Further evidence for family-genetic risk factors in attention deficit hyperactivity disorder. Patterns of comorbidity in probands and relatives psychiatrically and pediatrically referred samples.

We examined 140 probands with attention deficit hyperactivity disorder, 120 normal controls, and their 822 first-degree relatives using "blind" raters and structured diagnostic interviews. Compared with controls, probands with attention deficit hyperactivity disorder were more likely to have conduct, mood, and anxiety disorders. Compared with relatives of controls, relatives of probands with attention deficit hyperactivity disorder had a higher risk for attention deficit hyperactivity disorder, antisocial disorders, major depressive disorder, substance dependence, and anxiety disorders. Patterns of comorbidity indicate that attention deficit hyperactivity disorder and major depressive disorders may share common familial vulnerabilities, that attention deficit hyperactivity disorder plus conduct disorder may be a distinct subtype, and that attention deficit hyperactivity disorder and anxiety disorders are transmitted independently in families. These results extend previous findings indicating family-genetic influences in attention deficit hyperactivity disorder by using both pediatrically and psychiatrically referred proband samples. The distributions of comorbid illnesses in families provide further validation for subgrouping probands with attention deficit hyperactivity disorder by comorbidity.     

Comorbidity of substance abuse and other psychiatric disorders in adolescents

Psychopathology coexisting with substance abuse in adolescents is often encountered in a variety of clinical settings. Research findings suggest a major role for substance use in the etiology and prognosis of psychiatric disorders such as affective disorders, conduct disorder and antisocial personality disorder, attention-deficit hyperactivity disorder, and anxiety disorders. Psychiatric disorders also appear to have an important role in the etiology of and vulnerability to substance use problems in adolescents. Although the comorbidity of substance abuse and other psychiatric disorders in adolescents is recognized as an important factor in the treatment of adolescents, further research is needed to establish its prevalence, genetics, and clinical implications.     

Aggression and disruptive behavior disorders in children and adolescents

Aggression is a common symptom of many psychiatric disorders including attention deficit hyperactivity disorder, oppositional defiant disorder, conduct disorder, Tourette's disorder, mood disorders (including bipolar disorder), substance-related disorders, alcohol-related disorders, mental retardation, pervasive developmental disorders, intermittent explosive disorder and personality disorders (particularly antisocial personality disorder). Many forms of organic brain disorders may present with aggressive behavior. Aggression is common in some epileptic patients and some endocrinological diseases (e.g., diabetes and hyperthyroidism) may be associated with aggressive behavior. Physicians need to rule out many medical and psychiatric disorders before diagnosing aggressive behavior. A thorough diagnostic work up is the most important step in determining the nature of comorbid disorders associated with the behavioral problem. Structured interviews and rating scales completed by patients, parents, teachers and clinicians may aid the diagnosis and provide quantification for the change process related to treatment. The integration of medication, individual and family counseling, educational and psychosocial interventions including the school and community, may increase the effectiveness of interventions. Due to the common association of aggression and disruptive behaviors with attention deficit hyperactivity disorder, psychostimulants including new generation long-acting medications and other nonstimulant medications are considered the drug of choice for managing aggressive behavior and disruptive behavior disorders. Severe aggressive behavior not responding to these medications may require the single or combined use of mood regulators including lithium and/or antispychotic medications. Drugs such as risperidone (Risperdal, Janssen-Cilag) have documented effectiveness and safety in children and adolescents, and can be used in treatment.     

Psychiatric diagnoses of treatment-seeking cocaine abusers

In a sample of 298 cocaine abusers seeking inpatient (n = 149) or outpatient (n = 149) treatment, rates of psychiatric disorders were determined by means of the Schedule for Affective Disorders and Research Diagnostic Criteria. Overall, 55.7% met current and 73.5% met lifetime criteria for a psychiatric disorder other than a substance use disorder. In common with previous reports from clinical samples of cocaine abusers, these overall rates were largely accounted for by major depression, minor bipolar conditions (eg, hypomania, cyclothymic personality), anxiety disorders, antisocial personality, and history of childhood attention deficit disorder. Affective disorders and alcoholism usually followed the onset of drug abuse, while anxiety disorders, antisocial personality, and attention deficit disorder typically preceded drug abuse.     

The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women

BACKGROUND: Patterns of comorbidity suggest that the common psychiatric and substance use syndromes may be divisible into 2 broad groups of internalizing and externalizing disorders. We do not know how genetic and environmental risk factors contribute to this pattern of comorbidity or whether the etiologic structure of these groups differ in men and women. METHODS: Lifetime diagnoses for 10 psychiatric syndromes were obtained at a personal interview in more than 5600 members of male-male and female-female twin pairs ascertained from a population-based registry. Multivariate twin modeling was performed using the program Mx. RESULTS: We first fit models to the following 7 syndromes: major depression, generalized anxiety disorder, phobia, alcohol dependence, drug abuse/dependence, adult antisocial behavior, and conduct disorder. The full model, which could be constrained to equality in male and female subjects, identified 2 genetic factors. The first had strongest loadings on alcohol dependence, drug abuse/dependence, adult antisocial behavior, and conduct disorder; the second, on major depression, generalized anxiety disorder, and phobia. Alcohol dependence and drug abuse/dependence had substantial disorder-specific genetic risk factors. Shared environmental factors were most pronounced for conduct disorder and adult antisocial behavior. No clear internalizing/externalizing structure was seen for the unique environmental common factors. We then fit models to 5 internalizing syndromes. The full model, which could also be constrained to equality in men and women, revealed one genetic factor loading most heavily on major depression and generalized anxiety disorder and another loading most strongly on animal and situational phobia. CONCLUSIONS: The underlying structure of the genetic and environmental risk factors for the common psychiatric and drug abuse disorders in men and women is very similar. Genetic risk factors predispose to 2 broad groups of internalizing and externalizing disorders. Within the internalizing disorders, 2 genetic factors are seen that predispose to disorders dominated by anxious-misery and fear. Substance use disorders have disorder-specific genetic risks. The externalizing disorders of conduct disorder and adult antisocial behavior are significantly influenced by the shared environment. The pattern of lifetime comorbidity of common psychiatric and substance use disorders results largely from the effects of genetic risk factors.     

Anxiety, Substance Use, and Their Co-Occurrence: Advances in Clinical Science

Research and clinical literatures are replete with examples that psychological disorders are related to drug use, abuse, and dependence. The preponderance of scientific work addressing relations among psychopathological processes and drug use, abuse, and dependence has been focused primarily on psychotic disorders, major depression, antisocial personality disorder, and attention deficit hyperactivity disorder. This corpus of empirical work has indicated that there are clinically meaningful relations among particular types of psychopathology and the onset and maintenance of substance use behaviors and disorders and, in turn, that substance use and use-related problems can impact vulnerability for psychopathology. Within this public health context, it is striking that despite the fact that anxiety disorders are one of the most common classes of psychological problems (Kessler et al., 2005), there has been limited programmatic study of the relations between anxiety vulnerability processes and substance use disorders.     

Tourette's syndrome - a review

Tourette's syndrome (TS) is a neuropsychiatric disorder characterised by the occurrence of chronic motor and vocal tics that usually begin in childhood. A prevalence of 4-5/10.000 individuals is estimated. Tourette's syndrome patients frequently show comorbidity with other psychiatric disorders such as obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), anxiety, and affective disorders. Some forms of OCD seem to share a common genetic etiology with TS and to be a facultative part of the TS phenotypic spectrum. Based on MRI, positron emission tomography (PET), and single photon emission computed tomography (SPECT), data alterations in the cortico-striato-pallido-thalamo-cortical functional systems have been discussed. Within these systems, dopaminergic neurotransmission is thought to play an important role in the pathophysiology of TS. Autoimmunological mechanisms seem to be important in some subtypes of TS and OCD that are triggered or exacerbated by infections with hemolytic streptococci. In these cases, immune modulatory therapy proved to be efficient. To date, there is no established treatment regimen for TS. The medications used most frequently are antipsychotics.     

Psychiatric implications of language disorders and learning disabilities: risks and management

This article reviews the relationship between different learning disabilities, language disorders, and the psychiatric disorders that are commonly associated with learning disabilities and language disorder: attention-deficit hyperactivity disorder (ADHD), anxiety disorders, depression, and conduct or antisocial personality disorder. The complex associations between language disorders and specific learning disabilities--dyslexia, nonverbal learning disorder, dyscalculia--and the various psychiatric disorders are discussed. Clinical vignettes are presented to highlight the impact of these disorders on a child's social and psychological development and the importance of early recognition and treatment.     

Patterns of psychiatric comorbidity with attention-deficit/hyperactivity disorder

Attention deficit/hyperactivity disorder (ADHD) is frequently comorbid with a variety of psychiatric disorders. These disorders include oppositional defiant (ODD) and conduct disorders (CD), and affective, anxiety, and learning disorders. Studies which have examined the comorbidity of these disorders with ADHD are reviewed. ADHD and ADHD with CD seem to be distinct subtypes; children with ADHD/CD are at higher risk of antisocial personality as adults. Coexisting anxiety may attenuate impulsivity in ADHD. Studies examining stimulant response in children with ADHD/anxiety have recently yielded conflicting results. Anxiety and ADHD seem to be inherited independently. The prevalence of major depressive disorder (MDD) and bipolar disorder among children with ADHD is controversial, but there clearly exists a subgroup of severely emotionally labile children with ADHD who present serious management issues for the clinician. About 20% to 25% of children with ADHD meet criteria for a learning disorder (LD), but LD seems to be independent of ADHD.     

Psychopathology risk transmission in children of parents with substance use disorders

OBJECTIVE: Children of fathers with substance use disorders are at increased risk for psychopathology, including conduct disorder, attention deficit hyperactivity disorder (ADHD), major depressive disorder, and anxiety disorders. This study examined the distinct influences of parent substance use disorder and other psychopathology in the transmission of the risk for psychopathology to their children. METHOD: The subjects were 1,167 children (ages 6-14 years; 62% were male, 38% were female) from 613 families recruited according to a high-risk paradigm. Of these families, 294 had fathers with a substance use disorder (high-risk group), and 319 had fathers without a substance use disorder or other mental disorder (low-risk group). In all families, father, mother, and children were directly assessed. Mixed-effects ordinal regression analyses controlled for the nested data structure. RESULTS: For conduct disorder, ADHD, major depression, and anxiety disorders, the results indicated that the predominant predictor of specific mental disorders in offspring was a history of the corresponding disorders in both parents. CONCLUSIONS: These results support specific parent-child transmission for childhood psychopathology.     

Comorbidity of internalizing disorders in children with oppositional defiant disorder

Oppositional defiant disorder (ODD) is often comorbid with other psychiatric disorders in childhood. Its association with attention deficit hyperactivity disorder and conduct disorder has been well studied. Recent studies suggest that children with ODD have substantial comorbidity with anxiety and depressive (internalizing) disorders, as well. Identifying the pattern of internalizing comorbidity with ODD in childhood and adolescence and how this varies across age and gender may help to identify mechanisms of such comorbidity. This systematic review presents evidence on the association of internalizing disorders with ODD across childhood and adolescence. Data from cross-sectional and longitudinal studies in clinic, community and epidemiologic samples are considered separately. Findings suggest that while internalizing comorbidity with ODD is present at all ages, the degree of comorbidity may vary over time in particular groups of children. Girls and boys appear to have different patterns of ODD comorbidity with either anxiety or depression, as well as ages of onset of ODD, however more large studies are required. Children with ODD in early life require further study as they may be a subgroup at increased risk for anxiety and affective disorders. This could have important implications for the treatment of these ODD children and the prevention of sequential comorbidity.     

Differential diagnosis of childhood depression: Using comorbidity and symptom overlap to generate multiple hypotheses

Childhood depression is often found to share symptoms and coexist with several other childhood disorders and physiological conditions, leading to diagnostic errors and possibly inappropriate treatment. Literature relevant to the differential diagnosis of childhood depression is reviewed with particular attention given to the similarities and differences between depression and coexisting conditions such as anxiety disorders, conduct disorders, and attention deficit hyperactivity disorder. The characteristics of childhood depression are compared and contrasted with other possible coexisting disorders. Diagnostic reasoning, confirmatory bias, and the advantages of considering multiple hypotheses when diagnosing depression are discussed.     

万拉法新临床应用125例分析

目的：探讨盐酸万拉法新治疗各种精神障碍的疗效与副反应。方法：对2000年12月－2001年12月在心理科门诊的各种精神障碍患者，包括抑郁症、注意缺陷多动障碍、焦虑症、社交焦虑症、强迫症和创伤后应激障碍等，作回顾性研究。应用Conner's简易量表、抑郁自评量表、焦虑自评量表、90项症状清单进行评估。结果：万拉法新对某些精神障碍均有一定疗效。结论：万拉法新是一种起新较快的抗抑郁剂，对某些精神障碍有一定疗效，且较为安全。     

Young adults with attention deficit hyperactivity disorder: subtype differences in comorbidity, educational, and clinical history

The present study sought to examine subtype differences in comorbidity and in antisocial, educational, and treatment histories among young adults (ages 17-27) with attention deficit hyperactivity disorder (ADHD). Comparisons were made between ADHD Combined Type (ADHD-C; N = 60) and Predominantly Inattentive Type (ADHD-I; N = 36) relative to each other and to a community control group of 64 adults. Both ADHD groups had significantly less education, were less likely to have graduated from college, and were more likely to have received special educational placement in high school. Both groups also presented with a greater likelihood of dysthymia, alcohol dependence/abuse, cannabis dependence/abuse, and learning disorders, as well as greater psychological distress on all scales of the SCL-90-R than the control group. Both ADHD groups were more likely to have received psychiatric medication and other mental health services than control adults. In comparison with ADHD-I, adults with ADHD-C differed in only a few respects. The C-type adults were more likely to have oppositional defiant disorder, to experience interpersonal hostility and paranoia, to have attempted suicide, and to have been arrested than the ADHD-I adults. These results are generally consistent with previous studies of ADHD in children, extend these findings to adults with ADHD, and suggest that the greater impulsivity associated with the ADHD-C subtype may predispose toward greater antisocial behavior and its consequences than does ADHD-I type in adults.     

Effect of anxiety on cognition, behavior, and stimulant response in ADHD

The effect of the comorbidity of overanxious disorder (ANX) in attention deficit hyperactivity disorder (ADHD) on laboratory measures of behavior, cognition, and stimulant response was examined. Seventy-nine children who met DSM-III-R criteria for ADHD were tested further for an oppositional defiant disorder (ODD), conduct disorder (CD), or ANX. Subjects with comorbid ANX showed less impulsiveness on a laboratory measure of behavior and had longer, sluggish reaction times on the Memory Scanning Test than those without ANX. ADHD subjects with comorbid ANX were less frequently diagnosed as CD. Forty-three of the subjects completed a double-blind trial of methylphenidate; subjects with comorbid anxiety had a significantly poorer response to the stimulant than those without anxiety, while the comorbidity of ODD or CD did not affect stimulant response. The results suggest that ADHD with comorbid ANX may represent children with primary anxiety who develop secondary inattentiveness, or they may represent a different subtype of ADHD, perhaps similar to the condition of attention deficit disorder without hyperactivity under DSM-III.     

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.     

Chernobyl exposure as stressor during pregnancy and behaviour in adolescent offspring

Objective: Research in animals has shown that exposure to stressors during pregnancy is associated with offspring behavioural disorders. We aimed to study the effect of in utero exposure to the Chernobyl disaster in 1986, and maternal anxiety presumably associated with that exposure, on behaviour disorder observed at age 14. Method: Exposed (n = 232) and non‐exposed Finnish twins (n = 572) were compared. A semi‐structured interview was used to assess lifetime symptoms of depression, generalized anxiety disorder, attention deficit hyperactivity disorder, conduct disorder and oppositional defiant disorder symptoms. Results: Adolescents who were exposed from the second trimester in pregnancy onwards, had a 2.32‐fold risk (95% CI: 1.13–4.72) of having lifetime depression symptoms, an increased risk of fulfilling DSM‐III‐R criteria of a major depressive disorder (OR = 2.48, 95% CI: 1.06–5.7), and a 2.01‐fold risk (95% CI: 1.14–3.52) of having attention deficit hyperactivity disorder symptoms. Conclusion: Perturbations in fetal brain development during the second trimester may be associated with the increased prevalence of depressive and attention deficit hyperactivity disorder symptoms.     

Hyperactive boys almost grown up. I. Psychiatric status

We report a prospective longitudinal study of 101 male adolescents (ages 16 to 23 years) who had been diagnosed hyperactive in childhood (ages 6 to 12 years), compared with 100 normal controls. The DSM-III diagnoses were made blind to group membership. Information was obtained for 98% of the original cohort. The full attention deficit disorder with hyperactivity (ADDH) syndrome persisted in 31% of the probands vs in 3% of the controls. The only other two conditions that distinguished the groups significantly were conduct and substance use disorders. These disorders aggregated significantly among the probands with continued ADDH. The results indicate that the greatest risk factor for the development of antisocial behavior and drug abuse is the maintenance of ADDH symptoms. Substance use disorders followed the onset of conduct disorder in the overwhelming majority of the cases.     

Anxiety disorders moderate the association between externalizing problems and substance use disorders: Data from the National Comorbidity Survey-Revised

Anxiety disorders and externalizing problems are both associated with substance use disorders. However, the nature of this relationship remains unclear. To examine whether presence of an anxiety disorder changes the association between externalizing problems (conduct disorder, oppositional defiant disorder, and attention deficit hyperactivity disorder) and substance use disorders, we analyzed data from the National Comorbidity Survey-Replication, which is based on a nationally representative sample of 9282 English-speaking adults. Presence of externalizing problems was associated with an increased odds for alcohol abuse (OR: 6.7, CI: 5.6–8.1), alcohol dependence (OR: 7.6, CI: 5.9–9.6), substance abuse (OR: 9.9, CI: 8.1–12.2), and substance dependence (OR: 13.1, CI: 9.6–17.8). Similarly, anxiety disorders were associated with increased odds for substance use disorders. The highest association was found between post-traumatic stress disorder and substance use disorder (OR: 9.2, CI: 5.4–15.5). Individuals who met diagnostic criteria for an anxiety disorder and externalizing problems showed consistently and significantly lower odds for substance use problems than subjects with externalizing problems without a comorbid anxiety disorder. The results suggest that presence of any anxiety disorder reduces the association between externalizing problems and substance use disorders, possibly because the fear of bodily symptoms prevents individuals with externalizing problems from engaging in drug-seeking behaviors.     

Psychiatric and cognitive phenotype in children and adolescents with myotonic dystrophy

Myotonic dystrophy type 1 (DM1) is the most frequent inherited neuromuscular disorder. The juvenile form has been associated with cognitive and psychiatric dysfunction, but the phenotype remains unclear. We reviewed the literature to examine the psychiatric phenotype of juvenile DM1 and performed an admixture analysis of the IQ distribution of our own patients, as we hypothesised a bimodal distribution. Two-thirds of the patients had at least one DSM-IV diagnosis, mainly attention deficit/hyperactivity disorder and anxiety disorder. Two-thirds had learning disabilities comorbid with mental retardation on one hand, but also attention deficit, low cognitive speed and visual spatial impairment on the other. IQ showed a bi-modal distribution and was associated with parental transmission. The psychiatric phenotype in juvenile DM1 is complex. We distinguished two different phenotypic subtypes: one group characterised by mental retardation, severe developmental delay and maternal transmission; and another group characterised by borderline full scale IQ, subnormal development and paternal transmission.