Immature brain in adolescence


  • Conflict of interest: None declared.

The period of adolescence has increased over the past century with earlier onset of puberty and with recognition that brain maturation extends into the mid-20s. Initially regarded as a fairly abrupt transition from childhood to adulthood on a particular birthday, currently 18, adolescence is now acknowledged as a specific and unique period of development and many of the problems presenting to health professionals at this age relate to brain immaturity, including the management of chronic medical conditions such as diabetes, pervasive developmental disorders, behaviour disturbance that may reflect immaturity or the emergence of adult psychiatric disorders, and drug- and alcohol-related psychological problems.

Adolescence is also a period of achievement, of learning and social development, a time for determining a career and embarking on appropriate training. It has been a period of artistic creativity, particularly in music. But society has expected much more of this age group. In the past, adolescents (physically mature people in their late teens and 20s) were responsible for defending their country at war, of initiating and supporting a family

But the cultures of youth, and the expectations held for them, have changed in our society. It was the very characteristics of adolescent boys, the feeling of immortality, of taking risks without fear of consequences that made them fearless fighters and hunters, and their sexual drives that committed them as parents. These are no longer relevant for most young people, but may lead to risky behaviour affecting safety and health. To a large extent, culture determines adolescence, both in its social expression and in its duration. It is a period when sense of self develops and this is susceptible to peer influence.[1]

The changing culture has contributed to the problems in behaviour and mental health that present at this age, but what is particularly relevant is understanding the immaturity of the adolescent brain. It has become increasingly important for the profession, both as paediatricians and medical practitioners in general to recognise this.

Research in the psychology of adolescents and structural and functional brain development at this age has advanced over the last two decades with understanding of the immaturity of the brain,[2, 3] together with determining the relationship between early experience and genetics.[4]

Understanding the immaturity of the brain long after achievement of physical maturity has wide relevance in medical practice. In particular, it is important in

  • Understanding the development of some mental disorders at this age and avoiding confusion with behaviour that reflects the immature brain,
  • Recognising the vulnerability of the adolescent brain in response to drugs, especially cannabis and alcohol, and
  • Acknowledging gaps in research on the effect (and lack of effect) and potential dangers of some psychotropic drugs prescribed to adolescents.

Brain Maturation and Influence on Adolescent Behaviour

There is now considerable knowledge on the development of the brain during adolescence and the relation of this to behaviour.[5, 6] This includes in particular the relation of prefrontal cortex and limbic development.

From the onset of puberty until the mid-20s, there is protracted development of neural circuitry, especially in the prefrontal cortex and limbic system structures and white matter-associated fibres. The process to achieve maturity proceeds at different rates and regions of the brain, concluding in the dorso-lateral prefrontal cortex.

This process involves thinning of the grey matter of the brain from early puberty with concurrent growth of white matter volume with synaptic proliferation, myelination and pruning. This is most prominent in the frontal regions and shows differences between the sexes.

The development of the prefrontal cortex involves three specific areas

  1. Dorso-lateral prefrontal circuit, responsible for executive behaviour
  2. Orbito-frontal pre frontal region, responsible for social behaviour
  3. Medial circuit, responsible for motivation.

These developments influence attentional control, the manipulation of stored knowledge and the modulation of complex actions, cognition and emotional behaviour.

Neurotransmitter changes, especially the dopamine pathway, occur in synchrony with the changes in the prefrontal cortex.

Maturity of the limbic system occurs in conjunction with the prefrontal cortex, and in each area, the influence of maturity (and delayed maturity) is relevant to behaviour.

The components of the limbic system include the hypothalamus, which is responsible for homeostasis, and in particular for general body function with recognition of body signals, endocrine function, sexuality and the circadian rhythms. It is therefore expected that the developing maturity and vulnerability imposed by change may be expressed by disordered behaviour at this age. The confusion in recognition of body signals may be expressed in disturbed perception of body image and lead to eating disorders. Some confusion in sexuality and sexual behaviour is also to be expected as the limbic system develops. Altered sleep patterns are seen commonly in adolescents and may relate to development of circadian rhythms at this age.

The amygdala is responsible for reaction to the environment with fear and anxiety as a protective response. In adolescence, there may be a weaker sensitivity in considering harmful behaviour.[7] The hippocampus relates to memory functions and the prefrontal cortex to reward response and to susceptibility to drugs of addiction and mood, also placing the vulnerable adolescent at risk.

The prefrontal cortex matures later the other areas, affecting attention, reward evaluation and behaviour that is directed to specific goals.

Male and female brains differ in architecture and functional activity in limbic cortex and frontal cortex at this age. It is likely that these are innate biological differences started in utero. There are differences in the neurobiology of learning.[8]

Male and female response to stress differs at adolescence and there may be differences in response to selective serotonin reuptake inhibitor antidepressants. This may also explain differences in presentation of psychiatric disorders in males and females in adolescence.[2, 9, 10]

Reward-Seeking Behaviour

At this stage of development, there is increased drive to seek rewarding outcomes of behaviour, especially immediate rewards which may include response to alcohol and recreational drugs, sexual activity and to fast-food intake. This also relates to the characteristic behaviour we associate with adolescents. It is a critical period in the development of skills and sophisticated cognitive functioning, together with changes in emotional processing. It also poses a window of vulnerability to the unhealthy environmental influences such as adverse social pressures, aggressive marketing, the media, the Internet, alcohol, pornography, altered relationships with parents in a dysfunctional family or social environment. Teenagers may be well aware of risks but weigh these against the much more desirable quick rewards from their impulsive behaviour. This may explain the poor results of most efforts of health education to influence behaviour at this age.

It is also suggested that there is increased vulnerability to neurotoxic substances and possible change in response to psychoactive medication drugs.

Behaviour driven by emotion and seeking immediate rewards (e.g. social, sexual, risk-taking) is influenced by biological factors of puberty. At best, this is shown by creativity and sporting prowess and leadership. At worst, it leads to drug seeking, alcohol abuse, eating disorders, inappropriate sexual activity, antisocial activity and excessive Internet commitment, especially to gaming and virtual social interaction, for example, with hundreds of ‘friends’ on Facebook.

These drives have both societal and personal outcomes, but with maturity of the prefrontal region, there is development of a stronger regulatory control which inhibits impulses and leads to delay in gratification and allows for long-term planning. Further, it recognises experience and benefits from this. Adolescence could be regarded as a critical period for reorganisation of regulatory systems for behaviour.[11]

For some adolescents, maturation of these areas of the brain may be disordered. An example is a mismatch between prefrontal cortical areas responsible for self-control and consideration of consequences of one's actions on the one hand, with areas influencing spontaneous behaviour directed to quick rewards (fun, social satisfaction) without considering the consequences, on the other.

Problems of behaviour may arise if these areas are out of balance, or the area for control is significantly delayed in development in relation to the immediate reward-seeking area. This leads to the notion of prefrontal development being ‘out of sync’ in some adolescents.

During adolescence, there is development of social cognition with maturity of what is referred to as the social brain.[12]

The Influence of Developing Brain Maturity on Health

Pervasive developmental disorders may evolve during adolescence. This may become apparent for example, in the presentation of attention deficit hyperactivity disorder (ADHD) at this time with the demonstrable delay in development in the prefrontal cortex. It is particularly during adolescence that co-morbidities of developmental disorders such as ADHD may become apparent and influence behaviour outcomes. These include autistic spectrum disorder, specific learning disorders, obsessive compulsive disorder and conduct disorders, and in particular, bipolar disorders.[13]

It is also at this time that adolescents with primary learning disorders, including ADHD may present with secondary disorders which include anxiety/depression, social disability and substance abuse.

It is during adolescence, particularly with diminishing parental control and influence, that management of developmental disorders and chronic physical illness such as diabetes and asthma may be influenced by difficulties in compliance. Compliance with medical advice and management is often poor in adolescence[14] and may be due to many factors – forgetfulness, erratic life-style routines, inability to accept future consequences (‘It won't happen to me’, ‘All that's ages away from now’), reluctance to accept responsibility or to conform, side effects of the medication, social embarrassment and not wanting to appear different in a social setting, and a feeling of hopelessness. It may be affected by a poor relationship with a young person's doctor, to poor family functioning and parental supervision.

With the widespread use of cannabis in youth, it is reported that heavy cannabis use is associated with smaller volumes of the hippocampus, demonstrated by three-dimensional magnetic resonance imaging, and this persists after abstinence, at least at 6 months follow-up[15] It is associated with deficits in neurocognitive function and white matter development.[16, 17]

It has been proposed that maturation of neural circuitries in the prefrontal cortical areas is vulnerable to tetrahydrocannabinol[18] and may relate to the association of cannabis use in adolescence and later development of schizophrenia.

Recognition of the Evolving Maturity of the Adolescent Brain May Raise Contraversial Questions

These changes in brain maturation during the extended adolescent development from early teens to the mid-20s raise a number of questions.

  • 1.Are symptoms consistent with a diagnosis of mental illness in some vulnerable adolescents really a reflection of their immature brain development and their culture of social disorder and substance abuse, rather than evidence of an established psychiatric illness? On the other hand, is there danger of missing early signs of psychosis presenting at this age, leading to delay in diagnosis and treatment?
  • 2.This leads to the question: Are there dangers in diagnostic labelling in adolescents? This may be relevant in the diagnosis of disorders such as personality disorder and bipolar disorder. Diagnostic and statistical manual of mental disorder is gender neutral and may fail to identify differences in presentations between the sexes.

It was reported on a conference on adolescent health recently that mood deregulation in adolescents mimicking bipolar disorder is 10 times more common than bipolar disorder itself. The headline in The Australian newspaper was ‘Moody teens get Bipolar treatment’.[19]

  • 3.Are we fully aware of the long-term outcomes of mental health disorders in young people as they enter adulthood? An example may be the outcome of self-harming. In a study reported from Melbourne, of 1800 children, it was reported that 10% of girls and 6% of boys reported an incident of self-harm. This was associated independently with depression and anxiety, antisocial behaviours, high alcohol use, cannabis use, cigarette smoking. What was significant in this study was that most self-harming resolves spontaneously with maturity.[20]
  • 4.This raises the question of the use of psychoactive drugs in adolescents. How confident are we of their safety, particularly in the long term, and their efficacy in this age group?

Psychoactive drugs are widely prescribed for adolescents, particularly for mood disorders.[21, 22] As an example of the use of atypical antipsychotics, McCracken et al., for instance, reported that risperidone is widely used in child psychiatry to treat irritability associated with pervasive developmental disorders.[23]

There has been limited research on the safety and effectiveness of some forms of psychoactive medication during the adolescent years.

Many drugs such as valproate, carbamazepine and lamotrigine have been researched as antiepileptic drugs and are used for behaviour modification due to the side effects of the drugs. Drugs used for adults such as the antidepressants and the antipsychotics have been researched in adults, but there is limited research indicating either their safety on a long-term basis or their effectiveness on the immature brain.

  • 5.Of particular importance is the question of whether we, as health professionals, should be more assertive in advising on the use of alcohol and cannabis and other street drugs in teenage years? This has little to do with moral or legal aspects of underage drinking and drug use, but everything to do with the vulnerability of the immature brain. Despite popular teenage views and widespread adult opinion, there is considerable research on the adverse effect on the immature brain with early cannabis use[24-26] and alcohol,[5, 27, 28] and later mental disorders,[29] including substance-induced psychosis.[30]
  • 6.Further questions relate to whether adult psychiatric disorders may have a different presentation in early adolescence and may confuse diagnosis and lead to inappropriate management principles. Alternatively, we may be seeing earlier onset of genetically determined mood disorders due to inherent reflection of genetic expression. It is reported that over the last century, there has been progressively earlier diagnosis and increased rate of diagnosis of unipolar and bipolar disorder in young people.[31]
  • 7.Finally, it raises the question of whether we may be placing too much emphasis on management directed to disturbed adolescents with emotional and mental health problems, rather than addressing the broader circumstances surrounding them, whether family, school, employment or social life. Is there a risk of parents handing over responsibility of their disturbed teenager to mental health professionals?

In summary, it is now increasingly realised that adolescence is an extended and unique phase of human development in relation to the maturation of the brain and the vulnerability and risks involved in brain immaturity. Adolescence enters the domain of paediatricians, psychiatrists and adult physicians, whether in the management of medical illness, the adverse effects of drugs, or the manifestations of emotional and social disordered behaviour.