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Biomedical subjects

Salvatore Mannuzza

Publications and source records attributed to Salvatore Mannuzza.

16 recordsLinked to original sources

Memory deficits in children with and at risk for anxiety disorders.

There are limited data on the neurocognitive correlates of childhood anxiety disorders. The objective of this study was to examine whether visual and verbal memory deficits of nonemotional stimuli are (1) a shared feature of three common childhood anxiety disorders (social phobia, separation anxiety disorder, and generalized anxiety disorder) or whether these deficits are restricted to specific anxiety disorders, and (2) present in offspring who possess at least one of the following established risk factors for anxiety disorders, parental history of panic disorder (PD), or major depressive disorder (MDD). One hundred and sixty offspring, ages 9-20 years, were recruited from parents with lifetime diagnoses of PD, MDD, PD plus MDD, or neither illness. Different clinicians blindly administered semistructured diagnostic interviews to offspring and parents. Verbal and visual memory subtests of the Wide Range Assessment of Memory and Learning were administered to offspring. The results showed that offspring with ongoing social phobia demonstrated reduced visual but not verbal memory scores compared to those without social phobia when controlling for offspring IQ, separation anxiety disorder, and generalized anxiety disorder. No other offspring anxiety disorder predicted memory performance. Neither parental PD nor parental MDD was associated with offspring memory performance. These findings are relevant to understanding the phenomenology of childhood anxiety disorders and may provide insights into the neural circuits underlying these disorders.

Adolescent↗

Stress responsivity and HPA axis activity in juveniles: results from a home-based CO2 inhalation study.

OBJECTIVE: A previous laboratory-based study found elevated cortisol levels in anxious children susceptible to CO(2)-induced panic, but the effects of parent diagnosis were not considered. The current home-based study tested the hypothesis that parental panic disorder and offspring response to CO(2) are associated with elevated cortisol levels in juvenile offspring. METHOD: A total of 131 offspring (ages 9-19) of parents with panic disorder, major depression, and no mental disorder underwent CO(2) inhalation. Parent and child diagnoses were assessed. Salivary cortisol was assayed before and after CO(2) inhalation. RESULTS: Neither parents with panic disorder, parents with major depression, or offspring anxiety predicted offspring cortisol levels. Independent of parent and child diagnoses, anxiety response to CO(2) predicted elevated cortisol levels in offspring. CONCLUSIONS: As in adults, anxiety response to CO(2) in juveniles is associated with elevated cortisol levels, but elevated cortisol levels are not related to parent or child diagnoses.

Administration, Inhalation↗

Response to 5% carbon dioxide in children and adolescents: relationship to panic disorder in parents and anxiety disorders in subjects.

BACKGROUND: Carbon dioxide (CO(2)) sensitivity is postulated to be a familial risk marker of panic disorder (PD). Exaggerated responses to CO(2) inhalation have been reported in adults with PD and their unaffected adult relatives, as well as in clinic-referred children with anxiety disorders. OBJECTIVE: To test in a family-based design whether CO(2) hypersensitivity is a familial risk marker for PD and associated with current anxiety disorders in children and adolescents. SETTING AND PARTICIPANTS: One hundred forty-two offspring (aged 9-19 years) of parents with PD, major depressive disorder, or no disorder. Forty-five (32%) had a current anxiety disorder, excluding specific phobia. DESIGN AND MAIN OUTCOME MEASURES: Parents and offspring received diagnostic assessments. Offspring underwent 5% CO(2) inhalation at home. Panic symptoms and panic attacks were rated with the Acute Panic Inventory at baseline, while anticipating CO(2) delivery ("threat"), and during CO(2) inhalation. Respiratory rate and volume were measured with spirometry. RESULTS: No group differences were found in Acute Panic Inventory ratings at baseline or in respiratory measures during threat. Risk for PD was not associated with CO(2) sensitivity (panic symptoms and respiratory physiologic response). During CO(2) inhalation, offspring with anxiety disorders, relative to offspring without anxiety disorders, experienced significantly more panic symptoms and panic attacks, as well as elevated respiratory rates. During threat, panic symptoms were significantly and independently associated with both parental PD and offspring anxiety disorders. CONCLUSIONS: No support was obtained for CO(2) hypersensitivity as a familial risk marker for PD in children and adolescents. Links between childhood anxiety disorders and CO(2) sensitivity were replicated. Familial risk for PD in children and adolescents may be associated with vulnerability to anticipatory anxiety.

Adolescent↗

A direct interview family study of obsessive-compulsive disorder. II. Contribution of proband informant information.

BACKGROUND: Overall findings of our first direct interview family study of obsessive-compulsive disorder (OCD) indicated that OCD is familial. In this replication study, we carefully examined the role of informant data in ascertaining OCD in relatives. METHOD: We interviewed 112 relatives of 57 OCD patients and 115 relatives of 41 not ill controls predominantly by telephone. Additional analyses included a combined sample of relatives about whom any diagnostic information was available (228 OCD and 239 controls). To examine the contribution of proband information about relatives, we considered two sets of best-estimate diagnoses. First, we ascertained best-estimate diagnoses for relatives using information from direct interviews and from all informants except the proband. Then, we re-diagnosed relatives based on all available information, including reports from the proband about their relatives. RESULTS: When relative diagnoses were derived without the benefit of proband informant reports, no evidence of familial OCD transmission was found. When diagnoses were made including information from the proband about the relative, evidence of familial OCD was found, but only when the diagnostic threshold was lowered to include cases with probable OCD or OCD symptoms. Other diagnoses (generalized anxiety disorder, social phobia, drug use disorder) were also higher among OCD relatives. CONCLUSIONS: This second study provides less robust support for familial transmission of OCD. Evidence for familial transmission of OCD was found only when diagnoses were made using information from the affected proband about their relatives. Taken in context of past findings, our own inconsistent results suggest that OCD may be heterogeneous with regard to familial transmission. Also, more careful attention should be paid to the contribution of informant reports, especially from relatives affected by the same disorder.

Adult↗

A direct interview family study of obsessive-compulsive disorder. I.

BACKGROUND: This and the companion paper present two sequential family studies of obsessive-compulsive disorder (OCD) conducted by the same research group, but with different sampling and best-estimate procedures. In addition to providing further data on familial transmission of OCD, we used comparison of disparate findings (moderate, specific familial aggregation in this first study versus a stronger effect for other anxiety disorders than for OCD alone in the second) to examine possible effects of proband characteristics and informant data on outcome. METHOD: In this initial study we interviewed 179 first-degree relatives of 72 OCD probands and 112 relatives of 32 never mentally ill (NMI) controls. Informant data were obtained on an additional 126 relatives (total "combined" samples of 263 and 154 respectively). Analyses used best-estimate diagnoses made by consensus of two "blinded" senior clinicians who reviewed all diagnostic materials including proband informant data about relatives. RESULTS: Significantly higher risk for OCD but not other anxiety disorders was found in relatives of OCD probands compared to relatives of controls in both the directly interviewed and combined samples. There was no relationship between proband age at onset of OCD and strength of familial aggregation. CONCLUSIONS: These data indicate moderate familial aggregation of OCD, but do not support increased transmission by early onset probands, or a familial relationship between OCD and other anxiety disorders with the possible exception of generalized anxiety disorder.

Adult↗

Face-emotion processing in offspring at risk for panic disorder.

OBJECTIVE: Panic disorder (PD) has been linked to perturbed processing of threats. This study tested the hypotheses that offspring of parents with PD and offspring with anxiety disorders display relatively greater sensitivity and attention allocation to fear provocation. METHOD: Offspring of adults with PD, major depressive disorder (MDD), or no disorder (ages 9-19) viewed computer-presented face photographs depicting angry, fearful, and happy faces. Offspring rated (1) subjectively experienced fear level, (2) how hostile the face appeared, and (3) nose width. Attention allocation was indexed by latency to perform ratings. RESULTS: Compared with offspring of parents without PD (n = 79), offspring of PD parents (n = 65) reported significantly more fear and had slower reaction times to rate fear, controlling for ongoing anxiety disorder in the offspring. Offspring with an anxiety disorder (n = 65) reported significantly more fear than offspring without an anxiety disorder but not when parental PD was controlled. Social phobia but no other anxiety disorder in offspring was associated with slower reaction times for fear ratings (but not greater fear ratings). Parental PD and offspring social phobia independently predicted slower reaction time. CONCLUSIONS: Results support an association between parental PD and offspring responses to fear provocation. Social phobia in children may have a specific relationship to allocation of attention to subjective anxiety during face viewing.

Adolescent↗

Significance of childhood conduct problems to later development of conduct disorder among children with ADHD: a prospective follow-up study.

This study investigates whether low to moderate levels of childhood oppositional defiant disorder (ODD) and conduct disorder (CD) behaviors contribute to the development of clinically diagnosed CD in adolescence, in children with attention deficit hyperactivity disorder (ADHD). Participants were 207 White boys (ages 6-12) with ADHD free of conduct disorder diagnoses. Parent and teacher ratings were obtained. Participants were assessed at mean age 18 by clinicians blind to childhood status. A non-ADHD group (recruited in adolescence) was also studied. ODD behavior ratings did not predict CD in adolescence, whereas CD behavior ratings did. No single ODD or CD behavior predicted adolescent outcome. ADHD probands with very low ratings (Not at all, Just a little) by parents and teachers on all CD behaviors were still at significantly increased risk for CD in adolescence, compared to non-ADHD controls. The same relationships were found between childhood ODD and CD behaviors, and antisocial personality disorder in adulthood (mean age, 25). We conclude that childhood ADHD is a developmental precursor of later antisocial disorder, even in the absence of comorbid ODD or CD in childhood. However, low levels of CD-type problems are not innocuous, because they predict later CD among children with ADHD without comorbid CD.

Adolescent↗

Face-memory and emotion: associations with major depression in children and adolescents.

BACKGROUND: Studies in adults with major depressive disorder (MDD) document abnormalities in both memory and face-emotion processing. The current study used a novel face-memory task to test the hypothesis that adolescent MDD is associated with a deficit in memory for face-emotions. The study also examines the relationship between parental MDD and memory performance in offspring. METHODS: Subjects were 152 offspring (ages 9-19) of adults with either MDD, anxiety disorders, both MDD and anxiety, or no disorder. Parents and offspring were assessed for mental disorders. Collection of face-memory data was blind to offspring and parent diagnosis. A computerized task was developed that required rating of facial photographs depicting 'happy,"fearful,' or 'angry' emotions followed by a memory recall test. Recall accuracy was examined as a function of face-emotion type. RESULTS: Age and gender independently predicted memory, with better recall in older and female subjects. Controlling for age and gender, offspring with a history of MDD (n = 19) demonstrated significant deficits in memory selectively for fearful faces, but not happy or angry faces. Parental MDD was not associated with face-memory accuracy. DISCUSSION: This study found an association between MDD in childhood or adolescence and perturbed encoding of fearful faces. MDD in young individuals may predispose to subtle anomalies in a neural circuit encompassing the amygdala, a brain region implicated in the processing of fearful facial expressions. These findings suggest that brain imaging studies using similar face-emotion paradigms should test whether deficits in processing of fearful faces relate to amygdala dysfunction in children and adolescents with MDD.

Adolescent↗

Does stimulant treatment place children at risk for adult substance abuse? A controlled, prospective follow-up study.

The sensitization hypothesis posits a neuroadaptation model in which exposure to stimulants results in dopamine system alterations that, in turn, increase sensitivity to the reinforcing effects of the previously experienced drug. This study examines whether stimulant treatment in childhood confers increased risk for substance use and abuse in later life, as the model predicts. Children, ages 7-12 years, with developmental reading disorders but no other psychiatric diagnoses were randomly assigned to methylphenidate treatment (n = 43) or matching placebo (n = 66) for 12-18 weeks. At 16-year follow-up (mean age 26 years), 94% of probands and 129 normal comparisons were evaluated by trained clinicians who were blind to group and treatment status. There were no significant differences between groups on the prevalence of substance use disorder (abuse or dependence) for any of the seven drug categories studied. There were no significant group differences among substance abusers regarding age at onset, duration, or number of episodes of substance abuse and dependence. Significantly more normals (60%) than treated (46%) and untreated probands (41%) ever used stimulants in adolescence or adulthood. Findings from this randomized trial contradict the notion that stimulant treatment in childhood leads to substance use or abuse in later life. The sensitization hypothesis is not supported.

Adolescent↗

Persistence of Attention-Deficit/Hyperactivity Disorder into adulthood: what have we learned from the prospective follow-up studies?

OBJECTIVES: Longitudinal studies of children with Attention-Deficit/Hyperactivity Disorder (ADHD) into adolescence have all reported high rates of ADHD. However, findings from studies into adulthood are inconsistent. This article reviews factors that may account for disparate rates found in adult follow-ups, and recommends optimal methodologies for prospective studies of children with ADHD in particular and childhood mental disorders in general. METHOD: Follow-up studies of children with ADHD into adulthood are critically reviewed to identify factors that influence adult ADHD prevalence estimates. RESULTS: Four factors are identified: (1) ascertainment procedure, (2) attrition rate, (3) reporting source, and (4) disorder criteria. CONCLUSIONS: Estimates of the proportion of children with ADHD who will experience symptoms of the childhood syndrome in adulthood are likely to vary considerably, as a function of multiple factors. Several recommendations are made for designing future follow-up investigations.

Adult↗

Anxiety sensitivity among children of parents with anxiety disorders: a controlled high-risk study.

We investigated whether parental anxiety was related to anxiety sensitivity (AS) in offspring. Subjects were 261 offspring (aged 6-17 years) of parents with lifetime DSM-IV anxiety and/or mood disorders, and 79 offspring of parents with no lifetime anxiety, mood, or psychotic disorder. Parents and offspring were interviewed by blind clinicians. Children were administered the Child Anxiety Sensitivity Index (CASI). There were no significant differences between CASI scores of the offspring of parents with anxiety and/or mood disorders, and offspring of comparison parents. We conclude that parental anxiety or mood disorder does not predispose offspring to high anxiety sensitivity.

Adolescent↗

Young adult outcome of children with "situational" hyperactivity: a prospective, controlled follow-up study.

To examine the importance of symptom pervasiveness in ADHD, we conducted a prospective, 12-year follow-up study of boys (ages 6-12) considered hyperactive at school and home (Pervasive ADHD), boys considered hyperactive by teachers but not parents (School Only ADHD), boys considered hyperactive by parents but not teachers (Home Only ADHD), and nonhyperactive comparisons. Follow-up was completed on 82-94% participants. Clinicians interviewed participants and their parents, blind to childhood status. At follow-up, antisocial disorder was significantly more prevalent among Pervasive and School Only ADHD (29% for both) than Home Only ADHD (0%) and comparisons (8%). In a similar manner, severity of behavioral problems distinguished groups (Pervasive, School > Home, comparisons), as did educational attainment and academic performance (poorest for Pervasive and School). These findings stress the validity of teacher reports in the diagnosis of ADHD.

Achievement↗

Relationship between separation anxiety disorder, parental panic disorder, and atopic disorders in children: a controlled high-risk study.

OBJECTIVE: To test the hypotheses that rates of atopic disorders are elevated in offspring of parents with panic disorder (PD) and in children with separation anxiety disorder (SAD). METHOD: Rates of atopic disorders were assessed in 343 offspring (aged 6-17 years) of parents with PD, nonpanic psychiatric disorders, and no psychiatric disorder. Lifetime history of atopic disorders was determined by parental responses to a clinician-administered questionnaire assessing medical treatment for asthma and allergies. Logistic regression analyses assessed the association between atopic disorders and parental PD, and between atopic disorders and probable or definite childhood SAD. Analyses controlled for age, sex, socioeconomic status, and treatment for other medical illnesses. RESULTS: Increased rates of atopic disorders were found in offspring of parents with PD (odds ratio [OR] = 2.56, 95% confidence interval [CI] = 1.27-5.16, p = .009) and in children with SAD (OR = 2.71, 95% Cl = 1.22-6.03, p = .015). Associations remained significant when both parental PD and SAD were included in the model, suggesting that each contributed independently to increased rates of atopy. The interaction of parental PD and child SAD was not significant. CONCLUSIONS: Atopic disorders in children are associated with parental PD and with childhood SAD. Results do not appear to support that having both childhood SAD and a parent with PD confers increased risk for atopic disorders above and beyond either condition alone.

Adolescent↗

Clinical features of four DSM-IV-specific phobia subtypes.

Seventy-three patients (ages 18 to 66) with specific phobias from one of four DSM-IV subtypes (animal, situational, blood-injection-injury, and natural environment) were assessed by experienced clinicians using a semistructured diagnostic interview. All patients were free of lifetime anxiety comorbidity. Subtype groups were compared on age of onset, mode of onset, presence of unexpected panic attacks, and focus of fear. Consistent with earlier findings, participants with situational phobia had a later age of onset and more unexpected panic attacks. No differences were found across subtypes in mode of onset. Contrary to previous findings, natural environment and situational phobias were most frequently associated with a focus on danger or harm rather than other foci such as internal sensations associated with panic attacks. Implications for the usefulness of current subtype categories are discussed.

Adolescent↗

Accuracy of adult recall of childhood attention deficit hyperactivity disorder.

OBJECTIVE: Although reports of childhood status are necessary for making a diagnosis of adult attention deficit hyperactivity disorder (ADHD), systematic investigation of the accuracy of retrospective self-reports has been limited. This study examined accuracy of adult recall of childhood ADHD. METHOD: Participants were from a controlled, prospective 16-year follow-up of children with ADHD. At a mean age of 25 years, 176 probands (85% of the 207 subjects in the initial cohort) and 168 non-ADHD comparison subjects were interviewed by clinicians who were unaware of the subjects' childhood status. Subjects were asked about specific childhood ADHD behaviors, and the diagnosis of childhood ADHD was retrospectively established. RESULTS: Seventy-eight percent of the probands and 11% of the comparison subjects were identified as having childhood ADHD. Six symptoms demonstrated high discriminating power in differentiating the subject groups: distractibility, concentration difficulties, complaints of inattention, acting before thinking, being on the go, and fidgeting/squirming. When findings were adjusted for the prevalence of ADHD in the general population, the power of prediction was low. Positive predictive value was 0.27, i.e., of all adults retrospectively given a diagnosis of childhood ADHD, only 27% would be correctly identified. As expected, positive predictive value increased with increases in the estimated prevalence of ADHD. CONCLUSIONS: Retrospective diagnoses of childhood ADHD made on the basis of self-reports will in most cases be invalid in settings such as epidemiological surveys and primary care facilities. Greater accuracy can be expected in settings in which childhood ADHD is frequent. The results stress the importance of obtaining contemporaneous information on childhood symptoms in establishing a childhood history of ADHD. Future directions and implications for DSM-V are discussed.

Adolescent↗

Alcohol use disorders in relatives of patients with panic disorder.

OBJECTIVE: The aim of this study was to use data from a family study of anxiety disorders to examine the familial association between alcohol use disorders and panic disorder (PD), controlling for alcohol use disorders in the proband. METHOD: Data from a family study of anxiety disorders were used to compare rates of alcohol use disorders in the relatives of 3 proband groups (PD with lifetime alcohol use disorders, PD without lifetime alcohol use disorders, and not-ill controls). RESULTS: There was a significantly higher rate (12%) of alcohol use disorders among the relatives of PD probands compared with relatives of controls (5%), even in the absence of alcohol use disorders in the proband and after adjusting for differences in sociodemographic characteristics and lifetime drug use disorders (chi2 = 5.4; df = 1; P = .02). Anxiety symptoms were more frequent among the male relatives of panic probands who received an alcohol diagnosis, compared with those who did not have alcohol use disorders (10/25 vs 22/111; chi2 = 4.6; df = 1; P = .03). A similar pattern was found in women (8/11 vs 63/156; chi2 = 4.4; df = 1; P = .036). CONCLUSIONS: These findings suggest a familial association between PD and alcohol use disorders. Future studies with more refined alcohol diagnoses are needed to replicate and investigate the mechanism of this association.

Alcoholism↗