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Biomedical subjects

Michael C Monuteaux

Publications and source records attributed to Michael C Monuteaux.

At least 19 recordsLinked to original sources

Deriving phenotypes for molecular genetic studies of substance use disorders: a family study approach.

Although, family, twin, and adoption studies indicate that genes play a significant etiologic role in the development of substance use disorders (SUDs), the specific genes involved have been difficult to detect due, in part, to uncertainties about how best to define SUDs, the possibility of genetic heterogeneity and the variable phenotypic expression of SUD genotypes. The goal of the present work was to determine if phenotypes external to the diagnosis of SUD such as psychopathology and cognitive functioning would show evidence of utility as phenotypes for genetic studies of SUD. We did this by applying factor analysis to multiple measures collected from our family-study program and then determining if these factors were heritable and were co-familial with SUDs. We used data from families recruited into six contemporaneous studies of four psychiatric conditions in children and adults. We found evidence for two SUD related phenotypes. One was an index of Psychopathology and Psychosocial Impairment; the other was an index of school failure and cognitive dysfunction. Both factors showed evidence of heritability, longitudinal stability and familial association with Parental SUD but these findings were stronger for the index of school failure and cognitive dysfunction. Results provide some support for the idea that candidate SUD phenotypes such as psychopathology and cognitive functioning, which are external to the diagnostic criteria for SUDs, may be useful for genetic studies of SUD.

Adolescent↗

Dorsolateral prefrontal and anterior cingulate cortex volumetric abnormalities in adults with attention-deficit/hyperactivity disorder identified by magnetic resonance imaging.

OBJECTIVES: Gray and white matter volume deficits have been reported in a number of studies of children with attention-deficit/hyperactivity disorder (ADHD); however, there is a paucity of structural magnetic resonance imaging (MRI) studies of adults with ADHD. This structural MRI study used an a priori region of interest approach. METHODS: Twenty-four adults with DSM-IV ADHD and 18 healthy controls comparable on age, socioeconomic status, sex, handedness, education, IQ, and achievement test performance had an MRI on a 1.5T Siemens scanner. Cortical and sub-cortical gray and white matter were segmented. Image parcellation divided the neocortex into 48 gyral-based units per hemisphere. Based on a priori hypotheses we focused on prefrontal, anterior cingulate cortex (ACC) and overall gray matter volumes. General linear analyses of the volumes of brain regions, adjusting for age, sex, and total cerebral volumes, were used to compare groups. RESULTS: Relative to controls, ADHD adults had significantly smaller overall cortical gray matter, prefrontal and ACC volumes. CONCLUSIONS: Adults with ADHD have volume differences in brain regions in areas involved in attention and executive control. These data, largely consistent with studies of children, support the idea that adults with ADHD have a valid disorder with persistent biological features.

Adult↗

Psychopathology in females with attention-deficit/hyperactivity disorder: a controlled, five-year prospective study.

BACKGROUND: Despite the importance of understanding the long-term outcome of children with attention-deficit/hyperactivity disorder (ADHD), the available literature is predominantly based on male samples. This study estimated the lifetime burden of comorbid psychopathology in a large sample of girls with and without ADHD followed up over five years. METHODS: We conducted a blind, five-year prospective longitudinal study of girls with (n=140) and without (n=122) ADHD, aged 6-18 years at baseline, consecutively ascertained from either community pediatricians or psychiatrists at an academic medical center. At the five-year follow-up, 123 (88%) and 112 (92%) of the ADHD and control children, respectively, were re-assessed at a mean age of 16.7 years. Psychiatric disorders were assessed using blinded structured diagnostic interviews. RESULTS: At follow-up, females with ADHD were at significantly higher risk than controls to manifest disruptive behavior, mood and anxiety disorders, and substance dependence. The magnitude of increased risk was greatest for major depression and oppositional-defiant disorder, followed by substance dependence and anxiety disorders. CONCLUSIONS: These prospective follow-up findings documenting high morbidity associated with ADHD extend to females previously reported findings in male samples and underscore the importance of early recognition and intervention efforts for youth with ADHD of both genders.

Adolescent↗

Young adult outcome of attention deficit hyperactivity disorder: a controlled 10-year follow-up study.

BACKGROUND: Our objective was to estimate the lifetime prevalence of psychopathology in a sample of youth with and without attention deficit hyperactivity disorder (ADHD) through young adulthood using contemporaneous diagnostic and analytic techniques. METHOD: We conducted a case-control, 10-year prospective study of ADHD youth. At baseline, we assessed consecutively referred male, Caucasian children with (n=140) and without (n=120) DSM-III-R ADHD, aged 6-18 years, ascertained from psychiatric and pediatric sources to allow for generalizability of results. At the 10-year follow-up, 112 (80%) and 105 (88%) of the ADHD and control children, respectively, were reassessed (mean age 22 years). We created the following categories of psychiatric disorders: Major Psychopathology (mood disorders and psychosis), Anxiety Disorders, Antisocial Disorders (conduct, oppositional-defiant, and antisocial personality disorder), Developmental Disorders (elimination, language, and tics disorder), and Substance Dependence Disorders (alcohol, drug, and nicotine dependence), as measured by blinded structured diagnostic interview. RESULTS: The lifetime prevalence for all categories of psychopathology were significantly greater in ADHD young adults compared to controls, with hazard ratios and 95% confidence intervals of 6.1 (3.5-10.7), 2.2 (1.5-3.2), 5.9 (3.9-8.8), 2.5 (1.7-3.6), and 2.0 (1.3-3.0), respectively, for the categories described above. CONCLUSIONS: By their young adult years, ADHD youth were at high risk for a wide range of adverse psychiatric outcomes including markedly elevated rates of antisocial, addictive, mood and anxiety disorders. These prospective findings provide further evidence for the high morbidity associated with ADHD across the life-cycle and stress the importance of early recognition of this disorder for prevention and intervention strategies.

Adolescent↗

Neuropsychological functioning in girls with attention-deficit/hyperactivity disorder with and without learning disabilities.

The authors' goal was to assess neuropsychological performance in girls with attention-deficit/hyperactivity disorder (ADHD) and evaluate the role of comorbid learning disabilities (LDs). Participants were 140 girls with ADHD and 122 girls without ADHD, ages 6-17 years. Neuropsychological performance was measured in a standardized manner, blind to clinical status. LD was defined by a combined regression-based and low-achievement classification. ADHD was associated with modest, but significant, neuropsychological impairment, as measured with an aggregate measure of performance and with the Stroop Color-Word Test, independent of age, social class, IQ, and psychiatric comorbidity. Neuropsychological deficits were most pronounced in girls with both ADHD and an LD and in those without medications. These results extend to females the previously documented association of LDs with neuropsychological functioning in males with ADHD.

Adolescent↗

Characteristics of adolescents and young adults with ADHD who divert or misuse their prescribed medications.

OBJECTIVE: Little is known about the risks and characteristics of attention-deficit/hyperactivity disorder (ADHD) patients who misuse or divert their stimulant medications. As part of a 10-year longitudinal study of youths with ADHD, the authors evaluated medication diversion or misuse at the last follow-up period. METHOD: Structured psychiatric interviews for diagnosis and a self-report questionnaire regarding medication use in medicated subjects with ADHD compared with controls without ADHD receiving psychotropics for non-ADHD treatment were employed. RESULTS: Of 98 subjects receiving psychotropic medications (mean age of 20.8 +/- 5 years), 55 (56%) were ADHD subjects and 43 (44%) were controls receiving medications for other purposes. The authors found that 11% of the ADHD group reported selling their medications compared with no subjects in the control group (z = 0.00, p <.05). An additional 22% of the ADHD group reported misusing their medications compared with 5% of the control subjects (z = 1.7 p =.09) and that those with conduct or substance use disorders accounted for the misuse and diversion. A minority of subjects reported escalating their doses and concomitant use with alcohol and drugs. CONCLUSIONS: The data indicate that the majority of ADHD individuals, particularly those without conduct or substance use disorders, use their medications appropriately. The authors' findings also highlight the need to monitor medication use in ADHD individuals with conduct and/or substance use disorders and to carefully select agents with a low likelihood of diversion or misuse in this group.

Adolescent↗

Maternal smoking during pregnancy and offspring overt and covert conduct problems: a longitudinal study.

BACKGROUND: Empirical evidence demonstrates that conduct disorder (CD) symptoms tend to cluster into covert and overt domains. We hypothesized that overt and covert CD symptoms may be distinct constructs with distinct risk factors. An important risk factor for CD is maternal smoking during pregnancy. We further investigated this association, attending to overt and covert CD symptom subtypes. Also, we tested whether gender and socioeconomic status (SES) modified this association. METHOD: Participants were male and female adult offspring (n = 682) of a community sample of pregnant women followed longitudinally from prenatal life to age 22. Prospective assessments of maternal smoking during pregnancy were used to predict self-reported DSM-III CD symptoms. RESULTS: Prenatal exposure to smoking was significantly associated with increased overt CD symptoms for participants of low SES, but not for participants of high SES, whereas covert CD symptoms were not associated with prenatal exposure. Gender did not significantly modify the relationship between maternal smoking and CD symptom subtypes. CONCLUSIONS: These results suggest that the previously documented association between maternal smoking and CD may be specific to overt CD symptoms, providing support for the heuristic value of differentiating overt and covert CD symptoms as distinct syndromes. These findings further support smoking prevention programs for pregnant women.

Adolescent↗

Diagnosing adult attention deficit hyperactivity disorder: are late onset and subthreshold diagnoses valid?

OBJECTIVE: Diagnosing attention deficit hyperactivity disorder (ADHD) in adults is difficult when diagnosticians cannot establish an onset before the DSM-IV criterion of age 7 or if the number of symptoms recalled does not achieve DSM's diagnosis threshold. METHOD: The authors addressed the validity of DSM-IV's age-at-onset and symptom threshold criteria by comparing four groups of adults: 127 subjects with full ADHD who met all DSM-IV criteria for childhood-onset ADHD, 79 subjects with late-onset ADHD who met all criteria except the age-at-onset criterion, 41 subjects with subthreshold ADHD who did not meet full symptom criteria for ADHD, and 123 subjects without ADHD who did not meet any criteria. The authors hypothesized that subjects with late-onset and subthreshold ADHD would show patterns of psychiatric comorbidity, functional impairment, and familial transmission similar to those seen in subjects with full ADHD. RESULTS: Subjects with late-onset and full ADHD had similar patterns of psychiatric comorbidity, functional impairment, and familial transmission. Most children with late onset of ADHD (83%) were younger than 12. Subthreshold ADHD was milder and showed a different pattern of familial transmission than the other forms of ADHD. CONCLUSIONS: The data about the clinical features of probands and the pattern of transmission of ADHD among relatives found little evidence for the validity of subthreshold ADHD among such subjects, who reported a lifetime history of some symptoms that never met DSM-IV's threshold for diagnosis. In contrast, the results suggested that late-onset adult ADHD is valid and that DSM-IV's age-at-onset criterion is too stringent.

Adolescent↗

Functional impairments in adults with self-reports of diagnosed ADHD: A controlled study of 1001 adults in the community.

OBJECTIVE: The objective of this study was to evaluate functional impairments in a nonreferred sample of adults identifying themselves as having been diagnosed with attention-deficit/hyperactivity disorder (ADHD) by a clinician in their community. METHOD: We completed a survey in April and May 2003 of a community sample of 500 adults who reported having received a diagnosis of ADHD in the community and 501 gender- and age-matched comparisons from a national sample representative of the U.S. population. RESULTS: Adults with self-reports of diagnosed ADHD in the community were significantly less likely to have graduated high school (83% vs. 93% of controls; p < or = .001) or obtain a college degree (19% vs. 26%; p < .01), were less likely to be currently employed (52% vs. 72%; p < or = .001), and had significantly more mean job changes over 10 years (5.4 vs. 3.4 jobs; p < or = .001). They also were significantly more likely to have been arrested (37% vs. 18% of controls; p < or = .001) or divorced (28% vs. 15%; p < or = .001) and were significantly less satisfied (p < or = .001) with their family, social, and professional lives. CONCLUSION: Adults who reported having received a diagnosis of ADHD in the community had significant impairment in multiple domains of functioning compared with age- and gender-matched controls without this diagnosis, highly consistent with findings derived from carefully diagnosed referred samples.

Adolescent↗

Is cigarette smoking a gateway to alcohol and illicit drug use disorders? A study of youths with and without attention deficit hyperactivity disorder.

BACKGROUND: The goal of this study was to assess whether cigarette smoking is a gateway drug for subsequent alcohol and illicit drug abuse and dependence in youth with Attention Deficit Hyperactivity Disorder (ADHD), and to test if this association is stronger in ADHD youth relative to controls. METHODS: We used data from a case-control family study of female youth with and without ADHD. We studied 97 ADHD and 203 control youth of both sexes, aged at least 12 years. We assessed ADHD, smoking, and substance use status using structured diagnostic interviews. We tested the association between cigarette smoking and subsequent substance use outcomes using Cox proportional hazard regression models. RESULTS: ADHD youth who smoked cigarettes (n = 15) were significantly more likely to subsequently use alcohol and illicit drugs as well as to develop abuse and dependence compared to ADHD youth who did not smoke (n = 76; p < .05). CONCLUSIONS: These results extend the gateway hypothesis to an ADHD sample and provide evidence that this effect may be particularly robust in ADHD youth. If replicated in larger, community-based samples, these findings have important public health consequences, and underscore the already pressing need to prevent smoking in ADHD children.

Adolescent↗

The clinical dilemma of using medications in substance-abusing adolescents and adults with attention-deficit/hyperactivity disorder: what does the literature tell us?

OBJECTIVE: Adolescents and adults with attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUD) are increasingly recognized in clinical practice. The role of pharmacological treatment for ADHD in these comorbid individuals remains unclear. METHODS: A systematic review of the medical literature was conducted through PubMed, supplemented with data from scientific presentations, to evaluate the role of medication treatment of ADHD in substance abusing individuals with ADHD. Meta-analysis was used to evaluate the effects of medication therapy on ADHD and SUD outcomes in general, while specifically addressing trial design, trial duration, retention, class of medication, age group, concurrent psychotherapy, and outcome in both SUD and ADHD domains. RESULTS: Four studies in adolescents and five studies in adults with ADHD plus SUD were identified (two controlled and seven open studies; n = 222 subjects). The standard mean difference (SMD) indicated statistically significant improvements in ADHD and SUD that were not maintained when evaluating controlled studies only. Albeit limited by power, trial duration, retention rate, and age group did not influence outcome. No worsening of SUD or drug-drug interactions were observed in any of the studies. The results could not be accounted for by any single study or by publication bias. CONCLUSION: Treating ADHD pharmacologically in individuals with ADHD plus SUD has a moderate impact on ADHD and SUD that is not observed in controlled trials and does not result in worsening of SUD or adverse interactions specific to SUD. Further controlled trials evaluating the effect of novel combinations of psychotherapy and ADHD pharmacotherapy on SUD relapse in these groups are warranted.

Adolescent↗

Reexamining the familial association between asthma and ADHD in girls.

The objective of this study is to further evaluate the association between asthma and ADHD, addressing issues of familiality in female probands. A case control study of referred ADHD proband girls, controls, and relatives are used. Participants include 140 ADHD proband girls and 122 non-ADHD comparisons, with 417 and 369 first-degree biological relatives, respectively. Relatives are stratified into four groups according to proband ADHD and asthma status. The authors compare rates of asthma and ADHD in relatives. ADHD does not increase the risk for asthma in probands. Patterns of familial aggregation are mostly consistent with independent transmission of ADHD and asthma in families of girl probands. The results extend to female probands' previously reported findings that asthma and ADHD are independently transmitted in families. These findings further support the conclusion that ADHD symptoms should not be dismissed as part of asthma symptomatology or a consequence of its treatment.

Adult↗

Impact of gender and age on executive functioning: do girls and boys with and without attention deficit hyperactivity disorder differ neuropsychologically in preteen and teenage years?

ADHD is known to have neuropsychological correlates, characterized mainly by executive function (EF) deficits. However, most available data are based on studies of boys through age 12. Our goal was to assess whether girls with ADHD express neuropsychological features similar to those found in boys, and whether these impairments are found in both preteen and teen samples. Participants were 101 girls and 103 boys with DSM-III-R ADHD, and 109 comparison girls and 70 boys without ADHD, ages 9 to 17 years. Information on neuropsychological performance was obtained in a standardized manner blind to clinical status. Primary regression analyses controlled for age, socioeconomic status, learning disability, and psychiatric comorbidity. Girls and boys with ADHD were significantly more impaired on some measures of EFs than healthy comparisons but did not differ significantly from each other. With the exception of 1 test score there were no significant Sex x Diagnosis interactions. Moreover, there were no more significant interactions among age, gender, and diagnosis than would be expected by chance. Neuropsychological measures of EFs were comparably impaired in girls compared to boys with ADHD, and these impairments are found at ages 9 to 12 and ages 13 to 17. These findings suggest that executive dysfunctions are correlates of ADHD regardless of gender and age, at least through the late teen years.

Adolescent↗

Does referral bias impact findings in high-risk offspring for anxiety disorders? A controlled study of high-risk children of non-referred parents with panic disorder/agoraphobia and major depression.

BACKGROUND: Previous findings in referred samples documented significant diagnostic specificity in patterns of transmission between parents with panic disorder (PD) and parents with major depression (MD) and their offspring. This study evaluated whether these patterns of transmission between parents and high-risk offspring are moderated by referral bias. METHODS: Parental PD/agoraphobia (AG) and parental MD were used to predict rates of offspring psychiatric disorders and functional outcomes using data from an opportunistic sample of parents (n = 991) and offspring (n = 734) ascertained from case-control family genetic studies of youth with and without attention-deficit hyperactivity disorder. Subjects were comprehensively assessed with structured diagnostic interview methodology to evaluate psychiatric disorders in parents and offspring. RESULTS: Parental PD/AG increased the risk for anxiety disorders in offspring, independently of parental MD while parental MD increased the risk for mood and disruptive behavior disorders in offspring, independently of parental PD/AG. Parental psychopathology was also associated with functional impairment in offspring. LIMITATIONS: The use of a sample ascertained by ADHD and control probands, and parent psychiatric diagnostic reports for children under 12. CONCLUSIONS: These results extend to non-referred samples previous findings from referred samples documenting diagnostic specificity in the familial transmission of PD/AG and MD from parents to offspring, suggesting that these patterns of transmission are not due to referral bias. These results could inform and enhance community programs aimed at screening for and treating pediatric psychopathology.

Adolescent↗

Gender effects on attention-deficit/hyperactivity disorder in adults, revisited.

BACKGROUND: This study reexamined gender differences in a large sample of adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: We assessed the effects of ADHD, gender, and their interaction on rates of psychiatric comorbidity and cognitive functioning in 219 adults with ADHD who were referred to an outpatient psychiatric clinic over the last 7 years compared with 215 control subjects group-matched to control subjects on age and gender, and ascertained from ongoing family genetic case control adults with ADHD. RESULTS: There was no evidence that gender moderated the association between ADHD and other psychiatric disorders. Attention-deficit/hyperactivity disorder was associated with cognitive deficits and higher rates of major depression, anxiety, substance use disorders, and antisocial personality disorder. CONCLUSIONS: Attention-deficit/hyperactivity disorder in adults is associated with psychiatric and cognitive impairment in both genders. These results bear striking similarities to findings reported in pediatric samples, supporting the validity of ADHD and stressing the importance of identifying and treating the disorder in adulthood.

Adult↗

Impact of executive function deficits and attention-deficit/hyperactivity disorder (ADHD) on academic outcomes in children.

The association between executive function deficits (EFDs) and functional outcomes were examined among children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Participants were children and adolescents with (n = 259) and without (n = 222) ADHD, as ascertained from pediatric and psychiatric clinics. The authors defined EFD as at least 2 executive function measures impaired. Significantly more children and adolescents with ADHD had EFDs than did control participants. ADHD with EFDs was associated with an increased risk for grade retention and a decrease in academic achievement relative to (a) ADHD alone, (b) controlled socioeconomic status, (c) learning disabilities, and (d) IQ. No differences were noted in social functioning or psychiatric comorbidity. Children and adolescents with ADHD and EFDs were found to be at high risk for significant impairments in academic functioning. These results support screening children with ADHD for EFDs to prevent academic failure.

Achievement↗

Effectiveness of collaborative problem solving in affectively dysregulated children with oppositional-defiant disorder: initial findings.

Oppositional-defiant disorder (ODD) refers to a recurrent pattern of negativistic, defiant, disobedient, and hostile behavior toward authority figures. Research has shown that children with ODD and comorbid mood disorders may be at particular risk for long-term adverse outcomes, including conduct disorder. In this study, the authors examined the effectiveness of a cognitive-behavioral model of intervention--called collaborative problem solving (CPS)--in comparison with parent training (PT) in 47 affectively dysregulated children with ODD. Results indicate that CPS produced significant improvements across multiple domains of functioning at posttreatment and at 4-month follow-up. These improvements were in all instances equivalent, and in many instances superior, to the improvements produced by PT. Implications of these findings for further research on and treatment selection in children with ODD are discussed.

Attention Deficit and Disruptive Behavior Disorder↗

How informative are parent reports of attention-deficit/hyperactivity disorder symptoms for assessing outcome in clinical trials of long-acting treatments? A pooled analysis of parents' and teachers' reports.

OBJECTIVE: The validity of parent reports of children's attention-deficit/hyperactivity disorder (ADHD) symptoms has been questioned, especially in clinical trials. Some advocate the exclusive use of teacher reports, maintaining that parent reports are not sensitive to changes in ADHD symptoms. This study compares the ability of parent and teacher reports to document change during clinical trials of long-acting treatments. METHODS: We conducted a literature search of Medline to identify any published clinical trials in pediatric ADHD that met the following criteria: 1) used a randomized design, 2) examined the efficacy of long-acting agents or standard formulations using 3-times-a-day dosing, and 3) used both parent and teacher reports of the same measure of ADHD symptoms as a study outcome. For each measurement of ADHD symptoms, we calculated effect sizes for parent and teacher reports. RESULTS: Three large, randomized, controlled clinical trials were identified (N = 1445 subjects). For every outcome for which teacher reports documented significant improvement, parent reports did also. Pooled analysis revealed a larger effect captured by the parent report relative to the teacher report. CONCLUSION: Results suggest that parent reports are at least as sensitive to detecting change in ADHD symptoms as teacher reports in clinical trials that assess the efficacy of long-acting agents. These results suggest that parent reports are informative for detecting change during treatment of children with ADHD.

Attention Deficit Disorder with Hyperactivity↗