Pediatric Generalized
Anxiety Disorder
Andel V. Nicasio, MSEd
University of Central Florida
7936 Child Psychopathology
October 23, 2013
Aims of this presentation
1.
2.
3.
4.
5.
Illustrate the historical evolution of Generalized Anxiety
Disorder (GAD)
Review the DSM-5 taxonomy for GAD
Explain etiology, onset, prevalence and course of GAD
Review the main theoretical and conceptual models of
GAD
Present a new theoretical model for pediatric GAD
Aim 1
•
Illustrate the historical evolution of
Generalized Anxiety Disorder (GAD)
Nosology and Historical Developments


18th Century - Anxiety was considered a medical illness (Berrios, 1996).
19th Century - Freud viewed Anxiety as resulting from sexual libido
unable to find discharge either because of inadequate sexual activity or
by inhibitions due to repression (Haggard et al. 2008).



Distinguished between Anxiety Neurosis from Neurasthenia, a condition first
described by George Beard in 1868.
Neurasthenia at the time was a common diagnosis that broadly included anxiety
symptoms among other symptoms (e.g., easy fatigability), many of which are now
characteristics of chronic fatigue syndrome.
Later, Freud modified his theory - “Anxiety was more closely related to
fear, occurring in response to perceived dangers, either external or
internal. This led to focus on the ego, one of whose functions is to
anticipate and negotiate danger situations” (Haggard et al. 2008 , p. 471).
GAD in the DSM
DSM-I
Anxiety Reaction
DSM-II
Anxiety Neurosis
DSM-III
GAD
(1 month duration)
Panic Disorder
DSM-IV
GAD
(6 month duration)
Includes Overanxious
Disorders of
Childhood
Anxiety Disorders
NOS
Diagnostic criteria for GAD in DSM-III
A - Generalized persistent anxiety is manifested by symptoms from three of the following four
categories:
(1) Motor tension: shakiness, jitteriness, jumpiness, trembling, tension, muscle aches, fatigability,
inability to relax, eyelid twitch, furrowed brow, strained face, fidgeting, restlessness, easy
startle
(2) Autonomic hyperactivity: sweating, heart pounding or racing, cold, clammy hands, dry
mouth, dizziness, light-headedness, paresthesias (tingling in hands or feet), upset stomach, hot
or cold spells, frequent urination, diarrhea, discomfort in the pit of the stomach, lump in the
throat, flushing, pallor, high resting pulse and respiration rate
(3) Apprehensive expectation: anxiety, worry, fear, rumination, and anticipation of misfortune
to self or others
(4) Vigilance and scanning: hyperattentiveness resulting in distractibility, difficulty in
concentrating, insomnia, feeling “on edge,” irritability, impatience
B - The anxious mood has been continuous for at least one month.
C - Not due to another mental disorder, such as a depressive disorder or schizophrenia.
D - At least 18 years of age
Diagnostic criteria for GAD in DSM-III-R
A - Unrealistic or excessive anxiety and worry (apprehensive expectation) about two or more life circumstances, e.g.,
worry about possible misfortune to one’s child (who is in no danger) and worry about finances (for no good reason), for a
period of six months or longer, during which the person has been bothered more days than not by these concerns. In
children and adolescents, this may take the form of anxiety and worry about academic, athletic, and social performance.
B - If another Axis I disorder is present, the focus of the anxiety and worry in A is unrelated to it, e.g., the anxiety or
worry is not about having a panic attack (as in panic disorder), being embarrassed in public (as in social phobia), being
contaminated (as in OCD), or gaining weight (as in anorexia nervosa).
C - The disturbance does not occur only during the course of a mood disorder or a psychotic disorder.
D - At least 6 of the following 18 symptoms are often present when anxious (do not include symptoms present only during
panic attacks):
Motor tension - (1) trembling, twitching, or feeling shaky; (2) muscle tension, aches, or soreness; (3) restlessness; (4)
easy fatigability.
Autonomic hyperactivity - (5) shortness of breath or smothering sensations; (6) palpitations or accelerated heart
rate (tachycardia); (7) sweating, or cold clammy hands; (8) dry mouth; (9) dizziness or lightheadedness; (10) nausea,
diarrhea, or other abdominal distress; (11) flushes (hot flashes) or chills; (12) frequent urination; (13) trouble
swallowing or “lump in throat”.
Vigilance and scanning - (14) feeling keyed up or on edge;(15) exaggerated startle response; (16) difficulty
concentrating or “mind going blank” because of anxiety; (17) trouble falling or staying asleep; (18) irritability.
E - It cannot be established that an organic factor initiated and maintained the disturbance, e.g., hyperthyroidism,
caffeine intoxication.
DSM-III-R

Motor tension
(1) trembling, twitching, or feeling shaky
(2) muscle tension, aches, or soreness
(3) restlessness
(4) easy fatigability

Autonomic hyperactivity
DSM-IV
(1) restlessness or feeling keyed up or on edge
(2) being easily fatigued
(3) difficulty concentrating or mind going blank
(4) irritability
(5) muscle tension
(5) shortness of breath or smothering sensations
(6) sleep disturbance (difficulty falling or
(6) palpitations or accelerated heart rate (tachycardia)
staying asleep, or restless unsatisfying sleep)
(7) sweating, or cold clammy hands
(8) dry mouth
(9) dizziness or lightheadedness
(10) nausea, diarrhea, or other abdominal distress
(11) flushes (hot flashes) or chills
(12) frequent urination
(13) trouble swallowing or “lump in throat”
Vigilance and scanning
(14) feeling keyed up or on edge
(15) exaggerated startle response
(16) difficulty concentrating or “mind going blank” because of anxiety
(17) trouble falling or staying asleep
(18) irritability
Aim 2
•
Review the DSM-5 taxonomy for GAD
•
DSM-5 GAD Model
What is Generalized Anxiety Disorder?
DSM-5 Taxonomy of GAD
A. Excessive anxiety and worry (apprehensive expectation), occurring
more days than not for at least 6 months, about a number of events or
activities (such as work or school performance).
B. The individual finds it difficult to control the worry.
C. The anxiety and worry are associated with three (or more) of the
following six symptoms (with at least some symptoms having been
present for more days than not for the past 6 months):
Note: only one item is required for children.
1. Restlessness or feeling keyed up or on edge
2. Being easily fatigued
3. Difficulty concentrating or mind going blank
4. Irritability
5. Muscle tension.
6. Sleep disturbance (difficulty falling or staying asleep, or restless, unsatisfying sleep)
DSM-5 Taxonomy of GAD
D. The anxiety, worry, or physical symptoms cause clinically
significant distress or impairment in social, occupational, or
other important areas of functioning.
E. The disturbance is not attributable to the physiological effects
of a substance (e.g., a drug of abuse, a medication) or
another medical condition (e.g., hyperthyroidism).
F. The disturbance is not better explained by another mental
disorder (e.g. anxiety or worry about having panic attacks in panic disorder, negative
evaluation in social anxiety disorder [social phobia], contamination or other obsessions in
OCD, separation from attachment figures in SAD, reminder of traumatic events in PTSD,
gaining weight in anorexia nervosa, physical complains in somatic symptom disorder,
perceived appearance flaws in body dysmorphic disorder, having a serious illness in illness
anxiety disorder, or the content of delusional beliefs in schizophrenia or delusional disorder).
GAD in the DSM-5

Children with GAD tend
to worry excessively about
their competence or the
quality of their
performance. During the
course of the disorder, the
focus of worry may shift
from one concern to
another.
Associated Features Supporting Dx





Muscle tension – trembling, twitching, feeling
shaky, and muscle aches or soreness.
Somatic symptoms – sweating, nausea, diarrhea
Exaggerated startle response
Symptoms of autonomic hyperarousal – (e.g.
accelerated heart rate, shortness of breath,
dizziness) are less prominent than in panic
disorder.
Other conditions associated with stress (e.g.
irritable bowel syndrome, headaches) frequently
accompany GAD.
GAD Prevalence

12-month prevalence is 0.9% among adolescents and 2.9% among
adults in the general community of U.S.

In other countries, the 12-month prevalence is 0.4% - 3.6%.

Lifetime morbid risk is 9.0%



Prevalence of diagnosis peaks in middle age and declines across the
later years in life.
European-descent individuals tend to experience GAD more frequently
than non-European descent (i.e., Asian, African, Native American and Pacific
Islander).
Persons from developed countries are more likely to report that they
have experience GAD than those from nondeveloped countries.
Onset and Course of GAD

Many people with GAD report that they have
felt anxious and nervous all of their lives.

The median age at onset is 30 y/o.

Age at onset is spread over a broad range.



Symptoms of worry and anxiety may occur
early in life, but are then manifested as an
anxious temperament.
Symptoms tend to be chronic and wax and
wane across lifespan, fluctuating from
syndromal to subsyndromal forms of disorder.
Rates of full remission are very low.
Gender Differences and Comorbidity


More frequently diagnosed in females (55-60%) than males. In
epidemiological studies 2/3 are females.
Female and males appear to have the same symptoms, but present
different patterns of comorbidity.
Females - Comorbidity confined to anxiety
disorders and unipolar depression.
Males - Comorbidity more likely to extend to
substance abuse disorders.


Comorbidity – People with GAD are likely to have met, or currently
meet, criteria for other anxiety and unipolar depression disorder.
Comorbidity with substance abuse, conduct, psychotic,
neurodevelopmental, and neurocognitive disorders LESS common.
GAD Risk and Prognosis Factors

Temperamental – Behavioral inhibition,
negative affectivity (neurotism), and harm
avoidance have been associated with GAD.

Environmental – No environmental factors have
been identified as specific to GAD or necessary
or sufficient for making the diagnosis.

Genetic and physiological – 1/3 of the risk
of experiencing generalized anxiety disorder is
genetic, and these genetic factors overlap with
the risk of neurotism and are shared with other
anxiety and mood disorders, particularly MDD.
Culture




Considerable cultural variation in the
expression of GAD.
In some cultures somatic symptoms
predominate, but in other cultures cognitive
symptoms predominate.
Cultural expressions are more evident in
the initial presentation; over time more
symptoms tend to be reported.
Important to consider the social and cultural
context when evaluating whether worries
about certain situations are excessive.
Differential Diagnosis
Other Disorders
GAD
Social Anxiety Disorder
Often have anticipatory anxiety focused
on upcoming social situations in which
they must perform or be evaluated by
others
People with GAD worry whether or
not they are being evaluated.
Obsessive-Compulsive Disorder
The obsessions are inappropriate ideas
that take the form of intrusive and
unwanted thoughts, urges, or images.
Focus of worry is about
forthcoming problems and it is the
excessiveness of the worry about
future events that is abnormal.
DSM-5 Model
Aim 3
•
Literature Review of Pediatric GAD
Prevalence


Anxiety is the most common mental disorder in children and
adolescents (Anderson et al. 1987).
Prevalence rates range from 6% to 20% (Costello et al. 2004).
Generalized Anxiety Disorder


In community samples, prevalence rates range from 0.1%
(Merikangas et al., 2010) to 3.3% (Kessler et al., 2005).
In clinical samples, prevalence rates range from 3%
(Chorpita et al., 2005) to 15% (Ebesutani et al., 2010).
Comorbidity


Isolated cases of “pure” anxiety disorders (no co-occurring dx) are
relatively rare (Comer & Olfson, 2010).
About 70–80% with a lifetime anxiety disorder and 60–90% with
an anxiety disorder in the past year meet criteria for at least one
additional disorder (Kessler et al. 2006, Lampe et al. 2003, Jacobi et al. 2004,
Torres et al. 2008).

Individuals with SP, GAD, and SAD are at 15, 9, and 6 times
increased odds, respectively, for having a co-occurring anxiety
disorder (Grant et al. 2005, Stinson et al. 2007, Ruscio et al. 2008).
Cont… Comorbidity

Those diagnosed with 12-month GAD, SAD, and SP are at
19, 5, and 3 times increased odds, respectively, for having
a co-occurring mood disorder (Merikangas et al. 2002, Grant et al.
2005, Stinson et al. 2007).


GAD or SP are at greatest risk for co-occurring bipolar
disorder.
In cases of co-occurring anxiety and mood disorders, onset
of anxiety disorders typically occurs prior to mood disorders
(Brady & Kendall,1992)
Rate and comorbidity
GAD - Lifetime Prevalence
GAD Comorbidity
Walkup, J. T. et al (2008) - Child-Adolescent Multimodal Treatment Study: GAD was the most common disorder;
however, GAD, SAD, and SoP were highly comorbid.
GAD Comorbidity
Separation Anxiety Disorder
Social Phobia
Generalized Anxiety Disorder
Walkup, J. T. et al (2008)
Onset

Among all Anxiety Disorders, GAD has the latest mean and median
age at onset (early 30s) (Grant et al. 2005, Kessler et al. 2005, Lieb et al.
2005).

However, substantial numbers of children and adolescents do meet full
criteria (Albano & Hack 2004 , Comer et al. 2004 , Robin et al. 2005 , Alyahri &
Goodman 2008).



In community samples, 0.1% for children 8-11 y/o and 1.1% for
adolescents 12-15 y/o (Merikangas et al. 2010); 8.6% for 8 y/o and
17.1% for 17 y/o (Kashani and Orvaschel, 1990).
The onset of GAD may be gradual or sudden and, unsurprisingly,
symptoms are often exacerbated by stress (Rapoport & Ismond, 1996)
Early GAD onset is associated with greater excessiveness and
uncontrollability of worry, as well as a more chronic course with more
severe life impairment (Ruscio et al. 2005 ).
Gender



Gender differences in the prevalence of GAD in children and
adolescents are inconsistent.
Merikangas et al. (2010) reported no gender differences in a
sample of 8–15-year-olds, using the DSM-IV
In another study, girls (of all ages) were found to have higher
rates than boys (15 % of girls and 9 % of boys (Kashani et al.,
1990).


Clinical samples have reported no gender differences in GAD
in children 9–13 years of age (Last et al., 1992).
With respect to symptoms of GAD and/or worry, females
report more GAD symptoms than males.
Course




GAD, phobias, panic disorder, and depressive disorders
predicted each other over time, and early-onset GAD was a
stronger predictor of later anxiety rather than depressive
disorders.
Predictors of GAD onset over time - Parental GAD and
depression, childhood behavioral inhibition, childhood
separation events, and parental overprotection.
GAD was associated with the personality trait “reward
dependence” (based on self-reported personality) and
dysfunctional family functioning.


Community sample; N= 3,021;
14–24 years at time 1) for 10 years.
Bessdo et al., 2010
Race/Ethnicity



Lower lifetime rates of anxiety disorders among immigrants
than among US-born natives of the same national origins (Vega
et al. 1998 , Grant et al. 2004).
Early age at immigration and longer duration residing in the
USA are both associated with increased risk for mental disorders among immigrants relative to natives (Breslau et al. 2007).
A epidemiological survey conducted in South Africa revealed
that rates of GAD were significantly higher in men than women
(Bhagwanjee et al. 1998).
Suicidality



Any single anxiety disorder (phobia, GAD, panic disorder) increased
the odds of suicidal ideation by 7.96 times [95% confidence interval
(CI) 5.69–11.13] and increased the rate of suicide attempts by 5·85
times (95% CI 3.66–9.32).
Rates of suicidal behavior increased with the number of anxiety
disorders.
Estimates of the population attributable risk suggested that anxiety
disorders accounted for 7–10% of the suicidality in the cohort.
 Christchurch Health and Development Study (CHDS).
 25-year longitudinal study; over 1000 participants.
 Subjects aged 16–18, 18–21 and 21–25 years.
Boden et al., 2007
Temperament and Genes

Genetic correlations
between GAD and
neuroticism were high
0.80 (95% confidence
interval=0.52–1.00), with
no significant difference
between men and women
(1.00 and 0.58,
respectively) (Hettema et al,
2004).
Bivariate Twin Model for Neuroticism and Generalized Anxiety Disorder
aThe phenotypic correlation is decomposed into the additive genetic correlation (rg) between additive genetic
factors (AN and AG), the common environmental correlation (rc) between common familial environmental factors
(CN and CG), and the individual-specific environmental correlation (re) between individual-specific environmental
factors (EN and EG) for neuroticism and generalized anxiety disorder, respectively.
Temperamental Trait and GAD
Distribution of harm avoidant scores and presence/absence of current DSM-IV GAD in children and adolescents.
Genes and Anxious Brains (Monkeys)
Genes and Anxious Temperament (AT)
Neurological Pathways

Contradictory research findings - Youth with GAD exhibited greater
amygdala volumes (De Bellis, et al., 2000), whereas reduced amygdala
volume was identified in adolescents with GAD, SAD, or SoPh (Milham et
al., 2005).


Patients with GAD fail to engage regulatory regions in response to
heightened displays of amygdala activity resulting from emotional
stimuli (Etkin et al., 2010).
Compared to healthy controls, adolescents with GAD displayed a
relatively weaker negative task-dependent functional connectivity
(TDFC) between the lateral prefrontal cortices and the amygdala
during an emotional attention orienting task (Thomas et al., 2001).

This is consistent with the notion that individuals with anxiety are less able to
regulate neural responses to emotion, even prior to adulthood.
Schematic Framework
Pine, et al 2008
Areas of the Brain Affected by GAD
The noradrenaline pathways in GAD
Noradrenaline Pathways
Serotenergic Pathways
GABAergic pathways
The Septohippocampal Circuit
Fear and Anxiety in the Brain
Networks that Support Negative Reactivity and Regulation
Etkin, A. & Wager, T. D. (2010)
Genes

A meta-analysis of family and twin studies of anxiety disorder
estimated GAD heritability to be 32% (Hettema et al. 2001).
Genes Associated with GAD
Gene Name and Abbreviation
Serotonergic System
Serotonin transporter (SLC6A4 )
Location
17q11.1–q12
Modulation of monoamine metabolism
Monoamine oxidase A (MAOA )
Xp11.4-p11.23
Dopaminergic system
Dopamine transporter (DAT1 )
Regulator of G-protein signaling
Regulator of G-protein signaling 2
(RGS2 )
Studies Supporting the
Association
Ohara et al. 1999
You et al. 2005
Samochowiec et al . 2004
Tadic et al. 2003
p15.3
Rowe et al. 1998
q31
Koenen et al. 2009
Cognitive Symptoms


Worry and the disturbance of mental processes (e.g., thinking,
planning, abstract reasoning, problem solving, and recall)
encompass the cognitive features of anxiety (Kendall et al., 2004).
With GAD, there is an overall attitude of apprehension.
Children and adolescents with GAD are often described as
self-conscious, perfectionistic “worriers” (Beidel, Turner, 2005; Eisen &
Kearney, 1995).
Cognitive Factors

Youth with GAD display problematic cognitive processes
(Ginsburg & Affrunti, 2013).

Youth with GAD are:
more likely to overestimate the negative consequences of
their actions,
 expect negative consequences to occur with greater
frequency,
 overestimate the likelihood of threatening situations,
 interpret ambiguity as threatening, and
 have impaired problem-solving skills

Albano et al., 1996; Bögels et al., 2003; Léger et al., 2003
Attentional Bias


Youth with GAD are more likely to
interpret ambiguous information
as threatening and have an
attentional bias toward
threatening stimuli.
Waters et al. (2008) examined
the attentional bias for angry and
happy faces in 7-12 y/o with
GAD (N= 23) and nonanxious
controls ( N= 25).

Found that GAD severity was
associated with greater attentional
bias toward angry faces.
Mean attention bias scores (+SE) for angry and
happy faces as a function of group
(CON = control; LCA = low clinical anxiety;
HCA = high clinical anxiety).
Attention Orienting


A process that involves focusing one’s
attention on salient stimuli.
Recent RCTs have demonstrated that training
anxious children to modify their attentional
threat biases can facilitate disengagement
of attention to threat, which in turn can
reduce anxiety symptoms (Bar-Haim et al.,2011;
Eldar et al., 2012).

These findings suggest that attention biases
might emerge over time through
reinforcement or as a means to reconcile
ambiguous situations (Field et al., 2010).
Dot-probe paradigm
Threat Learning


Youth with GAD tend to have
difficulties learning to discriminate
threat cues from safety cues, term
Threat Learning.
Threat learning involves correctly
determining what cues and in which
situations indicate potential danger
or safety (Pine et al., 2009; Britton et al.,
2011).

Youth with GAD underestimate their
ability to cope with threatening
events (Weems & Wattas, 2005).
Physiological Symptoms



The physiological element of anxiety revolves around the
biological effects anxiety has on the body.
Physical symptoms generally reflect elevated sympathetic
autonomic nervous system activity and include increased heart
rate and blood pressure, increased muscle tension, muscle
tremor, alterations in salivation and perspiration, bodily
temperature changes, and modifications of stomach gastric
and acidic actions (Beidel & Turner, 2005).
These symptoms are caused by the release of cortisol and
epinephrine in the brain when a threat is detected (Wood &
McLeod, 2008).
Physiological Symptoms

Tracey et al. (1997) found that
youth with GAD endorsed
experiencing several physical
symptoms, including restlessness
(74% of the sample), irritability
(68%), difficulties concentrating
(61%), sleep disturbance (58%)
headaches (36%), muscle tension
(29%), and stomachaches (29%).
Behavioral Symptoms



In GAD, the anxiety and avoidance behavior generalizes to
non-threatening cues; as a result, numerous objects and events
that were previously harmless become cues that evoke anxiety.
In essence, individuals with GAD are in a constant state of
vigilance (Rapoport & Ismond, 1996).
Due to the self-conscious, perfectionistic nature of youth with
GAD, they ask for and require repeated reassurance from
others (Beidel & Turner, 2005; Eisen & Kearney, 1995).
Children and adolescents with GAD usually demonstrate a
rather debilitating restriction of age-appropriate social
functioning and activities (Eisen & Kearney, 1995).
Parenting and Parent-Child Factors

Longitudinal studies suggests a reciprocal relationship: parental
behaviors affect child anxiety and child anxiety symptoms
affect parental behaviors (Wijsbroek et al., 2011; Murray et al., 2008)
Peer Relationship



Children with GAD may be more
selective and may avoid friendships
with `adventurers' or `risk-takers‘ who
are not similarly concerned with rules
and/or about possible injury.
Social activities may be restricted due
to concerns about safety and
performance.
Children with GAD and Healthy Control
group had similar relationships with
peers, with the exception of an overall
reduced number of friends.
Scharfstein, et al. 2011
Aim 4
•
Theoretical Models
Kertz Woodruff-Borden (2010)
Etiological Model of Pediatric GAD
Beck’s Model & Metacognitive Model


Pathological anxiety derives from
the misperception of danger,
resulting from distortions in the way
information is perceived.

Based on cognitive therapy as
applied to appraisal of threat (Beck,
Distinguishes between two types
of worries – type 1 (worries
about everyday events and
physical sensations) and type 2
(worries about – both positive
and negative appraisals of
worrisome activity) (Wells, 1995).
& Emery,1985).

GAD sufferers view the world as a
dangerous place, and in order to avoid
possible danger or to plan ways to deal
with the occurrence of danger, they feel
that it is imperative to constantly scan the
environment for cues of threat.

Beliefs are centered on two
main themes: (1) beliefs about
the uncontrollability of worry,
and (2) beliefs about the
dangerous consequences of
worrying for mental, physical,
and/or social functioning.
Barlow’s Emotion Theory (2002)



GAD is the major feature of all Anxiety
disorders.
Synergy between genetic vulnerability
(genetic contribution) and psychological
vulnerability (diminished sense of control)
Early experiences (uncontrollable or
unpredicted events) plus
overprotective/intrusive/punitive
parenting styles lead to low perception of
control, increased neurobiological activity
and varied somatic outputs.
Barlow’s Model
Translational Development Neuroscience
Figure depicts the time course
of atypical versus typical
development. The red arrow
at an early childhood
indicates a perturbation
followed by an immediate or
later onset trajectory involving
dynamic changes in molecular
systems, information processes
running on hierarchically
distributed neural networks,
and resulting sychopathology,
which when sufficiently altered
(brown circle) comes to clinical
attention.
March, 2011
What is like to live with GAD



Across the anxiety disorders, GAD may be the most profound
and have the most deleterious effect on functioning and healthrelated quality of life (Grant et al. 2005).
Significantly increased risk of impaired social and role
functioning, mental health, and overall physical and mental
well-being (Mendlowicz & Stein 2000; Stein & Heimberg 2004).
Associated with poor marriage stability, as afflicted individuals
are almost twice as likely to have their first marriage end in
divorce (Kessler et al. 1998). Occupational impairment is also
common (Merikangas et al. 2007).
Cost to Society and Individuals with BP



When untreated - reduced quality of
life, including decrements in social
functioning, role functioning, educational
attainment, financial independence, and
mental health (Mendlowicz & Stein 2000).
Associated with decrements in
educational achievement.
Predictor of failure to complete high
school, failure to enter college among
high-school completers, and failure to
complete college among college entrants
(Kessler et al. 1995).
Aim 5
•
Present a new theoretical model for pediatric
bipolar disorder
Generalized Anxiety Disorder Model
Nicasio, A. (2013)
References




Albano, A. M., & Hack, S. (2004). Children and adolescents. In R. G. Heimberg, C. L. Turk, & D.S. Mennin (Eds.). Generalized Anxiety Disorder: Advances in
Research and Practice. New York, NY: Guilford.
Albano, A. M., Chorpita, B. F., Barlow, D. H. (2006). Childhood anxiety disorders. In: Mash, E. J., Barkley, R. A., Mash, E. J., Barkley, R. A., (Eds). Child
psychopathology. New York: Guilford, p. 196–241.
Albano, A. M., Chorpita, B. F., Barlow, D. H. (1996). Childhood anxiety disorders. In: Mash, E. J., Barkley, R. A., Mash, E. J., Barkley, R. A, editors. Child
psychopathology. New York: Guilford; p. 196–241.
Alyahri, A. , & Goodman, R. (2008). The prevalence of DSM-IV psychiatric disorders among 7–10 year old Yemini schoolchildren. Social Psychiatry and Psychiatric
Epidemiology, 43, 224–2.

American Psychiatric Association (1952). Diagnostic and Statistical Manual of Mental Disorders(DSM-I). Washington, DC : APA.

American Psychiatric Association (1968). Diagnostic and Statistical Manual of Mental Disorders, 2nd ed. (DSM-II). Washington, DC: APA.

American Psychiatric Association (1980). Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. (DSM-III). Washington, DC: APA.

American Psychiatric Association (1987). Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised (DSM-III-R). Washington, DC : APA

American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV). Washington, DC: APA.

American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision (DSM-IV-TR). Washington, DC: APA.

American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders, 5th ed., text revision (DSM-5). Washington, DC: APA.









Anderson, J. C., Williams, S., McGee, R., & Silva, P. (1987). DSM-III disorders in preadolescent children: Prevalence in a large sample from the general population.
Archives of General Psychiatry, 44, 69-76.
Barlow, D. H. (2002). Anxiety and its disorders. The nature and treatment of anxiety and panic (2nd Ed.) New York: Guilford Press.
Bar-Haim, Y., Morag, I., Glickman, S. (2011). Training anxious children to disengage attention from threat: a randomized controlled trial. J Child Psychol Psychiatry.
52(8), 861–9. Epub 2011/01/22. 57.
Bhagwanjee, A., Parekh, A., Paruk, Z. et al (1998). Prevalence of minor psychiatric disorders in an adult African rural community in South Africa. Psychological
Medicine, 28, 1137-1147.
Beck, A.T., & Emery, G. (1985). Anxiety disorders and phobias: A cognitive perspective. New York: Basic Books.
Beesdo, K., Pine, D. S., Lieb, R., Wittchen, H. (2010). Incidence and risk patterns of anxiety and depressive disorders and categorization of generalized anxiety
disorder. Arch Gen Psychiatry, 67(1), 47–57.
Beesdo, K., Pine, D.S., Lieb, R. & Wittchen, H.U. (2010). Incidence and Risk of Patterns of Anxiety and Depressive Disorders and Categorization of Generalized
Anxiety Disorder. Archives of General Psychiatry, 67, 47–57.
Beidel, D. C. & Turner, S. M. (2005). Childhood Anxiety Disorders: A Guide to Research and Treatment. Routledge, Taylor & Francis Group, New York.
Berrios, G. E. (1996). The history of mental symptoms: Descriptive psychopathology since the nineteenth century. Cambridge University Press. Cambridge England
and New York, NY, USA.
References
















Boden, J., Fergusson, D. M., & Horwood, L. J. (2007). Anxiety disorders and suicidal behaviours in adolescence and young adulthood: findings from a longitudinal
study. Psychological Medicine, 37(3), 431-440.
Bögels, S. M., Snieder, N., Kindt, M., (2003). Specificity of dysfunctional thinking in children with symptoms of social anxiety, separation anxiety and generalised
anxiety. Behav Change, 20(3):160–9.
Brady, E. U. , & Kendall P. C. (1992). Comorbidity of anxiety and depression in children and adolescents. Psychological Bulletin, 111, 244 –25.
Breslau, J., Aguilar-Gaxiola, S., Borges, G., et al. (2007). Risk for psychiatric disorder among immigrants and their US-born descendants: Evidence from the
National Comorbidity Survey Replication. Journal of Nervous and Mental Disease, 195, 189–195.
Britton, J. C., Lissek, S., Grillon, C., Norcross, M. A., Pine, D.S. (2011). Development of anxiety: the role of threat appraisal and fear learning. Depress Anxiety.
28(1), 5–17.
Chorpita, B. F., Moffitt, C. E., Gray, J. (2005). Psychometric properties of the revised child anxiety and depression scale in a clinical sample. Behav Res Ther.
43(3), 309–22.
Comer, J. S. , & Kendall, P. C. (2004). A symptom-level examination of parent–child agreement in the diagnosis of anxious youths. Journal of the American
Academy of Child and Adolescent Psychiatry, 43, 878 –88.
Costello, E. J., Mustillo, S., Erkanli, A., Keeler, G., & Angold, A. (2003 ). Prevalence and development of psychiatric disorders in childhood and adolescence.
Archives of General Psychiatry, 60, 837 –844.
CNSforum Image Bank: Anxiety – GAD- generalised anxiety disorder. Retrieved on 10/20/2013 from
http://www.cnsforum.com/imagebank/section/neurochemical_pathways_GAD/default.aspx
CNSforum. The septohippocampal circuit. In L’Encephale 1983; IX, 161B-166B. Retrieved on 10/23/2013 from
http://www.cnsforum.com/imagebank/item/septotohippo_circ/default.aspx
CNSforum. The areas of the brain affected in generalised anxiety disorder (advanced). In J Clin Psychiatry 2001, 62(11), 22-27. Retrieved on 10/20/2013
from http://www.cnsforum.com/imagebank/item/Neuro_biol_GAD_2/default.aspx
CNSforum. Anxiolytics and sedative-hypnotics. In: Essential Psychopharmacology. Neuroscientific basis and practical applications. Stahl S. Cambridge, UK: Cambridge
University Press, 1996 167–215. Retrieved on 10/20/2013: http://www.cnsforum.com/imagebank/item/Neuro_path_N_GAD/default.aspx
De Bellis, M. D., Casey, B. J., Dahl, R. E., Birmaher, B., Williamson, D. E., Thomas, K. M., et al. (2000). A pilot study of amygdala volumes in pediatric generalized
anxiety disorder. Biol Psychiatry, 48(1), 51–7. Epub 2000/07/29.33.
Ebesutani, C., Bernstein, A., Nakamura, B. J., Chorpita, B. F., Weisz, J. R. (2010). A psychometric analysis of the revised child anxiety and depression scale-parent
version in a clinical sample. J Abnorm Child Psychol. 38(2), 249–60.
Eisen, A. R. & Engler, L. B. (2007). Helping Your Socially Vulnerable Child: What to do when your child is Shy, Socially Anxious, Withdrawn or Bullied. New
Harbinger Publications.
Eisen, A. R. & Kearney, C. A. (1995). Practicioner’s guide to treating fear and anxiety in children and adolescents: A cognitive-behavioral approach. Northvale,
NJ: Aronson.
References
















Eldar, S., Apter, A., Lotan D., Perez-Edgar, K., Naim , R. Fox, N. A., Pine, D. S., Bar-Haim, Y. (2012). Attention bias modification treatment for pediatric
anxiety disorders: a randomized controlled trial. Am J Psychiatry, 169, 213–220.
Etkin, A., Prater, K. E., Hoeft, F., Menon, V., Schatzberg, A. F. (2010). Failure of anterior cingulate activation and connectivity with the amygdala during implicit
regulation of emotional processing in generalized anxiety disorder. Am J Psychiatry, 167(5), 545-54.
Etkin, A., & and Wager, T. D. (2010). “Brain systems underlying anxiety disorders: a view from neuroimaging", Anxiety Disorders. 1st ed. Cambridge: 2010.
192-203. Cambridge Books Online. Web. 10 October 2013. http://dx.doi.org/10.1017/CBO9780511777578.019
Field, A. P., Lester, K. J. (2010). Is there room for ‘development’ in developmental models of information processing biases to threat in children and adolescents?
Clin Child Fam Psychol Rev., 13(4), 315–32.
Grant, B. F. , Hasin, D. S., Stinson, F. S., et al. (2005). Prevalence, correlates, co-morbidity, and comparative disability of DSM-IV generalized anxiety disorder
in the USA: results from the National Epidemiologic Survey on Alcohol and Related Conditions . Psychological Medicine, 35, 1747 –1759.
Grant, B. F., Stinson, F. S., Hasin, D. S., et al. (2004). Immigration and lifetime prevalence of DSM-IV psychiatric disorders among Mexican Americans and nonHispanic whites in the United States: results from the National Epidemiologic Survey of Alcohol and Related Conditions. Archives of General Psychiatry, 61, 1226
–1233.
Ginsburg, G. S. & Affrunti, N. W. (2013). Generalized Anxiety Disorder in Children and Adolescents. R.A. Vasa and A. K. Roy (Eds), Pedriatric Anxiety
Disorders: A clinical guide, Current Clinical Psychiatry, 71-90, Springer Science+Business Media, New York.
Haggard, P., Furman, A., Levy, S. T., et al. (2008). Psychoanalytic theories. In Tasman, A., Kay, J., Lieberman, J., First, M., & Maj, M., eds., Psychiatry, 3rd edn.
Chichester : Wiley , pp. 464–485.
Hans-Ulrich, W. & Jürgen, H. (2001). Generalized Anxiety Disorder: Nature and Course. J Clin Psychiatry, 62(11), 15–19.
Hettema, J. M., Prescott, C. A. & Kendler, K. S. (2004) Genetic and environmental sources of covariation between generalized anxiety disorder and neuroticism.
American Journal of Psychiatry, 161, 1581-1587.
Jacobi F., Wittchen, H. U., Holting, C., et al. (2004). Prevalence, comorbidity and correlates of mental disorders in the general population: results from the
German Health Interview and Examination Survey (GHS). Psychological Medicine, 34, 597 –61.
Kashani, J. H., & Orvaschel, H. (1990). A community study of anxiety in children and adolescents. Am J Psychiatry, 147(3), 313–8.
Kendall, P.C., Safford, S., Flannery-Schroeder, E., & Webb, A. (2004). Child anxiety treatment: Outcomes in adolescence and impact on substance use and
depression at 4 year follow-up. Journal of Consulting and Clinical Psychology, 72, 276–287.
Kessler, R. C., Chiu, W. T., J i n , R . , et al. (2006). The epidemiology of panic attacks, panic disorder, and agoraphobia in the National Comorbidity Survey
Replication. Archives of General Psychiatry, 63, 415 –42.
Kessler, R. C., Berglund, P., Demler, O., et al. (2005). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity
Survey Replication. Archives of General Psychiatry, 62, 593 –60.
Kessler, R. C., Walters, E. E., Forthofer, M. S. (1998). The social consequences of psychiatric disorders, III: Probability of marital stability. Arch Gen Psychiatry,
155, 1092–1096.
References





Kertz, S. J., Woodruff-Borden, J. (2011). The developmental psychopathology of worry. Clin Child Fam Psychol Rev, 14(2), 147–97.
Lampe, L., Slade, T., Issakidis, C., & Andrews, G. (2003). Social phobia in the Australian National Survey of Mental Health and Well-Being. Psychological
Medicine, 33, 637-646.
Last, C. G., Perrin, S., Hersen, M., Kazdin, A. E. (1992). DSM-III-R anxiety disorders in children: sociodemographic and clinical characteristics. J Am Acad Child
Adolesc Psychiatry, 31(6), 1070–6.
Lau, J. Y., Lissek, S., Nelson, E. E., Lee, Y., Roberson-Nay, R., Poeth, K., et al. (2008). Fear conditioning in adolescents with anxiety disorders: results from a novel
experimental paradigm. J Am Acad Child Adolesc Psychiatry, 47(1), 94–102.
Léger, E., Ladouceur, R., Dugas, M. J., Freeston, M. H. (2003). Cognitive-behavioral treatment of generalized anxiety disorder among adolescents: a case series.
J Am Acad Child Adolesc Psychiatry, 42(3), 327–30.

Lieb, R., Becker, E., & Altamura, C. (2005). The epidemiology of generalized anxiety disorder in Europe. European Neuropsychopharmacology, 15, 445–452.

March, J. S. (2011). Looking to the future of research in pediatric anxiety disorders. Depression and anxiety, 28, 88–98.

Mendlowicz, M. V. & Stein, M. B. (2000). Quality of life in individuals with anxiety disorders. Am J Psychiatry, 157(5), 669-82.









Merikangas, K. R., He, L. P., Burstein, M., Swanson, S.A., Avenevoli, S. Cui, L., . . . Swendsen, J. (2010). Lifetime prevalence of mental disorders in U.S.
adolescents: results from the National Comorbidity Survey Replication-Adolescent Supplement (NCS-A). J Am Acad Child Adolesc Psychiatry, 49(10), 980-9.
Merikangas, K. R., Avenevoli, S., Acharyya, S., Zhang, H., & Angst, J. (2002). The spectrum of social phobia in the Zurich Cohort Study of Young Adults.
Biological Psychiatry, 51, 81 –91.
Merikangas, K. R., Ames, M., Cui, L., Stang, P. E., Ustun, T. B., Von Korff, M., Kessler, R. C. (2007). The impact of comorbidity of mental and physical conditions on
role disability in the US adult household population. Arch Gen Psychiatry, 64(10), 1180-8.
Milham, M. P., Nugent, A. C., Drevets, W. C., Dickstein, D. P., Leibenluft, E., Ernst, M., et al. (2005). Selective reduction in amygdala volume in pediatric anxiety
disorders: a voxel-based morphometry investigation. Biol Psychiatry, 57(9), 961–6.
Murray, L., de Rosnay, M., Pearson, J., Bergeron, C., Schofield, E., Royal-Lawson, M., et al. (2008). Intergenerational transmission of social anxiety: the role of
social referencing processes in infancy. Child Dev. 79(4),1049–64.
Oler, J. A., Fox, A. S., Shelton, S. E., Rogers, J. Dyer, T. D., Davidson, R. J., …Kalin, N. H. (2010). Amygdalar and hippocampal substrates of anxious
temperament differ in their heritability. Nature, 466(7308), 864-8.
Pine, D. S. (2009). Integrating research on development and fear learning: a vision for clinical neuroscience? Depress Anxiety, 26(9), 775–9.
Pine, D. S., Guyer, A. E., Leibenluft, E. (2008). Functional magnetic resonance imaging and pediatric anxiety. J Am Acad Child Adolesc Psychiatry, 47(11), 121721.
Pine, D. S., Helfinstein, S. M., Bar-Haim, Y., Nelson, E., Zfox, N. A. (2009). Challenges in developing novel treatments for childhood disorders: lessons from
research on anxiety. Neuropsychopharmacology, 34(1), 213-28.
Rapoport, J., & ismond, D. R. (1996). DSM-IV training guide for diagnosis of childhood disorders. Brunner/Mazel (New York).
References

















Rettew, D. C., Doyle, A. C., Kwan, M., Stanger, C. Hudziak, J. J. (2006). Exploring the boundary between temperament and generalized anxiety disorder: a
receiver operating characteristic analysis. Journal of Anxiety Disorder, 20(7).
Ruscio, A. M., Lane, M., Roy-Byrne, P., et al. (2005). Should excessive worry be required for a diagnosis of generalized anxiety disorder? Results from the U.S.
National Comorbidity Survey Replication. Psychological Medicine, 35, 1761 –1772.
Ruscio, A. M., Brown, T. A., Chiu, W. T., et al. (2008). Social fears and social phobia in the USA: results from the National Comorbidity Survey Replication.
Psychological Medicine, 38, 15 –28.
Scharfstein, L., Alfano, C., beidel, D., Wong, N. (2011). Children with generalized anxiety disorder do not have peer problems, just fewer friends. Child
Psychiatry Hum Dev., 42(6), 712-23.
Stein, M. B. & Heimberg, R. G. (2004). Well-being and life satisfaction in generalized anxiety disorder: comparison to major depressive disorder in a
community sample. J Afffect Disord, 79(1-3), 161-6.
Stinson , F. S. , Dawson , D. A. , Chou , S. P. , et al. (2007). The epidemiology of DSM-IV specific phobia in the USA: results from the National Epidemiologic
Survey on Alcohol and Related Disorders. Psychological Medicine, 37, 1047 –105
Torres, A. R., Prince, M. J., Bebbington, P. E., et al. (2006). Obsessive–compulsive disorder: prevalence, comorbidity, impact, and help-seeking in the British
National Psychiatric Morbidity Survey of 2000. American Journal of Psychiatry, 163, 1978–198.
Thomas, K. M., Drevets, W. C, Whalen, P. J., Eccard, C. H., Dahl, R. E., Ryan, N. D., Casey, B. J. (2001). Amygdala response to facial expressions in children and
adults. Biological Psychiatry, 49, 309–316.
Tracey, S. A., Chorpita, B. F., Douban, J., & Barlow, D. H. (1997). Empirical evaluation of DSM-IV generalized anxiety disorder criteria in children and
adolescents. Journal of Clinical Child Psychology, 26, 404–414.
Vega, W. A., Kolody, B., Aguilar-Gaxiola, S., et al. (1998). Lifetime prevalence of DSM-III-R psychiatric disorders among urban and rural Mexican Americans in
California. Archives of General Psychiatry, 55, 771–7.
Walkup, J. T., Albano, A. M., Piacentini, J., Birmaher, B., Compton, S. N., Sherrill, J. T., Kendall, P. C. (2008). Cognitive behavioral therapy, sertraline, or a
combination in childhood anxiety. New England Journal of Medicine, 359, 2753–2766.
Waters, A. M., Henry, J., Neumann, D. L. (2009). Aversive Pavlovian conditioning in childhood anxiety disorders: impaired response inhibition and resistance to
extinction. J Abnorm Psychol, 118(2), 311–21.
Waters, A. M., Mogg, K., Bradley, B. P., Pine, D. S. (2008). Attentional bias for emotional faces in children with generalized anxiety disorder. J Am Acad Child
Adolesc Psychiatry, 47(4), 435–42.
Weems, C. F. & Watts, S. E. (2005). Cognitive models of childhood anxiety. In: Velotis CM, editor. Anxiety Disorder Research. Nova Science Publishers, Inc.;
Hauppauge, NY, pp. 205–232
Wells, A. (1995). Meta-cognition and worry: A cognitive modelof generalised anxiety disorder. Behavioural and Cognitive Psy-chotherapy, 23, 301-320.
Wijsbroek, S. A., Hale, III, W. W., Raaijmakers, Q. A., Meeus, W. H. (2011). The direction of effects between perceived parental behavioral control and
psychological control and adolescents’ self-reported GAD and SAD symptoms. Eur Child Adolesc Psychiatry, 20(7), 361–71.
Wood, J. J., & McLeod, B. D. (2008). Child anxiety disorders: A family-based treatment manual for practitioners. New York: Norton.