Psychiatry for Neurologists - part 7 pot

DEVELOPMENTAL DISORDERS Pervasive Developmental Disorders/Autistic Disorder The initial description by Leo Kanner in 1943 of children having “come into the world with innate inability to

becomes clear with ongoing maturation, a more persistent pattern of symptoms, or environmental

stabilization ( 1 ).Table 1 outlines the components of a thorough child and adolescent psychiatric ation Components may be added or omitted as clinically appropriate

evalu-Early-onset psychiatric disorders may have a profound effect on development in multiple domains.Social, academic, and adaptive capacities are all vulnerable to disruption which may negatively affectthe child’s ability to function and damage self-esteem Regardless of the etiology of the primary psy-chiatric disorder, the prognosis is multidetermined by biological, social, cultural, familial, economic,and interventional factors Interventions that enhance the compensatory capacities and promote

resilience may markedly improve the child’s long-term functional capabilities and achievements ( 2 ).

DEVELOPMENTAL DISORDERS

Pervasive Developmental Disorders/Autistic Disorder

The initial description by Leo Kanner in 1943 of children having “come into the world with innate

inability to form the usual, biologically provided affective contact with people” ( 3 ) has remained the

Table 1

Essentials of the Child and Adolescent Psychiatric Evaluation

1 History from multiple sources (parents, teachers, pediatrician, child)

a Reason for Referral

b History of Present Illness

c Review of Psychiatric Symptoms

d Prenatal, Developmental and Social History (including obstetrical and birth history, early

temperament, developmental milestones, toilet training, history of trauma or abuse, risk-taking

behaviors, substance abuse, friendships, sexual behaviors, legal difficulties)

e Psychiatry History

f Educational History

g Stress level/psychosocial adversity

h Medical History and Review of systems

i Family psychiatric/medical/genetic history

j Child and Family Strengths and Weaknesses

2 Mental Status Examination

a Appearance and grooming (including tics, mannerisms)

b Speech fluency, volume, rate and language skills

c Ability to cooperate and engage with assessment

d Motor activity level, attention, frustration tolerance, impulsivity

e, Mood and affect, neurovegetative symptoms, manic symptoms

f Psychotic symptoms (hallucinations, delusions, thought disorder)

g Anxiety, fears and phobias, obsessions or compulsions, post-traumatic anxiety

h Oppositionality, conduct symptoms, aggression (verbal or physical)

i Clinical estimate of cognitive skills

j Insight and judgment

3 Screening physical and neurological examination

4 Diagnostic tests, where appropriate

a Lead level

b Thyroid and other screening laboratory tests

c ECG, EEG or neuroimaging procedures as indicated

d Psychoeducational testing to rule out learning disability and intellectual impairment (at times,

neuropsychological testing, to assess executive functioning and more subtle or complex deficits)

5 Rating scales (such as Conners for ADHD, Beck Depression Inventory for depression, etc) to assess the number and severity of symptoms Baseline and follow-up rating scales are helpful in monitoring the effectiveness of treatment interventions and medication regimens.

essential feature of children suffering from autistic disorder These are children who from birth (and

at least evident by the age of three) demonstrate functional disabilities in social interaction, social munication, and symbolic or imaginative play Autistic disorder is one of the pervasive developmen-tal disorders (PDDs), the others including Rett’s disorder, childhood disintegrative disorder, Asperger’sdisorder, and PDD not otherwise specified (NOS) Co-existing mental retardation or learning diffi-

com-culties are very common, but not essential for the diagnosis ( 4 ).

Epidemiology

The overall prevalence estimates of the PDDs have been steadily increasing, probably because ofchanges in case definition and improved recognition Autistic disorder is estimated to have a preva-

lence of 5–10 per 10,000 in the United States ( 5 ) Broader autism spectrum disorders may occur at a

rate of 20 per 10,000 Rett’s disorder (estimated prevalence of 0.44 to 2.1 per 10,000 females) andchildhood disintegrative disorder (fewer than 100 cases reported) are much less common Except forRett’s disorder, which appears to affect predominantly girls, the PDDs are more common in boys (4–5

to 1) Girls who are affected tend to be more severely mentally retarded These disorders are evenly

distributed in all socioeconomic classes ( 6 ).

Signs and Symptoms

PDDs are characterized by severe and pervasive impairment in the developmental areas of rocal social interaction skills, communication skills, or the presence of stereotyped behavior, inter-ests, and activities These disorders are usually evident in the first years of life and are often associatedwith mental retardation or learning disabilities (LDs) The PDDs are sometimes observed with a diversegroup of other general medical conditions, including chromosomal abnormalities, congenital infec-

recip-tions, or structural abnormalities of the central nervous system (CNS) ( 4 ).

Etiology and Pathogenesis

Genetic Factors

Research (family studies, twin studies, and chromosome studies) indicates that genetic factors play

a major contributory role in a subgroup of autistic individuals Although the exact etiology of the tic spectrum disorders remains unknown and is likely quite heterogeneous and multifactorial, thereare a large number of studies identifying association with various and diverse chromosomal abnor-malities (including deletions, duplications, translocations, trisomies, inversions, mosaicism, ringchromosomes, and complex chromosomal rearrangements) The prevalence of autism in siblings is

autis-4.5%, a rate 50 times higher than the risk for autism in the general population ( 7 ) A family study

by Folstein and Rutter ( 8 ) found that although only 36% of monozygotic (MZ) twin pairs were

con-cordant for autism, when a broader spectrum of related cognitive or social abnormalities wasapplied, 92% of the same MZ pairs were concordant for the spectrum, compared with 10% of dizy-gotic pairs These findings suggest that autism is under a high degree of genetic control, with mul-tiple genetic loci, and that a combination of genetic predisposition and environmental insult may

be involved

The search for candidate genes for autism has resulted in quite variable findings—genomewidescreens for susceptibility genes have demonstrated limited concordance of linked loci There may benumerous genes of weak effect and/or genetically heterogeneous factors contributing to the disorders.The 7q31-35, 15q11-13, and 16p13.3 chromosomes have perhaps demonstrated the most consistent

evidence for a linkage with autism ( 9 ) There is evidence of a link between the serotonin-transported

gene (HTT) in the 15q11-13 region and autism (a genetic area known to cause Angelman’s syndrome)

Although a direct link between the HTT alleles alone may not directly convey risk for autism, they

may modify the severity of autism in the social and communication domains

Some known genetic syndromes are also associated with autism, including phenylketotonuria,fragile-X syndrome, tuberous sclerosis, and Angelman’s syndrome

Neurodevelopmental Factors

Researchers have reported an association between unfavorable events in prenatal, perinatal, and

neonatal period and autism ( 10 ) Nonspecific neurological abnormalities are common In several series

of studies with autistic patients, 30–50% were noted to display signs of dysfunction possibly ated with the basal ganglia and neostriatum, including hypotonia or hypertonia, coordination deficits,

associ-abnormal reflexes, posture and gait associ-abnormalities, and movement disorders of various types ( 6 ).

Macrocephaly is a common finding (between 12 and 46%) ( 11 ) Seizure disorders appear in 35–50%

of patients by the age of 20 years, more commonly in the presence of concurrent mental retardation

Neuroanatomical Factors

There is a great deal of variability in neuroanatomical findings in autism Postmortem brain ies have revealed both negative and positive findings Imaging studies demonstrate a wide range ofabnormalities, as well Computed tomography scans show variable nonspecific changes, such asporencephalic cysts, ventricular enlargement, and abnormal symmetry Magnetic resonance imagingstudies have reported cerebellar hypoplasia and small brainstem structures in autistic patients, as well

stud-as forebrain morphological abnormalities ( 6 ).

Autoimmune Factors

Autoimmune abnormalities have been suggested as etiological in autistic disorder Autoantibodies

to serotonin-1A receptor, which are not present in brain-damaged non-autistic patients, have been

reported in 40% of autistic patients ( 12 ) Peripheral serotonin levels are also frequently elevated,

pos-sibly affecting CNS development via potentiation of synapses Concerns about the link between themumps, measles, and rubella vaccine and autism have not been substantiated

Diagnosis

Autism and the autistic spectrum disorders are clinical diagnoses, with criteria for the diagnosis

of autism in Table 2 ( 4 ) Delayed social smile, poor eye contact, delayed speech, or suspected

deaf-ness are some of the earliest manifestations that may concern parents The evaluation of a child withsuspected autistic disorder should be a multidisciplinary collaborative process In addition to stan-dard assessment procedures, hearing testing is essential, as are assessments of cognitive, language,social, and adaptive functioning Neurological examination is important to detect possible inbornmetabolic, structural, or degenerative diseases or seizures An electroencephalogram (EEG) (to ruleout a seizure disorder or developmental regression), chromosome analysis (for fragile X, etc.), andlabwork for lead level and other toxic/metabolic screeners may be indicated Standardized diagnos-tic rating scales such as the Autistic Diagnostic Observation Schedule or the Childhood Autism Rating

Scale may be utilized ( 13 ).

The PDDs have unique diagnostic characteristics that should be differentiated Asperger’s der does not cause delays in language development, cognitive development, age-appropriate self-helpskills, or adaptive behavior The child typically develops intense but unusual interests and loses socialskills At times, there is a discrepancy in cognitive functioning, with language-related abilities supe-rior to visuospacial skills Rett’s disorder occurs almost exclusively in females and includes deceler-ation of head growth, severe mental retardation, hand-washing stereotypical movements, and loss ofpurposeful motor skills Childhood disintegrative disorder has a characteristic pattern of severe devel-opmental regression beginning at age 2 years PDD NOS includes individuals with a number of autis-tic behaviors, but not meeting full criteria or not as functionally impairing The other psychiatric andmedical diagnoses to be ruled out are given in Table 3

disor-There is a high degree of co-morbidity of autistic spectrum-disordered patients with mental dation (approx 80% of autistic patients are mentally retarded) Occasionally, savant skills (special capac-ities) in drawing, music, mathematics, or calendar calculation is observed Additionally, anxietydisorders (generalized anxiety or obsessive-compulsive features) and ADHD are frequently co-morbid

retar-Course and Prognosis

Autistic disorder is often apparent in early infancy, with delayed developmental milestones, delayedsocial smile, eye contact, and language and communication (pointing and shared attentional activi-ties) Sometimes an initial period of seemingly normal development may be followed by arrested orregressed developmental trajectory

Early diagnosis and multimodal intervention may markedly improve prognosis Predictors of all better adaptive outcome include later manifestation of symptoms, higher IQ, language skills (verbalcommunication by the age of 5 years), and less impaired social skills The course of the disorder isquite variable, characterized generally by gradual but erratic improvement punctuated by intermittentregressions (often precipitated by environmental stress or illness) Some children may demonstrateself-abusive or aggressive behavior in the face of frustrations The onset of adolescence may precip-itate behavioral deterioration, with seizures more likely to appear during this time Adults with autis-tic disorder typically continue to improve gradually but retain clinical evidence of organic impairment.Depending on the degree of mental retardation and severity of the autistic disorder, adults may achieveadaptive functioning within the normal range About one-third are able to function independently asadults, although deficits in social skills, empathy, and rigid coping skills frequently persist

over-Treatment

Initially thought to be resistant to treatment, autistic individuals with early rigorous multimodaltreatment have demonstrated the potential for significant improvement Essential interventions include

Table 2

DSM-IV TR Diagnostic Criteria for Autistic Disorder

A A total of six (or more) items from (1), (2), and (3), with at least two from (1), and one each from (2) and (3):

1 Qualitative impairment in social interaction, as manifested by at least two of the following:

a marked impairment in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction

b failure to develop peer relationships appropriate to developmental level

c a lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (e.g., by a lack of showing, bringing, or pointing out objects of interest)

d lack of social or emotional reciprocity

2 Qualitative impairment in communication as manifested by at least one of the following:

a delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gesture or mime)

b in individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others

c stereotyped and repetitive use of language or idiosyncratic language

d lack of varied, spontaneous make-believe play or social imitative play appropriate to developmental level

3 Restricted repetitive and stereotyped patterns of behavior, interests, and activities, as manifested by at least one of the following:

a encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus

b apparently inflexible adherence to specific, nonfunctional routines or rituals

c stereotyped and repetitive motor mannerisms (e.g., hand or finger flapping or twisting, or complex whole-body movements)

d persistent preoccupation with parts of objects

B Delays or abnormal functioning in at least one of the following areas, with onset prior to age 3 years: (1) social interaction, (2) language as used in social communication, or (3) symbolic or imaginative play

C The disturbance is not better accounted for by Rett’s disorder or childhood disintegrative disorder

early and intensive speech and language therapy, special educational services, adaptive skill training,and behavioral therapy The treatments should be integrated across settings (school and home, etc.),and include continual rewards for positive behavior, speech, social interaction, self-care skills, andadaptive functioning Parent guidance is critical Parenting children with autistic spectrum disorders

is quite challenging, and parents require support to deal with emotional reactions such as denial orguilt Additionally, psychoeducation about the nature of the disorder, how to access essential services,and the crucial nature of parental participation as a member of the treatment team is needed Parentsare extremely important collaborators in the child’s learning of language and self-care skills Training

in behavior management skills is essential to the child’s learning of more adaptive behaviors to copewith frustration and ensuring a safe home environment

Long-term treatment and services are generally required Vocational training is important as theautistic individual enters adolescence Acute hospitalization or longer term residential treatment may

be required if symptoms are serious and disabling Co-morbid mood, anxiety disorders, attentionalproblems or the onset of seizures should be assessed in an ongoing way

Medication Treatment

Although medications are not specific to the treatment of the autistic spectrum disorders, tropics may be used to target specific disabling psychiatric and behavioral symptoms, such as aggres-sion or agitation, anxiety, depression, and attentional issues Individuals with developmental disordersmay be quite sensitive to the therapeutic, but also side effects of psychotropic medications In gen-eral, beginning with very low doses of medication and increasing very gradually as needed for effec-tiveness is advised The risk of tardive dyskinesia with antipsychotic medications may be higher inthese patients because of the length of treatment and perhaps biological vulnerability Additionally,irritability or activation with the antidepressants or stimulant medications may be seen

psycho-The antipsychotic medications are the most widely studied of the medications used in children andadolescents with autistic spectrum disorders Controlled studies (primarily with haloperidol and risperi-done) demonstrate clinical effectiveness in the treatment of severe aggression, interpersonal with-drawal with paranoid or delusional thoughts and stereotypies Low doses of less-sedating antipsychotic

Table 3 Differential Diagnosis for Autism

Other Pervasive Developmental Disorders Rett’s Disorder

Asperger’s Disorder Childhood Disintegrative Disorder Pervasive Developmental Disorder, NOS Other Psychiatric Disorders

Mental Retardation Juvenile onset Schizophrenia Reactive Attachment Disorder Selective Mutism/Anxiety Disorders Developmental Expressive and Receptive Language Disorders Medical Disorders

Congenital Deafness Congenital Blindness Seizure Disorder Genetic abnormalities (such as Fragile X) Degenerative neurological diseases Toxic/metabolic disorders Heavy metal poisoning

medications, in conjunction with a highly structured psychoeducational program, may help controlbehavioral symptoms, reduce excessive agitation and activity, and enhance the effectiveness of behav-ioral therapies.

Co-morbid ADHD is common in individuals with pervasive developmental disorders stimulant medications may decrease the symptoms of overactivity, impulsivity, and distractibility.However, these medications must be used cautiously and monitored carefully, as the dopamine ago-nist effects may exacerbate rituals, stereotypies, and agitation The selective serotonin reuptakeinhibitors (SSRIs) such as fluvoxamine may reduce obsessive-compulsive behaviors Clomipraminemay decrease the frequency of some self-abusive behaviors Fluoxetine can relieve depressive symp-toms in adolescents with autism

Psycho-β-blockers and the α-2-agdrenergic receptor agonist clonidine have demonstrated effectiveness fordecreasing aggression in some individuals with autism Clonidine is also used for sleep disturbance,which is common However, tolerance often develops with longer term use There is evidence that theopiate antagonist naltrexone may decrease the frequency of self-injurious behaviors in some patients

with autistic disorder ( 13 ).

Parental distress and the hope for a significant breakthrough in treatment has resulted in a barrage

of unsubstantiated treatments for autism that are ineffective, toxic, or divert time and resources away

from the more scientifically grounded treatments ( 14 ) Parent education and discussion concerning

these unconventional treatments is an ongoing process in the care of children with autism and theirfamilies

MENTAL RETARDATION

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision IV-TR) diagnosis of mental retardation requires low intellectual functioning (IQ of 70 or below on anindividually administered IQ test); deficits in adaptive functioning in at least two areas (communica-tion, self-care, home living, social/interpersonal skills, use of community resources, self-direction, func-

(DSM-tional academic skills, work, leisure, health, and safety); with an onset before the age of 18 years ( 4 ).

Epidemiology

The prevalence of mental retardation in the United States is estimated at about 8%, with by far thelargest percent of individuals being in the mild mental retardation category Associated medical, neuro-logical, and sensory disorders are common Seizure disorders occur in up to 30%, with an increase inassociated seizures, physical, and sensory handicaps increasing with the increasing severity of themental retardation

Etiology and Pathogenesis

Insults to the CNS of any sort may result in cognitive and associated adaptive impairment.Alterations in fetal development, called errors in morphogenesis, may be caused by malformations(failure of tissue to form normally), deformations (alterations of normally forming tissue by abnor-

mal mechanical forces), and disruptions (in utero injury to developing CNS tissue) Many of these

disorders have a genetic etiology, although toxins (alcohol, illicit substances, medications, or otherchemicals), viruses, and other intrauterine insults may contribute Errors in metabolism (inborn or not),

as well as extraordinary extrinsic events (such as hypoxia, trauma, or poisoning) may also result inirreversible cognitive impairments

Diagnosis

Some genetic syndromes may be diagnosed via prenatal or postnatal screening Poor muscle toneand developmental delay may be the earliest manifestation However, by definition, both individu-alized cognitive testing and impairment in adaptive functioning are required for diagnosis Mental

retardation is not necessarily a lifelong disorder Some individuals may acquire a high level of tive and independence skills to the level that they no longer meet diagnostic criteria.

adap-The diagnostic evaluation of a child with developmental delay should include a detailed cal and perinatal history, family history, and developmental history Additionally, a thorough physi-cal and neurological examination, and labwork (genetic testing, lead level, thyroid, study of metabolicdisorders, etc.), an EEG , or neuroimaging may be indicated Psychological testing by a psychologistexperienced in working with young children or children with delays is important for early detection.Children and adolescents with mental retardation are generally at higher risk for developingpsychopathology Thus, the diagnostic assessment should not only identify the cognitive and adap-tive delays, but assess for concomitant PDD, ADHD, disruptive behavior disorders, mood disorders,and anxiety disorders Poor frustration tolerance, inadequate coping and verbal skills may lead to ahigher degree of behavioral symptoms Aggression is one of the most common reasons for psychi-atric referral for children and adolescents with mental retardation Helping the child gain more adap-tive methods of communicating wants, needs and frustrations may help in alleviating the aggressive

obstetri-behavior ( 15,16 ).

Treatment

Early diagnosis and intervention is essential for children with developmental disorders of any type.The Individuals with Disabilities Education Act specifies that children who qualify for special edu-

cation are entitled to a “free and appropriate public education” from birth to age 21 ( 17 )

Birth-to-Three services to address motor and communication skill deficits are indicated Additionally, childrenwith disabilities are eligible for special preschool services from the age of 3

Treatment approaches are designed to help improve overall level of functioning and quality of life.Coordination of medical, psychiatric, and educational services is crucial Family support and psy-choeducation is indicated Behavioral modification and supportive therapies may be quite helpful inalleviating maladaptive behaviors Individualized special educational services may include occupa-tional therapy, physical therapy, speech and language therapy, and other special services, in addition

to a curriculum that is adapted to the learning capabilities of the child Mainstream classes or small,self-contained classes may be appropriate, as long as the child is able to learn and adapt socially inthe environment provided Medications may be utilized to target secondary symptoms of psychiatricillness or aggression, as needed

Table 4

Features of Mental Retardation

Living Independent Minimal Supervised ADLs Assisted ADLs

Holds job Supervised job Minimal job skills

DEVELOPMENTAL DISORDERS OF LEARNING, MOTOR SKILLS,

AND COMMUNICATION

Learning, communication, and motor skills disorders are common developmental impairments thatmay negatively impact a child’s mental health and ability to function academically and socially.Unlike mental retardation, the learning, communication, and motor skills disorders do not have defi-cient intellectual functioning as a diagnostic feature Epidemiological and clinical research has demon-strated an association between ADHD and overlapping learning, language, and motor disorders, aconstellation of impairments which is sometimes referred to as deficits in attention, motor control,

and perception ( 18 ).

Epidemiology

LDs are very common, with an estimated 1–20% of children and adolescents suffering from somelevel of learning and/or communication disorder About 5.3% of all students in US public schoolsreceive a special education designation and special services for LD About 50% of these children have

a co-morbid psychiatric disorder, making these disorders a very significant public health issue ( 19 ).

Etiology and Pathogenesis

The etiology of LDs is unknown However, the complexity of neural circuitry involved in highercognitive processes suggests that functional neurocognitive deficits of multiple types that disrupt cog-nitive processing may lead to learning difficulties Both hereditary and environmental factors havebeen implicated in reading disorders Prematurity, perinatal adversity, poverty, malnutrition, poorschooling, early abuse, and neglect and parental substance abuse have all been described Additionally,genetic loci on chromosomes 6 and 15 have been identified as linked to some familial cases of read-

ing disability ( 20 ) There is also a link between reading disability and ADHD on a hereditary basis.

Diagnosis

The diagnosis of LD involves establishing a discrepancy between academic skill and the child’sintelligence, and then eliminating all other explanations for the discrepancy To establish this dis-crepancy, a psychoeducational evaluation is performed by a qualified psychologist, using scores onstandardized academic achievement tests as compared with standardized intelligence scores A signi-ficant difference is set as 1 to 2 standard deviation discrepancy, with achievement level lower than IQ.The types of LDs include reading disorder, mathematics disorder, disorder of written expression, and

LD NOS

Psychiatric evaluation for concomitant psychiatric disorders is indicated because of the high degree

of co-morbidity involved ADHD is the most common co-occurring disorder, but significant issues ofself-esteem with depression, anxiety, and disruptive behaviors are common as well

Treatment

Early diagnosis and intervention is helpful in the treatment of the LD and avoiding the secondarymorbidity associated with academic frustration and recurrent failures Although the scope of the chap-ter does not allow a full discussion of therapeutic modalities used, multimodal approaches, direct treat-ment of visuomotor deficits, and enhancing attention and motivation are used Identification forspecial education services, and an individualized educational program to provide interventions thatdirectly address the LD, is indicated Specialized tutoring or other types of educational support areindividualized to the child’s needs in the least-restrictive setting The physician is often quite helpful

in advocating for appropriate services for patients with special needs

Children with LDs are often helped by a clear explanation of the nature of their difficulty Childrenthat understand that every person has areas that come easily or are much more difficult, and that this

is part of each individual’s uniqueness, may not be as self-conscious about the disorder Framing thedisability as an area in which the child needs to work harder than many peers may help increase

motivation, decrease frustration, and improve self-esteem Highlighting areas of strength and ability,

as well as remediating difficulties, may also be quite helpful

Psychotherapy, family counseling, and the judicious use of medications may be indicated for somechildren and adolescents with co-occurring psychiatric issues Therapeutic interventions should becoordinated between the school, home, and therapist, and should be targeted to the child’s individual

needs Tutoring and special assistance in the area of the disability is indicated ( 19 ).

AXIS I DISORDERS USUALLY FIRST DIAGNOSED IN INFANCY,

CHILDHOOD, OR ADOLESCENCE

Attention Deficit Hyperactivity Disorder

ADHD is the most commonly diagnosed psychiatric disorder of childhood, and is characterized

by deficits in attention, concentration, activity level, and impulse control The public health impact

of ADHD on the child, his or her family, schools, and society is enormous, with billions of dollarsspent annually for school services, mental health services, and increased use of the juvenile justicesystem In contrast with historical notions, children do not typically “outgrow” ADHD Morbidity and

disability often persist into adult life ( 21 ).

Epidemiology

ADHD is relatively common, affecting an estimated 3–12% of school-age children The DSM-IVclassification of ADHD into three categories—inattentive type, hyperactive-impulsive type, or com-bined type—has led to a broadening of the disorder to include more girls, preschoolers, and adults,and has impacted the educational services and treatment modalities utilized

In community samples of children, boys are diagnosed with ADHD, combined type, in a frequency

of 3⬊1 as compared with girls Clinic samples tend to be higher, approaching a 9⬊1 male to femaleratio, most likely as a result of the higher proportion of disruptive behaviors in boys with ADHD, com-bined type, which may promote referral for treatment ADHD is diagnosed in as many as half of chil-dren referred for mental health services The inattentive subtype of ADHD is not associated with anincrease in disruptive behaviors, and is more nearly equal in prevalence between boys and girls.Psychosocial correlates with ADHD include low income/poverty, urban residence, family dysfunc-tion, and parents with psychiatric disorder These psychosocial risk factors suggest that there may bemultiple pathways leading to the clinical constellation of ADHD in vulnerable children

Signs and Symptoms

ADHD is a syndrome consisting of symptoms in several categories—inattention, hyperactivity andimpulsivity, or the combination of both sets of symptoms A variety of other psychiatric disorders maypresent with difficulties with sustained attention (such as anxiety, depression, or psychotic disorders),high levels of activity (such as bipolar disorder or PDD), or both Thus, the clinician must differenti-ate the core symptoms of ADHD from the secondary effects of the other psychiatric disorders or a pri-

mary medical disorder (e.g., fetal alcohol syndrome, atypical seizures, toxic/metabolic disorder) ( 22 ).

Etiology and Pathogenesis

Genetic Factors

Although the exact etiology of ADHD remains unknown, data from family genetic, twin, tion, and segregation analysis strongly suggest that there is genetic component in the etiology forthe disorder

adop-ADHD is thought to be a complex genetic disorder resulting from the combined effects of severalgenes and interactions with the environment Preliminary molecular genetic studies have implicatedcandidate genes associated with the dopamine system, including the dopamine D2 and D4 receptors andthe dopamine transporter There is also preliminary evidence that genes involved in norepinephrine

modulation are affected in some patients Given the importance of these catecholamines for the lation of attentional circuits, it is not surprising that alterations in these systems would result in impairedattention regulation However, there is a great deal of study left to be done on the role of genes and the

modu-gene–environment interaction in the etiology of ADHD ( 21 ).

Neurodevelopmental Factors

Prefrontal, parietal, and temporal association cortices, and their projections to the striatum, makedistinct contributions to the core ability to focus attention In particular, the prefrontal cortex uses work-ing memory to guide overt responses (movement) as well as covert responses (attention), allowing us

to inhibit inappropriate behaviors and to attenuate the processing of irrelevant stimuli The transmitters of dopamine and norepinephrine are both intricately involved in modulating prefrontalcortical functioning There is evidence that moderate amounts of these neurotransmitters are essen-tial to prefrontal cortical functioning, but that high levels (as is found in extreme stress) may actually

neuro-impair optimal functioning ( 23 ).

Brown has argued that the common etiological deficit in all types of ADHD is one of impaired utive functioning Developmental difficulties with activation, focus, sustaining effort, modulatingemotions, utilizing working memory and regulating behaviors are all subsumed under the rubric of

exec-executive functioning impairment ( 24 ).

Early neurodevelopmental problems such as obstetrical complications, prematurity, other genetic

abnormalities (such as fragile X disorder and others), and exposure in utero to alcohol, cocaine, or

other toxins, may predispose to ADHD It is postulated that fetal insults may cause subtle functionalabnormalities to the frontal cortex and other brain structures, resulting in the disorder Early findingsare also provocative regarding the neuronal–environmental interactions as related to brain function-ing Specifically, the efficiency of brain functioning may be molded in the perinatal period via neu-ronal pruning that is enhanced by appropriate levels of stimulation and nurturance Severe psychosocialadversity in infancy, thus, may predispose to subtle neurodevelopmental disorders such as ADHD

Neuroimaging Findings

Imaging studies of ADHD have focused on the prefrontal cortex, basal ganglia, and cerebellum.Although results have been mixed, there is evidence of structural and functional differences in thebrains of children and adults with ADHD Volumetric measures have detected smaller right-sidedprefrontal regions overall in boys with ADHD These reductions correlated with performance on tasksthat require response inhibition Girls with ADHD have been found to have smaller left and totalcaudate volumes A consistent finding in ADHD has been reduced volume of the posterior–inferiorcerebellar vermis, a region that exhibits a high degree of dopamine receptor reactivity

Functional neuroimaging has demonstrated decreased metabolism in the regions of the prefrontalcortex and striatum in adults with ADHD by positron emission tomography (PET) scanning Althoughfunctional MRI has not been conclusive, early results also indicate subtle deficits in frontal lobe activ-ity Preliminary results of PET imaging examining the neuropharmacology of ADHD support the notionthat catecholamine dysregulation is central to the pathophysiology of the disorder, and not just to its

treatment ( 23 ).

Diagnosis

ADHD is a clinical diagnosis There is no definitive diagnostic test or neuroimaging procedure forADHD, but rather the diagnosis is established by clinical judgment based on a comprehensive assess-ment that involves multiple domains, informants, methods, and settings Table 5 gives the DSM-IVdiagnostic criteria for the disorder Hyperactivity is a symptom of many disorders, and therefore thedifferential diagnosis of ADHD is quite extensive The clinician must complete a thorough assess-ment to clarify the diagnosis and nature of the disabling symptoms It is important to rule out aprimary medical disorder (such as thyroid disorder, lead intoxication, seizure or other toxic/metabolic,

b often has difficulty sustaining attention in tasks or play activities

c often does not seem to listen when spoken to directly

d often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions)

e often has difficulty organizing tasks and activities

f often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (such as schoolwork or homework)

g often loses things necessary for tasks or activities (e.g., toys, school assignments, pencils, books,

or tools)

h is often easily distracted by extraneous stimuli

i is often forgetful in daily activities

2 Six (or more) of the following symptoms of hyperactivity-impulsivity have persisted for at least

6 months to a degree that is maladaptive and inconsistent with developmental level:

Hyperactivity

a often fidgets with hands or feet or squirms in seat

b often leaves seat in classroom or in other situations in which remaining seated is expected

c often runs about or climbs excessively in situations in which it is inappropriate (in adolescents or adults, may be limited to subjective feelings of restlessness)

d often has difficulty playing or engaging in leisure activities quietly

e is often “on the go” or often acts as if “driven by a motor”

f often talks excessively

Impulsivity

g often blurts out answers before questions have been completed

h often has difficulty awaiting turn

i often interrupts or intrudes on others (e.g., butts into conversations or games)

B Some hyperactive-impulsive or inattentive symptoms that caused impairment were present before age

E The symptoms do not occur exclusively during the course of a Pervasive Developmental Disorder,

Schizophrenia, or other Psychotic Disorder and are not better accounted for by another mental disorder (e.g., Mood Disorder, Anxiety Disorder, Dissociative Disorder, or a Personality Disorder).

Code based on type:

314.01 Attention-Deficit/Hyperactivity Disorder, Combined Type: if both Criteria A1 and A2 are met for the past 6 months

314.00 Attention-Deficit/Hyperactivity Disorder, Predominantly Inattentive Type: if Criterion A1 is met but Criterion A2 is not met for the past 6 months

314.01 Attention-Deficit/Hyperactivity Disorder, Predominantly Hyperactive-Impulsive Type: if Criterion A2

is met but Criterion A1 is not met for the past 6 months

or neurological disorders) Table 6 lists the differential diagnosis of ADHD to be considered The onset

of ADHD impairment must be in early childhood, at least before the age of 7, even if it was not nosed until later in life There must be functional impairment in a variety of life settings (e.g., home,school, work) Milder forms of PDD may present with intractable hyperactivity as a primary symp-tom ADHD should not be diagnosed separately if it presents only concomitantly with a PDD or

diag-psychotic disorder ( 25 ).

A complete history and screening physical and neurological exam are necessary to provide rate assessment of ADHD in children and adolescents As with all psychiatric evaluations, the use ofmultiple informants is key Teacher ratings are particularly essential in assessing ADHD The struc-tured setting, individualized attention, and novelty may mask ADHD symptoms during assessment inthe physician’s office

accu-Many parents will relate difficult early temperament and poor impulse control from an early age.Often, early gross motor development, with more delayed fine motor and language development aredescribed The psychiatric history should focus on presenting symptoms, the longitudinal timeline ofsymptoms development, and associated features and/or confounding factors (e.g., mood disorders,developmental problems, recent stress or traumas, substance abuse) Co-morbidity with other psy-chiatric disorders is frequent (40–60% of children with ADHD), and negatively affects treatmentresponse and prognosis The most common co-morbid conditions include oppositional defiant and con-duct disorder (50%), anxiety disorders (25–33%), depression (around 30%), and bipolar disorder(around 10–20% of clinical populations) Thus, both the ADHD and concomitant disorders must be

Table 6 Differential Diagnosis for ADHD

Psychiatric Disorders Mood Disorders (depression and bipolar bisorder) Anxiety disorders

Tic disorders Substance use disorders Oppositional defiant or conduct disorder Pervasive developmental disorder Learning disorders

Post-traumatic stress disorder Mental retardation or borderline intellectual functioning Psychosocial Conditions

Abuse and/or neglect Poor nutrition Neighborhood violence Chaotic family situation Being bullied at school Medical Disorders Partial deafness Poor eyesight Seizure disorder Fetal alcohol syndrome Genetic abnormalities (such as Fragile X) Sedating or activating medications (common are asthma medications and caffeine) Substance abuse

Thyroid abnormality Heavy metal poisoning

the focus of treatment Rating scales of symptoms (Conners scale [ 26 ] or others) is essential in

quan-tifying the symptom severity and response to treatment

Psychoeducational testing to assess intellectual ability, academic achievement, and possible ing disabilities is a crucial component of a thorough assessment At times, more complete neuropsy-chological testing, to assess executive functioning and more subtle deficits of the disorder, may beindicated The Continuous Performance Task is a computerized test that assesses attentional abilitiesand impulsivity of response style Although not specifically diagnostic, it may help in the completediagnostic assessment Children with ADHD frequently have learning issues, and these must be welldelineated to ensure appropriate educational services

learn-Course and Prognosis

Although many of the symptoms of ADHD may remit, it has become clear that ADHD is frequently

a chronic disorder, which leads to a negative impact on functioning throughout the life cycle Aboutthree-quarters of these children continue to show symptoms of ADHD into adolescence, and perva-sive academic, social, self-esteem and conduct difficulties are common

Follow-up studies into adulthood suggest that up to 33% of ADHD vs 1–9% of controls drop out

of high school ADHD children go on to have less education overall (by 2–3 years) and fewer go on

to complete a graduate degree Likewise, the ADHD cohort demonstrates significantly lower pations rankings at the age of 25 Children with ADHD are also at increased risk for developing anti-social personality disorder and substance abuse disorders in adulthood An estimated 40–50% continue

occu-to suffer from clinically significant sympoccu-toms of ADHD ( 22 ).

Treatment

ADHD is a complex disorder affecting every area of functioning, and thereby requires a hensive treatment program Psychosocial interventions, medication treatment, and ensuring an appro-

compre-priate educational plan are all part of the effective treatment for ADHD ( 22 , 25 ) (seeTable 7)

The Multimodal Treatment Study of ADHD (MTA) was a large (N = 579) study sponsored by the

National Institute of Mental Health investigating the effects of various treatment modalities on dren with ADHD-combined type over a 14-month time period The aim of the MTA was to comparethe effectiveness of medication treatment combined with intensive and broad-based psychosocial treat-ment with medication management or psychosocial treatment alone, and to compare these treatmentprograms with regular community care In the MTA, the psychosocial treatments provided included an8-week, all-day summer treatment program that utilized contingency management and included socialskills training Additionally, parent training and teacher consultation on classroom behavior manage-ment were included The medication used was methylphenidate adjusted on a monthly basis withmonthly teacher feedback and family interview Children in the community-care arm of the study alsofrequently received medication, but overall on a lower dosage than the children in the study

chil-The study found that for the core symptoms of ADHD, intensive medication management was rior to behavioral treatment and treatment in the community However, for non-ADHD areas of func-tioning, the combined treatment was superior to the other groups in the treatment of oppositional andaggressive symptoms, internalizing symptoms, teacher-rated social skills, parent–child relations, and

supe-reading achievement ( 27 ).

Psychosocial Treatments

Psychosocial treatments may include psychoeducation, parent training in behavioral managementskills, classroom interventions, contingency management, social skills training, cognitive-behaviortherapy, and individual psychotherapy of the child Of these, parent training, classroom interventions,contingency management, and social skills training have demonstrated efficacy Psychoeducation,which includes intensive support and education of the family, is essential in developing an ongoingtherapeutic alliance between the therapist, the child and his or her family to ensure collaboration inthe complex task of helping the child achieve optimal functioning

School is where ADHD symptoms may be most disabling, as the demands to sit quietly, pay tion, and work cooperatively are inherent in the school setting School interventions include ensuringthat learning needs are appropriately assessed and addressed Additionally, contact with teachersregarding the diagnosis and effectiveness of treatment is required It is crucial that the teacher under-stands the disorder, and that he or she provides a classroom environment that optimizes the child’slearning Preferential seating (seating within the class to optimize paying attention and minimize dis-tractions), a behavioral management plan that highlights positive reinforcement for desired workhabits and behavior, social skills groups, and other interventions may help the child gain school suc-cess More intensive interventions (a small self-contained classroom, special educational services, or

atten-a more intensive theratten-apeutic educatten-ationatten-al platten-an) matten-ay be required for children who atten-are more impatten-aired

by the disorder and/or co-morbidities ( 21,22 ).

Medication Treatment

As highlighted in the MTA study, medication treatment may be highly effective in addressing the

core symptoms of ADHD ( 27,28 ) There is a large body of literature documenting the efficacy of

stimu-lants on core features of ADHD (motoric overactivity, impulsivity, and inattentiveness) as well as theirsubstantial effects on cognition, social function, and aggression The stimulant medications are themost thoroughly studied medications in child and adolescent psychiatry, and have demonstrated safetyand efficacy in more than 200 controlled studies Despite concerns of many families about the abusepotential of the medication, and the risk of precipitating an addictive personality, use of stimulant medi-cation treatment may actually decrease a child’s risk for substance abuse, legal difficulties, and othersequelae of poor impulse control Finally, concerns that stimulant medication might be responsible

for the smaller brain structures found in ADHD children do not appear supported ( 29 ).

At times, medication “holidays” may be indicated This is when the child does not take ADHD cation during non-school periods of time Although this practice may be helpful for children forwhom appetite and sleep are disturbed with the medication, many children may require the medica-tion even when not in school to maintain appropriate social behavior, to be able to enjoy and benefitfrom group activities, and to decrease highly impulsive behavior that may pose a safety issue

medi-In general, the stimulant medications are considered first line in the treatment of the core symptoms

of ADHD Atomoxetine is an antidepressant that has recently been marketed as a long-acting, trolled medication monotherapy for ADHD, and some clinicians are beginning to use this medicationfirst line, although the body of data on efficacy and effectiveness remains small Common side effects

noncon-of the stimulant medications are appetite suppression, sleep disturbances, and some changes in pulseand blood pressure Stimulants may precipitate or exacerbate tics At times, stimulant medications may

Table 7

Essentials of Treatment for ADHD

1 Treatment should include more than just medication management Parental guidance and counseling and psycho-education are cornerstones of treatment.

2 Unsuccessful treatment of ADHD often occurs when comorbid diagnoses, hyperactivity associated with another psychiatric disorder (such as PDD), or primary medical diagnoses are not identified and addressed.

3 Collaboration with a child’s school is usually critical to ensure academic progress.

4 Medication holidays should be individualized to the child’s unique situation, and utilized only if the child’s social functioning and safety will not be severely compromised Medication holidays over the summer or during weekends do not decrease the effectiveness of stimulants.

5 Treatment with stimulants does not increase the likelihood of substance use disorders, and may actually lower the risk.

6 In general, failure of an initial stimulant trial should be followed with one or two subsequent stimulant trials before treating with a different class of psychotropic medication.

cause more serious side effects, such as dsyphoria, irritability, or even hallucinations These symptomsmay be more common in very young children Clonidine or guanfacine or the tricyclic antidepressantsmay be considered first line in the treatment of patients with ADHD and tics However, stimulant medi-cations have been used successfully in some patients with tic disorders, if the dosages are started low

and increased slowly SeeTable 8 for an algorithm for the use of medications in the treatment of ADHD.The antipsychotic medications may be helpful in treating the agitation and aggression of childrenand adolescents with ADHD, but are used only third line and usually in low dose in combination withother ADHD medications General principles of pharmacotherapy should be followed in the medica-tion treatment of children, adolescents and adults with ADHD These include beginning with one medi-cation and slowly titrating medication dosages up as needed until optimal effectiveness is achievedwith minimal side effects At times, changing dosage timing may help decrease such side effects asappetite suppression or sleep disturbance Routine monitoring of vital signs (blood pressure andpulse), height, and weight are indicated If stimulant medications successfully treat ADHD, butco-morbid symptoms (such as depression) persist, addition of an antidepressant medication may beindicated Several studies have described safety and efficacy of combined SSRIs and stimulant pharma-cotherapy Alternatively, the use of an antidepressant medication with secondary ADHD effects (such

as bupropion or venlafaxine) may be considered However, venlafaxine has been recently implicated

in increased suicidal behavior for children and youth Pemoline has been associated with hepatitis,and should be used only when other medications have been tried, and only with close blood moni-toring of liver function every 2 weeks

OTHER AXIS I DISORDERS USUALLY FIRST DIAGNOSED IN INFANCY, CHILDHOOD, OR ADOLESCENCE

Oppositional defiant disorder and conduct disorder are disorders of behavior that may resolve, butincur increased risk in adulthood of antisocial behavior, substance abuse, and mood disorders Separationanxiety disorder, pica, rumination, encopresis, enuresis, and selective mutism nearly all remit by adult-hood Children with reactive attachment disorder remain impaired into adulthood, although moreresearch is needed into the types and levels of disability of psychiatric disability Table 9 gives anoverview of the clinical manifestations, treatments, and prognosis for these disorders

Clonidine (Catapres) Considered when most other medications are ineffective

Atypical Antipsychotics: risperidone, olanzapine, quetiapine, ziprasidone Typical Antipsychotics: haloperidol*, thioridazine*, chlorpromazine*, Pemoline (Cylert)*

*FDA approved for treatment of ADHD.

T Axis I Disorders Usually First Diagnosed in Infancy

CHILD AND ADOLESCENT MANIFESTATIONS OF AXIS I DISORDERS

Children may suffer from any of the psychiatric disorders (except antisocial personality disorder,which by definition requires an age of 18) Some disorders have a peak incidence in adolescence andearly adulthood, including anorexia and bulimia nervosa, substance-related disorders, schizophrenia,and mood disorders In general, the earlier the onset of the disorder then the more urgent the need fortreatment to decrease the intensity and chronicity of the disorder Early-onset disorders are morecommon in families with strong genetic loading for the disorder, and/or for children with serious psy-chosocial adversity The prognosis for early-onset psychiatric disorders tends to be worse, as normaldevelopment is interrupted

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