ADHD is highly heritable and one of the most common neurodevelopmental disorders in childhood. ADHD is characterized by substantial comorbidity including substance abuse, depression and anxiety. It is a neurodevelopmental disorder that typically starts during childhood or early adolescence. It is defined by age-inappropriate levels of inattention and/or hyperactivity-impulsivity. This interferes with the normal development or functioning of a person.

ADHD often remains undiagnosed in girls. It is common in all countries and affects the productivity, life expectancy and quality of life. The clinical presentation of ADHD is very heterogeneous. It is necessary to have a lifespan perspective on ADHD as it often persists into adulthood and because the clinical picture often differs between patients. It is a highly dynamic disorder.

Patients often experience that the services provides are not aimed specifically at ADHD. This lack of support contributes to people with ADHD experiencing more severe problems with age.

Defiance (1), hostility (2) or failure to understand the task or instruction (3) are not reflected by the ADHD symptoms but these symptoms often accompany ADHD. It is not clear to what degree ADHD persists in adulthood but it is clear that it often appears to persist into adulthood.

The definition of impairment is difficult for ADHD as ADHD symptoms are continually distributed throughout the population. The disorder is thus defined by a high level of symptoms when they interfere with normal functioning. Young children with ADHD are more likely to show externalising symptoms (e.g. hyperactive-impulsive behaviour) and at a later age, it is more likely that inattention is the main problem rather than motor hyperactivity.

Persistence of more overt hyperactivity-impulsivity is seen at higher rates among those with the most severe comorbid problems related to ADHD (e.g. substance abuse). ADHD is more often diagnosed in young boys than girls. This is not the case for adults. It is possible that this is the case because young boys with ADHD often show more hyperactivity-impulsivity symptoms whereas young girls often show more inattentive symptoms. However, there are more ADHD symptoms in the male population although the difference between hyperactivity-impulsivity symptoms becomes equal by late adolescence.  The expression of core ADHD symptoms is more similar across the sexes in an adult population. Comorbid problems (e.g. learning problems) also contribute to the difference in ADHD rates in young boys and girls.

There is a broader expression of symptoms commonly reported by adults with ADHD. This falls into three main categories:

1. Age-adjusted expression of core ADHD symptoms
   This includes internal restlessness, ceaseless unfocused mental activity and a difficulty focusing on conversations.
2. Behaviours reflecting problems with self-regulation
   This includes problems with controlling impulses, regulating emotional responses, switching attention, initiating tasks and problem-solving.
3. Additional problems that are commonly seen in ADHD
   This includes sleep problems and low self-esteem.

Secondary (i.e. acquired) ADHD refers to ADHD that is the result of brain injury at a later age (e.g. adulthood). Adult onset of ADHD appears to be rare. Adult onset of ADHD is probably due to subthreshold childhood ADHD.

Both the clinical phenotype of ADHD and the comorbidity profile changes over the lifespan. In children, oppositional defiant disorder (ODD) and conduct disorder (CD) are the most prevalent but substance abuse become more of a problem with age, starting in adolescence.

There are several common and prominent comorbidities with ADHD:

1. Autism spectrum disorder, tics and learning disorders
   About 20% - 50% of the children with ADHD meet the criteria for ASD. Social deficits, peer relationship problems and empathy problems are common in ADHD. Tics and learning disorders are also more common in ADHD than in the general population.
2. Rule breaking behaviours
   About 25% - 80% of the people (i.e. especially children) with ADHD meet the criteria for ODD or CD. There appears to be an increased risk for violence and incarceration in ADHD. ODD and CD predict a more severe symptomatology and more severe functional impairments (1), higher persistence of ADHD in adulthood (2) and worse outcome of the disorder (3). These disorders also mediate the risk for the development of other problems (e.g. substance abuse).
3. Substance use disorders
   About 9% - 40% of the people with ADHD also develop a substance use disorder. However, it is not clear whether ADHD increases the risk for substance use disorders or whether this is mediated by the effects of CD/ODD.
4. Mood anxiety disorders
   Mood anxiety disorders are the most common comorbidities of ADHD, especially in adolescence and adulthood.
5. Disruptive mood dysregulation disorder and bipolar disorder
   Emotional dysregulation shares genetic risk factors with ADHD, occurs in the absence of comorbid disorders and is an independent predictor of impairment. ADHD may co-exist with bipolar disorder and borderline personality disorder but in the presence of severe emotional dysregulation, ADHD may mimic these disorders.

The recommended treatment of ADHD is multimodal. Pharmacological treatments of ADHD consist of stimulants and non-stimulants. The same drugs are used throughout the lifespan but only some drugs that are used are approved for use in childhood and adulthood for the treatment of ADHD. ADHD medication is not associated with increased risk of substance abuse. Medication is recommended for the treatment of ADHD but for mild ADHD symptoms, non-pharmacological interventions could be used.

ADHD is associated with poor academic outcomes (1), negative occupational outcomes (2), sickness absence (3), financial problems (4) and increased mortality rates (5). Individuals with ADHD left untreated had worse outcomes than the individuals that were treated. It appears as if treatment reduces impairment and symptoms but not necessarily functioning, in the long-term.

Cognitive deficits in ADHD include both higher-level, effortful cognitive functions (e.g. inhibitory control) and lower-level, automatic cognitive processes (e.g. reward processing). There are smaller volumes in the brain of people with ADHD, especially in the basal ganglia. The subcortical volume reductions were less pronounced in adults.

Children with ADHD show hypoactivation in the fronto-parietal and ventral attentional networks involved in executive function and attention and a hyperactivation in the sensorimotor network and default-mode network (i.e. lower cognitive processes). Adult ADHD is mostly associated with a hypoactivation in the fronto-parietal system and a hyperactivation in the visual network, dorsal attention network and default-mode network.

Impairment in early childhood in executive functions, especially inhibition and working memory and impairment in IQ predict ADHD symptoms in later childhood. However, only IQ predicts beyond later childhood. It appears as if people who remit from ADHD do so because of maturation of higher cognitive functions but remain at ADHD level regarding lower cognitive functions. However, there is no consensus regarding this. It is possible that lower-level preparation vigilance cognitive functions may be markers of ADHD recovery. ADHD remitters demonstrate a slower cortical thinning from childhood to adulthood compared to ADHD persisters.

It is possible that lower functional correlation between posterior cingulate and medial prefrontal cortices during rest (1), lower connectivity between the thalamus and prefrontal regions during response preparation (2) and lower activations in areas of the prefrontal cortex involved in reward processing (3) may distinguish ADHD remitters from persisters. Impairments in executive functions do NOT distinguish the two groups.

ADHD is highly heritable. The genetics underlying the lifespan trajectory of ADHD are still unclear. The susceptibility to ADHD persistence may be a dynamic process with specific genetics influences acting at different developmental stages.

It is possible that the expression of specific genes is conditional on epigenetic programming. This programming is influenced by the genes and the environment of an individual. Environmental adversity, including pre- and perinatal risk factors (e.g. maternal stress) is associated with ADHD.

Most of the environmental factors that are considered to increase ADHD and comorbid disorder susceptibility act prenatally. Foetal, perinatal and adolescent periods are the periods of highest phenotypic plasticity, making these periods critical windows of development