Development Period of Prefrontal Cortex

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Chapter 1
Development Period of Prefrontal Cortex
Merve Cikili Uytun
Additional information is available at the end of the chapter
http://dx.doi.org/10.5772/intechopen.78697
Provisional chapter
DOI: 10.5772/intechopen.78697
© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
Development Period of Prefrontal Cortex
Merve CikiliUytun
Additional information is available at the end of the chapter
Abstract
This chapter outlines the issues associated with the development of prefrontal cortex
in children and adolescents, and describes the developmental prole of executive pro-
cesses across childhood. The prefrontal cortex plays an essential role in various cognitive
functions and lile is known about how such neural mechanisms develop during child-
hood yet. To beer understand this issue, we focus the literature on the development
of the prefrontal cortex during early childhood, the changes in structural architecture,
neural activity, and cognitive abilities. The prefrontal cortex undergoes maturation dur-
ing childhood with a reduction of synaptic and neuronal density, a growth of dendrites,
and an increase in white maer volume. With these neuroanatomical changes, neural
networks construct appropriate for complex cognitive processing. The organization of
prefrontal cortical circuitry may have been critical to the occurrence of human-specic
executive and social-emotional functions, and developmental pathology in these
same systems underlies many psychiatric disorders; therefore, if we understand these
developmental process well, we could beer analyze the development of psychiatric
disorders.
Keywords: development, prefrontal cortex, infancy, childhood
1. Introduction
In the past two decades, an increasing number of studies have examined the human frontal
lobe and PFC utilizing a wide variety of methodologies including stereology, MRI, minicol-
umn analysis, and DTI [1]. A number of recent studies have examined the relative size of gray
and white maer in the frontal lobe or PFC, while others have examined the volume, neuron
density, and columnar organization of functional subregions within the PFC. The frontal lobe
includes several anatomical components and dierent functional areas, and, so it is thought
that as a discrete unit can only tell us so much [2].
© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.

PFC plays most important roles in executive functions, which includes the organization of sev-
eral sensory inputs, the maintenance of aention, planning, reasoning, language comprehen-
sion, the working memory, and the coordination of goal-directed behaviors [3–6]. Therefore, the
functions of PFC are certainly a crucial aspect of what we think of as “human” in cognition [7].
The development of the brain occurs through the interaction of several processes, some of
these stages are completed before birth such as neurulation, cell proliferation, and migra-
tion, although others continue into adulthood [8]. It is showed that the PFC is one of the last
regions of the brain to mature, based on most indicators of development [9], and that the
neurons in these areas have more complex dendritic trees than primary somatosensory and
primary motor cortex those that mature earlier [10, 11]. Brain development begins in utero in
the third gestational week and continues into adolescence [12]. However, lateral regions of the
PFC are the latest developing areas that involved in executive functions [9].
When discussing the role of the PFC, other brain regions with which it shares intensive inter-
connections, including the basal ganglia, thalamus, brainstem, hippocampus, amygdala, and
other neocortical regions also play important role [13, 14]. Thus, its intrinsic connections with
other areas provide access to emotional responses and other information [5]. The lateral PFC
is implicated in language and executive functions, while the orbital and medial regions of the
PFC are thought to be involved in the processing and in the regulation of emotional behavior
[15]. The lateral orbital PFC, interconnected regions of the basal ganglia, and the supplemen-
tary motor area, these regions are called the frontostriatal system, and they work together
with many of the cognitive capacities [16].
PFC includes the following Broadman Areas (BA): 8, 9, 10, 11, 12, 44, 45, 46, 47. “The dor-
solateral frontal cortex (BA) 9/46 has been functioned in many cognitive process, including
processing spatial information [17–19], monitoring and manipulation of working memory
[20, 21], the implementation of strategies to facilitate memory [22], response selection [23],
the organization of material before encoding [24], and the verication and evaluation of rep-
resentations that have been retrieved from long-term memory [25, 26]. The mid-ventrolateral
frontal cortex (BA 47) has implicated cognitive functions, including the selection, comparison,
and judgment of stimuli held in short-term and long-term memory [21], processing nonspa-
tial information [27], task switching [28], reversal learning [29], stimulus selection [30], the
specication of retrieval cues [25], and the ‘elaboration encoding’ of information into episodic
memory [31, 32]. BA 10, the most anterior aspect of the PFC, is a region of association cor-
tex known to be involved in higher cognitive functions, such as planning future actions and
decision-making [33]. BAs 44 and 45, include part of the inferior frontal and these regions’
functions are language production, linguistic motor control, sequencing, planning, syntax,
and phonological processing [34, 35].
Finally, the orbitofrontal cortex mostly (BA 47, 10, 11, 13) in the orbitofrontal cortex has been
implicated in processes that involve the motivational or emotional value of incoming informa-
tion, including the representation of primary (unlearned) reinforcers such as taste, smell, and
touch [36, 37], the representation of learnt relationships between arbitrary neutral stimuli and
rewards or punishments [38, 39], and the integration of this information to guide response
selection, suppression, and decision making“ [40, 41].
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2. Structural development of the PFC
2.1. Development in gestational period
In the third week of gestation, the rst brain structure to arise is the neural tube, which is
formed from progenitor cells in the neural plate [42]. In the sixth week, neuron production
begins. Between gestational weeks 13 and 20, neuronal count increases rapidly in the tel-
encephalon [43], with 5.87⋅109 neurons at 20 weeks in the cortical plate and marginal zone
[44]. Through some receptors and ligands, the nerve cells move from the source sites in the
ventricular and subventricular regions to the main sites in the brain. Two basic types of cell
migration, radial and tangential, have been described, and the most characteristic paern
is radial migration. The peak time period with these events is between 12 and 16 weeks of
pregnancy [45, 46].
Cortical organizational events begin in 20 weeks of pregnancy and continues. The basic devel-
opmental paern in the cortical organization includes: (1) neurogenesis and dierentiation
of neurons, (2) formation and organization of cortical neuron layers, (3) dendritic and axonal
branching, (4) formation of synapses, (5) cell death and pruning of synapses, and (6) glial
proliferation and dierentiation [45].
Primary sulci (superior frontal, inferior frontal, and precentral) are the main regions of the
PFC, and develop during gestational weeks 25–26 [42]. The dorsolateral and lateral PFC arise
during gestational weeks 17–25 [47]. The dendrites in Layer III and V continue to mature, as
spines develop, basal dendritic length increases, and interneurons dierentiate in layer IV
between 26 and 34 weeks [48].
Synaptogenesis begins around the 20th gestational week. The formation and organization
of synapses in the PFC increases after birth, reaches a peak, and is followed by pruning and
decline like other neurodevelopmental processes. Also, synaptogenesis occurs later in the
PFC than it does in other areas.
After the other developmental stages, the latest developmental event is myelination [45].
Myelination begins in the 29th gestational week with the brain stem, and the development
of white maer also follows a caudal to rostral progression like gray maer It continues
until adulthood [49]. Figure 1 shows the main developmental stages of brain intrauterine
development.
2.2. Development in infancy
At birth, total brain weight is about 370 g [50]. In a meta-analysis, it is showed that in all PFC
areas, neuronal number measurements increase at every age point postnatally (0–72 months).
Assessing the cortex as a whole, neuronal number increases 60–70% between 24 and 72 months
postnatally [51]. Neuron density is 55% higher in the frontal cortex of 2-year-olds than it is in
adults [52].
Total gray maer volume is also greatest at the earlier stages of infancy. During infancy and
childhood, gray maer volume in the frontal lobe is positively correlated with total brain
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volume, and gray maer ratio with volume shows a decrease with age [53]. Around 6 months
of age, dendritic length is 5–10 times greater than at birth and in the middle frontal gyrus,
dendritic length is half of adult quantities at 2 years of age [54]. In infants, pyramidal neurons
in frontal lobe that mature later, have less complex dendritic trees than regions that mature
early, such as primary sensorimotor cortices [11].
At the age of 3 months, synaptic density in the PFC is less than half of what it will eventually
reach, and synaptic density in the PFC reaches the net highest value at age 3.5 years, showing
a level approximately 50% greater than that in adults [55]. White maer volume also increases
from infancy and it is 74% higher in mid-adolescence than infancy [56].
2.3. Development in early childhood
The neuroanatomical structure of the PFC in humans undergoes maturation particularly dur-
ing early childhood. During this period, the brain quadruples in size and grows to approxi-
mately 90% of the adult volume at age 6. The gray maer increases from early childhood until
the age of 6–9 [56]. Neuronal density in layer III of the PFC decreases with age between 2 and
7 years, from 55% to about 10% higher in 7-year-olds than in adults [52].
Synaptic density in the PFC decreasing more and more through adolescence [55]. During early
childhood, expansion of the dendritic trees of the pyramidal neurons has also been observed [57].
The results of fMRI studies in children suggested that the PFC of children aged 5 years, is also
active during performance of the same task as that for the adults. The region and character-
istics of the activity are similar in adults and children, but comprehensive comparison could
not be done due to technical limitations [58].
Figure 1. Timeline of brain development.
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2.4. Development in childhood and adolescence
During childhood and adolescence, both growth and then decline in gray maer volume,
and increase in white maer volume are observed in brain development. In the longitudinal
study of Giedd et al. across ages 4–22, showed that gray maer in the frontal lobe increases
in volume during preadolescence including early childhood [59]. However, several studies
have reported that during preadolescence, the increase in gray maer volume is observed
especially in the PFC among other frontal lobe regions [60]. Inside of the frontal lobe, gray
maer in the precentral gyrus develops the earliest, and the superior and inferior frontal
gyri mature later. The ventromedial areas commonly reach maturity earlier than more lateral
regions as well [9]. The rostral PFC develops more slowly than other regions, maturing into
late adolescence and beyond [61]. Additionally, the development of the dendritic systems in
rostral PFC matures later than in primary sensory and motor regions, and continue maturing
until late adolescence [11]. Regions in the PFC that intercommunicate with Broca’s area show
an increase in gray maer thickness relative to other regions at between the ages of 5 and
11, it is thought to be associated with the maturation of linguistic capacity [62]. Gray maer
volume reaches maximum volume in most of the frontal lobe between 11 and 12 ages [59].
The dorsolateral and medial PFC also expands nearly twice [63] and the dorsolateral PFC
reaches adult grades of cortical thickness in early adolescence [8]. However, according to
cerebral energy metabolism studies, lateral regions of the PFC and frontal pole mature earlier
than the most anterior regions [64]. When the brain increases in size throughout childhood
and adolescence, dendritic and axonal growth and synaptogenesis also occur such as many
other microstructural changes [51]. Adult neuronal density in the frontal lobe is reached by
10 years of age [52]. Pyramidal neurons in frontal lobe that mature later and they have the
most complex dendritic trees in adolescence and adulthood [10].
Moreover, reduction in gray maer volume and synapse elimination continues in the PFC
until adolescence and early adulthood [65]. The gray maer density in rostral PFC observed a
reduction in between adolescence (12–16 years) and adulthood (23–30 years) like as other pre-
frontal regions [65]. Although this decrease in gray maer volume in childhood is correlated
with age, one study showed that gray maer decreasing in the frontal lobe is signicantly and
positively associated with verbal memory abilities, independent of the age of the child [53].
In addition, as gray maer volume declines during childhood and adolescence, cross-sec-
tional and longitudinal studies have reported that white maer volume in the PFC increases
signicantly as ber tracts grow and myelinate during childhood [49, 59]. From ages 7 to 16,
the frontal lobe experiences an increase in white maer volume [53]. In the white maer, it
was found that diusion along ber tracks was more and more anisotropic with age (range
6–19 years) in a number of prefrontal regions, including right lateral, and medial, rostral PFC
[66]. White maer is primarily constituted of axons covered in myelin produced by oligo-
dendrocytes, and myelination increases nerve transmission rapidity [67], thereby, reduces
the eects of travel distance variability in networks and facilitating synchronous impulsion
of neurons [68]. For this reason, increase in white maer volume in the PFC and distributed
networks, may provide a structural basis for cognitive functions [69]. Additionally, macro
and microstructural changes in gray and white maer both continue during developmen-
tal process, even after adolescence, and these structural changes are parallel to behavioral
changes [70].
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The myelination of the frontal lobe can continue into the 3rd decade of life [71]. The anterome-
dial aspect of the frontal lobe is one of the last regions, to myelinate postnatally [72].
When reviewed the fMRI studies, many of these studies have reported that the responsible
regions in the PFC show age-related increases in activity through development in school-
age children and adolescents [73–75]. In the Kwon et al. study, they observed an age-related
linear increase in activity in the lateral PFC during the n-back working memory task from 7
to 22 years of age [73]. In contrast, in the brain regions less critical to the tasks tested has also
been reported age-related decrease in neural activity [75]. These paerns of age-related activ-
ity changes are thought to indicate a developmental shift in functional neural organizations
more focal, ne-tuned systems [76].
3. Cognitive development of PFC
PFC mediate several cognitive abilities and they develop fundamentally during early child-
hood in terms of age-related improvements, and functional neural systems for each function
become more separable through development [58]. In this section, we reviewed cognitive
abilities and their development which are mediated by the PFC.
3.1. Aentional development
The aention properties fall into ve basic categories: alertness, set, spatial aention, sus-
tained aention, and interference control [77].
Although by 3 years of age, children can make the occasional perseverative error; they inhibit
instinctive behaviors well [78]. Improvements in speed and accuracy on impulse control tasks
can be observed up to 6 years of age [78, 79]. However, an increase in impulsivity occurs for a
short period around 11 years of age, children aged 9 years and older are able to monitor and
regulate their actions well [80].
The components of aention seem to develop gradually toward full maturity at about 12 years,
with maximum development between the ages of 6 and 9 [81, 82].
3.2. Memory
Neuropsychological and functional neuroimaging evidence implicated the importance of the
PFC, supports particularly the development of episodic memory [83]. Functional neuroimag-
ing studies consistently show increasing in PFC activation that supports the formation [84]
and retrieval of episodic memories [85].
Although the frontal lobe damage usually does not cause loss of perceptual memory, it does
in some cases especially if the lesion involves the left prefrontal cortex that causes the inability
to encode and retrieve serial tasks [86], stories [87], and verbal material [88]. Particularly, if the
lesion includes the orbitolimbic region, it can cause the presence of spontaneous confabula-
tion and false recall or recognition [87].
Prefrontal Cortex8

In the recent study, the PFC contribution to subsequent memory (SM) in children, adoles-
cents, and young adults was investigated. It is showed that regions in the lateral PFC showed
positive SM eects, whereas regions in the superior and medial PFC showed negative SM
eects. Both positive and negative SM eects increased with age. The magnitude of nega-
tive SM eects in the superior PFC partially mediated the age-related increase in memory.
Functional connectivity between lateral PFC and regions in the medial temporal lobe (MTL)
increased with age during successful memory formation [83]. In the study of Qin et al., they
examined age-related changes in brain activity associated with memory-based arithmetic and
found increased working of memory-based strategies for solving arithmetic problems across
a period of 14 months in children ages 7–9. Paralleling these behavioral ndings, increased
functional connectivity between the lateral prefrontal cortex (IFG/MFG) and the hippocam-
pus was observed [89].
3.3. Working memory
Working memory is the one of neural functions for temporary storage and manipulation of
information [90]. It is necessary for other cognitive functions, such as language comprehen-
sion, reasoning, and learning [91]. Behavioral measures showed that working memory sys-
tems improve fundamentally during early childhood [92].
Kaldy and Sigala [93] observe that 9-month-old infants can integrate the visual features of
an object with its location as part of the content of working memory. On the conclusion of
ndings, they speculate that the early development of the what-where integration in working
memory [93].
Luciana and Nelson’s study showed that in normal children, aged 4–8 years, the prefrontal
working memory system emerges at around the age of 4 and improves between 5 and 7 years
of age [94], and capacity of visual short-term memory increases also substantially between
5 and 11 years of age [95]. Additionally, age-related improvement of working memory for
phonological information has also been observed during early childhood from 4 years of age
[96]. Consistent with these ndings, fMRI studies in children indicated that the lateral PFC
functions in healthy children as young as 4 years, and the neural systems of this area respon-
sible for working memory gradually mature at 4–7 years of age [97]. In conclusion all of them,
the child reaches the mature level of performance by age 10–12 years [77].
In the development of working memory, not only PFC plays role, but also stronger fronto-
parietal connectivity underlies the development of working memory. Edin et al. indicated
that the weak connectivity among subregions of the PFC might also be important for the
functional development of the PFC [98]. It can be summarized that functional maturation of
the PFC is tightly linked to changes in several other brain regions [99].
3.4. Planning
The eective planning is crucial to self-organization and it involves seing a goal, formulating
a checklist of tasks necessary to achieve it, and executing each one until the goal is achieved.
Studies suggest that children and adolescents are identied as decient in planning skills,
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which is not surprising given that executive functions improve especially through adoles-
cence [100, 101]. The failure to formulate plans, especially new plans, is generally accepted as
being a common feature of prefrontal syndromes. Especially, the symptom appears unique to
dysfunction of the prefrontal cortex [77].
Simple planning skills are observed by 4-year-olds [102]. Similarly by 4 years of age children
are skillful of create new concepts [103]. When the aims are made clear, at the age of 6 years
children can make detailed plans [104]. Planning and organizational skills develop rapidly
between 7 and 10 years of age [105] and gradually after into adolescence [102]. Young children
use simple strategies, which are usually ineective but between 7 and 11 years of age strategic
behavior and reasoning abilities become more organized [106]. The planning seems to develop
at about 12 years with the plateau and around 12–13 years of age, regression from conceptual
strategies to piecemeal strategies may occur and it suggesting a developmental period in which
cautious and conservative strategies are preferred. Improving of strategies and decision making
continues during adolescence [107]. Studies have reported improved the planning skills into
the 20s [108, 109]. In addition, the inter-correlations observed between planning skills and other
neuropsychological tasks and IQ, during adolescent development of planning abilities [110].
3.5. Temporal integration
Temporal integration is the ability to organize temporally separate items of perception and
action into goal-directed thinking, speech, or behavior. This ability derives from the joint and
temporally extended operation of aention, memory and planning. In neural terms, it derives
from the cooperation of the prefrontal cortex with other cortical and subcortical regions. In a
study, age-dependent comparisons were made between 9–10- and 13–14-year-olds and these
ndings suggested that children used a similar strategy as adults and indicate a stabilizing
and optimalizing process by the age of approximately 13–14 years with respect to subjective
rhythmization [111].
In conclusion, the temporal integration seem to develop at about 12–13 years as same as
development of working memory and planning [77].
3.6. Inhibitory control
Inhibitory controls the ability to suppress information and actions that are inappropriate
situations and it is important for several cognitive abilities and adaptive behaviors [99]. The
children aged 2.5 years were able to inhibit the prepotent tendency on the spatially incompat-
ible trials and by 3 years, they were correct 90% of the time [112].
Several studies have demonstrated that performance on the cognitive tasks that requires
inhibitory control, improves throughout childhood over the ages of 4 years [6, 99, 109].
The fMRI studies suggest a change in the recruitment of rostral PFC (BA10) in situations of
response inhibition during late childhood and adolescence. An increase in BOLD signal in
this region [113] initially and then a decrease in BOLD signal [114] seems consistent with the
anatomical ndings suggesting that gray maer volumes in the frontal cortex [59].
In summary, the ability inhibitory control develops both anatomically and functionally sig-
nicantly during early childhood.
Prefrontal Cortex10

3.7. Language
The spoken language is based on the exercise of temporal integration and the cognitive func-
tions. For this reason, language has been found to be adversely aected in a variety of ways
by frontal damage [115].
In early childhood, increase in speed and verbal uency of language is observed, particularly
between 3 and 5 years of age [102, 116]. Processing speed and uency continues to improve
during middle childhood [80, 102] with signicant gains in processing speed observed
between 9–10 and 11–12 years [117]. Improvements in eciency and uency occur during
adolescence [107, 117].
However, higher cognitive functions such as language and intelligence continue to develop
into the 3rd decade of life, supported by the lateral prefrontal cortex, which does not seem to
reach full maturity until that time [77].
3.8. Social behavior
Social cognition denes to identify and interpret social signals, and the use of those signals to
guide the exible performance of appropriate social behaviors given in changing situations
[118]. The PFC is connected with several cortical and subcortical regions of the brain, includ-
ing nucleus accumbens (NAc), amygdala, ventral tegmental area (VTA), hypothalamus, and
regions of the cortex involved in processing sensory and motor inputs. PFC is also connected
with which regions known as social brain, so PFC has been played rol in also social behavior
[119, 120]. Many studies have demonstrated the importance of the vmPFC for social motiva-
tion and reward. The vmPFC is also engaged with social acceptance feelings and is activated
learning with cues of related with social reward [121, 122]. The lateral PFC is also a part of a
network that process in the social domain, such as imitation, abstract social reasoning, and
resolving conict in social cues [123].
The mPFC is responsive to social stimuli in developing infants [124]. In particular, the mPFC
activates at the infant with viewing a mothers smile, or hearing infant directed speech [125].
Studies with children and adolescents focus on amygdala and ndings of these studies
showed an association between cerebral maturation and increased regulation of emotional
behavior; the laer mediated by prefrontal systems [126, 127]. In another study, ndings
suggest that the adult brain beer modulated OFC activity based on aention demands,
while the adolescent brain beer modulated activity based on the demands of emotion.
So, if there were no aentional demands, emotional content of the stimuli-induced higher
activity in ACC, OFC and amygdala in the adolescents compared with the adults [128].
These fMRI results show that both the brain’s emotion processing systems develop during
adolescence.
3.9. Theory of mind and mentalizing
Theory of mind (ToM) is the ability of an individual to mean the feelings, motives, opinions,
and emotions of another on the basis of his or her expressions. It is a necessary ability for
meaningful social interaction [77]. Some studies have investigated the development of men-
talizing, which to have been associated with rostral PFC.
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When investigating the development of ToM, children develop an understanding of desires,
goals, and intentions at around 18 months rstly, and then the understanding of many men-
tal states such as wanting, knowing, pretending, or believing is available in implicit form to
2-year-olds. Typical tests of mentalizing develop at about 4 years old in children [129]. At
the age of 6 years, all typically developing children understand the tasks, involving more
complex scenarios [130].
A functional MRI study investigated the development of mentalizing by the task and found
that children (between 9 and 14 years old) engaged frontal regions includes medial PFC and
left inferior frontal gyrus more than adults did in this task [131]. In another study, adolescent
(12–18 years) and adults participants (22–37 years) were scanned with functional MRI and
the results showed that adolescents activated part of the medial PFC more than adults did,
and adults activated part of the right superior temporal sulcus more than adolescents did.
These results suggest that the neural strategy for mentalizing changes between adolescence
and adulthood. Although the same neural network is active, the relative roles of the dier-
ent areas change, with activity moving from anterior (medial prefrontal) regions to posterior
(temporal) regions with age [132].
4. Conclusion
In this chapter, we have aempted to link structural and functional ndings of developmental
studies to PFC. Our knowledge and understanding of the neural mechanisms, a growing
body of evidence, point to the PFC as a central regulator. The review of the developmental
literature indicates that, in the child, the cognitive and emotional functions of the prefrontal
cortex develop in apparent synchrony with its structural maturation. The long-term develop-
ment of executive functions is likely to be aligned with neurophysiological changes, particu-
larly synaptogenesis and myelination in the prefrontal cortex.
All of cognitive functions seem to reach a relative plateau of maturity at about the age of
12 years. For example, development of aention reach maturity at about age 12, Working
memory and planning seem to develop also at the same pace and toward the same plateau
(about 12 years). Temporal integration development depends on both working memory and
planning and it develops at the same time with the others. However, higher cognitive functions
such as language and intelligence continue to develop into the third decade of life. In sum-
mary, these functions develop gradually, between 5 and 10 years of age, to reach completion
at about age 12.
In the future, longitudinal studies will be required to verify our understanding of cognitive
development. With the structural and functional neuroimaging studies, we are now in the
position to concurrently track the development of neural systems and cognitive functioning,
greatly enhancing our understanding of brain-behavior relationships.
It is known that abnormalities of PFC is associated with many of psychiatric disorders such
as aention decit and hyperactivity disorder, schizophrenia, obsessive compulsive disorder,
Prefrontal Cortex12

depression, autism, etc. As we know more about the prefrontal cortex, we think that we could
beer understand these psychiatric disorders and could develop new treatment options.
Author details
Merve Cikili Uytun
Address all correspondence to: mervecikili@yahoo.com
Department of Child and Adolescent Psychiatry, Kayseri Training and Research Hospital,
Kayseri, Turkey
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