Showing papers by "Stephen V. Faraone published in 1995"

Mania-like symptoms suggestive of childhood-onset bipolar disorder in clinically referred children.

Abstract: Objective To examine the prevalence, characteristics, and correlates of mania among referred children aged 12 or younger. Many case reports challenge the widely accepted belief that childhood-onset mania is rare. Sources of diagnostic confusion include the variable developmental expression of mania and its symptomatic overlap with attention-deficit hyperactivity disorder (ADHD). Method The authors compared 43 children aged 12 years or younger who satisfied criteria for mania, 164 ADHD children without mania, and 84 non-ADHD control children. Results The clinical picture was fully compatible with the DSM-III-R diagnosis of mania in 16% ( n = 43) of referred children. All but one of the children meeting criteria for mania also met criteria for ADHD. Compared with ADHD children without mania, manic children had significantly higher rates of major depression, psychosis, multiple anxiety disorders, conduct disorder, and oppositional defiant disorder as well as evidence of significantly more impaired psychosocial functioning. In addition, 21% ( n = 9) of manic children had had at least one previous psychiatric hospitalization. Conclusions Mania may be relatively common among psychiatrically referred children. The clinical picture of childhood-onset mania is very severe and frequently comorbid with ADHD and other psychiatric disorders. Because of the high comorbidity with ADHD, more work is needed to clarify whether these children have ADHD, bipolar disorder, or both. J. Am. Acad. Child Adolesc. Psychiatry , 1995, 34, 7:867–876.

Psychoactive substance use disorders in adults with attention deficit hyperactivity disorder (ADHD): effects of ADHD and psychiatric comorbidity.

Abstract: Objective: The authors evaluated the association between attention deficit hyperactivity disorder (ADHD) and psychoactive substance use disorders in adults with ADHD, attending to comorbidity with mood, anxiety, and antisocial disorders. It was hypothesized that psychiatric comorbidity would be a risk factor for psychoactive substance use disorders. Method: Findings for 120 referred adults with a clinical diagnosis ofchildhood-onset ADHD were compared with those for non-ADHD adult comparison subjects (N=268). All childhood and adult diagnoses were obtained by structured psychiatric interviews for DSM-III-R. R� �iiIt.�i There was a significantly higher lifetime risk for psychoactive substance use disorders in the ADHD adults than in the comparison subjects (52% versus 27%). Although the two groups did not differ in the rate ofalcohol use disorders, the ADHD adults had significantly higher rates ofdrug and drug plus alcohol use disorders than the comparison subjects. ADHD significantly increased the risk for substance use disorders independently ofpsychiatric comorbidity. Antisocial disorders significantly increased the risk for substance use disorders independently ofADHD status. Mood and anxiety disorders increased the risk for substance use disorders in both the ADHD and comparison subjects, but more demonstrably in the comparison subjects. Conclusions: Although psychiatric comorbidity increased the risk for psychoactive substance use disorders in adults with ADHD, by itself ADHD was a significant risk factor for substance use disorders. More information is needed to further delineate risk and protective factors mediating the development ofsubstance use disorders in persons with ADHD. (AmJ Psychiatry 1995; 152:1652-1658)

Family-environment risk factors for attention-deficit hyperactivity disorder. A test of Rutter's indicators of adversity.

Abstract: Background: This study investigated whether familyenvironment risk factors are associated with attentiondeficit hyperactivity disorder (ADHD). Compelling work by Rutter and coworkers revealed that it was the aggregate of adversity factors (severe marital discord, low social class, large family size, paternal criminality, maternal mental disorder, and foster care placement) rather than the presence of any single factor that led to impaired development. Based on the work of Rutter, we hypothesized a positive association between indicators of adversity and the diagnosis of ADHD and ADHD-associated impairments. Methods: We studied 140 ADHD and 120 normal control probands. Subjects were non-Hispanic white boys between the ages of 6 and 17 years. Rutter's indicators of adversity were used to predict ADHD-related psychopathology as well as impaired cognitive and psychosocial functioning. Results: The odds ratio for the diagnosis of ADHD increased as the number of Rutter's adversity indicators increased. Higher scores on Rutter's adversity index predicted ADHD-related psychopathology (depression, anxiety, and conduct disorder), learning disabilities, cognitive impairment, and psychosocial dysfunction. Conclusions: A positive association appears to exist between adversity indicators and the risk for ADHD as well as for its associated psychiatric, cognitive, and psychosocial impairments. These findings support the work of Rutter and stress the importance of adverse family-environment variables as risk factors for children with ADHD.

A Double-blind, Crossover Comparison of Methylphenidate and Placebo in Adults With Childhood-Onset Attention-Deficit Hyperactivity Disorder

Abstract: Background: There are few controlled studies of methylphenidate hydrochloride in adults with attentiondeficit hyperactivity disorder (ADHD), and their results have been equivocal. The discrepancies among these studies may be related to low doses, diagnostic uncertainties, and lack of attention to comorbid disorders. Methods: We conducted a randomized, 7-week, placebo-controlled, crossover study of methylphenidate in 23 adult patients with DSM-III-R ADHD using standardized instruments for diagnosis, separate assessments of ADHD and depressive and anxiety symptoms, and a robust daily dose of methylphenidate hydrochloride, 1.0 mg/kg per day. Results: We found a marked therapeutic response for methylphenidate treatment of ADHD symptoms that exceeded the placebo response (78% vs 4%, P Conclusion: Robust doses of methylphenidate are effective in the treatment of adult ADHD.

Differential heritability of adult and juvenile antisocial traits.

Abstract: Background: Studies of adult antisocial behavior or criminality usually find genetic factors to be more important than the family environment, whereas studies of delinquency find the family environment to be more important. We comparedDSM-III-Rantisocial personality disorder symptoms before vs after the age of 15 years within a sample of twins, rather than comparing across studies. Methods: We administered the Diagnostic Interview Schedule Version III—revised by telephone to 3226 pairs of male twins from the Vietnam Era Twin Registry. Biometrical modeling was applied to each symptom of antisocial personality disorder and summary measures of juvenile and adult symptoms. Results: Five juvenile symptoms were significantly heritable, and five were significantly influenced by the shared environment. Eight adult symptoms were significantly heritable, and one was significantly influenced by the shared environment. The shared environment explained about six times more variance in juvenile antisocial traits than in adult traits. Shared environmental influences on adult antisocial traits overlapped entirely with those on juvenile traits. Additive genetic factors explained about six times more variance in adult vs juvenile traits. The juvenile genetic determinants overlapped completely with genetic influences on adult traits. The unique environment (plus measurement error) explained the largest proportion of variance in both juvenile and adult antisocial traits. Conclusions: Characteristics of the shared or family environment that promote antisocial behavior during childhood and early adolescence also promote later antisocial behavior, but to a much lesser extent. Genetic causal factors are much more prominent for adult than for juvenile antisocial traits.

High risk for attention deficit hyperactivity disorder among children of parents with childhood onset of the disorder: a pilot study.

Abstract: Objective Although well-documented in clinical and epidemiological studies of attention deficit hyperactivity disorder (ADHD) in children, the familial nature of the adult syndrome has not been well investigated. One approach to evaluate the familial nature of adult ADHD is through a high-risk design aimed at estimating the risk for the disorder in children of parents with child-hood-onset ADHD. Method Children at risk for ADHD were ascertained from the study group of 84 referred adults with clinical diagnoses of childhood onset of the disorder, confirmed by structured interviews. Diagnostic information on the disorder was derived from the ADHD module of the Schedule for Affective Disorders and Schizophrenia for School Age Children--Epidemiologic Version, supplemented with information regarding treatment for ADHD for the affected child and school history including repeated grades, placement in special classes, and tutoring. Results Of the 84 children at risk, 48 (57%) met criteria for ADHD. The rate of the disorder in children of adults with the disorder was significantly higher than the previously reported rate of ADHD among siblings of children with the disorder. Of the 48 ADHD children of parents with the disorder, 36 (75%) were treated for it. The rates of school failure were almost identical to those previously reported in a group of referred children and adolescents with ADHD. Conclusions These results support the validity of the adult diagnosis of ADHD and suggest that the adult form of this disorder may have stronger familial etiological risk factors than its pediatric form. If these results are confirmed, families selected through adult probands with ADHD might be especially useful for testing genetic hypotheses about the disorder.

Attention deficit hyperactivity disorder and comorbid disorders: issues of overlapping symptoms.

Abstract: Objective Since some symptoms are shared by both attention deficit hyperactivity disorder (ADHD) and comorbid psychiatric conditions, it is possible that a diagnosis of ADHD is an artifact of the overlapping symptoms. This article focuses on the assessment of the influence of overlapping symptoms on the diagnosis of ADHD. Method Three groups of subjects were studied: a group of clinically referred children and adolescents, a group of nonreferred adults who were the parents of these children and adolescents, and a group of clinically referred adults with ADHD. The authors assessed the extent of symptom overlap between ADHD and the disorders that frequently co-occur with ADHD; major depression, bipolar disorder, and generalized anxiety disorder. To determine the degree to which this symptom overlap influences these diagnoses, each individual was rediagnosed on the basis of two different techniques that corrected for the overlapping symptoms, a subtraction method and a proportion method. Results The majority of subjects who had both ADHD and a comorbid psychiatric disorder maintained their diagnosis of ADHD when the overlapping symptoms were subtracted. Moreover, when overlapping ADHD symptoms were subtracted, on average, 79% maintained their diagnosis of major depression, 56% maintained their diagnosis of bipolar disorder, and 75% maintained their diagnosis of generalized anxiety disorder. Conclusions These findings show that ADHD is not an artifact of symptoms shared with other psychiatric disorders and that the comorbid conditions themselves are not an artifact of overlapping ADHD symptoms.

CBCL Clinical Scales Discriminate Prepubertal Children with Structured Interview—Derived Diagnosis of Mania from Those with ADHD

Abstract: Objective To evaluate the discriminative ability of the Child Behavior Checklist (CBCL) to identify children with structured interview-derived diagnosis of bipolar disorder. Method We evaluated the convergence of CBCL scales with the diagnosis of mania in 31 children with mania, 120 children with attention-deficit hyperactivity disorder, and 77 prepubertal normal control children aged 12 years or younger. We evaluated the strength of association between each CBCL scale and structured interview-derived diagnoses with total predictive value and the odds ratio. Results Excellent convergence was found between the CBCL scales of Delinquent Behavior, Aggressive Behavior, Somatic Complaints, Anxious/Depressed, and Thought Problems and the diagnosis of mania. Conclusions These findings indicate that the CBCL could serve as a rapid and useful screening instrument to identify manic children in clinical settings.

Neuropsychological functioning among the nonpsychotic relatives of schizophrenic patients: A diagnostic efficiency analysis.

Abstract: Numerous studies suggest that the relatives of schizophrenic patients exhibit neuropsychological impairments that are milder yet similar to those seen among schizophrenic patients. The authors assessed 35 nonpsychotic relatives of schizophrenic patients and 72 normal controls using a clinical and experimental neuropsychological test battery. Three neuropsychological functions met criteria for risk indicators of the schizophrenia genotype: abstraction, verbal memory, and auditory attention. These findings could not be attributed to parental socioeconomic status, education, general visual-spatial ability, or psychopathology. Furthermore, exploratory analyses were performed to determine whether the diagnostic efficiency of the indicators could be adjusted to meet the needs of genetic linkage analyses. These analyses suggest that psychometric considerations may help to create measures for genetic linkage studies.

Psychiatric Comorbidity among Referred Juveniles with Major Depression: Fact or Artifact?

Abstract: Objective The high levels of psychiatric comorbidity reported in juveniles meeting operational definitions at depressive disorders raise both substantive and methodological concerns about whether depression with comorbid disorders should be classified as two disorders or as different manifestations of the same condition. Our purpose was to clarify issues of diagnostic heterogeneity and diagnostic overlap in juvenile depression. Method The sample consisted of consecutively referred children and adolescents ( N = 424) comprehensively evaluated with structured diagnostic interviews and psychosocial assessments. Results A clinical picture compatible with the diagnosis of major depression was identified in 40% of these referred youths. Children meeting criteria for major depression had prototypical symptoms of the disorder, a chronic course, and severe psychosocial dysfunction. In addition, they frequently met criteria for attention-deficit hyperactivity disorder, conduct disorder, and anxiety disorders. These comorbidity findings were not due to symptom overlap among major depression and the co-occurring disorders. For the most part, comorbid disorders preceded the onset of major depression by several years. Conclusions Juvenile depression has a chronic course, severe dysfunction, and high levels of psychiatric comorbidity. Despite symptom overlap, our work suggests that major depression and other conditions may represent different disorders.

Impact of adversity on functioning and comorbidity in children with attention-deficit hyperactivity disorder.

Abstract: Objective Prior research on risk factors for attention-deficit hyperactivity disorder (ADHD) has shown that familial risk factors play a role in the disorder's etiology. This study investigated whether features of the family environment were associated with ADHD. Method One hundred forty children with ADHD and 120 normal control probands were studied. Subjects were Caucasian, non-Hispanic males between the ages of 6 and 17 years. Exposure to parental psychopathology and exposure to parental conflict were used as indicators of adversity, and their impact on ADHD and ADHD-related psychopathology and dysfunction in children was assessed. Results Increased levels of environmental adversity were found among ADHD compared with control probands. The analyses showed significant associations between the index of parental conflict and several of the measures of psychopathology and psychosocial functioning in the children. In contrast, the index of exposure to parental psychopathology had a much narrower impact, affecting primarily the child's use of leisure time and externalizing symptoms. Conclusion A relationship appears to exist between adversity indicators and the risk for ADHD as well as for its associated impairments in multiple domains. These findings confirm previous work and stress the importance of adverse family-environment variables as risk factors for children who have ADHD.

Genetic heterogeneity in attention-deficit hyperactivity disorder (ADHD): gender, psychiatric comorbidity, and maternal ADHD.

Abstract: The authors examined the siblings of 140 attention-deficit hyperactivity disorder (ADHD) and 120 control probands and classified families as antisocial if the proband had conduct disorder or a parent had antisocial personality. Partial support was found for the hypothesis that the ADHD gender effect would be limited to antisocial families. Boys had an increased risk for ADHD compared with girls, but only among siblings from antisocial families. The effect size for predicting ADHD in siblings of probands was greater for maternal compared with paternal ADHD, but only for families exhibiting antisocial disorders. Strong support was found for the hypothesis that, compared with siblings from nonantisocial families, those from antisocial families would have more psychopathology (ADHD, depression, substance use, and conduct disorders). The presence of antisocial disorders signals a distinct subtype of ADHD.

How reliable are maternal reports of their children's psychopathology? One-year recall of psychiatric diagnoses of ADHD children.

Abstract: Objective Although childhood psychiatric diagnoses often rely on maternal reports, little is known about their long-term reliability and diagnostic accuracy. Thus, the authors sought to examine these psychometric features in a cohort of ADHD and control children. Method The sample consisted of 140 referred children with ADHD and 120 normal controls. The authors compared childhood diagnoses based on maternal reports of their children's psychopathology at this baseline assessment with those collected 1 year later. Results Both reliability and accuracy were excellent for ADHD. Reliability and specificity were also excellent for conduct disorder, oppositional defiant disorder, major depression, bipolar disorder, separation anxiety, and multiple anxiety disorders. Reliability and sensitivity were relatively low for simple phobia, social phobia, agoraphobia, and overanxious disorder. Conclusions With some exceptions, maternal reports of their children's psychopathology provided a reliable and accurate means of assessment. Generally, maternally derived diagnoses were less accurate for internalizing compared with externalizing disorders. However, specificity was high for all diagnoses, suggesting that mothers were not biased to report symptoms that had not occurred. J. Am. Acad. Child Adolesc. Psychiatry , 1995, 34, 8:1001–1008.

A pilot family study of childhood-onset mania.

Abstract: Objective To investigate the familial association of attention-deficit hyperactivity disorder (ADHD) and bipolar disorder (BPD) among the first-degree relatives of children with comorbid ADHD and BPD. Background In contrast to a growing body of literature on childhood non-bipolar depression, little is known about childhood BPD. Among the explanations accounting for the lack of recognition and identification of these children is the symptomatic overlap of BPD with ADHD. Family-genetic studies provide information external to the clinical picture and thus are uniquely suited to clarify such issues of diagnostic comorbidity. Method Structured diagnostic interviews were used to obtain DSM-III-R psychiatric diagnoses on first-degree relatives (n = 46) of referred children (aged less or equal to 12 years) satisfying diagnostic criteria for mania using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version (n = 16). For comparison, diagnostic information on the first-degree relatives of non-bipolar ADHD children and control children was examined. Results The results show high rates of comorbidity between BPD and ADHD in children and high rates of both BPD and ADHD in the first-degree relatives of these children. Moreover, ADHD and BPD cosegregated among the relatives of children with BPD. Conclusions These findings, which are consistent with the authors' prior study of children with ADHD, provide family-genetic evidence for the validity of BPD and ADHD when they exist comorbidly in children. Moreover, they suggest that the comorbid condition of ADHD + BPD may be a distinct nosological entity.

Diagnostic accuracy and linkage analysis: how useful are schizophrenia spectrum phenotypes?

Abstract: Objective : Numerous studies suggest that the nonschizophrenic relatives of schizophrenic patients exhibit psychiatric and other features that discriminate them from normal comparison subjects. These features have been put forth as spectrum phenotypes that may be variant manifestations of the schizophrenia genotype. However, most of these studies do not address a key measurement question : does the diagnostic accuracy of these spectrum classifications warrant their use in genetic linkage studies of schizophrenia ? Method : The authors reviewed 30 studies of putative indicators of the schizophrenic genotype : schizotypal personality disorder, eye tracking dysfunction, attentional impairment, auditory evoked potentials, neurological signs, neuropsychological impairment, and allusive thinking. Results : Although each of 42 measures of these indicators discriminated the relatives of schizophrenic patients from the normal comparison subjects, a diagnostic accuracy analysis suggested that only six of these would improve the informativeness of genetic linkage data. Conclusions : Many proposed spectrum phenotypes for schizophrenia may not be useful for linkage analysis because of high false positive rates (poor specificity). Future work aimed at describing and developing phenotypes for linkage analysis should assess the diagnostic accuracy of proposed measures.

Effects of family history and comorbidity on the neuropsychological performance of children with ADHD: preliminary findings

Abstract: Objective Because ADHD is heterogeneous with respect to psychiatric comorbidity, familiality, and learning disabilities, it was hypothesized that such features might influence the severity and pattern of neuropsychological function in ADHD. Method Subjects were 9− to 20-year-old males with DSM-III-R ADHD (n = 65) and normal controls (n = 45). Information on neuropsychological performance was obtained in a standardized manner, blind to the proband's clinical status. Results ADHD probands were significantly impaired on neuropsychological functions compared with controls irrespective of composite psychiatric comorbidity status, and those with a family history of ADHD were most impaired. ADHD probands with learning disabilities showed a pattern suggestive of reduced motor dominance and extremely slow reading speed. Conclusions These results indicate that neuropsychological performance in ADHD is significantly affected by familial status and presence of learning disabilities. The similarity of findings between ADHD children with and without comorbid psychiatric disorders suggests that the neuropsychological impairments in our sample were associated with ADHD. These findings raise the possibility of alterations of cerebral dominance and of frontal networks in ADHD. Further research is needed to replicate these findings in larger samples, to clarify the role of specific comorbid psychiatric disorders, and to assess directly cerebral functioning in subjects with ADHD. J. Am. Acad. Child Adolesc. Psychiatry , 1995, 34, 8:1015–1024.

The Relationship between Tic Disorders and Tourette's Syndrome Revisited

Abstract: Objective The relationship between Tourette's syndrome (TS) and chronic tic disorder is of great clinical and scientific importance because of uncertainties in both prognosis and pharmacotherapeutic strategies. One approach to evaluating the relationship between TS and chronic tics is to examine whether they share similar neuropsychological and psychiatric correlates. Method : Children with TS ( n = 32) and children with chronic tics ( n = 39) were ascertained from an unselected sample of the children referred for psychopharmacological treatment and examined using standardized diagnostic assessments and testing procedures. Results Children with TS and those with chronic tics were similar to each other and different from controls in clinical correlates that included psychiatric comorbidity, as well as school, neuropsychological, and psychosocial impairments. Patients with TS also had higher rates of obsessive-compulsive disorder, oppositional defiant disorder, and simple phobia than did patients with chronic tic disorder. Conclusions These findings indicate that TS and chronic tic disorder are part of the same disease entity, with TS being a more severe form of tic disorder. J. Am. Acad. Child Adolesc. Psychiatry , 1995, 34, 9:1133–1139.

Performance of children with ADHD on the Rey-Osterrieth complex figure: a pilot neuropsychological study.

Abstract: This study evaluates the performance of boys with Attention Deficit Hyperactivity Disorder (ADHD) on the Rey-Osterrieth Complex Figure (ROCF) taking into consideration familiality and comorbid psychiatric and learning disorders (LD). Sixty-five children with ADHD performed at developmentally lower levels of Copy Organization and Recall Style than did 45 controls. ADHD children with LD scored significantly lower on Copy Organization than did ADHD children without LD, whereas psychiatric comorbidity and familiality had no effect. These results suggest that a developmental analysis of the ROCF identifies organizational difficulties associated with ADHD and that these impairments cannot simply be attributed to comorbidities associated with ADHD.

Clinical Correlates of Enuresis in ADHD and Non-ADHD Children

Abstract: Enuresis and attention deficit hyperactivity disorder (ADHD) are common childhood disorders that often co-occur. Although each has been linked to neurodevelopmental immaturity and increased risk for psychopathology, the clinical correlates of enuresis remain unclear. Subjects were 140 6–17–year-old boys with DSM-III-R ADHD and 120 non-ADHD controls. Information on enuresis and psychiatric diagnoses was obtained in a standardized manner blind to the child's clinical status. Our results show that (1) enuresis did not increase the risk for psychopathology in children with or without ADHD; (2) enuresis was not associated with psychosocial adversity or developmental immaturity; (3) enuresis was associated with increased risk for learning disability, impaired intellectual functioning, and impaired school achievement in normal control children but not in children with ADHD; and (4) the same pattern of findings was obtained after stratifying children with enuresis by primary versus secondary and by nocturnal versus diurnal subtypes. These results suggest that the clinical implications of enuresis may differ for ADHD and non-ADHD children.

The ‘3 Rs’ and neuropsychological function in schizophrenia: a test of the matching fallacy in biological relatives

Abstract: The 'matching fallacy' suggests that matching schizophrenic patients and normal control subjects on education or IQ may cause systematic mismatching of theoretically expected ability. This study supports a modest version of the matching fallacy effect in nonpsychotic biological relatives of schizophrenic patients. At equivalent levels of education, relatives and control subjects had similar Reading and Spelling scores on the Wide Range Achievement Test-Revised--measures that are largely unimpaired by schizophrenia-related processes. However, relatives showed a deficit in IQ (primarily verbal IQ) compared with what would be predicted from their Reading scores. A similar deficit in Arithmetic scores was found in non-college-educated relatives, but college-educated relatives showed an advantage. We discuss possible implications of the findings with regard to genetic and environmental factors.

Correlates of psychosis proneness in relatives of schizophrenic patients.

Abstract: The Magical Ideation Scale (MIS), Perceptual Aberration Scale (PABS), Social Anhedonia Scale (SAS), and Physical Anhedonia Scale (PAS) were administered to 98 relatives of schizophrenic patients along with a measure of personality disorders (the Personality Diagnostic Questionnaire--Revised). Hierarchical regression analysis indicated that the schizotypal and borderline personality disorder (PD) scales explained significant variance in both the MIS and PABS; the avoidant PD scale also explained significant variance in the PABS. The schizoid, paranoid, and avoidant PD scales explained significant variance in the SAS. Sibling intraclass correlations indicated a significant heritability of 0.62 for the PABS.

No confirmation of Geschwind's hypothesis of associations between reading disability, immune disorders, and motor preference in ADHD

Abstract: Geschwind and colleagues have proposed an association among reading disability, immune disorder, and motor preference. Although reading disability commonly overlaps with attention deficit hyperactivity disorder (ADHD), ADHD has not been previously examined in studies evaluating Geschwind's hypothesis. In this paper we evaluate whether ADHD is associated with either asthma or left motor preference and whether asthma and left motor preference are associated with each other. Subjects were 6- to 17-year-old boys with DSM-III-R ADHD (n= 140) and normal controls (n= 120). Information on reading disability, asthma, and motor preference was obtained in a standardized manner blind to the proband's clinical status. Neither ADHD nor reading disability was associated with either asthma or left motor preference nor was asthma and left motor preference associated with one another. Our results are not consistent with Geschwind's hypothesis linking reading disability, immune disorder, and left motor preference.

Endothelin-1 excretion in urine in active pulmonary sarcoidosis and in other interstitial lung diseases.

Abstract: Endothelin-1 (ET-1) is a vasoactive, mitogenic peptide that is variably increased in Bronchoalveolar Lavage Fluid (BALF) and immunohistochemically found in lung tissue of patients with Interstitial Lung Disease (ILD). To assess if endogenous ET-1 production is increased in ILD we evaluated 24 hour (24h) urine excretion of ET-1 in 20 patients with ILD and 10 healthy age-matched controls (HC). Eight patients with active pulmonary sarcoidosis (S), 6 with idiopathic pulmonary fibrosis (IPF) and 6 with focal lung fibrosis due to inactive pulmonary tuberculosis (hTB) were studied. Plasma ET-1 levels (ET-1pl, pg/ml) and 24h ET-1 levels in urine (ET-1ur, ng/24h) were measured by a specific radio-immunoassay. Determinations of ET-1p1 and ET-1ur were repeated in S and IPF patients after 30 days of prednisone (0.75 mg/kg/day) treatment. ET-1p1 concentrations were not different between HC (5.34 +/- 0.48), S (5.95 +/- 0.96), IPF (4.75 +/- 1.37) and hTB (5.97 +/- 1.05) groups. ET-1ur was significantly higher in S (189.50 +/- 60.57) than in HC (69.00 +/- 10.76), IPF (62.17 +/- 19.07) and hTB (82.00 +/- 24.97). After prednisone, ET-1ur in the S group decreased significantly (189.50 +/- 60.57 to 94.00 +/- 13.60), and the decrease paralleled the improved clinical status. In S patients, ET-1ur was not significantly correlated to the degree of respiratory impairment, but it was significantly correlated to the intensity of lymphocytic alveolitis (r = 0.80).(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic Heterogeneity of Schizophrenia

Abstract: The cumulative evidence from over a century of research overwhelmingly implicates genes in the etiology of Schizophrenia. Twin studies consistently find higher rates of schizophrenia among cotwins of monozygotic compared with dizygotic twins and adoption studies show that familial transmission is mediated by genetic, not adoptive relationships. Nevertheless, the hunt for schizophrenia genes with molecular genetic technologies has been disappointing. Although the available literature suggests that cytogenetic abnormalities cause some cases of schizophrenia, these abnormalities must account for only a small fraction of all schizophrenia. Attempts to scan the entire genome with DNA markers spaced at regular intervals have failed to produce unequivocal linkage findings. Notably, several groups have reported findings suggestive of linkage to chromosome 22 and other work provides weak evidence of a gene on the sex chromosomes. The search for schizophrenia genes has been complicated by its unknown mode of transmission, the possibility of phenocopies and genetic heterogeneity.

Differentiation of schizoaffective bipolar disorder from bipolar disorder and schizophrenia

Abstract: Differential diagnosis of patients whose course of illness includes substantial psychotic and mood syndromes is among the most challenging in psychiatry. The relative temporal preponderance of one or the other of these syndromes over course of illness forms the basis for distinctions among DSM-III-R diagnoses of schizoaffective disorder (SA), bipolar disorder (BPD), and schizophrenia (SZ); and such temporal assessments may be especially difficult to make reliably. Elsewhere we report relatively low reliability of SA and a tendency for it be “confused” with SZ and BPD. In this paper, we identify clinical variables that increase diagnostic differentiation. Data are from a Diagnostic Interview for Genetic Studies (DIGS) reliability study in which patients with independently assessed DSM-III-R lifetime diagnoses of SA-bipolar subtype,(SA-BP), BPD, and SZ were also clinically assessed and diagnosed by the DIGS on two occasions by two different interviewers blind to entry diagnoses. The relative strength of DIGS-based DSM-III-R diagnoses and individual DIGS clinical variables in predicting entry diagnoses is shown in a series of logistic regression analyses. Models incorporating DIGS variables are more predictive of entry diagnoses than models using DIGS diagnoses alone. Based on DIGS information, the SA-BP group is more clearly differentiated from the BPD group than from the SZ group. Different profiles of DIGS variables distinguish the groups. Findings are discussed in terms of their implications for nosologic research. Depression 3:309–315 (1995/1996). © 1996 Wiley-Liss, Inc1 .