Monozygotic twins discordant for schizophrenia

Summary The study of MZ twins discordant for schizophrenia can shed light on important experiential factors in the development of at least some cases of schizophrenia. The gradual development of paranoid schizophrenia was described in an MZ male twin who later recovered completely from his illness. His life pattern was compared with that of his non-psychotic co-twin, and his early characteristics and development were contrasted with features of schizophrenic twins in discordant pairs in a recently reported summary of such cases. It is suggested that late onset paranoid schizophrenia is different in many ways from other subtypes of schizophrenia beginning in adolescence.From Queen's University, Kingston, Ontario, Canada, this paper was submitted to theQuarterly on June 16, 1969.     

Attention problems and attention-deficit/hyperactivity disorder in discordant and concordant monozygotic twins: evidence of environmental mediators

OBJECTIVE: To study familial and nonfamilial environmental influences on attention problems and attention-deficit/hyperactivity disorder (ADHD) in monozygotic twins discordant and concordant-high and low for these traits. METHOD: Ninety-five twin pairs from The Netherlands Twin Register were selected. Longitudinal survey data were collected at 1, 2, 3, 5, 7, 10, and 12 years from parents, twins, and teachers. Mothers participated in a structured clinical interview when twins were between 10 and 17 years of age. RESULTS: Affected twins from discordant pairs scored higher than unaffected cotwins on multiple measures of attention problems, ADHD, and other behavior problems according to mother, teacher, and self. Behavioral discordance was evident at age 2 and all subsequent measurements. Compared with unaffected cotwins, affected twins had lower birth weight and delayed physical growth and motor development. Differences between discordant and concordant groups were reported for maternal smoking, sleeping in different rooms, and living with only one parent. CONCLUSIONS: Significant markers of ADHD are found in infancy and include low birth weight and delayed motor development. As the knowledge of specific genetic and environmental influences on ADHD increases, future studies may focus on their complex interplay.     

Monozygotic twins discordant for Klippel-Feil syndrome

In a pair of Japanese monozygotic twins, one manifested Klippel-Feil syndrome, a short neck with C(1-4) vertebra fusion, whereas the other was normal. The discordance between the twins suggests that Klippel-Feil syndrome results in part from a postzygotic somatic mutation or intrauterine environmental factors.     

Monozygotic twins discordant for Alzheimer's disease

We identified 3 pairs of monozygotic twins discordant for probable Alzheimer's disease from a twin register and found no systematic differences in potential risk factor exposures between affected and unaffected twins. Such cases predict a role for environmental factors in the etiology or clinical onset of Alzheimer's disease.     

Testing for neuropsychological endophenotypes in siblings discordant for attention-deficit/hyperactivity disorder.

BACKGROUND: Neurocognitive deficits associated with attention-deficit/hyperactivity disorder (ADHD) might be useful intermediate endophenotypes for determining specific genetic pathways that contribute to ADHD. METHODS: This study administered 17 measures from prominent neuropsychological theories of ADHD (executive function, processing speed, arousal regulation and, motivation/delay aversion) in dizygotic (DZ) twin pairs discordant for ADHD and control twin pairs (ages 8-18 years) to compare performance between twins affected with ADHD (n = 266), their unaffected co-twins (n = 228), and control children from twin pairs without ADHD or learning difficulties (n = 332). RESULTS: The ADHD subjects show significant impairment on executive function, processing speed, and response variability measures compared with control subjects. Unaffected co-twins of ADHD subjects are significantly impaired on nearly all the same measures as their ADHD siblings, even when subclinical symptoms of ADHD are controlled. CONCLUSIONS: Executive function, processing speed, and response variability deficits might be useful endophenotypes for genetic studies of ADHD.     

Quantitative electroencephalography and attention-deficit/hyperactivity disorder: Implications for clinical practice

Although behavioral symptoms of inattention, impulsivity, and hyperactivity serve as a foundation for the accurate diagnosis of attention-deficit/hyperactivity disorder (ADHD), the low interrater reliability and specificity of behavioral rating scales and the absence of comprehensive screening for medical conditions that mimic ADHD have created a barrier to the effective treatment of ADHD. Recently published studies using quantitative electroencephalographic techniques have identified abnormal patterns of cortical activation through power spectral analysis, in event-related cortical potentials, and in slow cortical potentials that may serve as a basis for overcoming these barriers. This paper reviews the initial evidence indicating that power spectral analysis and event-related cortical potentials may be useful in differentiating ADHD from other psychiatric disorders, helping in medication selection, evaluating medication response, and improving the rate of treatment initiation and maintenance. Studies examining electroencephalogram biofeedback (neurotherapy) are reviewed using published efficacy guidelines.     

Monozygotic twins with severe myoclonic epilepsy in infancy discordant for clinical features

Male monozygotic twins with genetically determined severe myoclonic epilepsy in infancy are described. Although seizure onset, clinical seizure symptomatology, and motor and mental development were almost identical until age 38 months, their clinical courses then became discordant. The emergence of myoclonus was delayed by 12 months in twin 1 compared with twin 2. Regression in language development, which is a common feature of severe myoclonic epilepsy in infancy, was obvious in twin 2 after the emergence of myoclonus, whereas twin 1 did not demonstrate any regression. The clinical-course discordance between twins was attributable to bacterial meningitis, which twin 1 developed at age 35 months. Bacterial meningitis may have affected the clinical course of severe myoclonic epilepsy in infancy in twin 1, resulting in delayed onset of myoclonus and more favorable language development in twin 1 than in twin 2, who did not experience bacterial meningitis.     

Psychosocial treatments for attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a chronic disorder requiring developmentally sensitive interventions across the lifespan. Although pharmacotherapy traditionally has been considered the first-line treatment for ADHD, many individuals continue to experience significant functional impairment or choose not to pursue pharmacotherapy. Thus, evidence-based alternatives or adjuncts to pharmacologic treatment for individuals with ADHD are needed. Behavioral parent training and behavioral school interventions are the only empirically supported nonpharmacologic interventions for children and adolescents with ADHD. This article reviews recent additions to the ADHD literature, including evaluations of behavioral interventions in traditional clinical practice and schools, treatment efficacy for preschool-aged children and adults, and the investigation of a novel treatment for individuals with the predominantly inattentive subtype of ADHD.     

Monozygotic twins discordant for schizophrenia are discordant for N-CAM and L1 in CSF

While schizophrenia has a genetic component, its pathogenesis is unknown. Abnormal concentrations of two cell recognition molecules (CRMs), neural-cell adhesion molecule (N-CAM) and L1 antigen have been described in the cerebrospinal fluid (CSF) of patients with schizophrenia. Studies of monozygotic twins discordant for schizophrenia may help separate genetic and environmental contributions to the disease. In the present study of monozygotic twins discordant for schizophrenia, the affected twins had increased N-CAM and decreased L1 antigen in their CSF. Non-affected twins were not different from normals. Although processes related to genetic instability cannot be entirely ruled out, these results suggest that these abnormalities are not a part of the genetic predisposition to become schizophrenic. Thus the changes in N-CAM and L1 antigen may reflect either the events which precipitated the onset of schizophrenia, or events which are associated with the experience of having the disease.© 1997 Elsevier Science B.V. All rights reserved.     

Anatomic brain abnormalities in monozygotic twins discordant for attention deficit hyperactivity disorder

OBJECTIVE: To examine brain-behavior relationships in attention deficit hyperactivity disorder (ADHD), the authors obtained magnetic resonance imaging (MRI) scans of monozygotic twins discordant for ADHD. METHOD: National recruitment was followed by in-person assessment. MRI scans were measured algorithmically for nine pairs of monozygotic twins discordant for ADHD. RESULTS: The affected twins had significantly smaller caudate volumes (mean difference=-0.56 ml, CI=-0.92 to -0.21) than their unaffected co-twins. CONCLUSIONS: These results provide further support for striatal models of ADHD pathophysiology.     

Monozygotic twins discordant for Huntington disease after 7 years

BACKGROUND: Huntington disease (HD) has only rarely been identified in identical twins. All described twins have had disease onset within 1 year of each other, suggesting that disease onset is determined solely by genetic influences. OBJECTIVE: To describe a unique set of monozygotic twins in whom clinical HD onset is at least 7 years apart. DESIGN: A 71-year-old woman was diagnosed as having HD based on medical history, physical examination results consistent with HD, and a CAG trinucleotide repeat number of 39 in the HD gene on chromosome 4. Her onset was 6 years earlier. Her genetically confirmed identical twin, carrying the same number of CAG repeats, was neurologically healthy when examined the next year. Only the HD-manifest twin had chronic bronchitis, rheumatoid arthritis, type 2 diabetes mellitus, and chronic anemia. Both had hypertension. CONCLUSIONS: To our knowledge, this is the first report of monozygotic twins discordant for HD by more than 2 years. The onset of HD symptoms in a patient with 39 triplet repeats at least 7 years earlier than her identical twin suggests the possibility that the disease may be initiated (or delayed) by environmental factors. We have identified increased cigarette use and longer exposure to various industrial toxins as potential explanations for the earlier onset in one twin.     

Monozygotic female twins discordant for phenotype of Wilson's disease

Wilson's disease (WD) is an autosomal recessive disorder characterized by the functional disruption of the copper‐transporting protein adenosine triphosphatase 7B (ATP‐ase 7B). The disease is caused by mutations in ATP7B gene. It seems that the type of mutation in ATP7B only to some degree determines phenotypic manifestation of WD. We examined two pairs of monozygotic twins discordant for WD phenotype. The first set of twins were ATP7B compound heterozygotes c.3207C>A (p.H1069Q)/c.1211_1212insA (p.N404Kfs). The index case developed severe liver failure followed by depressive symptoms, dysarthria, and tremor at the age of 36. Her sister remained presymptomatic at diagnosis at the age of 39. The second twins were ATP7B c.3207C.A (p.H1069Q) homozygotes. The index case presented with dysarthria and tremor at the age of 26. Her sister remained clinically presymptomatic at diagnosis at the age of 28. We concluded that the phenotypic characteristics of WD are possibly attributable to epigenetic/environmental factors. © 2009 Movement Disorder Society     

Zinc in attention-deficit/hyperactivity disorder

OBJECTIVE: The aim of this study was to review the published evidence for a role of zinc nutrition in attention-deficit/hyperactivity disorder (ADHD). METHOD: A computer literature search was supplemented by the authors' knowledge. RESULTS: Numerous controlled studies report cross-sectional evidence of lower zinc tissue levels (serum, red cells, hair, urine, nails) in children who have ADHD, compared to normal controls and population norms. A few studies show correlations of zinc level with either clinical severity or a change thereof in response to stimulant or chemical challenge. Two placebo-controlled trials--one of zinc monotherapy, the other of zinc supplementation of methylphenidate--reported significant benefit. However, diagnostic procedures and sample representativeness were often not clear, and most such reports have come from countries and cultures with different diets and/or socioeconomic realities than are found in the United States (only one American sample in nine published reports). In particular, both positive clinical trials of zinc supplementation came from the Mid-East (Turkey and Iran), an area with suspected endemic zinc deficiency. The largest of these trials used zinc doses above the recommended upper tolerable limit and had a 2 in 3 dropout rate. CONCLUSION: It is not clear how well the accumulating evidence for a possible role of zinc in ADHD applies to middle-class American children. However, the evidence appears strong enough to warrant further controlled study in well-diagnosed samples representative of the socioeconomic spectrum. Hypothesis-testing clinical trials are needed of this potential treatment that, if found effective, might become a relatively safe, cheap substitute for, or adjunct to, current treatments in some patients. At present, it should remain an investigational treatment.     

A clinical perspective of attention-deficit/hyperactivity disorder into adulthood

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder that affects all age groups. Recent data on the clinical presentation, comorbidity, neurobiology, and treatment are reviewed. METHOD: Using the search term ADHD, a selective PubMed review of the clinical literature was undertaken to evaluate recent data relevant to ADHD with attention to a life span perspective of the disorder. RESULTS: A growing literature indicates that ADHD is more persistent than previously thought and has a developmental variability in its presentation. The disorder impairs academic, social, and occupational functioning and is often associated with comorbidity, including cigarette smoking and substance abuse. Considerable evidence suggests that the disorder has a strong genetic component and a biological underpinning; the pathophysiology includes dysfunction in both noradrenergic and dopaminergic systems. Both psychosocial therapy and pharmacotherapy have been shown effective in the treatment of the disorder throughout the life span. The therapeutic effectiveness of pharmacologic agents in the treatment of ADHD has been attributed to noradrenergic and/or dopaminergic effects. CONCLUSION: ADHD is associated with impairment and comorbidity throughout the life span. Growing evidence suggests the importance of short- and long-term management of the disorder. While the long-term treatment of ADHD is expected to lessen the individual's impairment, the outcome for adults who have received treatment since childhood requires further study.     

Inattentiveness in attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a long-term impact on functioning, productivity and quality of life of patients. This impact is largely due to the symptoms of inattentiveness. However, despite its impairing role in the lives of ADHD patients, inattentiveness has been studied relatively less frequently than have symptoms of impulsivity/hyperactivity and problems with executive function. This review therefore seeks to integrate the neuropsychological theories and current findings in the research fields of neuropsychology, neurophysiology, and neuroimaging, in an attempt to gain a more complete understanding of the role that inattentiveness plays in ADHD, as well as to suggest directions for future studies. The need for a more comprehensive understanding of inattentiveness and ADHD, which integrates findings from each of the three disciplines mentioned above, is emphasized.