bs_bs_banner

doi:10.1111/jpc.12241

VIEWPOINT

Immature brain in adolescence

John M Court
Albert Road Clinic, Melbourne, Victoria, Australia

The period of adolescence has increased over the past century • Understanding the development of some mental disorders at
with earlier onset of puberty and with recognition that brain this age and avoiding confusion with behaviour that reflects
maturation extends into the mid-20s. Initially regarded as a the immature brain,
fairly abrupt transition from childhood to adulthood on a par- • Recognising the vulnerability of the adolescent brain in
ticular birthday, currently 18, adolescence is now acknowledged response to drugs, especially cannabis and alcohol, and
as a specific and unique period of development and many of the • Acknowledging gaps in research on the effect (and lack of
problems presenting to health professionals at this age relate to effect) and potential dangers of some psychotropic drugs pre-
brain immaturity, including the management of chronic medical scribed to adolescents.
conditions such as diabetes, pervasive developmental disorders,
behaviour disturbance that may reflect immaturity or the emer-
gence of adult psychiatric disorders, and drug- and alcohol- Brain Maturation and Influence on
related psychological problems. Adolescent Behaviour
Adolescence is also a period of achievement, of learning and
There is now considerable knowledge on the development of
social development, a time for determining a career and
the brain during adolescence and the relation of this to behav-
embarking on appropriate training. It has been a period of
iour.5,6 This includes in particular the relation of prefrontal
artistic creativity, particularly in music. But society has expected
cortex and limbic development.
much more of this age group. In the past, adolescents (physi-
From the onset of puberty until the mid-20s, there is pro-
cally mature people in their late teens and 20s) were responsible
tracted development of neural circuitry, especially in the
for defending their country at war, of initiating and supporting
prefrontal cortex and limbic system structures and white
a family
matter-associated fibres. The process to achieve maturity pro-
But the cultures of youth, and the expectations held for them,
ceeds at different rates and regions of the brain, concluding in
have changed in our society. It was the very characteristics of
the dorso-lateral prefrontal cortex.
adolescent boys, the feeling of immortality, of taking risks
This process involves thinning of the grey matter of the brain
without fear of consequences that made them fearless fighters
from early puberty with concurrent growth of white matter
and hunters, and their sexual drives that committed them as
volume with synaptic proliferation, myelination and pruning.
parents. These are no longer relevant for most young people,
This is most prominent in the frontal regions and shows differ-
but may lead to risky behaviour affecting safety and health. To
ences between the sexes.
a large extent, culture determines adolescence, both in its social
The development of the prefrontal cortex involves three spe-
expression and in its duration. It is a period when sense of self
cific areas
develops and this is susceptible to peer influence.1
1 Dorso-lateral prefrontal circuit, responsible for executive
The changing culture has contributed to the problems in
behaviour
behaviour and mental health that present at this age, but what
2 Orbito-frontal pre frontal region, responsible for social
is particularly relevant is understanding the immaturity of the
behaviour
adolescent brain. It has become increasingly important for the
3 Medial circuit, responsible for motivation.
profession, both as paediatricians and medical practitioners in
These developments influence attentional control, the
general to recognise this.
manipulation of stored knowledge and the modulation of
Research in the psychology of adolescents and structural and
complex actions, cognition and emotional behaviour.
functional brain development at this age has advanced over the
Neurotransmitter changes, especially the dopamine pathway,
last two decades with understanding of the immaturity of the
occur in synchrony with the changes in the prefrontal cortex.
brain,2,3 together with determining the relationship between
Maturity of the limbic system occurs in conjunction with the
early experience and genetics.4
prefrontal cortex, and in each area, the influence of maturity
Understanding the immaturity of the brain long after achieve-
(and delayed maturity) is relevant to behaviour.
ment of physical maturity has wide relevance in medical prac-
The components of the limbic system include the hypotha-
tice. In particular, it is important in
lamus, which is responsible for homeostasis, and in particular
Correspondence: Dr John M Court, Albert Road Clinic, Melbourne, Vic.
for general body function with recognition of body signals,
3004, Australia. Fax: +61 9686 5157; email: johncourt@iprimus.com.au endocrine function, sexuality and the circadian rhythms. It is
therefore expected that the developing maturity and vulner-
Conflict of interest: None declared.
ability imposed by change may be expressed by disordered
Accepted for publication 20 January 2013. behaviour at this age. The confusion in recognition of body

Journal of Paediatrics and Child Health 49 (2013) 883–886 883

© 2013 The Author
Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
The immature brain in adolescence
signals may be expressed in disturbed perception of body
image and lead to eating disorders. Some confusion in sexu-
ality 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 behav-
iour.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 ado-
lescent 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 differ-
ences 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 psy-
choactive 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 sport-
ing prowess and leadership. At worst, it leads to drug seeking,
alcohol abuse, eating disorders, inappropriate sexual activity,
antisocial activity and excessive Internet commitment, espe-
cially 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.
884
Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
JM Court
Further, it recognises experience and benefits from this. Ado-
lescence 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 prefron-
tal 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 devel-
opment 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 adoles-
cence. This may become apparent for example, in the presen-
tation 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 disor-
ders which include anxiety/depression, social disability and sub-
stance abuse.
It is during adolescence, particularly with diminishing paren-
tal control and influence, that management of developmental
disorders and chronic physical illness such as diabetes and
asthma may be influenced by difficulties in compliance. Com-
pliance with medical advice and management is often poor in
adolescence14 and may be due to many factors – forgetfulness,
erratic life-style routines, inability to accept future conse-
quences (‘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 hopeless-
ness. 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-up15 It is associated with deficits in neurocog-
nitive function and white matter development.16,17
It has been proposed that maturation of neural circuitries in
the prefrontal cortical areas is vulnerable to tetrahydrocannabi-
nol18 and may relate to the association of cannabis use in ado-
lescence and later development of schizophrenia.
Journal of Paediatrics and Child Health 49 (2013) 883–886
© 2013 The Author
JM Court
Recognition of the Evolving Maturity
of the Adolescent Brain May Raise
Contraversial Questions
These changes in brain maturation during the extended adoles-
cent 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 imma-
ture 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 disor-
der 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, par-
ticularly 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 irri-
tability associated with pervasive developmental disorders.23
There has been limited research on the safety and effective-
ness of some forms of psychoactive medication during the ado-
lescent years.
Many drugs such as valproate, carbamazepine and lamot-
rigine 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 antip-
sychotics 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
Journal of Paediatrics and Child Health 49 (2013) 883–886
© 2013 The Author
Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
The immature brain in adolescence
teenage views and widespread adult opinion, there is consid-
erable research on the adverse effect on the immature brain
with early cannabis use24–26 and alcohol,5,27,28 and later mental
disorders,29 including substance-induced psychosis.30
6 Further questions relate to whether adult psychiatric disor-
ders may have a different presentation in early adolescence
and may confuse diagnosis and lead to inappropriate man-
agement principles. Alternatively, we may be seeing earlier
onset of genetically determined mood disorders due to inher-
ent 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 disor-
der 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 surround-
ing 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 rela-
tion 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.
References
1 Sebastian C, Burnett S, Blakemore SJ. Development of the
self-concept during adolescence. Trends Cogn. Sci. 2008; 12: 441–6.
2 Dunston S, Hulshoff Pol HE, Casey BJ, Giedd JN, Buitelaar JK, van
Engeland H. Anatomical MRI of the developing human brain: what
have we learned? J. Am. Acad. Child Adolesc. Psychiatry 2001; 40:
1012–20.
3 Yurgelun-Todd D. Emotioonal and cognitive changes during
adolescence. Curr. Opin. Neurobiol. 2007; 17: 251–7.
4 Spenrath M, Clarke M, Kutcher S. The science of brain and biological
development. J. Can. Acad. Child Adolesc. Psychiatry 2011; 20:
298–304.
5 Bava S, Tapert SF. Adolescent brain development and the risk for
alcohol and other drug problems. Neuropsychol. Rev. 2010; 20:
398–413.
6 Casey BJ, Jones R, Hare TA. The adolescent brain. Ann. N. Y. Acad. Sci.
2008; 1124: 111–26.
7 Ernst M, Nelson EE, Jazbec S et al. Amygdala and nucleus accumbens
in responses to receipt and omission of gains in adults and
adolescents. Neuroimage 2005; 25: 1279–91.
8 Cahill L. His brain, her brain. Sci. Am. 2005; 292: 40–7.
9 Cahill L. Why sex matters for neuroscience. Nat. Rev. Neurosci. 2006;
7: 477–84.
10 Andreano JM, Cahill L. Sex influences on the neurobiology of learning
and memory. Learn. Mem. 2009; 16: 248–66.
11 Steinberg L. Cognitive and affective development in adolescence.
Trends Cogn. Sci. 2005; 9: 69–74.
12 Burnett S, Sebastian C, Cohen K, Blakemore SJ. The social brain in
adolescence: evidence from functional magnetic resonance imaging
and behavioural studies. Neurosci. Biobehav. Rev. 2011; 35:
1654–64.
885
The immature brain in adolescence
13 Kovacs M, Pollock M. Bipolar disorder and comorbid conduct disorder
in childhood and adolescence. J. Am. Acad. Child Adolesc. Psychiatry
1995; 34: 715–23.
14 Shaw RJ, Palmer L, Blasey C, Sarwal M. A typology of nonadherence in
pediatric renal transplant recipients. Pediatr. Transplant. 2003; 7:
489–93.
15 Ashtari M, Avants B, Cyckowski L et al. Medial temporal structures
and memory functions in adolescents with heavy cannabis use.
J. Psychiatr. Res. 2011; 45: 1055–66.
16 Schweinsburg AD, Brown SA, Tapert SF. The influences of marijuana
use on neurocognitive functioning in adolescents. Curr. Drug Abuse
Rev. 2008; 1: 99–111.
17 Bava S, Jacobus J, Mahmood O, Yang TT, Tapert SF. Neurocognitive
correlates of white matter quality in adolescent substance users.
Brain Cogn. 2010; 72: 347–54.
18 Bossong MG, Niesink RJ. Adolescent brain maturation, the
endogenous cannabinoids system and the neurobiology of
cannabis induced schizophrenia. Prog. Neurobiol. 2010; 92:
370–85.
19 Adam Creswell. Moody teens wrongly diagnosed with bipolar
disorder: psychiatrist. The Australian 2011; Nov 11 (Health).
20 Moran P, Coffey C, Romaniuk H et al. The natural history of self-harm
from adolescence to young adulthood: a population-based cohort
study. Lancet 2012; 379: 236–43.
21 Safer DJ, Zito JM, DosReis S. Concomitant psychotropic medication for
youths. Am. J. Psychiatry 2003; 160: 438–49.
22 Kowatch RA, DelBello MP. The use of mood stabilizers and atypical
antipsychotics in children and adolescents with bipolar disorders. CNS
Spectr. 2003; 8: 273–80.
Tonto in Tuscany, by Kimberley Lee (14) from Operation Art 2012.
886
Journal of Paediatrics and Child Health © 2013 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
JM Court
23 McCracken JT, McGough J, Shah B et al. Risperidone in children with
autism and serious behavioural problems. N. Engl. J. Med. 2002; 347:
314–21.
24 Wittchen HU, Frohlich C, Behrendt S et al. Cannabis use and cannabis
use disorders and their relationship to mental disorders: a 10-year
prospective-longitudinal community study in adolescents. Drug
Alcohol Depend. 2007; 88 (Suppl. 1): s60–70.
25 Patton GC, Coffey C, Carlin JB, Degenhardt L, Lynskey M, Hall W.
Cannabis use and mental health in young people: cohort study. BMJ
2002; 325: 1195–8.
26 Schneider M. Puberty as a highly vulnerable developmental period for
the consequences of cannabis exposure. Addict. Biol. 2008; 13:
253–63.
27 Sgueglia LM, Sorg SF, Schweinsburg AD, Wetherill RR, Pulido C,
Tapert SF. Binge drinking differently affects adolescent male and
female brain morphometry. Psychopharmacology (Berl) 2011;
220: 529–39.
28 Brown SA, McGue M, Maggs J et al. Underage alcohol use: summary
of developmental processes and mechanisms: ages 16–20. Alcohol
Res. Health 2009; 321: 41–52.
29 Squeglia LM, Jacobus J, Tapert SF. The influence of substance use
on adolescent brain development. Clin. EEG Neurosci. 2009; 40: 31–8.
30 Fiorentini A, Volonteri LS, Dragogna F et al. Substance-induced
psychoses: a critical review of the literature. Curr. Drug Abuse Rev.
2011; 4: 228–40.
31 Post RM. Genetic Mechanisms in Bipolar Illness Onset Clinic Manual
for management of Bipolar Disorder in Children and Adolescents,
Kowatch R, Fristad M, Findling R, Post R, eds. Washington, DC,
London, England: American Psychiatric Publishing, Inc., 2009.
Journal of Paediatrics and Child Health 49 (2013) 883–886
© 2013 The Author
Copyright of Journal of Paediatrics & Child Health is the property of Wiley-Blackwell and its
content may not be copied or emailed to multiple sites or posted to a listserv without the
copyright holder's express written permission. However, users may print, download, or email
articles for individual use.