; inflammation of the gut resulting in food intolerance; as well as dysautonomia or orthostatic intolerance, resulting in dysregulation of blood pressure, dizziness, and palpitations ⁶ . Also, failure of the immune system to deal with infections such as COVID‐19, resulting in long COVID, has been detected more often in children with ADHD. Other immune‐related disorders have also been associated with ADHD, such as selective immunoglobulin A deficiency, and familial mediterranean fever ⁷ .

In summary, if genetic susceptibility for ADHD is associated with weakness of connective tissue, failure of the immune system, and low‐grade inflammation related to obesity, chronic sleep loss and an unhealthy lifestyle, we may get a better understanding of the complex etiology of ADHD and its broad range of mental and physical manifestations.

Women have a share of 50% in the total prevalence of ADHD, but they have been remarkably understudied. Cortese et al correctly state that we need high‐quality research including large numbers of female participants across all the different phases of life. I would like to add that this research should focus on the specific female presentation of ADHD, the late recognition and underdiagnosis in girls and women, the interaction between neurotransmitters such as dopamine and female hormones associated with increased premenstrual, postpartum and peri‐menopausal mood and ADHD symptoms, the best treatment of ADHD in women, as well as the understudied comorbidity with hormonal, gynaecological and cardiovascular disorders ⁸ , ⁹ .

Regarding ADHD in the elderly, further research is clearly needed, especially on differentiation from cognitive decline, which may not be so easy as it seems. A growing number of patients ask for help for their parent who is already living in a nursing home, when it may be really too late to disentangle ADHD symptoms from cognitive decline and dementia. They may occur together, and studies have not sufficiently looked into differences and overlap using biological and neuropsychological measures. There are no randomized controlled trials using stimulants in older people, and clinical guidance on treatment of somatic comorbidities, such as hypertension or cardiovascular diseases, when using stimulants is missing. It is therefore not surprising that elderly people living with ADHD get treatment only in 0.09% of cases. The number of these people is rapidly increasing, and the relevant questions to science are becoming more urgent.

People living with ADHD pointed out that there are important health care gaps due to “not being seen, not being recognized, not being diagnosed nor treated”. When they are treated, the available treatment often does not include family support and cognitive behavior therapy. At the same time, there is an enduring stigma from society towards people with a diagnosis of ADHD. This is even more true for women, people of color, other minorities, and people with low income, multiplying inequities. The elephant in the room here may be education, that is needed for health care professionals, society, schools and workplaces, in order to reduce stigma and increase recognition and support for people living with ADHD.