ArticlePDF Available

Maturation of the adolescent brain

Authors:

Abstract

Adolescence is the developmental epoch during which children become adults - intellectually, physically, hormonally, and socially. Adolescence is a tumultuous time, full of changes and transformations. The pubertal transition to adulthood involves both gonadal and behavioral maturation. Magnetic resonance imaging studies have discovered that myelinogenesis, required for proper insulation and efficient neurocybernetics, continues from childhood and the brain's region-specific neurocircuitry remains structurally and functionally vulnerable to impulsive sex, food, and sleep habits. The maturation of the adolescent brain is also influenced by heredity, environment, and sex hormones (estrogen, progesterone, and testosterone), which play a crucial role in myelination. Furthermore, glutamatergic neurotransmission predominates, whereas gamma-aminobutyric acid neurotransmission remains under construction, and this might be responsible for immature and impulsive behavior and neurobehavioral excitement during adolescent life. The adolescent population is highly vulnerable to driving under the influence of alcohol and social maladjustments due to an immature limbic system and prefrontal cortex. Synaptic plasticity and the release of neurotransmitters may also be influenced by environmental neurotoxins and drugs of abuse including cigarettes, caffeine, and alcohol during adolescence. Adolescents may become involved with offensive crimes, irresponsible behavior, unprotected sex, juvenile courts, or even prison. According to a report by the Centers for Disease Control and Prevention, the major cause of death among the teenage population is due to injury and violence related to sex and substance abuse. Prenatal neglect, cigarette smoking, and alcohol consumption may also significantly impact maturation of the adolescent brain. Pharmacological interventions to regulate adolescent behavior have been attempted with limited success. Since several factors, including age, sex, disease, nutritional status, and substance abuse have a significant impact on the maturation of the adolescent brain, we have highlighted the influence of these clinically significant and socially important aspects in this report.
© 2013 Arain et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article
which permits unrestricted noncommercial use, provided the original work is properly cited.
Neuropsychiatric Disease and Treatment 2013:9 449–461
Neuropsychiatric Disease and Treatment
Maturation of the adolescent brain
Mariam Arain
Maliha Haque
Lina Johal
Puja Mathur
Wynand Nel
Afsha Rais
Ranbir Sandhu
Sushil Sharma
Saint James School of Medicine,
Kralendijk, Bonaire, The Netherlands
Correspondence: Sushil Sharma
Saint James School of Medicine,
Plaza Juliana 4, Kralendijk, Bonaire,
The Netherlands
Tel +31 599 717 7550
Fax +31 599 717 7570
Email sharma@mail.sjsm.org
Abstract: Adolescence is the developmental epoch during which children become adults
intellectually, physically, hormonally, and socially. Adolescence is a tumultuous time, full of
changes and transformations. The pubertal transition to adulthood involves both gonadal and
behavioral maturation. Magnetic resonance imaging studies have discovered that myelinogenesis,
required for proper insulation and efficient neurocybernetics, continues from childhood and
the brain’s region-specific neurocircuitry remains structurally and functionally vulnerable to
impulsive sex, food, and sleep habits. The maturation of the adolescent brain is also influenced
by heredity, environment, and sex hormones (estrogen, progesterone, and testosterone), which
play a crucial role in myelination. Furthermore, glutamatergic neurotransmission predominates,
whereas gamma-aminobutyric acid neurotransmission remains under construction, and this might
be responsible for immature and impulsive behavior and neurobehavioral excitement during
adolescent life. The adolescent population is highly vulnerable to driving under the influence
of alcohol and social maladjustments due to an immature limbic system and prefrontal cortex.
Synaptic plasticity and the release of neurotransmitters may also be influenced by environmental
neurotoxins and drugs of abuse including cigarettes, caffeine, and alcohol during adolescence.
Adolescents may become involved with offensive crimes, irresponsible behavior, unprotected
sex, juvenile courts, or even prison. According to a report by the Centers for Disease Control
and Prevention, the major cause of death among the teenage population is due to injury and
violence related to sex and substance abuse. Prenatal neglect, cigarette smoking, and alcohol
consumption may also significantly impact maturation of the adolescent brain. Pharmacological
interventions to regulate adolescent behavior have been attempted with limited success. Since
several factors, including age, sex, disease, nutritional status, and substance abuse have a sig-
nificant impact on the maturation of the adolescent brain, we have highlighted the influence of
these clinically significant and socially important aspects in this report.
Keywords: myelinogenesis, neurocircuitry, molecular imaging, drug addiction, behavior,
social adjustment
Introduction
Significant progress has been made over the last 25 years in understanding the brain’s
regional morphology and function during adolescence. It is now realized that sev-
eral major morphological and functional changes occur in the human brain during
adolescence.1 Molecular imaging and functional genomics studies have indicated that
the brain remains in an active state of development during adolescence.1 In particu-
lar, magnetic resonance imaging (MRI) studies have discovered that myelinogenesis
continues and the neurocircuitry remains structurally and functionally vulnerable to
significant increases in sex hormones (estrogen, progesterone, and testosterone) during
Dovepress
submit your manuscript | www.dovepress.com
Dovepress 449
REVIEW
open access to scientific and medical research
Open Access Full Text Article
http://dx.doi.org/10.2147/NDT.S39776
Video abstract
Point your SmartPhone at the code above. If you have a
QR code reader the video abstract will appear. Or use:
http://dvpr.es/W6umNa
Number of times this article has been viewed
This article was published in the following Dove Press journal:
Neuropsychiatric Disease and Treatment
2 April 2013
Neuropsychiatric Disease and Treatment 2013:9
puberty which, along with environmental input, influences
sex, eating, and sleeping habits. Particularly significant
changes occur in the limbic system, which may impact self-
control, decision making, emotions, and risk-taking behav-
iors. The brain also experiences a surge of myelin synthesis
in the frontal lobe, which is implicated in cognitive processes
during adolescence.1
Brain maturation during adolescence (ages 10–24 years)
could be governed by several factors, as illustrated in
Figure 1. It may be influenced by heredity and environment,
prenatal and postnatal insult, nutritional status, sleep pat-
terns, pharmacotherapy, and surgical interventions during
early childhood. Furthermore, physical, mental, economical,
and psychological stress; drug abuse (caffeine, nicotine, and
alcohol); and sex hormones including estrogen, progesterone,
and testosterone can influence the development and matura-
tion of the adolescent brain. MRI studies have suggested that
neurocircuitry and myelinogenesis remain under construc-
tion during adolescence because these events in the central
nervous system (CNS) are transcriptionally regulated by sex
hormones that are specifically increased during puberty.
Neurobehavioral, morphological, neurochemical, and
pharmacological evidence suggests that the brain remains
under construction during adolescence,1,2,3,7,12,21,22,23,27,49 as illus-
trated in Figure 2. Thus, the consolidation of neurocybernetics
occurs during adolescence by the maturation of neurocircuitry
and myelination. Although tubulinogenesis, axonogenesis, and
synaptogenesis may be accomplished during prenatal and
immediate postnatal life, myelinogenesis remains active
during adolescent life. Neurochemical evidence suggests
that glutamatergic neurotransmission is accomplished during
prenatal and immediate postnatal life while gamma-amin-
obutyric acid (GABA)ergic neurotransmission, particularly
in the prefrontal cortex, remains under construction during
adolescence.2 Hence, delayed development of GABAergic
neurotransmission is held responsible for neurobehavioral
excitement including euphoria and risk-taking behavior,
whereas dopaminergic (DA)ergic neurotransmission, par-
ticularly in the prefrontal area, is developmentally regulated
by sex hormones and is implicated in drug-seeking behavior
during adolescence;3 thus, brain development in critical areas
is an ongoing process during adolescence. Indeed, adolescents
are risk-taking and novelty-seeking individuals and they are
more likely to weigh positive experiences more heavily and
negative experiences less so than adults. This behavioral
bias can lead to engagement in risky activities like reckless
driving, unprotected sex, and drug abuse.1–3 In fact, most
drug addictions initiate during adolescence, and early drug
abuse is usually associated with an increased incidence of
physical tolerance and dependence. The hormonal changes
Heredity and
environment
Pre and
postnatal
insult
Pharmaco-
therapy
Drug abuse
nicotine,
caffeine,
alcohol etc
Age
10–25 years
Maturation of
adolescent
brain
Nutritional
status
Sex hormones
(Estrogen,
progesterone,
testosterone
Physical,
mental,
economical,
psychological
status
Surgical
interventions
Sleep
Figure 1 Factors inuencing adolescent brain maturation.
Notes: Brain maturation is inuenced by heredity and environment, prenatal and postnatal insult, nutritional status, sleep patterns, pharmacotherapy, and surgical
interventions during early childhood. Furthermore, physical, mental, economical, and psychological stress; drug abuse (caffeine, nicotine, and ethanol); and sex hormones,
including estrogen, progesterone, and testosterone inuence the development and maturation of the adolescent brain. MRI studies have suggested that neurocircuitry and
myelinogenesis remain under construction during adolescence because these events in the CNS depend on sex hormones that are specically increased during puberty.
Abbreviations: CNS, central nervous system; MRI, magnetic resonance imaging.
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
450
Arain et al
Neuropsychiatric Disease and Treatment 2013:9
in puberty contribute to physical, emotional, intellectual,
and social changes during adolescence. These changes do
not just induce maturation of reproductive function and the
emergence of secondary sex characteristics, but they also
contribute to the appearance of sex differences in nonre-
productive behaviors. Physical changes, including acceler-
ated body growth, sexual maturation, and development of
secondary sexual characteristics occur simultaneously along
with social, emotional, and cognitive development during
adolescence. Furthermore, the adolescent brain evolves its
capability to organize, regulate impulses, and weigh risks and
rewards; however, these changes can make adolescents highly
vulnerable to risk-taking behavior. Thus, brain maturation is
an extremely important aspect of overall adolescent develop-
ment, and a basic understanding of the process might aid in
the understanding of adolescent sexual behavior, pregnancy,
and intellectual performance issues.
There are several other crucial developmental aspects
of adolescence that are associated with changes in physical,
cognitive, and psychosocial characteristics, as well as with
attitudes toward intimacy and independence, and these may
also influence brain maturation; these will also be discussed
in the present report. Furthermore, we emphasize the del-
eterious effects of drug abuse and the clinical significance
of nutrition from fish oils and fatty acids in adolescent brain
maturation.
Neuronal plasticity
and neurocircuitry
The term “plasticity” refers to the possible significant neu-
ronal changes that occur in the acquisition of new skills.1–3
These skills initiate the process of elaboration and stabili-
zation of synaptic circuitry as part of the learning process.
Plasticity permits adolescents to learn and adapt in order to
acquire independence; however, plasticity also increases an
individual’s vulnerability toward making improper decisions
because the brain’s region-specific neurocircuitry remains
under construction, thus making it difficult to think critically
and rationally before making complex decisions. Moreover,
the neurocircuitry may be forged, refined or weakened, and
damaged during plasticity. Thus, neuronal proliferation,
rewiring, dendritic pruning, and environmental exposure are
important components of brain plasticity during adolescence.
A significant portion of brain growth and development occur-
ring in adolescence is the construction and strengthening of
regional neurocircuitry and pathways; in particular, the brain
stem, cerebellum, occipital lobe, parietal lobe, frontal lobe,
and temporal lobe actively mature during adolescence. The
frontal lobes are involved in movement control, problem
solving, spontaneity, memory, language, initiation, judgment,
impulse control, and social and sexual behavior. Furthermore,
the prefrontal cortex, which is implicated in drug-seeking
behavior, remains in a process of continuous reconstruction,
consolidation, and maturation during adolescence.
The adolescent brain
It is well established that various morphological and
physiological changes occur in the human brain during
adolescence. The term “adolescence” is generally used to
describe a transition stage between childhood and adulthood.
Adolescence” also denotes both teenage years and puberty,
as these terms are not mutually exclusive. The second surge
of synaptogenesis occurs in the brain during the adolescent
years. Hence, adolescence is one of the most dynamic events
of human growth and development, second only to infancy
in terms of the rate of developmental changes that can occur
within the brain. Although there is no single definition of
adolescence or a set age boundary, Kaplan4 has pointed out
that puberty refers to the hormonal changes that occur in
early youth, and adolescence may extend well beyond the
teenage years. In fact, there are characteristic developmental
changes that almost all adolescents experience during their
transition from childhood to adulthood. It is well established
that the brain undergoes a “rewiring” process that is not
complete until approximately 25 years of age.5 This discovery
Maturation of adolescent brain
(consolidation of brain regional neurocybernetics)
Neurobehavioral
evidence
Neurochemical and
pharmacological
evidence
Glutamatergic
neurotransmission
GABA-ergic
neurotransmission
Development and
maturation of
prefrontal cortex
Prenatal and immediate
postnatal life (>25 years)
Sex, food intake
and sleep changes
Learning, intelligence,
memory and behavior
Myelinogenesis
and maturation
of brain regional
neurocircuitry
Tubulinogenesis
axonogenesis
synaptogenesis
Morphological
evidence
CT/MRI
evidence
Figure 2 A diagram illustrating various stages of human brain development.
Notes: Several neurobehavioral, morphological, neurochemical, and
pharmacological evidences suggest that the brain remains under construction during
adolescence.1,2,3,7,12,21,22,23,25,42 Tubulinogenesis, axonogenesis, and synaptogenesis may
be accomplished during prenatal and immediate postnatal life, yet myelinogenesis
remains active during adolescent life. Furthermore, glutamatergic neurotransmission
is accomplished during prenatal and immediate postnatal life, while GABAergic
neurotransmission in the prefrontal cortex remains under construction. Delayed
development of GABAergic neurotransmission among adolescents is implicated in
neurobehavioral excitement and risk-taking behavior.
Abbreviations: CT, computed tomography; GABAergic, gamma amino butyric
acid ergic; MRI, magnetic resonance imaging.
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
451
Adolescent brain maturation
Neuropsychiatric Disease and Treatment 2013:9
has enhanced our basic understanding regarding adolescent
brain maturation and it has provided support for behaviors
experienced in late adolescence and early adulthood. Several
investigators consider the age span 10–24 years as adoles-
cence, which can be further divided into substages specific
to physical, cognitive, and social–emotional development.5,6
Hence, understanding neurological development in conjunc-
tion with physical, cognitive, and social–emotional adoles-
cent development may facilitate the better understanding of
adolescent brain maturation, which can subsequently inform
proper guidance to adolescents.7
Longitudinal MRI studies have confirmed that a second
surge of neuronal growth occurs just before puberty.1,7 This
surge is similar to that noticed during infancy and consists of
a thickening of the grey matter. Following neuronal prolifera-
tion, the brain rewires itself from the onset of puberty up until
24 years old, especially in the prefrontal cortex. The rewir-
ing is accomplished by dendritic pruning and myelination.
Dendritic pruning eradicates unused synapses and is gen-
erally considered a beneficial process, whereas myelina-
tion increases the speed of impulse conduction across the
brain’s region-specific neurocircuitry. The myelination also
optimizes the communication of information throughout the
CNS and augments the speed of information processing.
Thus, dendritic pruning and myelination are functionally
very important for accomplishing efficient neurocybernetics
in the adolescent brain.
During adolescence, the neurocircuitry strengthens and
allows for multitasking, enhanced ability to solve prob-
lems, and the capability to process complex information.
Furthermore, adolescent brain plasticity provides an oppor-
tunity to develop talents and lifelong interests; however,
neurotoxic insult, trauma, chronic stress, drug abuse, and
sedentary lifestyles may have a negative impact during this
sensitive period of brain maturation.8,9
Out of several neurotransmitters in the CNS, three play
a significant role in the maturation of adolescent behavior:
dopamine, serotonin, and melatonin.3,8,9 Dopamine influences
brain events that control movement, emotional response, and
the ability to experience pleasure and pain. Its levels decrease
during adolescence, resulting in mood swings and difficul-
ties regulating emotions. Serotonin plays a significant role in
mood alterations, anxiety, impulse control, and arousal. Its
levels also decrease during adolescence, and this is associated
with decreased impulse control. Lastly, melatonin regulates
circadian rhythms and the sleep–wake cycle. The body’s daily
production of melatonin increases the requirement for sleep
during adolescence.8,9
Behavioral problems and puberty
It is now known that hormones are not the only explanation
for erratic adolescent behavior; hence, investigators are
now trying to establish the exact nature of the interrela-
tionship between pubertal processes and adolescent brain
maturation. Dahl has explained three main categories of
brain changes related to puberty: (1) changes that precede
puberty; (2) changes that are the consequence of puberty;
and (3) changes that occur after puberty is over.9 The timing
of these changes may underlie many aspects of risk-taking
behavior. These changes, which are the consequence of
puberty, occur primarily in the brain regions closely linked
to emotions, arousal, motivation, as well as to appetite and
sleep patterns. Brain changes independent of puberty are
those related to the development of advanced cognitive
functioning.
Animal studies have shown that sex hormones (estrogen,
progesterone, and testosterone) are critically involved in
myelination.12 These studies have provided a relationship
between sex hormones, white matter, and functional con-
nectivity in the human brain, measured using neuroimaging.
The results suggest that sex hormones organize structural
connections and activate the brain areas they connect. These
processes could underlie a better integration of structural and
functional communication between brain regions with age.
Specifically, ovarian hormones (estradiol and progesterone)
may enhance both corticocortical and subcorticocortical
functional connectivity, whereas androgens (testosterone)
may decrease subcorticocortical functional connectivity but
increase the functional connectivity between subcortical
brain areas. Therefore, when examining brain development
and aging, or when investigating the possible biological
mechanisms of neurological diseases, the contribution of
sex hormones should not be ignored.10
A recent study has described how the social brain devel-
ops during adolescence.10 Adolescence is a time character-
ized by change hormonally, physically, psychologically,
and socially. Functional MRI studies have demonstrated the
developmental changes that occur during adolescence among
white matter and grey matter volumes in regions within the
“social brain.1,7,12 Activity in the mesolimbic brain regions
also showed changes between adolescence and adulthood
during social cognition tasks. A developmental clock – along
with the signals that provide information on somatic growth,
energy balance, and season of the year – times the awakening
of gonadotropin-releasing hormone (GnRH) neurons at the
onset of puberty. High-frequency GnRH release results in
the disinhibition and activation of GnRH neurons at the onset
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
452
Arain et al
Neuropsychiatric Disease and Treatment 2013:9
of puberty, leading to gametogenesis and an increase in sex
hormone secretion. Sex hormones and adrenocorticotropic
hormones both remodel and activate neurocircuits during
adolescent brain development, leading to the development
of sexual salience of sensory stimuli, sexual motivation,
and expression of copulatory behavior. These influences of
hormones on reproductive behavior depend on changes in
the adolescent brain that occur independently of gonadal
maturation. Reproductive maturity is therefore the prod-
uct of developmentally timed, brain-driven, and recurrent
interactions between steroid hormones and the adolescent
nervous system.11,12
Limbic system
The limbic system is a group of structures located deep
within the cerebrum. It is composed of the amygdala, the
hippocampus, and the hypothalamus. These brain regions are
involved in the expression of emotions and motivation, which
are related to survival. The emotions include fear, anger, and
the fight or flight response. The limbic system is also involved
in feelings of pleasure that reward behaviors related to spe-
cies survival, such as eating and sex. In addition, the limbic
system regulates functions related to memory storage and
retrieval of events that invoke a strong emotional response.
Neuroimaging studies have revealed that when interacting
with others and making decisions, adolescents are more likely
than adults to be swayed by their emotions.12–16 In addition,
adolescents often read others’ emotions incorrectly. These
studies involved comparing a teen brain to an adult brain
determined that adolescents’ prefrontal cortices are used less
often during interpersonal interactions and decision making
than their adult counterparts. In fact, adolescents relied more
on the emotional region of their brains when reading others’
emotions, which is more impulsive when compared to a
logical or measured interpretation. Thus, an understanding
of how the limbic system and the prefrontal cortex are used
has provided a partial explanation for certain characteristics
of adolescents and adolescent behaviors, such as quickness
to anger, intense mood swings, and making decisions on the
basis of “gut” feelings. Because adolescents rely heavily on
the emotional regions of their brains, it can be challenging to
make what adults consider logical and appropriate decisions,
as illustrated in Figure 3.
Prefrontal cortex
Recently, investigators have studied various aspects of the
maturation process of the prefrontal cortex of adolescents.17,18
The prefrontal cortex offers an individual the capacity to
exercise good judgment when presented with difficult life
situations. The prefrontal cortex, the part of the frontal lobes
lying just behind the forehead, is responsible for cognitive
analysis, abstract thought, and the moderation of correct
behavior in social situations. The prefrontal cortex acquires
information from all of the senses and orchestrates thoughts
and actions in order to achieve specific goals.
The prefrontal cortex is one of the last regions of the brain
to reach maturation, which explains why some adolescents
exhibit behavioral immaturity. There are several executive
functions of the human prefrontal cortex that remain under
construction during adolescence, as illustrated in Figures 3
and 4. The fact that brain development is not complete until
near the age of 25 years refers specifically to the development
of the prefrontal cortex.19
MRI studies have discovered that developmental pro-
cesses tend to occur in the brain in a back-to-front pat-
tern, explaining why the prefrontal cortex develops last.
These studies have also shown that teens have less white
matter (myelin) in the frontal lobes compared to adults,
and that myelin in the frontal lobes increases throughout
adolescence.1,7,21 With more myelin comes the growth of
important neurocircuitry, allowing for better flow of infor-
mation between brain regions.20,21 These findings have led to
the concept of frontalization, whereby the prefrontal cortex
develops in order to regulate the behavioral responses initi-
ated by the limbic structures. During adolescence, white
matter increases in the corpus callosum, the bundle of
Executive human brain functions
Ability to balance
short-term rewards
with long term goals
Impulse control
and delaying
gratification
Modulation of
intense emotions
Shifting/adjusting
behavior when
situations change
Foreseeing and
weighing possible
consequences of
behavior
Simultaneously
considering multiple
streams of information
when faced with
complex and challenging
information
Inhibiting inappropriate
behavior and initiating
appropriate behavior
Forming strategies
and planning
Organizing thoughts
and problem solving
Focusing
attention
Considering future and
making predictions
Prefrontal
cortex
Figure 3 A diagram illustrating the developmental regulation of executive functions
by the prefrontal cortex, which remains under construction during adolescence.
Notes: Several executive brain functions are governed by the prefrontal cortex,
which remains in a state of active maturation during adolescence. These complex
brain functions are regulated by the prefrontal cortex as illustrated in this gure
(based on the original discoveries by Gedd and Steinberg).1,21–23,25 Due to immature
functional areas in the prefrontal cortex, adolescent teens may take part in risk
seeking behavior including unprotected sex, impaired driving, and drug addiction.
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
453
Adolescent brain maturation
Neuropsychiatric Disease and Treatment 2013:9
nerve fibers connecting the right and left hemispheres of the
brain, which allows for efficient communication between
the hemispheres and enables an individual to access a
full array of analytical and creative strategies to respond
to complex dilemmas that may arise in adolescent life.
Hence, the role of experience is critical in developing the
neurocircuitry that allows for increased cognitive control
of the emotions and impulses of adolescence. Adolescents,
who tend to engage in risky behaviors in relatively safe
environments, utilize this circuitry and develop the skills
to tackle more dangerous situations; however, with an
immature prefrontal cortex, even if adolescents understand
that something is dangerous, they may still engage in such
risky behavior.21
Risk-taking behavior
The exact biological basis of risk-taking behavior in ado-
lescents remains enigmatic. Adolescents are at their peak
of physical strength, resilience, and immune function, yet
mortality rates among 15–24 year olds are more than triple
the mortality rates of middle school children. The Centers
for Disease Control and Prevention has identified the leading
causes of death and illness among adolescents,22,23,59 as illus-
trated in Figure 5. It is generally held that adolescents take
risks to test and define themselves, as risk-taking can be both
beneficial and harmful. It can lead to situations where new
skills are learned and new experiences can prepare them for
future challenges in their lives. Risk-taking serves as a means
of discovery about oneself, others, and the world at large. The
proclivity for risk-taking behavior plays a significant role in
adolescent development, rendering this a period of time for
both accomplishing their full potential and vulnerability.
Hence, acquiring knowledge regarding adolescent brain
maturation can help understand why teens take risks, while
keeping in mind that risk-taking behavior is a normal and
necessary component of adolescence. This knowledge may
help in developing physiologically and pharmacologically
effective interventions that focus on reducing the negative
consequences associated with risk-taking behavior among
the adolescent population.22
Risk perception
It has been established that, around the age of 12 years,
adolescents decrease their reliance on concrete thinking and
begin to show the capacity for abstract thinking, visualization
of potential outcomes, and a logical understanding of cause
and effect.23 Teens begin looking at situations and deciding
whether they are safe, risky, or dangerous. These aspects of
Motivation
and reward
Nucleus
accumbens
Highly
sensitized
To accomplish
desirable goals Drive for
riskier decisions
(Steinberg; 2005, 2007) (Lopex 2008) (Carls; 2004)
(Casey;
2008)
Decrease
of
dopamine
Vulnerability
to drug
addiction
Limbic system and sensation seeking
behavior among adolescents
(management of emotions and motivation)
Emotional volatility
and impulsivity
Augmentation
of sex drive
Immature
Self
regulation
Prefrontal
cortex
Amygdala
Estrogen and
testosterone
Receptor binding
Increased
sex
drive
Figure 4 An algorithmic diagram illustrating the management of emotions and motivation by the limbic system in the adolescent brain.
Notes: The nucleus accumbens and amygdala are the two most prominent parts of the central nervous system involved in riskier behavior and increased sex drive among
teenage adolescents. The nucleus accumbens is highly sensitized to accomplish desirable goals. A decrease in dopamine in the nucleus accumbens is involved in increased
vulnerability to drug addiction and risky decisions. Sex hormones (estrogen and testosterone) bind with their receptors to induce increased sex drive and emotional
volatility and impulsivity. Due to an immature prefrontal cortex, adolescents also have an increased sex drive and problems in self-regulation as illustrated in this ow
diagram.19,23,26,27,54
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
454
Arain et al
Neuropsychiatric Disease and Treatment 2013:9
development correlate with the maturation of the frontal lobe,
and is marked by a shift from the development of additional
neural connections to synaptic pruning, as well as by an
increase in the release of hormones, all of which drive an
adolescent’s mood and impulsive behavior.
By the age of 15 years, there is little difference in
adolescents’ and adults’ decision-making patterns per-
taining to hypothetical situations. Teens were found to be
capable of reasoning about the possible harm or benefits
of different courses of action; however, in the real world,
teens still engaged in dangerous behaviors, despite under-
standing the risks involved.22,23,59 Hence, both the role of
emotions and the connection between feeling and think-
ing need to be considered while studying the way teens
make decisions.
Investigators have differentiated between “hot” cognition
and “cold” cognition.24 Hot cognition is described as thinking
under conditions of high arousal and intense emotion. Under
these conditions, teens tend to make poorer decisions. The
opposite of hot cognition is cold cognition, which is criti-
cal and over-analyzing.25 In cold cognition, circumstances
are less intense and teens tend to make better decisions.
Then, with the addition of complex feelings – such as fear
of rejection, wanting to look cool, the excitement of risk, or
anxiety of being caught – it is more difficult for teens to think
through potential outcomes, understand the consequences of
their decisions, or even use common sense.26 The apparent
immaturity of the connections between the limbic system,
prefrontal cortex, and the amygdala provides further support
for this concept.
Sensation seeking
The nucleus accumbens, a part of the brain’s reward sys-
tem located within the limbic system, is the area that pro-
cesses information related to motivation and reward. Brain
imaging has shown that the nucleus accumbens is highly
sensitive in adolescents, sending out impulses to act when
faced with the opportunity to obtain something desirable.27
For instance, adolescents are more vulnerable to nicotine,
alcohol, and other drug addictions because the limbic brain
regions that govern impulse and motivation are not yet fully
developed.28 During puberty, the increases in estrogen and
testosterone bind receptors in the limbic system, which not
only stimulates sex drive, but also increases adolescents’
emotional volatility and impulsivity. Changes in the brain’s
reward sensitivity that occur during puberty have also been
explored. These changes are related to decreases in DA,
a neurotransmitter that produces feelings of pleasure.29 Due
to these changes, adolescents may require higher levels of
DAergic stimulation to achieve the same levels of pleasure/
reward, driving them to make riskier decisions.
Self-regulation
Self-regulation has been broadly classified as the manage-
ment of emotions and motivation.30 It also involves directing
and controlling behavior in order to meet the challenges of
STD: 19 M
diagnosed/
year (15–24
years)
Risky sexual
behavior
Motor vehicle
crashes (30%)
Deaths
(41%)
Suicide
(12%)
Injury and violence
Homicide
(15%)
Unprotected
sex (39%)
Center of disease control
Steinberg (2004)
Figure 5 Leading cause of death among adolescents (10–24 years).
Notes: Injury and violence are the two most common leading causes of death during adolescence. Out of 19 million adolescents (15–24 years) in the US that were
diagnosed with HIV/AIDs, 39% admitted that they had unprotected sex. In addition to risky sex behavior, 30% of adolescents had been involved in motor vehicle accidents,
with 41% of these linked to deaths; 12% committed suicide; and 15% were victims of homicide as illustrated in this gure (Steinberg 2004, Centers for Disease Control and
Prevention).18
Abbreviations: AIDS, acquired immune deciency syndrome; HIV, human immunodeciency virus; M, million; STD, sexually transmitted disease.
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
455
Adolescent brain maturation
Neuropsychiatric Disease and Treatment 2013:9
the environment and to work toward a conscious purpose.
Self-regulation also entails controlling the expression of
intense emotions, impulse control, and delayed gratification.
As adolescents progress toward adulthood with a body that is
almost mature, the self-regulatory parts of their brains are still
maturing. An earlier onset of puberty increases the window
of vulnerability for teens, making them more susceptible to
taking risks that affect their health and development over a
prolonged period.31
Behavioral control requires a great involvement of
cognitive and executive functions. These functions are local-
ized in the prefrontal cortex, which matures independent
of puberty and continues to evolve up until 24 years of
age. It has been suggested that, during this period, adoles-
cents should not be overprotected, but be allowed to make
mistakes, learn from their own experiences, and practice
self-regulation. Parents and teachers can help adolescents
through this period by listening and offering support and
guidance.
Recently, Steinberg studied risk-taking behavior in teens
and how this was influenced by their peers.32 He used a driv-
ing simulation game in which he studied teens deciding on
whether or not to run a yellow light, and found that when
teens were playing alone they made safer decisions, but in the
presence of friends they made riskier decisions. When teens
find themselves in emotionally arousing situations, with their
immature prefrontal cortices, hot cognitive thinking comes
into play, and these adolescents are more likely to take riskier
actions and make impulsive decisions.
Societal inuences
Mass media, community, and adult role models can also
influence adolescent risk-taking behaviors. Teens are con-
stantly exposed to emotionally arousing stimuli through
multimedia, which encourages unprotected sex, substance
abuse, alcohol abuse, and life-threatening activities.32,33 Even
neighborhoods, friends, and communities provide teens with
opportunities to engage in risky behaviors, although local
law enforcement authorities regulate the purchase of ciga-
rettes, access to and acceptability of guns, and the ability to
drive cars. Even adults can have trouble resisting engaging in
some of these risky behaviors; however, the temptation must
be much harder for teens, whose judgment and decision-
making skills are still developing.34
Recent functional MRI studies have demonstrated
the extent of development during adolescence in the
white matter and grey matter regions within the social
brain. Activity in some of these regions showed changes
between adolescence and adulthood during social
cognition tasks. These studies have provided evidence
that the concept of mind usage remains developing late
in adolescence.1,21,33
Substance abuse
The mechanisms underlying the long-term effects of prenatal
substance abuse and its consequent elevated impulsivity dur-
ing adolescence are poorly understood. Liu and Lester34 have
reported on developmentally-programmed neural maturation
and highlighted adolescence as a critical period of brain
maturation. These investigators have studied impairments
in the DAergic system, the hypothalamic–pituitary–adrenal
axis, and the pathological interactions between these two
systems that originate from previous fetal programming in
order to explain insufficient behavioral inhibition in affected
adolescents. In addition, Burke35 has examined the develop-
ment of brain functions and the cognitive capabilities of
teenagers. Specifically, these two sets of investigators have
explored the effect of alcohol abuse on brain development,
and the fundamental cognitive differences between adoles-
cents and adults, and have suggested that the adultification
of youth is harsh for those whose brains have not fully
matured.
Cannabis
Cannabis is the most commonly consumed drug among
adolescents, and its chronic use may affect maturational
refinement by disrupting the regulatory role of the endocan-
nabinoid system.36 Adolescence represents a critical period
for brain development and the endocannabinoid system
plays a critical role in the regulation of neuronal refine-
ment during this period. In animals, adolescent cannabinoid
exposure caused long-term impairment in specific compo-
nents of learning and memory, and differentially affected
emotional reactivity with milder effects on anxiety behavior
and more pronounced effects on depressive behavior.37
Epidemiological studies have suggested that adolescent
cannabis abuse may increase their risk of developing cogni-
tive abnormalities, psychotic illness, mood disorders, and
other illicit substance abuse later in life.36,38–40 Cannabis
abuse in adolescence could increase the risk of developing
psychiatric disorders, especially in people who are vulner-
able to developing psychiatric syndromes. So far, only a few
studies have investigated the neurobiological substrates of
this vulnerability;56 hence, further investigation is required
to clarify the molecular mechanisms underlying the effect
of cannabis on the adolescent brain.
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
456
Arain et al
Neuropsychiatric Disease and Treatment 2013:9
Nicotine
Recent studies have provided a neural framework to
explain the developmental differences that occur within the
mesolimbic pathway based on the established role of DA in
addiction.41,42 During adolescence, excitatory glutamatergic
systems that facilitate DAergic neurotransmisson are over-
developed, whereas inhibitory GABAergic systems remain
underdeveloped. DAergic pathways originate in the ventral
tegmental area and terminate in the nucleus accumbens,
where dopamine is increased by nicotine, but decreased
during withdrawal. Thus, it has been hypothesized that
adolescents display enhanced nicotine reward and reduced
withdrawal via enhanced excitation and reduced inhibition
of ventral tegmental area cell bodies that release DA in the
nucleus accumbens.44,45 Although this framework focuses
on both adolescents and adults, it may also apply to the
enhanced vulnerability to nicotine in adults that were previ-
ously exposed to nicotine during adolescence, suggesting that
the diagnostic criteria developed for nicotine dependence in
adults (based primarily on withdrawal) may be inappropri-
ate during adolescence, when nicotine withdrawal does not
appear to play a major role in nicotine use.39 Furthermore,
treatment strategies involving nicotine replacement may
be harmful for adolescents because it may cause enhanced
vulnerability to nicotine dependence later in adulthood.
Adolescents that initiate tobacco abuse are more vulnerable
to long-term nicotine dependence. A unifying hypothesis has
been proposed based on animal studies, and it suggests that
adolescents (as compared to adults) experience enhanced
short-term positive effects and reduced adverse effects toward
nicotine, and they also experience fewer negative effects
during nicotine withdrawal.39 Thus, during adolescence, the
strong positive effects associated with nicotine are inad-
equately balanced by the negative effects that contribute to
nicotine dependence in adults.
Alcohol
Recently, the development of brain functions, the cognitive
capabilities of adolescents, and the effect of alcohol abuse
on brain maturation have been examined.49,50 Cognitive
differences between adolescents and adults suggest that
the adultification of youths is deleterious for youths whose
brains have not fully matured. Adolescence is the time during
which most individuals first experience alcohol exposure, and
binge drinking is very common during this period.29,50,43 There
is increasing evidence for long-lasting neurophysiological
changes that may occur following exposure to ethanol dur-
ing adolescence in animal models.50 If alcohol exposure is
neurotoxic to the developing brain during adolescence, then
understanding how ethanol affects the developing adolescent
brain becomes a major public health issue. Adolescence is a
critical time period when cognitive, emotional, and social mat-
uration occurs and it is likely that ethanol exposure may affect
these complex processes. During a period that corresponds to
adolescence in rats, the relatively brief exposure to high levels
of alcohol via ethanol vapors caused long-lasting changes in
functional brain activity.51 The following observations were
recorded: disturbances in waking electroencephalography; a
reduction in the P3 wave (P3a and P3b) component of event-
related potential measurements; reductions in the mean dura-
tion of slow-wave sleep; and the total amount of time spent
in slow-wave sleep – findings that are consistent with the
premature sleep patterns observed during aging.50
Sex differences
Sex differences in many behaviors, including drug abuse, have
been attributed to social and cultural factors.43,46 A narrowing
gap in drug abuse between adolescent boys and girls supports
this hypothesis;52 however, some sex differences in addiction
vulnerability reflect biologic differences in the neurocircuits
involved in addiction. A male predominance in overall drug
abuse appears by the end of adolescence, while girls develop
a rapid progression from the time of the first abuse to depen-
dence, and this represents female-based vulnerability. Recent
studies have emphasized the contribution of sex differences
in the function of the ascending DAergic systems, which
are critical in reinforcement.3,43 These studies highlight the
behavioral, neurochemical, and anatomical changes that
occur in the DAergic functions that are related to the addic-
tions that occur during adolescence. In addition, these studies
have presented novel findings about the emergence of sex
differences in DAergic function during adolescence.43,46–48
Sex differences in drinking patterns and the rates of alcohol
abuse and dependence begin to emerge during the transition
from late puberty to young adulthood. Increases in pubertal
hormones, including gonadal and stress hormones, are a
prominent developmental feature of adolescence and could
contribute to the progression of sex differences in alcohol
drinking behavior during puberty. Witt46 reviewed experimen-
tal and correlational studies of gonadal and stress-related hor-
mone changes, as well as their effects on alcohol consumption
and the associated neurobehavioral actions of alcohol on the
mesolimbic dopaminergic system. Mechanisms have been
suggested by which reproductive and stress-related hormones
may modulate neural circuits within the brain reward system,
and these hormones may produce sex differences in terms of
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
457
Adolescent brain maturation
Neuropsychiatric Disease and Treatment 2013:9
alcohol consumption patterns and adolescents’ vulnerability
to alcohol abuse and dependence, which become apparent
during the late pubertal period.
Chemotherapy
Recently, Vázquez et al53 emphasized the need for the early
and accurate diagnosis of CNS complications during and after
pediatric cancer treatment because of the improvement in over-
all survival rates related to innovative and aggressive oncologic
therapies. A major concern in this issue is recognizing the
radiologic features of these CNS complications. Radiologists
are supposed to be familiar with the early and late effects of
cancer therapy in the pediatric CNS (toxic effects, infection,
endocrine or sensory dysfunction, neuropsychological impair-
ment, and secondary malignancies) in order to provide an
accurate diagnosis and to minimize morbidity. The acquisition
of further knowledge about these complications will enable
the development of more appropriate therapeutic decisions,
effective patient surveillance, and an improved quality of life
by decreasing the long-term consequences in survivors. Certain
chemotherapeutic compounds and environmental agents, such
as anesthetics, antiepileptics, sleep-inducing and anxiolytic
compounds, nicotine, alcohol, and stress, as well as agents of
infection have also been investigated quite extensively and have
been shown to contribute to the etiopathogenesis of serious
neuropsychiatric disorders.54
All of these agents have a delete-
rious influence on developmental processes during the time
when the brain experiences major changes in early childhood
and during adulthood. Several of these agents have contributed
to the structural and functional brain abnormalities that have
been observed in the biomarker profiles of schizophrenia and
fetal alcohol syndrome. The effects of these agents are gener-
ally permanent and irreversible.54
Nutrition
The rapid expansion of knowledge in this field, from
basic science to clinical and community-based research, is
expected to lead to urgently needed research in support of
effective, evidence-based medicine and treatment strate-
gies for undernutrition, overnutrition, and eating disorders
in early childhood. Eating is necessary for survival and
provides a sense of pleasure, but may be perturbed, leading
to undernutrition, overnutrition, and eating disorders. The
development of feeding in humans relies on the complex
interplay between homeostatic mechanisms; neural reward
systems; and adolescents’ motor, sensory, and emotional
capabilities. Furthermore, parenting, social factors, and food
influence the development of eating behavior.
Recently, the neural development of eating behavior in
children has been investigated.55 Furthermore, developmen-
tally programmed neural maturation has been discussed in
order to highlight adolescence as the second most critical
period of brain maturation.56 These studies used impairments
of the DAergic system, the hypothalamic–pituitary–adrenal
axis, and pathological interactions between these two sys-
tems originating from fetal programming in a dual-system
model to explain insufficient behavioral inhibition in affected
adolescents.
The range of exogenous agents, such as alcohol and
cocaine, which are generally likely to detrimentally affect
the development of the brain and CNS defies estimation,
although the accumulated evidence is substantial.57–60
Pubertal age affects the fundamental property of nervous
tissue excitability; excessive excitatory drive is seen in early
puberty and a deficiency is seen in late puberty. It has been
postulated that, with adequate fish oils and fatty acids, the risk
of psychopathology can be minimized, whereas a deficiency
could lead to subcortical dysfunction in early puberty, and a
breakdown of cortical circuitry and cognitive dysfunctions
in late puberty.61 Thus, postpubertal psychoses, schizophre-
nia, and manic–depressive psychosis during the pubertal
age, along with excitability, may be the result of continuous
dietary deficiency, which may inhibit the expression of the
oligodendrocyte-related genes responsible for myelino-
genesis. The beneficial effect of fish oils and fatty acids
in schizophrenia, fetal alcohol syndrome, developmental
dyslexia, attention deficit hyperactivity disorder, and in other
CNS disorders supports the hypothesis that the typical diet
might be persistently deficient in the affected individuals, as
illustrated in Figure 6. However, the amount of fish oils and
fatty acids needed to secure normal brain development and
function is not known. It seems conjectural to postulate that a
dietary deficiency in fish oils and fatty acids is causing brain
dysfunction and death; however, all of these observations tend
to suggest that a diet focusing on mainly protein is deficient,
and the deficiency is most pronounced in maternal nutrition
and in infancy, which might have a deleterious impact on the
maturation of the adolescent brain.
Conclusion
Neuromorphological, neurochemical, neurophysiological,
neurobehavioral, and neuropharmacological evidence sug-
gests that the brain remains in its active state of maturation
during adolescence.1,7,19,21 Such evidence supports the hypoth-
esis that the adolescent brain is structurally and functionally
vulnerable to environmental stress, risky behavior, drug
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
458
Arain et al
Neuropsychiatric Disease and Treatment 2013:9
addiction, impaired driving, and unprotected sex. Computed
tomography and MRI studies also provide evidence in sup-
port of this hypothesis.19
Brain maturation occurs during adolescence due to a
surge in the synthesis of sex hormones implicated in puberty
including estrogen, progesterone, and testosterone. These sex
hormones augment myelinogenesis and the development of the
neurocircuitry involved in efficient neurocybernetics. Although
tubulinogenesis, axonogenesis, and synaptogenesis can occur
during the prenatal and early postnatal periods, myelinogenesis
involved in the insulation of axons remains under construction
in adolescence. Sex hormones also significantly influence food
intake and sleep requirements during puberty. In addition to
dramatic changes in secondary sex characteristics, sex hor-
mones may also influence the learning, intelligence, memory,
and behavior of adolescents.
Furthermore, it can be observed that the development of
excitatory glutamatergic neurotransmission occurs earlier in
the developing brain as compared to GABAergic neurotrans-
mission, which makes the pediatric population susceptible
to seizures.
The development and maturation of the prefrontal
cortex occurs primarily during adolescence and is fully
accomplished at the age of 25 years. The development of the
prefrontal cortex is very important for complex behavioral
performance, as this region of the brain helps accomplish
executive brain functions.
A detailed study is required in order to determine the
exact biomarkers involved, as well as the intricate influence of
diet, drugs, sex, and sleep on the maturation of the adolescent
brain as discussed briefly in this report.
Acknowledgments
The moral support and encouragement of President Kallol
Guha is gratefully acknowledged.
Disclosure
The authors report no conflicts of interest in this report.
References
1. Giedd JN, Blumenthal J, Jeffries NO, et al. Brain development during
childhood and adolescence: a longitudinal MRI study. Nat Neurosci.
1999;2(10):861–863.
2. Li K, Xu E. The role and the mechanism of gamma-aminobutyric
acid during central nervous system development. Neurosci Bull.
2008;24(3):195–200.
3. Wahlstrom D, Collins P, White T, Luciana M. Developmental changes
in dopamine neurotransmission in adolescence: behavioral implications
and issues in assessment. Brain Cogn. 2010;72(1):146–159.
4. Kaplan PS. Adolescence. Boston, MA: Houghton Mifflin Company;
2004.
5. Gavin L, MacKay AP, Brown K, et al; Centers for Disease Control
and Prevention (CDC). Sexual and reproductive health of persons
aged 10–24 years – United States, 2002–2007. MMWR Surveill Summ.
2009;58(6):1–58.
6. Sylwester R. The Adolescent Brain: Reaching for Autonomy. Newbury
Park (CA): Corwin Press; 2007.
7. Baird AA, Gruber SA, Fein DA, et al. Functional magnetic resonance
imaging of facial affect recognition in children and adolescents. J Am
Acad Child Adolesc Psychiatry. 1999;38(2):195–199.
8. Frontline: Inside the Teenage Brain [webpage on the Internet]. Arlington
(TX): Public Broadcasting Service; 2002. Available from: http://www.
pbs.org/wgbh/pages/frontline/shows/teenbrain/. Accessed August 6,
2009.
9. Dahl RE. Beyond raging hormones: the tinderbox in the teenage brain.
Cerebrum. 2003;5(3):7–22.
10. Blakemore SJ. Development of the social brain in adolescence. J R Soc
Med. 2012;105(3):111–116.
11. Sisk CL, Foster DL. The neural basis of puberty and adolescence. Nat
Neurosci. 2004;7(10):1040–1047.
12. Peper JS, van den Heuvel MP, Mandl RC, Hulshoff Pol HE, van
Honk J. Sex steroids and connectivity in the human brain: a review
of neuroimaging studies. Psychoneuroendocrinology. 2011;36(8):
1101–1113.
13. Choudhury S, Blakemore SJ, and Charman T. Social cogni-
tive development during adolescence. Soc Cogn Affect Neurosci.
2006;1(3):165–174.
14. den Bos (2011) W.V The neurocognitive development of social deci-
sion making. Doctoral Research Thesis. (P 1–189) Amsterdam.
15. Somerville LH, Fani N, and Erin B. McClure-Tone E.B. Behavioral
and neural representation of emotional facial expressions across the
lifespan. Dev Neuropsychol. 2011;36(4):408–428.
16. Sales JM and Irvin CE. Theories of adolescent risk taking (2009) The
biopsychological model. In Adolescent Health. Diclemente R.J, Santelli,
J.S, Crosby RA (Eds) (pp 31–50) San Fransisco: John Wiley and Sons.
17. Frontline: Interview Deborah Yurgelun-Todd [webpage on the Internet].
Arlington: Public Broadcasting Service; 2002. Available form: http://
www.pbs.org/wgbh/pages/frontline/shows/teenbrain/interviews/todd.
html. Accessed February 14, 2013.
18. Guyer AE, McClure-Tone EB, Shiffrin ND, Pine DS, Nelson EE. Probing
the neural correlates of anticipated peer evaluation in adolescence. Child
Dev. 2009;80(4):1000–1015.
Figure 6 Effect of seafood on the maturation of the adolescent brain.
Notes: MRI studies have provided evidence that in addition to the prefrontal
cortex and limbic system, myelinogenesis and neurocircuitry remains under
construction during adolescence.1,7,19,21 Myelinogenesis requires precursors such
as polyunsaturated fatty acids, of which many seafoods are a rich source. Hence,
consuming seafood may accelerate brain maturation in adolescents. However,
malnutrition and substance abuse may inhibit maturation of the adolescent brain.
(+) induction; () inhibition.
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
459
Adolescent brain maturation
Neuropsychiatric Disease and Treatment 2013:9
19. Casey BJ, Jones RM, Hare TA. The adolescent brain. Ann N Y Acad Sci.
2008;1124:111–126.
20. Walsh D, Bennett N. Why Do They Act That Way? A Survival Guide
to the Adolescent Brain for You and Your Teen. New York: Simon and
Schuster; 2004.
21. Giedd JN. Structural magnetic resonance imaging of the adolescent
brain. Ann N Y Acad Sci. 2004;1021:77–85.
22. Steinberg L. Risk taking in adolescence: what changes and why? Ann
N Y Acad Sci. 2004;1021:51–58.
23. Steinberg L. Cognitive and affective development in adolescence. Trends
Cogn Sci. 2005;9(2):69–76.
24. Abelson, R. P. (1963). Computer simulation of “hot cognition”, in S.
S. Tomkins and S. Messick (Eds.), Computer simulation of personality
(pp. 277–302). New York: Wiley.
25. Ziva K (1990). “The case for motivated reasoning”. Psychological
Bulletin 108(3): 480–498.
26. Benes FM. The development of the human frontal cortex: The matura-
tion of neurotransmitter system and their interactions. In: Nelson CA,
Luciana M, editors. Handbook of Developmental Cognitive Neurosci-
ence. Cambridge, MA: MIT Press; 2001:79–92.
27. Gardner M, Steinberg L. Peer Influence on risk taking, risk preference
and risky decision-making in adolescence and adulthood. Dev Psychol.
2005;41(4):625–635.
28. http://www.hhs.gov [homepage on the Internet]. New Research on
Adolescent Brain Development. Center for Substance Abuse Preven-
tion;2004. http://www.hhs.gov/opa/familylife/tech_assistance/etrain-
ing/adolescent_brain/risk_taking/changes/sensation_seeking/index.
html#fn3. Accessed March 14, 2013.
29. Lopez B, Schwartz SJ, Prado G, Campo AE, Pantin H. Adolescent
neurological development and implications for adolescent substance
abuse prevention. J Prim Prev. 2008;29(1):5–35.
30. Steinberg L, Belsky J. An evolutionary perspective on psychopathol-
ogy in adolescence. In: Cicchetti D, Toth SL, editors. Adolescence:
Opportunities and Challenges: Volume 7 of Rochester Symposium
on Developmental Psychology Series. Rochester, NY: University of
Rochester Press; 1996:93–124.
31. Simpson RA. Raising Teens: A Synthesis of Research and a Founda-
tion for Action. Center for Health Communication, Harvard School of
Public Health. 2001. Available from: http://www.hsph.harvard.edu/chc/
parenting/report.pdf.
32. Steinberg L. A social neuroscience perspective on adolescent risk-taking.
Dev Rev. 2008;28(1):78–106.
33. Blakemore SJ. Development of the social brain in adolescence. J R Soc
Med. 2012;105(3):111–116.
34. Liu J, Lester BM. Reconceptualizing in a dual-system model the effects
of prenatal cocaine exposure on adolescent development: a short review.
Int J Dev Neurosci. 2011;29(8):803–809.
35. Burke AS. Under construction: brain formation, culpability, and the
criminal justice system. Int J Law Psychiatry. 2011;34(6):381–385.
36. Palmer RH, Young SE, Hopfer CJ, et al. Developmental epidemiology
of drug use and abuse in adolescence and young adulthood: evidence
of generalized risk. Drug Alcohol Depend. 2009;102(1–3):78–87.
37. Bossong NG, Niesink RJ. Adolescent brain maturation, the endogenous
cannabinoid system and the neurobiology of cannabis-induced schizo-
phrenia. Prog Neurobiol. 2010 Nov;92(3):370–385.
38. Vik P, Brown SA. Life events and substance abuse during adolescence.
In: Miller TW, editor. Children of Trauma. Madison, CT: International
Universities Press; 1998:179–204.
39. Rubino T, Zamberletti E, Parolaro D. Adolescent exposure to can-
nabis as a risk factor for psychiatric disorders. J Psychopharmacol.
2012;26(1):177–188.
40. Gonzalez R, Swanson JM. Long-term effects of adolescent-onset and
persistent use of cannabis. Proc Natl Acad Sci U S A. 2012;109(40):
15970–15971.
41. O’Dell LE. A psychobiological framework of the substrates that mediate
nicotine use during adolescence. Neuropharmacology. 2009;56 Suppl 1:
263–278.
42. Philpot R, Kirstein C. Developmental Differences in the Accumbal
Dopaminergic Response to Repeated Ethanol Exposure. Ann. N Y. Acad.
Sci. 2004;1021:422–426.
43. Kuhn C, Johnson M, Thomae A, et al. The emergence of gonadal
hormone influences on dopaminergic function during puberty. Horm
Behav. 2010;58(1):122–137.
44. Burke AS. Under construction: brain formation, culpability, and the
criminal justice system. Int J Law Psychiatry. 2011;34(6):381–385.
45. Spear LP. Adolescent period: biological basis of vulnerability to develop
alcoholism and other ethanol–mediated behaviors. In: Noronha A,
Eckardt M, Warren K, editors. Review of NiAAA’s Neuroscience and
Behavioral Research Portfolio. Bethesda, MD: National Institute on
Alcohol Abuse and Alcoholism; 2000:315–333.
46. Witt ED. Puberty, hormones, and sex differences in alcohol abuse and
dependence. Neurotoxicol Teratol. 2007;29(1):81–95.
47. Nolen-Hoeksema S, Girgus JS. The emergence of gender differ-
ences in depression during adolescence. Psychological Bulletin.
1994;115(3):424–443.
48. Lenroot RK, Giedd JN. Sex differences in the adolescent brain. Brain
Cogn. 2010;72(1):1–19.
49. Spear LP. The adolescent brain and age–related behavioral
manifestations. Neurosci Biobehav Rev. 2000;24(4):417–463.
50. Ehlers CL, Criado JR. Adolescent ethanol exposure: does it produce
long-lasting electrophysiological effects? Alcohol. 2010;44(1):27–37.
51. Allen CD, Lee S, Koob GF Rivier C . Immediate and prolonged effects
of alcohol exposure on the activity of the hypothalamic-pituitary-
adrenal axis in adult and adolescent rats. Brain Behav Immun. 2011
June;25(Suppl 1):S50–S60.
52. Schulte MT, Ramo D, and Brown SA. Gender Differences in Factors
Influencing Alcohol Use and Drinking Progression Among Adolescents.
Clin Psychol Rev. 2009 August;29(6):535–547.
53. Vázquez E, Delgado I, Sánchez-Montañez A, Barber I, Sánchez-
Toledo J, Enríquez G. Side effects of oncologic therapies in the
pediatric central nervous system: update on neuroimaging findings.
Radiographics. 2011;31(4):1123–1139.
54. Archer T. Effects of exogenous agents on brain development: stress, abuse
and therapeutic compounds. CNS Neurosci Ther. 2011;17(5):470–489.
55. Gahagan S. Development of eating behavior: biology and context.
J Dev Behav Pediatr. 2012;33(3):261–271.
56. Sisk CL and Foster DL. The neural basis of puberty and adolescence.
Nature Neuroscience 2004;7:1040–1047.
57. Liu J, Lester BM. Reconceptualizing in a dual-system model the effects
of prenatal cocaine exposure on adolescent development: a short review.
Int J Dev Neurosci. 2011;29(8):803–809.
58. Saugstad LF. From superior adaptation and function to brain dysfunction
the neglect of epigenetic factors. Nutr Health. 2004;18(1):3–27.
59. Steinberg L. Risk taking in adolescence: new perspectives from brain
and behavioral science. Curr Dir Psychol Sci. 2007;16(2):55–59.
60. Brown SA, Tapert SF, Granholm E, Delis DC. Neurocognitive function-
ing of adolescents: effects of protracted alcohol use. Alcohol Clin Exp
Res. 2000;24(2):164–171.
61. Rayyan M, Devlieger H, Jochum F, Allegaert K. Short-Term Use of
Parenteral Nutrition With a Lipid Emulsion Containing a Mixture of
Soybean Oil, Olive Oil, Medium-Chain Triglycerides, and Fish Oil. A
Randomized Double-Blind Study in Preterm Infants. JPEN J Parenter
Enteral Nutr. 2012 January;36(1 suppl):81S–94S.
submit your manuscript | www.dovepress.com
Dovepress
Dovepress
460
Arain et al
Neuropsychiatric Disease and Treatment
Publish your work in this journal
Submit your manuscript here: http://www.dovepress.com/neuropsychiatric-disease-and-treatment-journal
Neuropsychiatric Disease and Treatment is an international, peer-
reviewed journal of clinical therapeutics and pharmacology focusing
on concise rapid reporting of clinical or pre-clinical studies on a
range of neuropsychiatric and neurological disorders. This journal
is indexed on PubMed Central, the ‘PsycINFO’ database and CAS.
The manuscript management system is completely online and includes
a very quick and fair peer-review system, which is all easy to use. Visit
http://www.dovepress.com/testimonials.php to read real quotes from
published authors.
Neuropsychiatric Disease and Treatment 2013:9 submit your manuscript | www.dovepress.com
Dovepress
Dovepress
Dovepress
461
Adolescent brain maturation
... This cutoff point was based on previous reports about brain maturation to indicate a period of different vulnerability for environmental stress. Although brain volume seems to reach its peak around the age of 12 years, it is widely established that the brain, especially the prefrontal cortex, further matures and rewires until the mid-20s [36]. Besides, previous reports showed that development and maturation of a majority of white matter microstructures continues until the age of 25 years before it reaches a plateau phase [37,38]. ...
... Alosco et al. [31] demonstrated that exposure to tackle football at a younger age was associated with an earlier age of symptom onset among pathological confirmed CTE cases. It is widely acknowledged that brain development continues until an age of approximately 25 years, and it may be assumed that brain structures are more vulnerable to disruptions in this period [36,37]. These early disruptions may cause less resilience or higher vulnerability to neurodegenerative changes in the brain later at life, and the threshold to compensate for pathological burden may be lowered. ...
Article
Full-text available
b> Introduction: Traumatic brain injury (TBI) has been associated with a greater risk of developing Alzheimer’s disease (AD). Less is known about the clinical features of AD patients with TBI history. The objective of this study was to examine whether a history of TBI and specific injury characteristics are associated with differences in age of disease onset, cognitive features, and neuropsychiatric symptoms (NPSs) in AD patients. Methods: Biomarker-proven AD patients (CSF or amyloid PET) were selected from the Amsterdam Dementia Cohort. TBI events were classified by age at injury (TBI <25 or ≥25 years) and TBI severity (loss of consciousness, multiple events). Cognitive composite scores were calculated from results of a neuropsychological test battery. NPSs were assessed with the Neuropsychiatric Inventory Questionnaire (NPI-Q). Linear regression analyses were utilized to examine associations between TBI, TBI characteristics, and clinical outcome measures. Results: Among the 1,755 selected AD patients (mean age = 65.2 years), 166 (9.5%) had documented ≥1 TBI in their medical history. Overall, TBI history was not related to differences in age of disease onset, but age at injury <25 years old was associated with 2.3 years earlier age at symptom onset ( B = −2.34, p = 0.031). No significant associations were found between TBI history or TBI characteristics and differences in cognition or NPSs. Conclusion: Our results underscore previous findings on the vulnerability of the brain during critical maturation phases and suggest that an early TBI may contribute to lower resilience to neurodegenerative changes.
... The current literature lacks studies that examined drinking expectancies among young adults, who have a higher prevalence of drinking and binge drinking than any other age group in the East Asian region. Young adults represent a vulnerable group as the brain is still not completely developed [48]. Moreover, drinking in this age group has been associated with the use of psychotropic drugs and risky behaviors, such as drunk driving [49][50][51]. ...
Article
Full-text available
Background: Alcohol expectancies, i.e., the perceived consequences of drinking, were reported to be an important factor in predicting drinking behaviors. However, studies in the Asia region were largely limited to school-based samples. This study aimed to be the first to explore drinking expectancies among urban Chinese young adults. Methods: In 2020, eight focus group discussions were conducted with Hong Kong Chinese young adults aged 18–34 (n = 53). The participants included heavy drinkers, light drinkers, and non-drinkers from a wide range of occupations and educational backgrounds. Thematic analysis was conducted to uncover common alcohol expectancies. Results: Six themes emerged from this study. Four themes that were commonly reported in the literature were the negative consequences of drinking, social bonding, confidence enhancement, and tension reduction. The study also uncovered two culturally relevant alcohol expectancies: health benefits and business drinking expectancies. In contrast to Western samples, Chinese young adults did not report drinking expectancies related to cognitive enhancement or increased sexual interest. Conclusion: Alcohol harm reduction strategies will need to address the positive drinking expectancies uncovered in this study. Future policy discussions in this emerging alcohol market region should consider greater scrutiny of the role of alcohol marketing in the propagation of positive drinking expectancies.
... On the other hand, completely adult-like emotion regulation cannot be expected since the biological changes of adolescence involve brain structures and systems implicated in emotion expression and regulation as well. There is, for example, a second surge of synaptogenesis (dendritic pruning and myelinogenesis), making the teenage years one of the most dynamic periods of human development (Arain et al., 2013;Lynch et al., 2020). Due to the considerable increases in sex hormones, neurocircuitry is still functionally and structurally unstable resulting in marked vulnerability (Patel et al., 2021). ...
Article
Background The COVID-19 pandemic created unpredictable circumstances resulting in increased psychological strain. Here we investigate pandemic-related alterations in emotion regulation in adolescents assessed before and during the pandemic. We also take biological age into account in the response to the pandemic. Methods Mann-Whitney U tests were conducted to compare baseline data on the Difficulties in Emotion Regulation Scale (DERS) total scores of a pre-pandemic adolescent cohort (n = 241) with those obtained during the second wave of the pandemic (n = 266). We estimated biological age based on an ultrasonic boneage assessment procedure in a subgroup of males, including grammar school and vocational school students in the 9th and 10th grades, and analyzed their data independently. Findings There is a gender difference in the timing of vulnerability for pandemic-related stress in grammar school students: females are affected a year earlier than males. Vocational school male students mature faster than grammar school male students, and the timing of emotional vulnerability also precedes that of the grammar school students'. Discussion We interpret our findings within a developmental model suggesting that there might be a window of highest vulnerability in adolescent emotion regulation. The timing of the window is determined by both chronological and biological age, and it is different for females and males. Application to practice Defining the exact temporal windows of vulnerability for different adolescent cohorts allows for the timely integration of preventive actions into adolescent care to protect mental health during future chronic stressful situations.
... Sensitive periods, such as adolescence, refer to times in human development when heightened neuroplasticity renders the brain particularly sensitive to stressful or negative external factors (Blakemore, 2019). During adolescence, the brain does not grow significantly in size but rather through the creation and strengthening of neurocircuitry and pathways, including those responsible for controlling stress (Sharma et al., 2013). Chronic stress during this period can damage developing neural circuits and hormonal systems, resulting in dysfunctional stress response systems that will be oversensitive or slow to return to baseline levels when faced with a stressor throughout the lifespan (Loman & Gunnar, 2010). ...
Article
Adolescence is a time of dramatic change and growth across multiple systems. Simultaneous development of neural, biological, and social domains of functioning renders adolescence a heightened period of sensitivity to early life experiences. Among these experiences, stressful life events are shown to disrupt the architecture of the developing brain, increasing the risk of future mental health disorders, such as depression and anxiety. In this paper, I discuss the risk of adolescence, such as the vulnerabilities to stress, alongside the unique plasticity that creates an opportunity for positive external influences (e.g., family milieu). Finally, I propose a multidimensional construct, known as RISE, for adolescent flourishing borrowing from other validated positive psychology concepts. A workshop and specific interventions to improve each of the four elements of RISE are proposed that can be used by parents.
Article
Full-text available
Clinical findings show that the use of valproic acid (VPA) during pregnancy increases the risk of birth defects and autism spectrum disorder in offspring. Although there is a consensus that monitoring of potential long-term outcomes of VPA exposure is needed, especially in undiagnosed individuals, preclinical studies addressing this issue are rare. The present study examined the effects of continuous intrauterine exposure to a wide dose range of VPA (50, 100, 200, and 400 mg/kg/day) on the physical and behavioral response in peripubertal mice as a rodent model of adolescence. Body weight and the hot plate test [on postnatal days (PND) 25 and 32], the elevated plus-maze test (on PND35), and the open field test (on PND40) served to examine physical growth, the supraspinal reflex response to a painful thermal stimulus and conditional learning, anxiety-like/risk-assessment behavior, as well as novelty-induced psychomotor activity, respectively. VPA exposure produced the following responses: (i) a negative effect on body weight, except for the dose of 100 mg/kg/day in both sexes; (ii) an increase in the percentage of animals that responded to the thermal stimulus above the defined cut-off time interval and the response latency in both sexes; (iii) dose-specific changes within sexes in behavior provoked by a novel anxiogenic environment, i.e., in females less anxiety-like/risk-assessment behavior in response to the lowest exposure dose, and in males more pronounced anxiety-like/risk-assessment behavior after exposure to the highest dose and 100 mg/kg/day; (iv) dose-specific changes within sexes in novelty-induced psychomotor activity, i.e., in females a decrease in stereotypy-like activity along with an increase in rearing, and in males a decrease in stereotypy-like activity only. These findings show that continuous intrauterine exposure to VPA produces maladaptive functioning in different behavioral domains in adolescence and that the consequences are delicate to assess as they are dose-related within sexes.
Article
Abuse of toluene-containing volatile inhalants, particularly among youth, is of significant medical and social concern worldwide. Teenagers constitute the most abundant users of toluene and the majority of adult abusers of toluene started as teenagers. Although the euphoric and neurotoxic effects of acute toluene have been widely studied, lasting effects of chronic toluene exposure, especially in various age groups, have not been well investigated. In this study, we used adolescent and adult male Wistar rats to evaluate the short- and long-term effects of chronic toluene on various behaviors including cognitive function. Daily exposure to toluene (2000 ppm) for 40 days (5 min/day) resulted in age-dependent behavioral impairments. Specifically, adolescent animals showed recognition memory impairment the day after the last exposure, which had normalized by day 90 post- exposure, whereas such impairment in adult animals was still evident at day 90 post-exposure. Our data suggest that age-dependent responses should be taken into consideration in interventional attempts to overcome specific detrimental consequences of chronic toluene exposure.
Chapter
Gender-based violence (GBV) includes acts of violence that are directed towards an individual rooted in the desire for power and control, and based on sex, gender identity, or gender expression. GBV can include dating or intimate partner violence, sexual violence, femicide, genital mutilation or cutting, human trafficking, and online or digital forms of violence. This entry examines youth exposure to GBV, with a particular focus on the risk and protective factors within the family, as well as family-based programs and interventions. Youth between the ages of 11 and 18 are exposed to GBV at alarmingly high rates, which can place them at risk for health, social, and behavioral concerns, societal costs, and impact others in their life. We begin this entry with a conceptualization of GBV. Next, we illuminate the historical and current context, and discuss adolescence as a developmental period of heightened risk for GBV. We review the literature and prevention strategies surrounding adolescent dating violence and sexual violence, focusing on family-based approaches. Next, we posit recommendations for future research—we highlight the work of scholars who elevate the importance of an intersectionality framework, and we urge researchers to continue building scholarship in GBV measurement. Researchers should also continue building longitudinal evidence of possible risk and protective factors, especially in families and communities. Given the historical context, norms, and societal beliefs that have perpetuated GBV, scholars also need to be bringing in macro-level influences into the interpretation of their research and prevention strategies. Finally, there is an increasing need to bridge school-based work with family- and community-based prevention for a more comprehensive approach that shifts contexts rather than individual people. Across these recommendations, we hope to see adolescent GBV research and prevention as a top priority for global and local organizations, scholars, and practitioners.
Chapter
This chapter addresses some basic concepts of training professionals and explains practical techniques to improve the effectiveness of delivery. A brief discussion of how to keep training relevant and impactful follow. Finally, a review of how to enhance the learning experience is explored.KeywordsDelivery effectivenessADDIEMethods Managing distractions
Article
Different regions of the cortex have been implicated in the pathophysiology of schizophrenia. Recently published data suggested there are many more changes in gene expression in the frontal pole (Brodmann's Area (BA) 10) compared to the dorsolateral prefrontal cortex (BA 9) and the anterior cingulate cortex (BA 33) from patients with schizophrenia. These data argued that the frontal pole was significantly affected by the pathophysiology of schizophrenia. The frontal pole is a region necessary for higher cognitive functions and is highly interconnected with many other brain regions. In this review we summarise the growing body of evidence to support the hypothesis that a dysfunctional frontal pole, due at least in part to its widespread effects on brain function, is making an important contribution to the pathophysiology of schizophrenia. We detail the many structural, cellular and molecular abnormalities in the frontal pole from people with schizophrenia, with the symptoms of schizophrenia being closely linked to dysfunction in this critical brain region.
Chapter
Chronic cannabis exposure during adolescence can result in persistent deficits in cognitive domains such as attention, memory, and processing speed. Cannabis use during adolescence is also linked to an increased risk for psychiatric disorders, including psychosis (schizophrenia), depression, anxiety, and substance use disorders, later in life. Notably, not all cannabis users exhibit these long-lasting behavioral and cognitive impairments, suggesting there is a genetic vulnerability, i.e., a gene-environment relationship for cannabis sensitivity. Unfortunately, little is known about the mechanisms of individual susceptibilities to the adverse effects of cannabis use in adolescence. The molecular mechanisms of gene and environment interactions differ across cell types, and recent studies have only begun to identify the molecular cascades activated by delta-9-tetrahydrocannabinol (Δ⁹-THC) in a cell-type-specific manner. In this chapter, we review these interactions and their contributions to cannabis sensitivity and to the development of long-lasting behavioral abnormalities. We also lay out the known cell-type-specific mechanisms of the susceptibilities to the adverse effects of cannabis and discuss the proinflammatory signaling pathways involved in Δ⁹-THC-induced behavioral impairments. Finally, we highlight new avenues to study the vulnerability to adverse effects of Δ⁹-THC exposure, specifically, changes in brain cell energetics and the insights gleaned from studies in humans and animal models.
Article
Full-text available
Marijuana use has increased over the past 20 y in the United States, and current trends suggest it may continue to rise. Recent polls in the United States suggest that population acceptance is at an all-time high: 56% support the legalization for recreational use and 70% for medical use (http://healthland.time.com/2012/06/14). A survey of secondary school students in the United States (Monitoring the Future: http://monitoringthefuture.org) suggests a resurgence of marijuana use (Fig. 1): after a decade or more of decline to 22% in 1992, the annual prevalence of use in high school senior students climbed to nearly 40% in 2011, with a parallel decrease in perceived risk of regular use from almost 80% to approximately 45% (1). Although short-term trends reveal some temporary decreases (2), the recent trends of increasing use and acceptance of marijuana over the past 5 y (1) heighten the importance of a scientific basis for understanding effects of marijuana (cannabis).
Article
This thesis describes a series of experiments that investigated the relation between brain development and the development of social behavior
Article
Trying to understand why adolescents and young adults take more risks than younger or older individuals do has challenged psychologists for decades. Adolescents' inclination to engage in risky behavior does not appear to be due to irrationality, delusions of invulnerability, or ignorance. This paper presents a perspective on adolescent risk taking grounded in developmental neuroscience. According to this view, the temporal gap between puberty, which impels adolescents toward thrill seeking, and the slow maturation of the cognitive-control system, which regulates these impulses, makes adolescence a time of heightened vulnerability for risky behavior. This view of adolescent risk taking helps to explain why educational interventions designed to change adolescents' knowledge, beliefs, or attitudes have been largely ineffective, and suggests that changing the contexts in which risky behavior occurs may be more successful than changing the way adolescents think about risk.
Article
Eating is necessary for survival, gives great pleasure, and can be perturbed leading to undernutrition, overnutrition, and eating disorders. The development of feeding in humans relies on complex interplay between homeostatic mechanisms; neural reward systems; and child motor, sensory, and socioemotional capability. Furthermore, parenting, social influences, and the food environment influence the development of eating behavior. The rapid expansion of new knowledge in this field, from basic science to clinical and community-based research, is expected to lead to urgently needed research in support of effective, evidence-based prevention and treatment strategies for undernutrition, overnutrition, and eating disorders in early childhood. Using a biopsychosocial approach, this review covers current knowledge of the development of eating behavior from the brain to the individual child, taking into account important contextual influences.
Article
Adolescence is the developmental epoch during which children become adults—intellectually, physically, hormonally and socially. Brain development in critical areas is ongoing. Adolescents are risk-taking and novelty-seeking and they weigh positive experiences more heavily and negative experiences less than adults. This inherent behavioral bias can lead to risky behaviors like drug taking. Most drug addictions start during adolescence and early drug-taking is associated with an increased rate of drug abuse and dependence.The hormonal changes of puberty contribute to physical, emotional, intellectual and social changes during adolescence. These hormonal events do not just cause maturation of reproductive function and the emergence of secondary sex characteristics. They contribute to the appearance of sex differences in non-reproductive behaviors as well. Sex differences in drug use behaviors are among the latter. The male predominance in overall drug use appears by the end of adolescence, while girls develop the rapid progression from first use to dependence (telescoping) that represent a female-biased vulnerability. Sex differences in many behaviors including drug use have been attributed to social and cultural factors. A narrowing gap in drug use between adolescent boys and girls supports this thesis. However, some sex differences in addiction vulnerability reflect biologic differences in brain circuits involved in addiction. The purpose of this review is to summarize the contribution of sex differences in the function of ascending dopamine systems that are critical to reinforcement, to briefly summarize the behavioral, neurochemical and anatomical changes in brain dopaminergic functions related to addiction that occur during adolescence and to present new findings about the emergence of sex differences in dopaminergic function during adolescence.