An attention-deficit/hyperactivity disorder (ADHD) diagnosis later in life is associated with a milder clinical and genetic profile than a diagnosis during childhood or adolescence, a new study showed.

In a cross-sectional study of more than 13,000 adults with ADHD, those diagnosed in adulthood had fewer psychiatric and somatic comorbidities and less functional impairment than those diagnosed at a younger age. Both groups, however, had higher rates of psychiatric and somatic conditions than adults without ADHD, including depression and neurologic disorders.

“Adults diagnosed later may, on average, have a milder ADHD profile, with fewer comorbidities and somewhat lower genetic liability, allowing symptoms to go unrecognized for longer,” lead investigator Douglas Teixeira Leffa, MD, PhD, Department of Psychiatry, University of Pittsburgh in Pittsburgh, Pennsylvania, told Medscape Medical News.

“Importantly, adults diagnosed either as youths or adults still exhibited profiles characteristic of ADHD when compared with matched controls, supporting a continuum of severity rather than completely distinct forms of ADHD,” he added.

The study was published online on September 16 in JAMA Network Open.

Age at Diagnosis

Adult ADHD diagnoses have increased in recent years, but little is known about how the age at diagnosis might affect clinical presentation or outcomes.

Using data from the nationwide All of Us Research Program, which integrates health, clinical, and genetic information from participants across the US, investigators examined demographic, clinical, and genetic characteristics by age at diagnosis and compared each group with matched adults without ADHD.

The investigators identified 13,527 adults with ADHD. Most were non-Hispanic White (75.1%) and female (74.2%). ADHD status and age at first diagnosis were self-reported, and the majority (71.5%) were diagnosed at age 18 years or older.

For comparisons with adults without ADHD, the investigators used propensity score matching based on age, sex, race and ethnicity, education, and income.

Researchers measured self-reported prevalence of comorbid psychiatric conditions, including anxiety disorder, autism spectrum disorder, bipolar disorder, depression, eating disorder, personality disorder, posttraumatic stress disorder (PTSD), schizophrenia, and substance use disorder.

Somatic illnesses assessed included disorders categorized as bone, joint, and muscle; brain and nervous system; cancer; digestive; hearing and eye; heart and blood; hormone and endocrine; kidney; and lung.

Later Diagnosis, Lower Comorbidity

Eight of the nine psychiatric comorbidities studied were significantly less common in adults diagnosed with ADHD later in life than in those diagnosed during youth. The largest differences were for PTSD (-7.50 percentage points [pp]) lower in the adult-diagnosed group, followed by bipolar disorder (-7.44 pp) and personality disorder (-4.78 pp).

The group also had lower rates of six of nine categories of somatic conditions, including lung (-7.88 pp); digestive (-7.27 pp); and bone, joint, and muscle (-7.00 pp). Other categories with lower prevalence included brain and nervous system, heart and blood conditions, and kidney.

Similar differences were seen in health and daily functioning, with the adult-diagnosed group reporting less impairment across seven of nine measures. The largest differences were for physical health (-3.63 pp), being bothered by emotional problems during the previous 7 days (-2.51 pp), and general health (-2.26 pp).

However, the differences were reduced or no longer statistically significant after adjusting for education and household income. The adult-diagnosed group also had higher educational attainment and household income.

Those diagnosed as adults had lower ADHD polygenic risk scores than those diagnosed during childhood or adolescence (Cohen d, -0.17).

Other outcomes were significantly more common among those with ADHD than in matched adults without the condition, regardless of age at diagnosis, including higher polygenic risk scores (Cohen d, 0.12 and 0.21, respectively) and higher rates of psychiatric and somatic conditions.

The adjusted probability of depression was 39.33 pp higher in the adult-diagnosed group and 36.92 pp higher in the youth-diagnosed group. For brain and nervous system conditions, the differences were 21.86 and 22.84 pp, respectively. Cancer was the only somatic condition that did not differ significantly regardless of ADHD status.

Why Diagnosis May Come Later

Adults diagnosed with ADHD later in life may have a milder clinical profile, with fewer co-occurring conditions and somewhat lower genetic liability, which Leffa said may allow symptoms to go unrecognized longer.

Depression was the only psychiatric comorbidity that did not differ significantly by age at diagnosis.

“Depression seems to be particularly common across the ADHD spectrum,” he said. Depressive symptoms may bring adults into mental health care, where longstanding attention or executive function difficulties are then recognized.

Other factors earlier in life may also shape how ADHD affects people over time.

“Difficulties in school can begin very early for individuals with ADHD,” Leffa said. “These findings underscore the importance of identifying and addressing educational difficulties as early as possible and supporting individuals throughout their education.”

For adults with attention or executive function difficulties, he added, “clinicians should assess whether attention or executive function difficulties reflect a longstanding developmental pattern consistent with ADHD” while also considering alternative or co-occurring causes.

What’s Not Measured

The reasons for those differences remain unclear and unmeasured factors could have influenced the results, said David Goodman, MD, LFAPA, director of the Adult Attention Deficit Disorder Center of Maryland and assistant professor of psychiatry and behavioral sciences at Johns Hopkins School of Medicine in Baltimore.

“As an observational study, it is the variables not measured — like childhood home environment, educational environment, stability of the childhood household, level of parental support, insurance coverage, socio-cultural influences, intelligence level, and the accuracy of the diagnosis, for example — that may mitigate these findings,” Goodman told Medscape Medical News. “With such studies, it is important to remember that precision is not validation. So the clinical extrapolation needs to be measured.”

The differences may also reflect the range of severity with ADHD, rather than distinct forms of the disorder, said Goodman, who was not part of the new study.

“ADHD, like most medical disorders, presents within a spectrum of severity,” he said. “As a result, the clinical severity of a disorder strongly influences when a disorder is diagnosed.”

Disclosure information for study authors is available in the original study publication. Goodman reported having no relevant financial disclosures.