Psychiatry for Neurologists - part 7 pot

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 evalu- ation. Components may be added or omitted as clinically appropriate. 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 affect the 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 258 Stubbe 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. Childhood Disorders 259 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 com- 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’s disorder, and PDD not otherwise specified (NOS). Co-existing mental retardation or learning diffi- 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 of changes 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) and childhood disintegrative disorder (fewer than 100 cases reported) are much less common. Except for Rett’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 recip- 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 associated with mental retardation or learning disabilities (LDs). The PDDs are sometimes observed with a diverse group of other general medical conditions, including chromosomal abnormalities, congenital infec- 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 autis- tic spectrum disorders remains unknown and is likely quite heterogeneous and multifactorial, there are a large number of studies identifying association with various and diverse chromosomal abnor- malities (including deletions, duplications, translocations, trisomies, inversions, mosaicism, ring chromosomes, and complex chromosomal rearrangements). The prevalence of autism in siblings is 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 was applied, 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—genomewide screens for susceptibility genes have demonstrated limited concordance of linked loci. There may be numerous 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 associ- ated with the basal ganglia and neostriatum, including hypotonia or hypertonia, coordination deficits, abnormal reflexes, posture and gait 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 stud- ies have revealed both negative and positive findings. Imaging studies demonstrate a wide range of abnormalities, as well. Computed tomography scans show variable nonspecific changes, such as porencephalic cysts, ventricular enlargement, and abnormal symmetry. Magnetic resonance imaging studies have reported cerebellar hypoplasia and small brainstem structures in autistic patients, as well 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 the mumps, 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 with suspected 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 inborn metabolic, structural, or degenerative diseases or seizures. An electroencephalogram (EEG) (to rule out a seizure disorder or developmental regression), chromosome analysis (for fragile X, etc.), and labwork 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 disor- der does not cause delays in language development, cognitive development, age-appropriate self-help skills, or adaptive behavior. The child typically develops intense but unusual interests and loses social skills. 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 of purposeful 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 and medical diagnoses to be ruled out are given in Table 3. There is a high degree of co-morbidity of autistic spectrum-disordered patients with mental retar- 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, anxiety disorders (generalized anxiety or obsessive-compulsive features) and ADHD are frequently co-morbid. 260 Stubbe Course and Prognosis Autistic disorder is often apparent in early infancy, with delayed developmental milestones, delayed social 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 or regressed developmental trajectory. Early diagnosis and multimodal intervention may markedly improve prognosis. Predictors of over- all better adaptive outcome include later manifestation of symptoms, higher IQ, language skills (verbal communication by the age of 5 years), and less impaired social skills. The course of the disorder is quite variable, characterized generally by gradual but erratic improvement punctuated by intermittent regressions (often precipitated by environmental stress or illness). Some children may demonstrate self-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 achieve adaptive functioning within the normal range. About one-third are able to function independently as adults, although deficits in social skills, empathy, and rigid coping skills frequently persist. Treatment Initially thought to be resistant to treatment, autistic individuals with early rigorous multimodal treatment have demonstrated the potential for significant improvement. Essential interventions include Childhood Disorders 261 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, and adaptive 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 or guilt. 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. Parents are 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 cope with frustration and ensuring a safe home environment. Long-term treatment and services are generally required. Vocational training is important as the autistic individual enters adolescence. Acute hospitalization or longer term residential treatment may be required if symptoms are serious and disabling. Co-morbid mood, anxiety disorders, attentional problems 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, psycho- 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 disorders may 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 in these patients because of the length of treatment and perhaps biological vulnerability. Additionally, irritability or activation with the antidepressants or stimulant medications may be seen. The antipsychotic medications are the most widely studied of the medications used in children and adolescents 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 262 Stubbe 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 control behavioral 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. Psycho- 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 reuptake inhibitors (SSRIs) such as fluvoxamine may reduce obsessive-compulsive behaviors. Clomipramine may decrease the frequency of some self-abusive behaviors. Fluoxetine can relieve depressive symp- toms in adolescents with autism. β-blockers and the α-2-agdrenergic receptor agonist clonidine have demonstrated effectiveness for decreasing 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 the opiate 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 their families. MENTAL RETARDATION The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM- IV-TR) diagnosis of mental retardation requires low intellectual functioning (IQ of 70 or below on an individually 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- tional academic skills, work, leisure, health, and safety); with an onset before the age of 18 years (4). Table 4 provides an overview of the features of mental retardation. Epidemiology The prevalence of mental retardation in the United States is estimated at about .8%, with by far the largest 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 in associated seizures, physical, and sensory handicaps increasing with the increasing severity of the mental 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 other chemicals), 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 in irreversible cognitive impairments. Diagnosis Some genetic syndromes may be diagnosed via prenatal or postnatal screening. Poor muscle tone and 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 Childhood Disorders 263 retardation is not necessarily a lifelong disorder. Some individuals may acquire a high level of adap- tive and independence skills to the level that they no longer meet diagnostic criteria. The diagnostic evaluation of a child with developmental delay should include a detailed obstetri- 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 metabolic disorders, etc.), an EEG , or neuroimaging may be indicated. Psychological testing by a psychologist experienced 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 developing psychopathology. 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 a higher 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 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, children with 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 in alleviating 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 in the environment provided. Medications may be utilized to target secondary symptoms of psychiatric illness or aggression, as needed. 264 Stubbe Table 4 Features of Mental Retardation Mild Moderate Severe Profound IQ level 50–55 to 70 35–40 to 50–55 20–25 to 35–40 Below 20−25 Population .5% < .2% < .1% < .05% Prevalence Percentage of MR 85% 10% 4% 1% population Educational Educable Trainable Simple skills Mostly Expectations Nonverbal Functional Independent Sheltered Supervised Highly Expectations Living Living Living Supervised Living Independent Minimal Supervised ADLs Assisted ADLs ADLs assistance 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 that may 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, a constellation 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 some level of learning and/or communication disorder. About 5.3% of all students in US public schools receive 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 higher cognitive processes suggests that functional neurocognitive deficits of multiple types that disrupt cog- nitive processing may lead to learning difficulties. Both hereditary and environmental factors have been implicated in reading disorders. Prematurity, perinatal adversity, poverty, malnutrition, poor schooling, 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’s intelligence, 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 on standardized 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 of self-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 secondary morbidity 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 for special education services, and an individualized educational program to provide interventions that directly address the LD, is indicated. Specialized tutoring or other types of educational support are individualized 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. Children that 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 the disability as an area in which the child needs to work harder than many peers may help increase Childhood Disorders 265 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 some children and adolescents with co-occurring psychiatric issues. Therapeutic interventions should be coordinated 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 dollars spent annually for school services, mental health services, and increased use of the juvenile justice system. 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-IV classification 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 3Ϻ1 as compared with girls. Clinic samples tend to be higher, approaching a 9Ϻ1 male to female ratio, 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 an increase 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 be multiple 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 and impulsivity, or the combination of both sets of symptoms. A variety of other psychiatric disorders may present 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, adop- tion, and segregation analysis strongly suggest that there is genetic component in the etiology for the disorder. ADHD is thought to be a complex genetic disorder resulting from the combined effects of several genes and interactions with the environment. Preliminary molecular genetic studies have implicated candidate genes associated with the dopamine system, including the dopamine D2 and D4 receptors and the dopamine transporter. There is also preliminary evidence that genes involved in norepinephrine 266 Stubbe modulation are affected in some patients. Given the importance of these catecholamines for the modu- lation of attentional circuits, it is not surprising that alterations in these systems would result in impaired attention regulation. However, there is a great deal of study left to be done on the role of genes and the gene–environment interaction in the etiology of ADHD (21). Neurodevelopmental Factors Prefrontal, parietal, and temporal association cortices, and their projections to the striatum, make distinct 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 neuro- transmitters of dopamine and norepinephrine are both intricately involved in modulating prefrontal cortical 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 impair optimal functioning (23). Brown has argued that the common etiological deficit in all types of ADHD is one of impaired exec- utive functioning. Developmental difficulties with activation, focus, sustaining effort, modulating emotions, utilizing working memory and regulating behaviors are all subsumed under the rubric of 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 functional abnormalities to the frontal cortex and other brain structures, resulting in the disorder. Early findings are 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 psychosocial adversity 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 the brains of children and adults with ADHD. Volumetric measures have detected smaller right-sided prefrontal regions overall in boys with ADHD. These reductions correlated with performance on tasks that require response inhibition. Girls with ADHD have been found to have smaller left and total caudate volumes. A consistent finding in ADHD has been reduced volume of the posterior–inferior cerebellar vermis, a region that exhibits a high degree of dopamine receptor reactivity. Functional neuroimaging has demonstrated decreased metabolism in the regions of the prefrontal cortex and striatum in adults with ADHD by positron emission tomography (PET) scanning. Although functional 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 notion that 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 for ADHD, 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-IV diagnostic criteria for the disorder. Hyperactivity is a symptom of many disorders, and therefore the differential diagnosis of ADHD is quite extensive. The clinician must complete a thorough assess- ment to clarify the diagnosis and nature of the disabling symptoms. 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Hyperactivity Disorder: A Handbook for Diagnosis and Treatment, Secondnd Edition New York, NY: Guilford; 1998 26 Conners CK Conners ADHD DSM-IV Scales for Parents and Teachers: Technical Manual North Tonowanda, New York: Multi Health Systems; 19 97 27 MTA Cooperative Group Moderators and mediators of treatment response for children with attention-deficit/hyperactivity disorder Arch Gen Psychiatry 1999;56:1088–1096... developmental disorder-not otherwise specified, and the general population Pediatrics 2001;1 07: E63 11 Fidler DJ, Bailey JN, Smalley SL Macrocephaly in autism and other pervasive developmental disorders Dev Med Child Neurol 2000;42 :73 7 74 0 12 Todd RD, Hickok IM, Anderson GM, Cohen DJ Antibrain antibodies in infantile autism Biol Psychiatry 1988;23:644–6 47 13 American Academy of Child and Adolescent Psychiatry. .. was higher in a group of elderly depressed patients with the serotonin-linked promoter region polymorphism, which could translate to a higher risk of heart disease (5) However, two other polymorphisms, the very low-density lipoprotein receptor (VLDL-R) encoding for the VLDL cholesterol-receptor and DCP-1 encoding for the angiotensin-converting enzyme were not found to relate to increased depression in... 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Current Clinical Neurology: Psychiatry for Neurologists Edited by: D.V Jeste and J.H Friedman © Humana Press Inc., Totowa, NJ 279 280 Depp and Corey-Bloom Third, as opposed to some neurological disorders such as Huntington’s disease and AD, we do not have at our disposal pathognomonic signs, biological markers, or definitive neurobiological models for schizophrenia or depression For example, lesions in... disorder, similar attempts have been made to differentiate late-onset form early-onset bipolar disorder Limited data suggests that later onset is associated with a higher frequency of neurological illnesses, although the evidence for lower family history in late-onset groups is mixed (7) Features of depression that may indicate higher severity are co-morbid anxiety, psychosis, and cognitive impairment (14)... nervosa, substance-related disorders, schizophrenia, and mood disorders In general, the earlier the onset of the disorder then the more urgent the need for treatment to decrease the intensity and chronicity of the disorder Early-onset disorders are more common in families with strong genetic loading for the disorder, and/or for children with serious psychosocial adversity The prognosis for early-onset psychiatric... from the University of California, San Diego (UCSD) Center on Late-Life Psychosis, depressive symptoms ( 47) and anxiety symptoms (48) also appear to relate to substantially reduced health-related quality of life in middle-aged and older outpatients with schizophrenia As in depression, researchers have attempted to distinguish late-onset variants of schizophrenia from early-onset schizophrenia In a review . self-abusive behaviors. Fluoxetine can relieve depressive symp- toms in adolescents with autism. β-blockers and the -2 -agdrenergic receptor agonist clonidine have demonstrated effectiveness for decreasing. 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. disorder. Early-onset disorders are more common in families with strong genetic loading for the disorder, and/or for children with serious psy- chosocial adversity. The prognosis for early-onset psychiatric