Biomedical subjects

Stephen V Faraone

Publications and source records attributed to Stephen V Faraone.

At least 199 records · Page 11Linked to original sources

PubMed2002

Linkage of chromosome 13q32 to schizophrenia in a large veterans affairs cooperative study sample.

Several prior reports have suggested that chromosomal region 13q32 may harbor a schizophrenia susceptibility gene. In an attempt to replicate this finding, we assessed linkage between chromosome 13 markers and schizophrenia in 166 families, each with two or more affected members. The families, assembled from multiple centers by the Department of Veterans Affairs Cooperative Studies Program, included 392 sampled affected subjects and 216 affected sib pairs. By DSM-III-R criteria, 360 subjects (91.8%) had a diagnosis of schizophrenia and 32 (8.2%) were classified as schizoaffective disorder, depressed. The families had mixed ethnic backgrounds. The majority were northern European-American families (n = 62, 37%), but a substantial proportion were African-American kindreds (n = 60, 36%). Chromosome 13 markers, spaced at intervals of approximately 10 cM over the entire chromosome and 2-5 cM for the 13q32 region were genotyped and the data analyzed using semi-parametric affected only linkage analysis. For the combined sample (with race broadly defined and schizophrenia narrowly defined) the maximum LOD score was 1.43 (Z-score of 2.57; P = 0.01) at 79.0 cM between markers D13S1241 (76.3 cM) and D13S159 (79.5 cM). Both ethnic groups showed a peak in this region. The peak is within 3 cM of the peak reported by Brzustowicz et al. [1999: Am J Hum Genet 65:1096-1103].

Adult↗

PubMed2002

The molecular genetics of schizophrenia: an emerging consensus.

Schizophrenia is perhaps the most debilitating mental disease and determining the underlying cause has become a challenging area of psychiatric research. It is relatively well established that genes play a role in the aetiology of schizophrenia. In this article, a review of important findings related to schizophrenia as a genetic trait will be provided, including a discussion of family, twin and adoption studies. Molecular genetic studies of specific candidate genes are then reviewed. Some controversies within the literature are examined and possible directions for future research are discussed.

Adoption↗

PubMed2002

Temperamental correlates of disruptive behavior disorders in young children: preliminary findings.

BACKGROUND: Our objective was to test the hypothesis that temperamental behavioral disinhibition measured in early childhood would be associated with disruptive behavior disorders. METHODS: We used variables from laboratory-based behavioral observations originally devised to assess behavioral inhibition to construct a theory-based a priori definition of "behavioral disinhibition" in 200 young children at-risk for panic disorder, depression, or both and 84 children of parents without anxiety or major depressive disorder. We then compared behaviorally disinhibited and nonbehaviorally disinhibited children on rates of DSM-III-R disorders and measures of academic and social dysfunction. RESULTS: Behavioral disinhibition was significantly associated with higher rates of disruptive behavior disorders and mood disorders. Children with behavioral disinhibition were significantly more likely than nondisinhibited, noninhibited children to have attention-deficit/hyperactivity disorder (ADHD) and to have comorbid mood and disruptive behavior disorders. Moreover, disinhibited children had lower Global Assessment of Functioning Scale scores and were more likely to have been in special classes and to have problems with school behavior and leisure activities. CONCLUSIONS: These results suggest that behavioral disinhibition may represent a temperamental precursor to disruptive behavior problems, particularly ADHD. Longitudinal studies using behavioral assessments of behavioral disinhibition are needed to confirm these findings.

Agoraphobia↗

PubMed2002

An integration of schizophrenia with schizotypy: identification of schizotaxia and implications for research on treatment and prevention.

The liability to schizophrenia (schizotaxia) is associated with deficits in a variety of domains, including negative symptoms and neuropsychological deficits, even in the absence of psychosis or pre-psychotic prodromal symptoms. Conceptually, this view of schizotaxia is similar to negative schizotypy (i.e., schizotypal personality disorder minus the positive symptoms). It is broader than DSM-IV schizotypal personality disorder (SPD), however, in that more relatives of patients with schizophrenia show core symptoms of schizotaxia than meet the diagnostic criteria for SPD. Three lines of evidence support the validity of schizotaxia. First, evidence of concurrent validation was obtained by showing that schizotaxic subjects were more impaired than non-schizotaxic subjects on a variety of independent clinical scales. Second, schizotaxic subjects showed higher levels of negative symptoms on the Structured Interview for Schizotypy than non-schizotaxic subjects, but did not differ on positive symptoms. Third, subjects who met predetermined criteria for schizotaxia (i.e., negative symptoms and neuropsychological deficits) showed positive effects following treatment with low doses of risperidone (0.25-2.0 mg). Thus, clinical deficits in schizotaxia may be identifiable, and to a significant extent, reversible. Implications for the conception of schizotypy and the prevention of schizophrenia will be discussed.

Cognition Disorders↗

PubMed2002

A comparative profile analysis of neuropsychological functioning in patients with schizophrenia and bipolar psychoses.

Evidence for neuropsychological deficits in schizophrenia is substantial whereas evidence for the specificity of dysfunction is relatively sparse. To assess specificity, we compared neuropsychological function in patients with chronic schizophrenia, patients with chronic psychotic bipolar disorder and normal controls. Groups were comparable on age, ethnicity and expected intellectual ability (based on single word reading). Patients with schizophrenia and bipolar psychoses were also relatively similar on age at onset and number of hospitalizations. Using multivariate analyses of variance with sex and parental SES as covariates (our primary analyses), patients with schizophrenia were significantly more impaired than controls on seven of eight neuropsychological functions (all but verbal ability), and were significantly more impaired than bipolar patients on abstraction, perceptual-motor speed and vigilance. Bipolar patients were significantly impaired compared to controls on declarative verbal memory, and showed moderate-to-large effect size decrements on abstraction, perceptual-motor speed and vigilance. Results were not attenuated when IQ was controlled, which was significantly lower in patients with schizophrenia. Analyses indicated that the two psychiatric groups had similar profile patterns, but that patients with schizophrenia had a more severe impairment than patients with bipolar psychoses. Further research is required to determine whether similar mechanisms underly the neurocognitive deficits in these disorders.

Adult↗

PubMed2002

Impact of normal sexual dimorphisms on sex differences in structural brain abnormalities in schizophrenia assessed by magnetic resonance imaging.

BACKGROUND: Previous studies suggest that the impact of early insults predisposing to schizophrenia may have differential consequences by sex. We hypothesized that brain regions found to be structurally different in normal men and women (sexual dimorphisms) and abnormal in schizophrenia would show significant sex differences in brain abnormalities, particularly in the cortex, in schizophrenia. METHODS: Forty outpatients diagnosed as having schizophrenia by DSM-III-R were systematically sampled to be comparable within sex with 48 normal comparison subjects on the basis of age, ethnicity, parental socioeconomic status, and handedness. A comprehensive assessment of the entire brain was based on T1-weighted 3-dimensional images acquired from a 1.5-T magnet. Multivariate general linear models for correlated data were used to test for sex-specific effects regarding 22 hypothesized cortical, subcortical, and cerebrospinal fluid brain volumes, adjusted for age and total cerebrum size. Sex x group interactions were also tested on asymmetries of the planum temporale, Heschl's gyrus, and superior temporal gyrus, additionally controlled for handedness. RESULTS: Normal patterns of sexual dimorphisms were disrupted in schizophrenia. Sex-specific effects were primarily evident in the cortex, particularly in the frontomedial cortex, basal forebrain, cingulate and paracingulate gyri, posterior supramarginal gyrus, and planum temporale. Normal asymmetry of the planum was also disrupted differentially in men and women with schizophrenia. There were no significant differential sex effects in subcortical gray matter regions or cerebrospinal fluid. CONCLUSION: Factors that produce normal sexual dimorphisms may be associated with modulating insults producing schizophrenia, particularly in the cortex.

Adult↗

PubMed2002

A double-blind comparison of desipramine and placebo in children and adolescents with chronic tic disorder and comorbid attention-deficit/hyperactivity disorder.

BACKGROUND: Currently, there is no consensus on the best therapeutic approach to chronic tic disorders and comorbid attention-deficit/hyperactivity disorder (ADHD). To address this issue, we evaluated the tolerability and efficacy of the noradrenergic tricyclic antidepressant desipramine hydrochloride in the treatment of children and adolescents with chronic tic disorders and comorbid ADHD. METHODS: Forty-one children and adolescents with chronic tic disorders, including Tourette disorder and comorbid ADHD, were studied in a 6-week, double-blind, placebo-controlled, parallel trial. Desipramine was titrated weekly up to 3.5 mg/kg per day. We rated ADHD and tic symptoms weekly and monitored adverse effects, laboratory findings, and cardiovascular parameters. RESULTS: Treatment with desipramine (mean total daily dose, 3.4 mg/kg per day) was well tolerated without meaningful adverse effects. Desipramine significantly reduced core symptoms of ADHD (ADHD Rating Scale; 42% decrease from baseline relative to placebo, P<.001), with equal response in inattentive symptoms and hyperactive/impulsive symptoms (P<.001 for both). The ADHD response rate was robust (71% vs 0%; desipramine vs placebo, P<.001). Likewise, desipramine significantly reduced tic symptoms (Yale Global Tic Severity Scale; 30% decrease from baseline relative to placebo, P<.001), with equal response in motor and phonic tic symptoms (P<.01 for both). The tic response rate was substantial (58% vs 5%; desipramine vs placebo, P<.001). There were small but statistically significant differences between desipramine and placebo in heart rate and blood pressure. CONCLUSIONS: Treatment with desipramine was well tolerated and was associated with robust clinically significant reductions in tic and ADHD symptoms in children and adolescents with chronic tic disorders and ADHD diagnoses.

Adolescent↗

PubMed2002

Left hippocampal volume as a vulnerability indicator for schizophrenia: a magnetic resonance imaging morphometric study of nonpsychotic first-degree relatives.

BACKGROUND: Clues to the causes of schizophrenia can be derived from studying first-degree relatives because they are genetically related to an ill family member. Abnormalities observed in nonpsychotic relatives are indicators of possible genetic vulnerability to illness, independent of psychosis. We tested 4 hypotheses: (1) that hippocampal volume is smaller in nonpsychotic relatives than in controls, particularly in the left hemisphere; (2) that hippocampi will be smaller in multiplex relatives as compared with simplex relatives, and both will be smaller than in controls; (3) that hippocampal volumes and verbal declarative memory function will be positively correlated; and (4) that hippocampi will be smaller in patients with schizophrenia than in their nonpsychotic relatives or in controls. METHODS: Subjects were 45 nonpsychotic adult first-degree relatives from families with either 2 people ("multiplex," n = 17) or 1 person ("simplex," n = 28) diagnosed with schizophrenia, 18 schizophrenic relatives, and 48 normal controls. Sixty contiguous 3-mm coronal, T1-weighted 3-dimensional magnetic resonance images of the brain were acquired on a 1.5-T magnet. Volumes of the total cerebrum and the hippocampus were measured. RESULTS: Compared with controls, relatives, particularly from multiplex families, had significantly smaller left hippocampi. Verbal memory and left hippocampal volumes were significantly and positively correlated. Within families, hippocampal volumes did not differ between schizophrenic patients and their nonpsychotic relatives. CONCLUSIONS: Results support the hypothesis that the vulnerability to schizophrenia includes smaller left hippocampi and verbal memory deficits. Findings suggest that smaller left hippocampi and verbal memory deficits are an expression of early neurodevelopmental compromise, reflecting the degree of genetic liability to schizophrenia.

Adult↗

PubMed2002

Family, twin, and adoption studies of bipolar disease.

Bipolar disease features states of severe depression that usually fluctuate with at least one episode of intense elation or mania. It is a disorder that has been thought for some time to have a heritable component. The lifetime prevalence of bipolar disease in the general population is approximately 1%. In contrast, family studies have shown the approximate lifetime risk of a first-degree relative of a bipolar proband to be 5% to 10%. Moreover, studies of monozygotic twins show that their risk of contracting the disease is as much as 75 times greater than that for the general population. In addition, adoption studies have demonstrated that biological relatives of bipolar patients are substantially more likely to have the disorder than are adoptive relatives.

Adoption↗

PubMed2002

Familial links between attention deficit hyperactivity disorder, conduct disorder, and bipolar disorder.

Although family, twin, and adoption studies indicate that attention deficit hyperactivity disorder (ADHD) is a familial condition with a robust genetic component, molecular genetic studies of candidate genes have produced inconsistent findings. One of the challenges to elucidating the genetic architecture of ADHD is its potential genetic heterogeneity. Therefore, efforts are needed to identify etiologically homogeneous subgroups of subjects with ADHD for use in genetic studies. The current article reviews evidence suggesting that parsing ADHD subjects based on comorbidity with conduct and bipolar disorders may yield familial subtypes that are suitable for genetic analyses.

Attention Deficit Disorder with Hyperactivity↗

PubMed2002

Efficacy of Adderall and methylphenidate in attention deficit hyperactivity disorder: a drug-placebo and drug-drug response curve analysis of a naturalistic study.

Stimulant medication has, for many years, been the pharmacological treatment of choice for children and adults with attention deficit hyperactivity disorder (ADHD). Recently, several studies have documented the efficacy of a new stimulant, Adderall. Although these initial studies provide useful information for clinicians treating ADHD children, their method of data presentation has provided limited information about the clinical significance of drug effects. Thus, to address the issue of clinical significance, we completed drug-placebo response curve analyses of a blinded, placebo-controlled study of Adderall and methylphenidate (MPH). Our results show that the efficacy of Adderall and MPH to improve functioning is seen throughout the full range of improvement scores. Both drugs prevent worsening and, for a majority of patients, lead to improvements that are well into the normal range. The analyses also highlight an important subgroup of placebo responders, which suggests that future research should focus on how to predict robust placebo response in ADHD patients.

Amphetamines↗

PubMed2002

Nicotine and familial vulnerability to schizophrenia: a discordant twin study.

Tobacco use is significantly associated with schizophrenia. However, it is not clear if smoking is associated with the illness itself, treatment, or underlying vulnerability to the disease. Smoking was studied in a sample of schizophrenic probands (n = 24), their unaffected co-twins (n = 24), and controls (n = 3,347). Unaffected co-twins had higher rates of daily smoking than controls. Probands and co-twins were more frequently unsuccessful in attempts to quit than controls. Probands reported shaky hands and depression following smoking cessation more often than controls, whereas unaffected co-twins reported difficulty concentrating, drowsiness, nervousness, and headache following smoking cessation more often than controls. Results are consistent with the hypothesis that nicotine use is influenced by familial vulnerability to schizophrenia, not just clinical schizophrenia per se.

Adult↗

PubMed2002

Parsing the comorbidity between bipolar disorder and anxiety disorders: a familial risk analysis.

BACKGROUND: A growing literature suggests that anxiety disorders (ANX) co-occur with bipolar disorder (BPD), but the nature of this overlap is unknown. Thus, we investigated the familial association between BPD and ANX among the first-degree relatives of children with BPD with and without comorbid ANX. METHODS: We compared relatives of four proband groups defined by the presence or absence of BPD and ANX in the proband: (1) BPD + ANX (n = 23 probands, 74 relatives), (2) BPD without ANX (n = 11 probands, 38 relatives), (3) ANX without BPD (n = 48 probands, 167 relatives), and (4) controls without BPD or ANX (n = 118 probands, 385 relatives). All subjects were evaluated with structured diagnostic interviews. Diagnoses of relatives were made blind to the diagnoses of probands. RESULTS: The results show high rates of both BPD and ANX in relatives of children with BPD + ANX. Moreover, BPD and ANX cosegregated among the relatives of children with BPD + ANX. Although relatives of both ANX proband groups (with and without BPD) had high rates of ANX, and relatives of both BPD proband groups (with and without ANX) had high rates of BPD, the combined condition BPD + ANX was the predominant form of BPD among relatives of probands with BPD + ANX. CONCLUSIONS: These family-genetic findings suggest that the comorbid condition BPD+ANX may be a distinct clinical entity. More work is needed to evaluate whether the presence of comorbid ANX may be a marker of very early onset BPD.

Adolescent↗

PubMed2002

The Lifetime Dimensions of Psychosis Scale (LDPS): description and interrater reliability.

A new rating scale, the Lifetime Dimensions of Psychosis Scale (LDPS), is described. The LDPS creates a profile of the lifetime characteristics of each case based on retrospective ratings, encompassing the positive, bizarre, negative, and disorganized symptom factors identified by previous studies of psychotic disorders, plus mood-related symptomatology, degree of deterioration, and complicating factors over the course of illness. A preliminary 39-item scale and instruction manual were developed. Intraclass correlation coefficients (ICCs) for positive symptom and mood item total scores were 0.76 to 0.87 (mean of 0.70 for all items). Highly intercorrelated (tau-b coefficients) or unreliable items were eliminated to create the final 20-item version 2. Good-excellent reliability was observed in a second study using different raters. The LDPS is designed for use by experienced clinicians or researchers who have access to comprehensive clinical information, including semistructured diagnostic interviews, psychiatric records, and family history reports. Dimensional scores and multidimensional patterns might prove useful in studying the relationship of clinical phenotype to genotypes, treatment response, and other variables. They may also be useful in clinical practice.

Adult↗

PubMed2002

Attention-deficit/hyperactivity disorder in children and adolescents with obsessive-compulsive disorder: fact or artifact?

OBJECTIVE: To clarify whether the symptoms of inattention and distractibility commonly seen in children and adolescents with obsessive-compulsive disorder (OCD) represent true comorbidity with attention-deficit/hyperactivity disorder (ADHD) or a manifestation of obsessional anxiety. METHOD: Phenotypic features and functional correlates of ADHD-like symptoms were examined in youths with and without OCD from a large sample of pediatric psychiatry patients consecutively referred since 1997. RESULTS: The number, frequency, and types of core ADHD symptoms as well as ADHD-associated functional indices were identical in all youths with DSM-IV-diagnosed ADHD irrespective of the presence or absence of comorbid OCD. CONCLUSION: These findings suggest that when ADHD-like symptoms are seen in youths with OCD, they reflect a true comorbid state of OCD plus ADHD and that the ADHD syndrome may be independent of OCD in comorbid youths.

Adolescent↗

PubMed2002

Case-control study of attention-deficit hyperactivity disorder and maternal smoking, alcohol use, and drug use during pregnancy.

OBJECTIVE: To address the putative association between attention-deficit hyperactivity disorder (ADHD) and prenatal exposure to maternal cigarette smoking, drugs of abuse, and alcohol attending to potential confounding by familial ADHD, maternal depression, conduct disorder, and indicators of social adversity in the environment. METHOD: A retrospective, hospital-based, case-control study was conducted with 280 ADHD cases and 242 non-ADHD controls of both genders. The case and control children and their relatives were systematically assessed with structured diagnostic interviews. Logistic regression analysis was used to determine the adjusted effect of prenatal exposure to substance use and ADHD. RESULTS: ADHD cases were 2.1 times (95% confidence interval = 1.1-4.1;p = .02) more likely to have been exposed to cigarettes and 2.5 times (95% confidence interval = 1.1-5.5; p = .03) more likely to have been exposed to alcohol in utero than were the non-ADHD control subjects. Adjustment by familial psychopathology, Rutter's indicators of social adversity, and comorbid conduct disorder did not account for the effect of prenatal exposure to alcohol or the products of cigarettes. CONCLUSIONS: ADHD may be an additional deleterious outcome associated with prenatal exposure to alcohol independently of the association between prenatal exposure to nicotine and smoke products and other familial risk factors for the disorder.

Adolescent↗

PubMed2002

Impact of low birth weight on attention-deficit hyperactivity disorder.

The objective of the study was to evaluate an association between low birth weight (LBW) and attention-deficit hyperactivity disorder (ADHD) attending to potential family-genetic and environmental confounders. We examined 252 ADHD cases (boys and girls) and 231 non-ADHD controls and their parents. All subjects were extensively assessed with structured diagnostic interviews, cognitive assessments, and structured interviews of prenatal, infancy, and delivery complications. ADHD cases were three times more likely to have been born LBW than were non-ADHD controls, after attending to potential confounders such as prenatal exposure to alcohol and cigarettes, parental ADHD, social class, and comorbid disruptive behavior disorders in parents and offspring. If this association was causal, 13.8% of all ADHD cases could be attributed to LBW. These results converge with prior studies documenting similar associations and indicate that LBW is an independent risk factor for ADHD. Children with LBW, however, make up a relatively small proportion of children with ADHD.

Attention Deficit Disorder with Hyperactivity↗

PubMed2002

Comparative efficacy of Adderall and methylphenidate in attention-deficit/hyperactivity disorder: a meta-analysis.

Because methylphenidate is currently the most widely prescribed medication for attention-deficit/ hyperactivity disorder, several studies have used it as the active comparator medication for evaluating the efficacy of a newer stimulant, Adderall. These prior studies show Adderall to be superior to placebo and suggest it is at least as effective as the standard-release form of methylphenidate and has a longer duration of action. Although these initial studies provide useful information for clinicians treating children with attention-deficit/hyperactivity disorder, they are difficult to interpret because findings vary among studies and among the different types of measures used within each study. To provide a clearer picture of what conclusions can be drawn from these studies, we performed a meta-analysis. Data from the four available studies suggest that Adderall has a small but statistically significant advantage over the standard-release form of methylphenidate. This advantage was observed for both symptom measures and global ratings but was strongest for global ratings. The effect of Adderall was significant for clinician and parent ratings but not for teacher ratings and was significant for both fixed-dose and best-dose designs.

Adolescent↗