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Biomedical subjects

S V Faraone

Publications and source records attributed to S V Faraone.

At least 145 records · Page 8Linked to original sources

Anticipation in schizophrenia: biology or bias?

Anticipation is a genetic phenomenon wherein age of disease onset decreases and/ or severity increases in successive generations. Anticipation has been demonstrated for several neuropsychiatric disorders with expanding trinucleotide repeats recently identified as the underlying molecular mechanism. We report here the results of an analysis of anticipation performed with multiplex families segregating schizophrenia. Thirty-three families were identified through the NIMH Genetics Initiative that met the following criteria: had at least two affected members in successive generations and were not bilineal. Affectation diagnoses included schizophrenia, schizoaffective disorder-depressed, and psychosis NOS. Additional analyses included the Cluster A personality disorders. Three indices of age of onset were used. Disease severity was measured by several different indices. Four sampling schemes as suggested by McInnis et al. were tested, as well as additional analysis using pairs ascertained through the parental generation. Anticipation was demonstrated for age of onset, regardless of the index or sampling scheme used (P<0.05). Anticipation was not supported for disease severity. Analyses that took into account drug use and diminished fecundity did not affect the results. While the data strongly support intergenerational differences in disease onset consistent with anticipation, they must be viewed cautiously given unavoidable biases attending these analyses.

Age of Onset↗

Sex differences in neuropsychological function in non-psychotic relatives of schizophrenic probands.

Some recent studies suggest that men with schizophrenia may have greater neuropsychological deficits than women. It is not known, however, whether similar sex differences may be present in biological relatives of schizophrenic patients. We evaluated neuropsychological functioning of 54 relatives of schizophrenic patients and 72 normal volunteers. It was hypothesized that, if sex differences were present, they would be accounted for largely by deficits in male relatives. We were particularly interested in three neuropsychological functions that we previously identified as putative neuropsychological vulnerability indicators for schizophrenia: (1) abstraction/executive function; (2) verbal memory; and (3) auditory attention. There were significant group x sex interactions for verbal memory and motor function, and trends toward significant interactions for auditory attention and mental control/encoding. However, with the exception of motor function, it was the female relatives who accounted for most of the impairment. A speculative explanation for the findings is that women may have a higher threshold than men for developing schizophrenia. If so, female relatives might be able to withstand greater impairments than men before developing psychotic symptoms. Consequently, in a sample that was limited to non-psychotic relatives--as in the present study--there could be over-representation of both less impaired men and more impaired women. Alternative explanations and limitations of the study are also discussed.

Adolescent↗

Pregnancy, delivery and infancy complications and attention deficit hyperactivity disorder: issues of gene-environment interaction.

We evaluated the role of pregnancy, delivery, and infancy complications (PDICs) in the etiology of attention deficit hyperactivity disorder (ADHD) and addressed issues of comorbidity and familiarity by testing multiple hypotheses. Subjects were 6-17-year-old boys with DSM-III-R ADHD (n = 140) and normal controls (n = 120) and their first-degree biologic relatives. Information on PDICs was obtained from mothers in a standardized manner blind to the proband's clinical status. Using linear and logistic regression models, a positive association was found between ADHD and PDICs in the probands. Additionally, PDICs were associated with the correlates of ADHD (i.e., impaired cognitive functioning and poor school performance). Moreover, it was those specific complications that reflect chronic exposure, such as maternal bleeding, smoking, family problems, and illicit drug use during pregnancy that accounted for these findings. No interaction between genetic factors and PDICs were found. Our findings add to the literature supporting an association between ADHD and PDICs. Our results may help clinicians focus on particular complications rather than the wide range of possible perinatal complications.

Adolescent↗

Conduct disorder with and without mania in a referred sample of ADHD children.

OBJECTIVE: To test the hypothesis that dysphoric and non-dysphoric types of CD could be distinguished from one another in their patterns of familiality, adversity, and comorbidity. METHODS: We examined 140 ADHD and 120 normal controls at baseline and 4 years later using assessments from multiple domains. We compared ADHD subgroups with and without conduct (CD) and bipolar (BPD) disorders on psychiatric outcomes at a 4-year follow-up, familial psychopathology and psychosocial functioning. RESULTS: We found that ADHD children with both disorders had higher familial and personal risk for mood disorders than those with CD only, who had a higher personal risk for antisocial personality disorder. Among ADHD probands, having both CD and BPD was associated with poorer functioning and an increased risk for psychiatric hospitalization. DISCUSSION: Although preliminary, our findings suggest that the distinction between dysphoric and non-dysphoric CD may be clinically meaningful. If confirmed, our findings could have important diagnostic and therapeutic implications for the management of antisocial youth.

Attention Deficit Disorder with Hyperactivity↗

Mania in children with pervasive developmental disorder revisited.

OBJECTIVE: Although a small literature of case reports suggests that mania co-occurs with pervasive developmental disorder (PDD), little is known about this overlap. The authors systematically investigated the overlap between mania and PDD in a consecutive sample of referred youths, examining its prevalence and correlates. It was hypothesized that children with PDD plus manic features have both disorders. METHOD: Subjects were consecutively referred children meeting diagnostic criteria on structured interview for PDD without mania (n = 52), the comorbid condition PDD + mania (n = 14), and mania without PDD (n = 114). All subjects were evaluated using a comprehensive diagnostic battery that included assessment of psychopathology (structured diagnostic interview and Child Behavior Checklist), cognition, and functioning. RESULTS: Of the 727 referred children, 52 met criteria for PDD, 114 met criteria for mania, and 14 met criteria for both. The 14 children with both PDD + mania represented 21% of the PDD subjects and 11% of all manic subjects. Clinical characteristics of PDD were similar in PDD subjects with and without mania, and manic features were similar in manic children with and without PDD. CONCLUSIONS: Children with PDD and mania may suffer from two disorders. Comorbid mania among patients with PDD may be more common than previously thought. Identification of the comorbid condition may have important therapeutic and scientific implications.

Bipolar Disorder↗

Attention deficit disorder and conduct disorder: longitudinal evidence for a familial subtype.

BACKGROUND: An obstacle to the successful classification of attention deficit hyperactivity disorder (ADHD) is the frequently reported co-morbidity between ADHD and conduct disorder (CD). Prior work suggested that from a familial perspective, ADHD children with CD may be aetiologically distinct from those without CD. METHODS: Using family study methodology and three longitudinal assessments over 4 years, we tested hypotheses about patterns of familial association between ADHD, CD, oppositional defiant disorder (ODD) and adult antisocial personality disorder (ASPD). RESULTS: At the 4-year follow-up, there were 34 children with lifetime diagnoses of ADHD + CD, 59 with ADHD + ODD and 33 with ADHD only. These were compared with 92 non-ADHD, non-CD, non-ODD control probands. Familial risk analysis revealed the following: (1) relatives of each ADHD proband subgroup were at significantly greater risk for ADHD and ODD than relatives of normal controls; (2) rates of CD and ASPD were elevated among relatives of ADHD + CD probands only; (3) the co-aggregation of ADHD and the antisocial disorders could not be accounted for by marriages between ADHD and antisocial spouses; and (4) both ADHD and antisocial disorders occurred in the same relatives more often than expected by chance alone. CONCLUSIONS: These findings suggest that ADHD with and without antisocial disorders may be aetiologically distinct disorders and provide evidence for the nosologic validity of ICD-10 hyperkinetic conduct disorder.

Adolescent↗

Is ADHD a risk factor for psychoactive substance use disorders? Findings from a four-year prospective follow-up study.

OBJECTIVE: To evaluate whether attention-deficit hyperactivity disorder (ADHD) is a risk factor for psychoactive substance use disorders (PSUD), attending to issues of psychiatric comorbidity, family history, and adversity. METHOD: Using assessments from multiple domains, the authors examined 140 ADHD and 120 normal control subjects at baseline and 4 years later. Drug and alcohol abuse and dependence were operationally defined. RESULTS: No differences were detected in the rates of alcohol or drug abuse or dependence or in the rates of abuse of individual substances between the groups; both ADHD and control probands had a 15% rate of PSUD. Conduct and bipolar disorders predicted PSUD, independently of ADHD status. Family history of substance dependence and antisocial disorders was associated with PSUD in controls but less clearly so in ADHD probands. Family history of ADHD was not associated with risk for PSUD. ADHD probands had a significantly shorter time period between the onsets of abuse and dependence compared with controls (1.2 years versus 3 years, p < .01). CONCLUSIONS: Adolescents with and without ADHD had a similar risk for PSUD that was mediated by conduct and bipolar disorder. Since the risk for PSUD has been shown to be elevated in adults with ADHD when compared with controls, a sharp increase in PSUD is to be expected in grown-up ADHD children during the transition from adolescence to adulthood.

Adolescent↗

ADHD is associated with early initiation of cigarette smoking in children and adolescents.

OBJECTIVE: The association between attention-deficit hyperactivity disorder (ADHD) and cigarette smoking in children and adolescents was evaluated. METHOD: Subjects were 6- to 17-year-old boys with DSM-III-R ADHD (n = 128) and non-ADHD comparison boys (n = 109) followed prospectively for 4 years into mid-adolescence. Information on cigarette smoking was obtained in a standardized manner blind to the proband's clinical status. Cox proportional hazard models were used to predict cigarette smoking at follow-up using baseline characteristics as predictors. RESULTS: ADHD was a significant predictor of cigarette smoking at follow-up into mid-adolescence. Our findings also revealed that ADHD was associated with an early initiation of cigarette smoking. This was the case even after controlling for socioeconomic status, IQ, and psychiatric comorbidity. In addition, among children with ADHD, there was a significant positive association between cigarette smoking and conduct, major depressive, and anxiety disorders. CONCLUSIONS: ADHD, particularly the comorbid subtype, is a significant risk factor for early initiation of cigarette smoking in children and adolescents. Considering the prevalence and early childhood onset of ADHD, these findings highlight the importance of smoking prevention and cessation programs for children and adolescents with ADHD.

Adolescent↗

Associations between expressed emotion and child behavioral inhibition and psychopathology: a pilot study.

OBJECTIVE: To examine the relationship between behavioral inhibition and child psychopathology and measures of family adversity indexed through "expressed emotion." METHOD: Maternal expressed emotion was assessed via Five-Minute-Speech-Sample in two samples of children evaluated for prevalence of DSM-III disorders and assessed via laboratory observations for behavioral inhibition. The at-risk sample (N = 30) consisted of 4- to 10-year-old children of mothers with and without panic disorder (psychiatric controls). The Kagan sample (N = 41) consisted of children selected at age 21 months as behaviorally inhibited or uninhibited and followed through age 11. RESULTS: In the at-risk sample, child behavioral inhibition was associated with high/borderline maternal criticism, independent of other measures of child psychopathology. In both samples combined, high/borderline maternal criticism was associated with child externalizing symptoms and with the number of child mood and behavior disorders. Emotional overinvolvement was significantly associated with child separation anxiety disorder in the at-risk sample. CONCLUSIONS: Results suggest that child behavioral inhibition may be associated with maternal criticism/dissatisfaction and confirm other reports of associations between criticism and child behavior and mood disorders and between emotional overinvolvement and child separation anxiety.

Adult↗

Panic disorder and agoraphobia in consecutively referred children and adolescents.

OBJECTIVE: This report examines the clinical features and correlates of juvenile panic disorder in referred children and adolescents to test specific hypotheses about its relationship with adult panic disorder. METHOD: The sample consisted of consecutively referred children and adolescents (N = 472) comprehensively evaluated with structured diagnostic interviews, cognitive tests, and psychosocial assessments. RESULTS: Panic disorder was identified in 6% and agoraphobia in 15% of psychiatrically referred children and adolescents. Children meeting criteria for panic disorder also frequently met criteria for agoraphobia. The latter disorder was more prevalent and had an earlier age at onset than panic disorder. Children with panic disorder and those with agoraphobia had similar correlates with frequent comorbidity with other anxiety and mood disorders. A high level of comorbidity with disruptive disorders was also identified. CONCLUSIONS: These results support the hypothesis of continuity between the juvenile and the adult form of panic disorder. However, the high level of comorbidity with disruptive behavior disorders also suggests developmentally specific discontinuities between juveniles and adults with panic disorder.

Adolescent↗

A pilot study of neuropsychological function in girls with ADHD.

OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) is known to have neuropsychological consequences that are evident from psychological tests and from measures of school failure. However, most available data are based on studies of boys. Our goal was to assess, in this pilot study, whether ADHD in girls expressed neuropsychological features similar to those found in boys. METHOD: Subjects were 43 girls, aged 6 to 17 years, with DSM-III-R ADHD and 36 comparison girls without ADHD. Information on neuropsychological performance was obtained in a standardized manner blind to clinical status. RESULTS: Girls with ADHD were significantly more impaired on estimated IQ than comparison girls despite being matched on other demographic variables. Relative to comparison girls, the girls with ADHD were also significantly more impaired on the Freedom From Distractibility subtests of the WISC-R and on arithmetic and reading achievement scores. Although their mean performance on executive function tests was generally poorer than that of control girls, there were no statistically significant differences on these measures. CONCLUSIONS: Girls with ADHD have impairments in some tests of attention and achievement. However, neuropsychological performance on tests of executive function was less impaired than that previously documented in boys with ADHD. If confirmed in a larger sample, these findings suggest that girls with ADHD may be less vulnerable to executive function deficits than boys.

Adolescent↗

Predicting desipramine levels in children and adolescents: a naturalistic clinical study.

OBJECTIVE: To determine the predictability and stability of desipramine (DMI) concentrations in a clinically treated sample of children, estimating the risk of developing potentially toxic DMI levels at a higher dose after a most recent level in a clinically acceptable range. METHOD: Subjects were 90 consecutive psychiatrically referred children and adolescents treated with DMI with at least two assays of serum DMI concentrations (462 pairs). Assay data were analyzed after log transformation and linear regression. RESULTS: Despite wide between-patient variability in serum DMI levels at the same dose, future within-subject DMI blood levels were highly predictable from knowledge of current levels, current dose, and the future dose. When the DMI serum level was 200 to 300 ng/ml, there was a 7.0% risk for subsequent levels at the same dose to exceed 300 ng/mL, but potentially toxic levels above 500 ng/mL were very infrequent (1.7%). CONCLUSIONS: Although the results of this naturalistic clinical study may not generalize to other situations, the results indicate a reasonable stability, predictability, and safety of DMI levels in individual psychiatrically treated children that result from clinically chosen dose changes.

Adolescent↗

Expressed emotion toward children with behavioral inhibition: associations with maternal anxiety disorder.

OBJECTIVE: To examine the role of maternal psychopathology in influencing "expressed emotion" (EE) directed toward children with behavioral inhibition (BI) or psychiatric disorders. METHOD: Maternal EE was assessed via Five-Minute-Speech-Sample in two samples of children previously evaluated for child and maternal lifetime prevalence of DSM-III disorders and assessed via laboratory observations for BI. The authors previously reported that maternal EE was associated with BI and with the number of child behavior and mood disorders in these samples. The at-risk sample (N = 30) consisted of mothers with panic disorder and psychiatric controls and their 4-through 10-year-old children. The Kagan sample (N = 41) consisted of children selected at age 21 months as BI or uninhibited and followed through age 11. RESULTS: Interaction effects were found: in mothers with anxiety disorders, but not those without, maternal criticism (a component of EE) was significantly associated with child BI, independently of the child's number of disorders. Similarly, in mothers with anxiety disorders only, maternal criticism was significantly associated with a high number of child disorders. CONCLUSIONS: The relationships between mothers who have anxiety disorders and their children who have BI or psychiatric disorders may be marked by criticism or dissatisfaction. If confirmed, these findings offer opportunities for appropriate interventions.

Anxiety Disorders↗

Is comorbidity with ADHD a marker for juvenile-onset mania?

OBJECTIVE: To compare the characteristics and correlates of mania in referred adolescents and to determine whether attention-deficit hyperactivity disorder (ADHD) is a marker of very early onset mania. METHOD: From 637 consecutive admissions, 68 children (< or = 12 years) and 42 adolescents (> 13 years) who satisfied criteria for mania were recruited. These were compared with the 527 nonmanic referrals and 100 normal controls. RESULTS: With the exception of comorbidity with ADHD, there were more similarities than differences between the children and adolescents with mania in course and correlates. There was an inverse relationship between the rates of comorbid ADHD and age of onset of mania: higher in manic children intermediate in adolescents with childhood-onset mania, and lower in adolescents with adolescent-onset mania. CONCLUSIONS: ADHD is more common in childhood-onset compared with adolescent-onset cases of bipolar disorder, suggesting that in some cases, ADHD may signal a very early onset of bipolar disorder. Clinical similarities between the child- and adolescent-onset cases provide evidence for the clinical validity of childhood-onset mania.

Adolescent↗

Attention-deficit hyperactivity disorder with bipolar disorder: a familial subtype?

OBJECTIVE: To clarify the nosological status of children with attention-deficit hyperactivity disorder (ADHD) who also satisfy diagnostic criteria for bipolar disorder (BPD). METHOD: Blind raters and structured psychiatric interviews were used to examine 140 children with ADHD, a sample of 120 non-ADHD comparisons, and their 822 first-degree relatives. Data analyses tested specific hypotheses about the familial relationship between ADHD and BPD. RESULTS: After stratifying the ADHD sample into those with and without BPD, the authors found that (1) relatives of both ADHD subgroups were at significantly greater risk for ADHD than relatives of non-ADHD controls; (2) the two subgroups did not differ significantly from one another in their relatives' risk for ADHD; (3) a fivefold elevated risk for BPD was observed among relatives when the proband child had BPD but not when the proband had ADHD alone; (4) an elevated risk for major depression with severe impairment was found for relatives of ADHD + BPD probands; (5) both ADHD and BPD occurred in the same relatives more often than expected by chance alone; and (6) there was a trend for random mating between ADHD parents and those with mania. CONCLUSIONS: The data suggest that comorbid ADHD with BPD is familially distinct from other forms of ADHD and may be related to what others have termed childhood-onset BPD.

Adolescent↗

Correspondence between DSM-III-R and DSM-IV attention-deficit/hyperactivity disorder.

OBJECTIVE: To evaluate the correspondence between DSM-III-R and DSM-IV definitions of attention-deficit/hyperactivity disorder (ADHD) in clinically referred children. Results of the field trials led to the hypothesis that there would be a strong correspondence between DSM-III-R and DSM-IV subtypes. METHOD: The sample consisted of all children and adolescents consecutively referred to a pediatric psychopharmacology clinic (N = 405). Children were comprehensively evaluated with structured diagnostic interviews assessing both DSM-III-R and DSM-IV ADHD. DSM-III-R symptoms were used to approximate DSM-IV subtypes. Kappa statistics and conditional probabilities were used to examine the correspondence between DSM-III-R and DSM-IV ADHD. RESULTS: Ninety-three percent of children who received a DSM-III-R diagnosis of ADHD also received a DSM-IV ADHD diagnosis. The kappa coefficient assessing the agreement between DSM-III-R and DSM-IV ADHD was .73 (z = 14.6, p < .0001). The kappa coefficient assessing the agreement between the DSM-III-R-approximated subtypes and the actual DSM-IV subtypes was .71 (z = 15, p < .0001). CONCLUSION: These results confirm previous findings and indicate that the change from DSM-III-R to DSM-IV results in minimal changes in case identification and provides support for diagnostic continuity between the two classification systems.

Adolescent↗

Attention deficit hyperactivity disorder (ADHD) is associated with early onset substance use disorders.

We evaluated the association between attention deficit hyperactivity disorder (ADHD) and the age of onset of psychoactive substance use disorders (PSUD) in adults with ADHD. We hypothesized that ADHD and psychiatric comorbidity would be risk factors for early onset PSUD. We compared 120 referred adults having a clinical diagnosis of childhood-onset ADHD with 268 non-ADHD adults. All diagnoses were obtained using DSM-III-R based structured psychiatric interviews. We used group comparisons of age at onset and Cox proportional hazard models to examine the development of PSUD over time. ADHD was associated with earlier onset of PSUD independently of psychiatric comorbidity. Conduct and juvenile bipolar disorders conferred a significantly increased risk for early onset PSUD independently of ADHD. Psychiatric disorders commonly emerged before the onset of PSUD in both groups. Persistent ADHD with and without psychiatric comorbidity was associated with adolescent onset PSUD. In addition, comorbidity with conduct and juvenile bipolar disorders predicted very early onset PSUD in both ADHD and non-ADHD individuals. These findings confirm and extend previous findings documenting important associations between PSUD and psychiatric comorbidity including persistent ADHD.

Adolescent↗