Is there stimulant sensitivity in children?

It has been suggested that exposure to stimulants alters the dopamine system and thus enhances sensitivity to stimulants and possibly other drugs. Sensitization has been induced experimentally in animals, especially in rats, and has been shown to be long-lasting. In addition, cross-sensitization across different compounds has been demonstrated. The animal data have raised concern that exposure to methylphenidate in childhood may enhance the risk for later abuse of stimulants and other drugs. We review the evidence bearing on sensitization in children treated with stimulants and followed into adulthood. None of four clinic-based studies found an excess of drug abuse in children previously treated with stimulants. A school-based longitudinal study obtained a relationship between early stimulant treatment and later drug use, without controlling for dinical confounds. The single prospective-controlled study of children who received placebo or methylphenidate does not support the sensitization hypothesis.

Obsessive-compulsive disorder and separation anxiety co-morbidity in early onset panic disorder.

BACKGROUND: This study was undertaken to examine the relationship between anxiety co-morbidity and age of onset of panic disorder. METHODS: Age of onset of panic disorder and co-morbid anxiety disorders were assessed among 201 panic disorder probands with childhood separation anxiety disorder, obsessive-compulsive disorder, obsessive-compulsive symptoms, social phobia and specific phobia as part of a clinician-administered lifetime diagnostic interview. A generalized linear model was used to test the association between each anxiety co-morbidity and age of panic disorder onset while simultaneously controlling for the potential confounding effects of sociodemographic characteristics and other psychiatric co-morbidity. RESULTS: Earlier onset of panic disorder was found in patients with co-morbid obsessive-compulsive disorder, obsessive-compulsive symptoms and separation anxiety disorder, but not simple phobia or social phobia. Patients with both childhood separation anxiety disorder and obsessive-compulsive disorder had an even earlier panic onset than those with either childhood separation anxiety disorder or obsessive-compulsive disorder. CONCLUSIONS: The association between anxiety co-morbidity and earlier onset of panic disorder is specific to obsessive-compulsive disorder and childhood separation anxiety disorder.

Long-term prognosis in attention-deficit/hyperactivity disorder.

The authors have traced the developmental course of ADHD from childhood to adulthood, showing that it is a bumpy road for many. In early and middle adolescence, relative deficits are seen in academic and social functioning, ADHD symptoms remain problematic in two thirds to three quarters of these children, and antisocial behaviors, in some cases amounting to CD, are common. Many of these same difficulties persist into the late teenage years. Deficits continue to be observed in academic and social domains (compared with controls, probands exhibit lower grades, more courses failed, worse performance on standardized tests, have fewer friends, and are rated less adequate in psychosocial adjustment). About two fifths continue to experience ADHD symptoms to a clinically significant degree. One quarter to one third have a diagnosed antisocial disorder, and two thirds of these individuals are arrested. Also, drug abuse is observed in a significant minority of these youths. Importantly, the greatest risk factor for the development of antisocial behavior and substance abuse by the late teenage years is the maintenance of ADD symptoms. When evaluated in their mid-twenties, dysfunctions are apparent in these same areas. Compared with controls, probands complete less schooling, hold lower-ranking occupations, and continue to suffer from poor self-esteem and social skills deficits. In addition, significantly more probands than controls exhibit an antisocial personality and, perhaps, a substance use disorder in adulthood. Furthermore, many do not outgrow all facets of their childhood syndrome. These relative deficits, however, do not tell the whole story of the ADHD child's adult fate. Indeed, nearly all probands were gainfully employed. Furthermore, some had achieved a higher-level education (e.g., completed Master's degree, enrolled in medical school) and occupation (e.g., accountant, stock broker). In addition, a full two thirds of these children showed no evidence of any mental disorder in adulthood. In conclusion, although ADHD children, as a group, fare poorly compared with their non-ADHD counterparts, the childhood syndrome does not preclude attaining high educational and vocational goals, and most children no longer exhibit clinically significant emotional or behavioral problems once they reach their mid-twenties.

Specific phobia 10-16 years after treatment.

Twenty eight participants, initially treated for specific phobia as part of a comparative treatment study, were evaluated 10 to 16 years (X = 12 years) later. A comprehensive, in-person, semi-structured diagnostic interview was utilized, which also assessed comorbid disorders. Of 21 patients who had been rated as responders (much improved or very much improved) at treatment termination, 13 (62%) had clinically significant avoidance or endurance with dread subsequent to treatment. Among a subgroup of these responders who had been considered completely recovered (n = 11), 5 (45%) had clinically significant symptoms following treatment. None of the seven subjects who had been considered unimproved at treatment termination recovered from phobia symptoms in the intervening years. Positive response to treatment was associated with better long term outcome. Clinical characteristics, such as phobia subtype, age of onset, baseline severity, and lifetime comorbidity of other psychiatric disorders were not associated with long term outcome in this sample. Type of treatment was not associated with long term outcome. Results challenge the notion that recovery from specific phobia following treatment is characterized by complete and enduring cessation of symptoms.

Adolescent depression: controlled desipramine treatment and atypical features.

The study was designed to test the efficacy of desipramine in adolescents with major depression (MDD). In addition, we assessed the presence of atypical features of MDD, consisting of mood reactivity and two of four associated features (rejection sensitivity, hyperphagia, hypersomnia, and leaden paralysis). Patients were randomized to desipramine (DMI) or placebo for 6 weeks, provided they failed to improve (e.g., meeting MDD criteria and a Hamilton Depression Scale score > or = 18) after 2 weeks on single blind placebo. Of 94 adolescents (ages 13-18) who were diagnosed as having MDD, 64 entered the study and 62 received placebo for 2 weeks. Of these, 45 were randomized to DMI or placebo. Completed analyses did not reveal significant improvement for the active treatment compared to the placebo. A large proportion of adolescents responded to placebo (50%), suggesting the need for very large samples to detect differential treatment efficacy, should it exist. A relatively high rate of atypical depression was observed (47% in the 64 patients entered). In view of the demonstrated specificity of monoamine oxidase inhibitor efficacy in adults with atypical features of MDD, this clinical subtype may have relevance to future investigation of therapeutic interventions in adolescent MDD.

Adult psychiatric status of hyperactive boys grown up.

OBJECTIVE: Numerous studies have examined the adolescent and young adult fate of children with attention deficit hyperactivity disorder (ADHD). In marked contrast, relatively little is known about the adult outcome of these children. There have been only two controlled, prospective studies of psychiatric status into adulthood. The present study was conducted to gain further understanding of the natural course of this common childhood condition. METHOD: This was a prospective follow-up of clinically diagnosed, white boys of average intelligence who were referred by teachers to a child psychiatric research clinic at an average age of 7.3 years. At a mean age of 24.1 years, 85 probands (82% of the childhood cohort) and 73 comparison subjects (94% of adolescent comparison subjects) were directly interviewed by trained clinicians who were blind to group status. RESULTS: Evaluations of the probands and comparison subjects indicated significantly higher prevalences of antisocial personality disorder (12% versus 3%) and nonalcohol substance abuse (12% versus 4%) in the probands, whereas mood disorders (4% versus 4%) and anxiety disorders (2% versus 7%) were not significantly different. At adult follow-up, ADHD was rare, occurring in only 4% of the probands (no comparison subjects). CONCLUSIONS: The results of the present study are consistent with the authors' previously reported major findings. They strongly suggest that children with ADHD are at significantly higher risk for a specific negative course marked by antisocial and substance-related disorders.

Educational and occupational outcome of hyperactive boys grown up.

OBJECTIVE: Little is known about the adult outcome of attention-deficit hyperactivity disorder (ADHD), a very prevalent childhood disorder that is known to affect deleteriously academic performance and other areas of child functioning. This study represents a third wave of evaluations that examine the long-term educational achievement and occupational rank of children with ADHD. METHOD: This is a prospective follow-up of white boys of average intelligence whose ADHD was clinically diagnosed according to systematic criteria at an average age of 7 years. Follow-up intervals range from 15 to 21 years (mean, 17 years). At average age 24 years, 85 probands (representing 82% of the childhood cohort) and 73 controls (84%) were directly interviewed by trained clinicians who were blind to group membership. RESULTS: First, probands completed significantly less formal schooling than controls (about 2 years less, on average). Second, probands had lower-ranking occupational positions than controls. Finally, these disadvantages were not accounted for by adult mental status. CONCLUSIONS: The present study suggests that childhood ADHD predisposes to specific disadvantages and continues to affect important functional domains unrelated to current psychiatric diagnosis.

Panic disorder and quality of life: variables predictive of functional impairment.

OBJECTIVE: The authors sought to characterize the functional impairment in patients with panic disorder, specifically the variance in impairment explained by demographic and clinical variables. METHOD: Sixty-two patients with panic disorder and 61 comparison subjects from three primary care clinic sites were assessed with an adapted form of the Structured Clinical Interview for DSM-III-R. Impairment was assessed according to three measures from the 36-item Short-Form Health Survey (general health perception, mental health, and physical functioning) as well as a principal component factor of the survey. Subjects were also compared with respect to personality variables, presence and severity of chronic medical illness, and demographic characteristics. Stepwise multiple regressions with and without pairwise interactions were used to construct models of disability in the patients with panic disorder. RESULTS: The patients with panic disorder were more impaired than comparison subjects on each measure of the Short-Form Health Survey. The panic disorder diagnosis combined with major depression, increasing neuroticism and age, less education, and an interaction between panic disorder and age accounted for 48%-77% of the variance in impairment scores. Gender and ethnicity contributed modestly to the variance in impairment in physical functioning, whereas no contribution was demonstrated for chronic medical illness or city of residence. CONCLUSIONS: Factors in addition to panic phenomena contribute to the severe impairment seen in patients with panic disorder. Further research about factors that affect impairment may help improve clinical approaches to this illness.

Test-retest reliability of maternal reports of lifetime mental disorders in their children.

This study examined the test-retest reliability of maternal reports of lifetime psychopathology using DSM-III-R criteria in nonreferred offspring. Sixty-three mothers reported on 79 children, ages 6 to 18 years. Retest intervals were between one and 12 months. The results indicated acceptable reliability for all supraordinate categories (any disorder, any anxiety disorder, any disruptive disorder, externalizing disorders, internalizing disorders) as well as for most individual diagnoses (separation anxiety disorder, simple phobias, oppositional defiant disorder, attention deficit disorder with and without hyperactivity, simple phobias, and adjustment disorder). Maternal reports for any diagnosis were significantly better for intervals under 6 months than for longer retest intervals. Reliability of maternal reports was not significantly affected by child's age or gender. This study supports the expectation that a history of psychiatric disturbance in children can be obtained reliably from mothers.

The DSM-IV panic disorder field trial: panic attack frequency and functional disability.

The goal of the DSM-IV panic disorder field trial was to provide an empirical basis for choosing between alternate proposals (DSM-III-R and proposed DSM-IV) for the diagnostic threshold for panic disorder, in particular the number and frequency of panic attacks required for diagnosis. The two criteria sets were compared with respect to their ability to identify individuals whose panic attacks were associated with distress, impairment, or help-seeking. Subjects were a convenience sample screened in three geographically diverse primary care clinics for presence (past 6 months) or absence (lifetime) of panic attacks. Each underwent a clinician-administered semistructured interview which included assessment of panic frequency, panic-related impairment, psychiatric diagnosis, health services utilization, and medical illness. Self-perceived health-related quality of life was assessed using the Medical Outcome Study SF-36 Health Survey Questionnaire. Although both proposals diagnosed the same proportion of panic-impaired individuals, they were not completely overlapping. Twenty percent of subjects diagnosed by each criteria set were excluded by the other. Subjects who had been excluded by the DSM-III-R but included by the DSM-IV proposal were those with fewer than 4 attacks in 4 weeks who also denied worry about the "next" attack. Broadening the worry criterion to include concerns about the health implications of attacks enabled diagnosis of this group. Subjects who met DSM-III-R, but not the proposed DSM-IV criteria, had 4 attacks in 4 weeks but denied any panic related worry. Modification of the DSM-IV proposal to include a month of worry or "a significant change in behavior related to the attacks" allowed inclusion of this group in the diagnostic category. These data suggest that the finalized DSM-IV panic disorder criteria will diagnose a greater proportion of individuals whose panic attacks are associated with impairment without inflating the diagnostic category or significantly reducing specificity.

Panic disorder and social phobia: effects of comorbidity on familial transmission.

The aim of this study was to examine effects of comorbidity of panic disorder and social phobia on familial transmission of each of these disorders. Rates of panic disorder and social phobia were compared in directly interviewed relatives of four proband groups: (1) panic disorder, (2) social phobia, (3) panic disorder and social phobia, and (4) never ill controls. Anxiety disorder probands had no additional lifetime anxiety disorder comorbidity. The familial pattern of the comorbid (panic disorder and social phobia) probands resembled that of the panic disorder group: an increased rate of panic disorder but not social phobia as compared to relatives of controls. Relatives of social phobia probands had an increased rate of social phobia but not panic disorder. These data indicate that social phobia in individuals who subsequently develop panic disorder: (1) differs with respect to familial transmission from social phobia which occurs without lifetime anxiety comorbidity; and (2) may be nonfamilial and/or causally related to panic disorder. Additional studies in larger epidemiologic samples are required to assess generalizability of these findings.

Specificity in familial aggregation of phobic disorders.

BACKGROUND: To investigate whether each of three DSM-III-R phobic disorders (simple phobia, social phobia, and agoraphobia with panic attacks) is familial and "breeds true." DESIGN: Rates of each phobic disorder were contrasted in first-degree relatives of four proband groups: simple phobia, social phobia, agoraphobia with panic attacks, and not ill controls. Phobia probands were patients who had one of the phobia diagnoses but no other lifetime anxiety comorbidity. RESULTS: We found moderate (two- to fourfold increased risk) but specific familial aggregation of each of the three DSM-III-R phobic disorders. CONCLUSIONS: These results support a specific familial contribution to each of the three phobia types. However, conclusions are limited to cases occurring without lifetime anxiety comorbidity and do not imply homogeneity within categories.

Is self-esteem an important outcome in hyperactive children?

Using a prospective design, this study examined (a) whether hyperactive children suffer from low self-esteem as adolescents; (b) whether low self-esteem is associated with poor functioning in adolescence; (c) whether hyperactive children exhibit a positive illusory bias, in which self-esteem is independent of level of functioning; and (d) whether self-esteem in adolescence is associated with poor functioning in adulthood. Subjects were 65 children diagnosed as hyperactive in childhood, and 62 matched controls sampled from a medical clinic. After controlling for current mental disorder, the hyperactive cohort reported lower self-esteem in adolescence, was judged by clinicians to have lower levels of overall adjustment in adolescence, and had lower educational achievement and occupational rank in adulthood, as compared to controls.

Generalized social phobia. Reliability and validity.

OBJECTIVE: To investigate the reliability and validity of DSM-III-R "generalized" social phobia by examining interrater agreement and comparing patients with generalized and "nongeneralized" social phobia on demographic characteristics, clinical variables, and familial social phobia. DESIGN: Two senior clinicians classified 129 patients attending an anxiety clinic as having DSM-III-R social phobia that is generalized (fears most social situations) or nongeneralized (less than most) based on independent narrative review. RESULTS: Good reliability was achieved (kappa = 0.69). Patients with generalized social phobia were more often single, had earlier onsets of social phobia, had more interactional fears, and had higher rates of atypical depression and alcoholism. Familial social phobia was more common among patients with generalized social phobia than patients with nongeneralized social phobia and controls, with no difference between the latter two groups. CONCLUSIONS: Generalized social phobia (1) can be distinguished reliably from nongeneralized social phobia, (2) is a valid subtype, and (3) may characterize a familial form of the disorder.

Infrequent panic attacks: psychiatric comorbidity, personality characteristics and functional disability.

Primary care patients with infrequent panic attacks were found to have similar levels of disability in their social, family and vocational functioning to patients who met DSM-III-R criteria for panic disorder. Both panic subgroups had significantly more functional disability than controls. Patients with panic and infrequent panic had significantly more Axis I psychiatric comorbidity than primary care controls but similar levels of medical comorbidity. Patients with panic disorder had a significantly higher prevalence of one or more other lifetime psychiatric diagnoses, current major depression, and current DSM-III-R depressive symptoms compared to patients with infrequent panic. Patients with infrequent panic scored as high on the NEO personality measure of neuroticism as patients with panic disorder, and both panic subgroups had significantly higher neuroticism levels than controls.

Sodium lactate response and familial risk for panic disorder.

OBJECTIVE: The authors used the family study method to test the hypothesis that sodium lactate response defines two subtypes of panic disorder. METHOD: Rates of panic disorder in 142 first-degree relatives of patients who responded to sodium lactate, 88 first-degree relatives of patients who did not respond to sodium lactate, and 231 first-degree relatives of never mentally ill subjects were compared. RESULTS: No difference in familial transmission of panic disorder was found between the two patient groups. CONCLUSIONS: The findings do not support the notion that panic disorder subtypes are associated with lactate sensitivity.

Childhood separation anxiety disorder in patients with adult anxiety disorders.

The authors examined the relation between retrospectively reported childhood separation anxiety disorder and adult DSM-III-R anxiety disorders in 252 outpatients at an anxiety disorders research clinic. The prevalence of childhood separation anxiety disorder was significantly greater among patients with two or more lifetime adult anxiety disorder diagnoses than it was among patients with only one anxiety disorder, suggesting that childhood separation anxiety disorder may be a risk factor for multiple anxiety syndromes in adulthood.

Effects of informant mental disorder on psychiatric family history data.

OBJECTIVE: In family history interviews, mentally ill individuals ascribe their own disorders to relatives more frequently than informants who are not ill. Whether this reflects increased or decreased reporting accuracy remains unknown. This study addressed this issue by examining the sensitivity and specificity of diagnoses based on information from different types of informants classified by their own illness status. METHOD: Both members of 2,193 pairs of individuals participating in a psychiatric family study were directly interviewed. One individual in each pair (the informant) also provided family history data about the other (the subject). Informant-subject pairs were grouped according to the illness status of the informant based on the direct interview. Patterns of ascription of mental illness to subjects by groups of ill and not-ill informants were then compared with the subjects' psychiatric status based on direct interview. RESULTS: For depression, alcoholism, panic disorder, and "any diagnosis," ill informants demonstrated significantly increased sensitivity in family history reports when compared to never-mentally-ill informants; specificity, by contrast, was always significantly reduced. For each disorder, the aggregate disorder rate derived from family history reports was closer to the rate derived from direct interviews if information from ill informants as a group was used. CONCLUSIONS: The sensitivity and specificity of family history information appears to vary systematically with informant mental illness status. This may introduce a serious bias into psychiatric family study data, leading to overestimation of the strength of the tendency for mental disorders to "run in families." Family studies that rely on the informant method in their diagnostic evaluations should be aware of this problem.

Familial transmission of panic disorder: effect of major depression comorbidity.

This study assesses the effect of major depressive disorder (MDD) comorbidity on familial transmission of panic disorder (PD). The following questions are addressed: (1) is PD familial, i.e., do relatives of patients with PD show an increased risk for PD? (2) do PD and MDD share a common diathesis, i.e., do relatives of patients with PD without MDD show an increased risk for MDD? (3) is lifetime comorbid PD with MDD conjointly familial, i.e., do relatives of patients with PD and MDD show an increased risk for the combined syndrome? Subjects were: (1) 152 relatives of 54 anxiety clinic patients with PD and MDD; (2) 193 relatives of 72 patients with PD without MDD; (3) 231 relatives of 77 not ill controls. Relatives were interviewed by clinicians, and best estimate DSM-III-R diagnoses were formulated by senior staff. Relatives of PD with MDD (13%) and PD without MDD probands (9%) showed significantly higher rates of PD than relatives of controls (3%). Relatives of PD with MDD probands (37%) showed significantly higher rates of MDD than relatives of PD without MDD (24%) and controls (21%), with no difference between the latter two groups. Relatives of PD with MDD probands (9%) showed significantly higher rates of PD with MDD than relatives of PD without MDD (3%) and controls (1%). We conclude that: (1) PD is familial; (2) PD in the absence of MDD does not incur increased risk of MDD to relatives; and (3) PD with MDD may represent a distinct, complex syndrome.

Adult outcome of hyperactive boys. Educational achievement, occupational rank, and psychiatric status.

OBJECTIVE: The paucity of data concerning the long-term natural history of attention-deficit hyperactivity disorder (ADHD), a common childhood psychiatric disorder, prompted a longitudinal study to investigate the adult sequelae of the childhood disorder. DESIGN: Prospective study, follow-up intervals ranging from 13 to 19 years (mean, 16 years), with blind systematic clinical assessments. SUBJECTS: Ninety-one white males (mean age, 26 years), representing 88% of a cohort systematically diagnosed as hyperactive in childhood, and 95 (95%) of comparison cases of similar race, gender, age, whose teachers had voiced no complaints about their school behavior in childhood. RESULTS: Probands had significantly higher rates than comparisons of ADHD symptoms (11% vs 1%), antisocial personality disorders (18% vs 2%), and drug abuse disorders (16% vs 4%). Significant comorbidity occurred between antisocial and drug disorders. Educational and occupational achievements were significantly compromised in the probands. These disadvantages were independent of psychiatric status. We did not find increased rates of affective or anxiety disorders in the probands. CONCLUSIONS: Childhood ADHD predicts specific adult psychiatric disorders, namely antisocial and drug abuse disorders. In the adolescent outcome of this cohort, we found that these disturbances were dependent on the continuation of ADHD symptoms. In contrast, in adulthood, antisocial and drug disorders appeared, in part, independent of sustained ADHD. In addition, regardless of psychiatric status, ADHD placed children at relative risk for educational and vocational disadvantage. The results do not support a relationship between childhood ADHD and adult mood or anxiety disorders.