Renal dysfunction in psoriatic patients.

Psoriasis is a common chronic inflammatory disease of the skin that is increasingly being considered as a systemic inflammatory disorder due to its association with cardiovascular, metabolic, pulmonary, renal, liver, and neurologic diseases. Renal involvement is rare but well documented and psoriasis is recognized as an independent factor for CKD and ESKD. A careful monitoring of the urinalysis and of renal function is recommended in psoriatic patients, especially those with moderate-to-severe disease. In case of pathologic findings, the execution of a renal biopsy appears necessary to make an accurate diagnosis and to establish the most appropriate therapeutic strategies to prevent the progression of kidney damage. The mechanisms of kidney involvement are different and not yet fully clarified. We present here two case reports of renal dysfunction during psoriasis. In one case, we diagnosed IgA nephropathy with particularly severe clinical presentation; in the other, an advanced kidney injury due to nephrotoxicity after prolonged CNI treatment.

Profiling depression in childhood and adolescence: the role of conduct problems.

BACKGROUND: Depression is typically more common in females and rates rise around puberty. However, studies of children and adolescents suggest that depression accompanied by conduct problems may represent a different subtype not characterised by a female preponderance, with differing risk factors and genetic architecture compared to pure-depression. This study aimed to identify aetiologically distinct profiles of depressive symptoms, distinguished by the presence or absence of co-occurring conduct problems. METHODS: Latent profile analysis was conducted on a school sample of 1648 children (11-12 years) and replicated in a sample of 2006 twins (8-17 years). RESULTS: In both samples pure-depressive and conduct-depressive profiles were identified. The pure-depressive profile was associated with female gender, while the conduct-depressive profile was associated with lower cognitive ability but not with gender. Twin analyses indicated possible differences in genetic aetiology. CONCLUSIONS: There was evidence for aetiologically heterogeneous depression symptom profiles based on the presence or absence of co-occurring conduct problems.

Associations between obsessive-compulsive classes and pathological gambling in a national cohort of male twins.

IMPORTANCE: Because of shared characteristics, pathological gambling (PG) has been variously conceptualized as an obsessive-compulsive (OC) spectrum disorder or as an addictive disorder. Prior community-based studies have not systematically determined the association between PG and OC features and whether common genetic factors contribute to both conditions. OBJECTIVE: To examine the association and genetic correlation between PG and OC features. DESIGN, SETTING, AND PARTICIPANTS: We performed a latent class analysis (LCA) of OC features, cross-sectional tests of association, and classic twin genetic analysis using results of telephone interviews conducted from March 2002 through November 2003. Participants included 1675 male twin pairs from the Vietnam Era Twin Registry, aged 45 to 60 years. MAIN OUTCOMES AND MEASURES: Ten OC features were queried and used to derive OC classes identified via LCA. RESULTS: The best-fitting LCA model identified the following 4 OC classes: unaffected (class 1), ritual/symmetry compulsions (class 2), germ/contamination obsessions (class 3), and severe OC (class 4). All PG symptoms were more common in class 4 OC and 6 of 10 PG symptoms were significantly more common in class 4 OC (P < .01). Participants in the severe class were most likely to have 4 or more DSM-IV or DSM-5 PG diagnostic criteria (odds ratio, 3.8 [95% CI, 1.8-8.2]). The genetic correlation between phenotypes was 0.44 (95% CI, 0.16-0.75). CONCLUSIONS AND RELEVANCE: The association between OC features and diagnostic criteria for PG highlights a role of obsessions and compulsivity in PG, and the lifetime co-occurrence of these disorders results in part from common genetic variance. Phenotypic and genetic overlap between OC features and PG add to our understanding of the most appropriate classification of PG and offers insights for treatment development.

Age of onset and the subclassification of conduct/dissocial disorder.

BACKGROUND: Conduct Disorder (CD) is a markedly heterogeneous psychiatric condition. Moffitt (1993) proposed that subclassification of CD should be according to age of onset. Our goals were to compare childhood-onset and adolescent-onset CD in terms of differences in phenotypic risk factors, genetic analyses, and factors associated with the persistence of antisocial behavior into young adulthood. METHODS: The data are from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) and Young Adult Follow-Up (YAFU). Childhood-onset CD was defined as CD beginning at or before age 11. Adolescent-onset CD was defined as having CD onset between ages 14 and 17. These subgroups were compared on ADHD, young adult antisocial behavior (ASB), family dysfunction, and parental depression. Genetic analyses compare childhood-onset and adolescent-onset CD, as well as their cooccurrence with ADHD and ASB. Finally, predictors of persistence were examined. RESULTS: Childhood-onset CD was significantly associated with ADHD, ASB, family dysfunction, and parental depression. Adolescent-onset CD was marginally associated with parental depression (p = .05) but not with any of the other risk factors. Univariate genetic models showed that both childhood-onset and adolescent-onset CD involve a large genetic liability accounting for 62% and 65% of the variance, respectively. A common genetic factor (as well as an ADHD-specific factor) accounted for the cooccurrence of childhood-onset CD and ADHD. The cooccurrence of childhood-onset CD and ASB are reflected by a common genetic factor with genetic specific effects on ASB. There was no etiological link between adolescent-onset CD and either ADHD or ASB. Both ADHD and family dysfunction were significantly associated with the persistence of antisocial behavior into young adulthood. CONCLUSIONS: Phenotypic findings differentiated between childhood-onset and adolescent-onset CD. ADHD and family dysfunction predicted persistence of antisocial behavior into young adulthood.

Expectant management in type II selective intrauterine growth restriction and abnormal cord insertion in monochorionic twins.

OBJECTIVE: To assess perinatal outcome in type II monochorionic (MC) diamniotic twin pregnancies (DA) affected by selective intrauterine growth restriction (sIUGR) and abnormal cord insertion managed expectantly. METHODS: A prospective longitudinal study from June 2008 and July 2011 on 24 MCDA sIUGR twins. sIUGR was defined as estimated fetal weight below the 10th percentile in one twin and was classified into three groups based on umbilical artery (UA) Doppler diastolic flow (I: presence; II: constantly absent/reverse (AEDF/ARED); III: intermittently absent or reverse). Marginal cord insertion was defined as insertion within 2 cm of the placental disc edge, and velamentous insertion as a cord insertion into the fetal membranes. Expectant management was chosen in these twins, and absent or reverse A wave in the ductus venosus (DV) was a criterion for delivery. Neonatal outcome was available for all twins delivered. Pathological examination and vascular cast of placentas were performed in all cases. RESULTS: Fourteen twin pregnancies were type II sIUGR, and ten presented an abnormal umbilical cord insertion. Median gestational age (GA) at diagnosis of sIUGR was 18 weeks' gestation (range 16-20 weeks), and all sIUGR co-twins showed AEDF of UA at a median gestational age of 20 weeks (range 18-22 weeks). Median gestational age at delivery was 30 weeks (range 28-34 weeks) with a median birth weight of 1285 g (range 307-1725 g). pH at birth and base excess (BE) were normal in all IUGR co-twin (pH>7.10, median BE 5.5); Apgar score at 5 min was >7. Perinatal outcome was favorable in all cases. Placental pathological examination confirmed the marginal insertion of the umbilical cord and the absence of anastomosis between the two portions of umbilical insertion. CONCLUSIONS: This study highlights that expectant management for sIUGR type II twins with or without an abnormal cord insertion should be a valid option to time delivery for these fetuses as shown by the favorable neonatal outcome.

The joint structure of DSM-IV Axis I and Axis II disorders.

The Diagnostic and Statistical Manual (4th ed. [DSM-IV]; American Psychiatric Association, 1994) distinction between clinical disorders on Axis I and personality disorders on Axis II has become increasingly controversial. Although substantial comorbidity between axes has been demonstrated, the structure of the liability factors underlying these two groups of disorders is poorly understood. The aim of this study was to determine the latent factor structure of a broad set of common Axis I disorders and all Axis II personality disorders and thereby to identify clusters of disorders and account for comorbidity within and between axes. Data were collected in Norway, through a population-based interview study (N = 2,794 young adult twins). Axis I and Axis II disorders were assessed with the Composite International Diagnostic Interview (CIDI) and the Structured Interview for DSM-IV Personality (SIDP-IV), respectively. Exploratory and confirmatory factor analyses were used to investigate the underlying structure of 25 disorders. A four-factor model fit the data well, suggesting a distinction between clinical and personality disorders as well as a distinction between broad groups of internalizing and externalizing disorders. The location of some disorders was not consistent with the DSM-IV classification; antisocial personality disorder belonged primarily to the Axis I externalizing spectrum, dysthymia appeared as a personality disorder, and borderline personality disorder appeared in an interspectral position. The findings have implications for a meta-structure for the DSM.

The structure of genetic and environmental risk factors for syndromal and subsyndromal common DSM-IV axis I and all axis II disorders.

OBJECTIVE: The authors sought to clarify the structure of the genetic and environmental risk factors for 22 DSM-IV disorders: 12 common axis I disorders and all 10 axis II disorders. METHOD: The authors examined syndromal and subsyndromal axis I diagnoses and five categories reflecting number of endorsed criteria for axis II disorders in 2,111 personally interviewed young adult members of the Norwegian Institute of Public Health Twin Panel. RESULTS: Four correlated genetic factors were identified: axis I internalizing, axis II internalizing, axis I externalizing, and axis II externalizing. Factors 1 and 2 and factors 3 and 4 were moderately correlated, supporting the importance of the internalizing-externalizing distinction. Five disorders had substantial loadings on two factors: borderline personality disorder (factors 3 and 4), somatoform disorder (factors 1 and 2), paranoid and dependent personality disorders (factors 2 and 4), and eating disorders (factors 1 and 4). Three correlated environmental factors were identified: axis II disorders, axis I internalizing disorders, and externalizing disorders versus anxiety disorders. CONCLUSIONS: Common axis I and II psychiatric disorders have a coherent underlying genetic structure that reflects two major dimensions: internalizing versus externalizing, and axis I versus axis II. The underlying structure of environmental influences is quite different. The organization of common psychiatric disorders into coherent groups results largely from genetic, not environmental, factors. These results should be interpreted in the context of unavoidable limitations of current statistical methods applied to this number of diagnostic categories.

[VEGF antibodies as therapy for retinopathy of prematurity]. / VEGF-Antikörper in der Therapie der Frühgeborenenretinopathie.

Retinopathy of prematurity (ROP) is one of the three leading causes of legal blindness in childhood in the developed countries. Improved neonatal care has resulted in the increased survival of extremely immature infants at high risk to develop ROP. Current treatment for ROP with laser may prevent blindness by causing involution of pathological vessels and thus inhibit the development of retinal detachment. But this coagulation of the avascular retina is a destructive therapy and does not otherwise ameliorate retinal development. Recent reports have described vascular endothelial growth factor antibodies as therapy for ROP. This article reports our own experience with this new therapy and gives an overview of the recent literature.

Maternal ratings of attention problems in ADHD: evidence for the existence of a continuum.

OBJECTIVE: To investigate whether items assessing attention problems provide evidence of quantitative differences or categorically distinct subtypes of attention problems (APs) and to investigate the relation of empirically derived latent classes to DSM-IV diagnoses of subtypes of attention-deficit/hyperactivity disorder (ADHD), for example, combined subtype, predominantly inattentive type, and predominantly hyperactive/impulsive type. METHOD: Data on attention problems were obtained from maternal ratings on the Child Behavior Check List (CBCL). Latent class models, which assume categorically different subtypes, and factor mixture models, which permit severity differences, are fitted to data obtained from Dutch boys at age 7 (N = 8,079), 10 (N = 5,278), and 12 years (N = 3,139). The fit of the different models to the data is compared to decide which model, and hence, which corresponding interpretation of AP, is most appropriate. Next, ADHD diagnoses are regressed on latent class membership in a subsample of children. RESULTS: At all the three ages, models that distinguish between three mainly quantitatively different classes (e.g., mild, moderate, and severe attention problems) provide the best fit to the data. Within each class, the CBCL items measure three correlated continuous factors that can be interpreted in terms of hyperactivity/impulsivity, inattentiveness/dreaminess, and nervous behavior. The AP severe class contains all of the subjects diagnosed with ADHD-combined subtype. Some subjects diagnosed with ADHD-predominantly inattentive type are in the moderate AP class. CONCLUSIONS: Factor mixture analyses provide evidence that the CBCL AP syndrome varies along a severity continuum of mild to moderate to severe attention problems. Children affected with ADHD are at the extreme of the continuum. These data are important for clinicians, research scholars, and the framers of the DSM-V as they provide evidence that ADHD diagnoses exist on a continuum rather than as discrete categories.

A psychometric evaluation of the DSM-IV borderline personality disorder criteria: age and sex moderation of criterion functioning.

BACKGROUND: Despite its importance as a paradigmatic personality disorder, little is known about the measurement invariance of the DSM-IV borderline personality disorder (BPD) criteria; that is, whether the criteria assess the disorder equivalently across different groups. METHOD: BPD criteria were evaluated at interview in 2794 young adult Norwegian twins. Analyses, based on item-response modeling, were conducted to test for differential age and sex moderation of the individual BPD criteria characteristics given factor-level covariate effects. RESULTS: Confirmatory factor analytic results supported a unidimensional structure for the nine BPD criteria. Compared to males, females had a higher BPD factor mean, larger factor variance and there was a significant age by sex interaction on the factor mean. Strong differential sex and age by sex interaction effects were found for the 'impulsivity' criterion factor loading and threshold. Impulsivity related to the BPD factor poorly in young females but improved significantly in older females. Males reported more impulsivity compared to females and this difference increased with age. The 'affective instability' threshold was also moderated, with males reporting less than expected. CONCLUSIONS: The results suggest the DSM-IV BPD 'impulsivity' and 'affective instability' criteria function differentially with respect to age and sex, with impulsivity being especially problematic. If verified, these findings have important implications for the interpretation of prior research with these criteria. These non-invariant age and sex effects may be identifying criteria-level expression features relevant to BPD nosology and etiology. Criterion functioning assessed using modern psychometric methods should be considered in the development of DSM-V.

Increased prevalence of cardiovascular defects among 56,709 California twin pairs.

This study compared the prevalence of cardiovascular defects in twin and singleton births and explored the influences of zygosity (monozygotic and dizygotic) and maternal age (<35 and >or=35 years of age) on concordance. Data on twin and singleton infants with (n = 628 twin pairs and n = 14,078 singletons) and without (n = 53,974 twin pairs and n = 4,858,255 singletons) cardiovascular defects were obtained from the California Birth Defects Monitoring Program and the California vital statistics birth and fetal death records during the period 1983-2003. Prevalence ratios (PR) (prevalence of twin/singleton) and approximate 95% confidence intervals were calculated for 16 congenital cardiovascular categories. Poisson regression techniques using log-linear models were employed to assess whether the probability of concordance of defects within each cardiovascular category varied by zygosity or maternal age. An increased prevalence was observed in twins compared to singletons in all 16 cardiovascular categories. Seven of the cardiovascular categories had at least double the prevalence in twins compared to singletons. Like-sex twins, as a proxy of monozygosity, had an increased prevalence of cardiovascular defects compared to unlike sex twins. Probabilities of concordance for flow lesions were higher among monozygotic than dizygotic twins. Our study provides evidence that twinning is associated with more cardiovascular defects than singletons. Increased concordance for flow lesions in monozygotic twins was observed, an observation that is in agreement with findings from familial recurrence studies of cardiovascular defects.

Does bereavement-related major depression differ from major depression associated with other stressful life events?

OBJECTIVE: Of the stressful life events influencing risk for major depression, DSM-III and DSM-IV assign a special status to bereavement. A depressive episode that is bereavement-related and has clinical features and course characteristic of normal grief is not diagnosed as major depression. This study evaluates the empirical validity of this exclusion criterion. METHOD: To determine the similarities of bereavement-related depression and depression related to other stressful life events, the authors identified and compared cases on a range of validators in a large-population-based sample of twins. The authors evaluated whether cases of bereavement-related depression that also met DSM criteria for "normal grief" were qualitatively distinct from other depressive cases. RESULTS: Eighty-two individuals with confirmed bereavement-related depression and 224 with confirmed depression related to other stressful life events were identified. The two groups did not differ in age at onset of major depression, number of prior episodes, duration of index episode, number of endorsed "A criteria," risk for future episodes, pattern of comorbidity, levels of extraversion, risk for major depression in their co-twin, or the proportion meeting criteria for "normal grief." However, individuals with bereavement-related depression were slightly older, and more likely to be female, and had lower levels of neuroticism, treatment-seeking, and guilt and higher levels of fatigue and loss of interest. Interaction analyses failed to find unique features of people whose illness met criteria for both bereavement-related depression and normal grief compared to those whose illness was related to other life stressors. CONCLUSIONS: The similarities between bereavement-related depression and depression related to other stressful life events substantially outweigh their differences. These results question the validity of the bereavement exclusion for the diagnosis of major depression.

Genetics of personality disorders.

This review of the literature on genetic contributions to the etiology of personality disorders broadly follows the DSM classification, and begins by evaluating the current evidence for genetic influences on the DSM axis II disorders. One of the most exciting directions in psychiatric genetics is the rapidly developing field of molecular genetic studies aiming to identify specific genes correlated with psychiatric phenotypes. Personality disorders, like most other psychiatric diagnostic categories, are etiologically complex, which implies that they are influenced by several genes and several environmental factors. The interplay between genes and the environment is a field that is receiving increasing attention and is addressed both in relation to quantitative and molecular methods.

Passive-aggressive (negativistic) personality disorder: a population-based twin study.

The objective of this study was to investigate the familial aggregation of passive aggressive personality disorder (PAPD), and explore issues regarding PAPD raised by the DSM-IV Personality Disorder Work Group. Two thousand seven hundred and ninety-four Norwegian twins from the population-based Norwegian Institute of Public Health Twin Panel were interviewed with the Structured Interview for DSM-IV Personality (SIDP-IV). Because of the rarity of the twins meeting full diagnostic criteria for PAPD a dimensional representation of the disorder was used for the analyses. Overlap with other axis II disorders was assessed by polychoric correlations, while familial aggregation was explored by structural equation twin models. Overlap was highest with paranoid (r = 0.52) and borderline personality disorder (r = 0.53), and lowest with schizoid (r = 0.26). Significant familial aggregation was found for PAPD. The twin correlations and parameter estimates in the full model indicated genetic and shared environmental effects for females, and only shared environmental effects for males, but the prevalence of endorsed PAPD criteria in this community sample was too low to permit us to conclude with confidence regarding the relative influence of genetic and shared environmental factors on the familial aggregation of PAPD.

Predictors of stability of attention-deficit/hyperactivity disorder subtypes from childhood to young adulthood.

OBJECTIVE: To determine the 5-year prospective stability of population-based and DSM-IV subtypes of attention-deficit/hyperactivity disorder (ADHD) as well as to explore predictors of stability. METHOD: A total of 708 twins ages 7 to 19 years who were identified from birth records of the state of Missouri and had participated in a study of ADHD were reassessed 5 years later in a blinded fashion. Stabilities of DSM-IV and population-based ADHD subtypes were compared using percentage of agreement with significance tested by the kappa statistic. Predictors of stability of subtype diagnosis were determined using multivariate logistic regression. RESULTS: In general, 5-year ADHD subtype stability was poor to modest and ranged from 11.1% to 24.0% for DSM-IV for subtypes and from 14.3% to 35.3% for clinically significant population-derived subtypes. There were no predictors of diagnostic stability that applied across subtypes. There were subtype-specific predictors including a diagnosis of oppositional defiant disorder for DSM-IV primarily inattentive ADHD; lower verbal IQ for DSM-IV combined type ADHD; and younger age, oppositional defiant disorder, and medication use for population-defined severe combined ADHD. CONCLUSIONS: Population-defined ADHD subtype criteria demonstrated modestly improved diagnostic stability over 5 years compared to DSM-IV subtypes. Few correlates or predictors of stability were identified.

High familial risks for cerebral palsy implicate partial heritable aetiology.

Cerebral palsy is the commonest cause of severe childhood disability, the aetiology of which is largely unknown. Data on familial aggregation of cerebral palsy are very limited. We defined familial risks for siblings who were hospitalised because of cerebral palsy in Sweden. A nationwide database for neurological diseases was constructed by linking the Multigeneration Register to the Hospital Discharge Register for the years 1987-2001. Standardised hospitalisation ratios (SHRs) were calculated for affected singletons and twins by comparing them with siblings who had no cerebral palsy. A total of 3997 patients were recorded with cerebral palsy. Familial cerebral palsy was uncommon, and it accounted for 1.6% of all cerebral palsy cases. However, for parents who had had one affected child the risk of recurrence in another child was considerably increased. Parents of one affected child had a 4.8-fold risk of having a second affected child, and where the siblings were twins, the risk was 29-fold. These familial risks were particularly high in some clinical subgroups: 17-25 in singletons and 37-155 in twins, including hemiplegia, diplegia and quadriplegia. The remarkably high familial risks are difficult to explain without some contribution of heritable factors. The lack of discordant pairs may suggest that heritable factors are disorder type-specific. Affected concordant sibling pairs should be subjected to molecular studies aiming at identifying the susceptibility gene.

Nicotine dependence subtypes: association with smoking history, diagnostic criteria and psychiatric disorders in 5440 regular smokers from the Vietnam Era Twin Registry.

Studies suggest empirically derived subtypes of nicotine dependence exist in young adult populations with short smoking careers. It is not known if classes of dependence exist in middle aged smokers with longer smoking careers and whether these classes reflect quantitative or qualitative differences. It is not known if psychiatric disorders are associated with classes of nicotine dependence. Nicotine dependence symptoms were obtained from a 1992 administration of the Diagnostic Interview Schedule. Latent Class Analyses (LCA) was computed using data from 5440 members of the Vietnam Era Twin Registry. LCA was used to derive significantly different classes of nicotine dependence, which were assessed for their association with smoking history, nicotine dependence, and other psychiatric disorders. The LCA model which best fit the data was a 4 class solution characterized by severity. Age onset of regular smoking decreased with more severe classes. Cigarette consumption, failed cessation and psychiatric disorders were associated with more severe classes. Empirically derived subtypes of nicotine dependence are mostly characterized by increasing severity. Suggestions for refinement of nicotine dependence diagnostic criteria are discussed.

Validation of population-based ADHD subtypes and identification of three clinically impaired subtypes.

Statistically based classification methods have successfully refined ADHD into homogenous and heritable subtypes. External validity and impairment of these subtypes was examined using the Child Behavior Checklist (CBCL). We compared mean CBCL syndrome and competency t-scores across ADHD subtypes defined by latent class analysis in a sample of 1,346 individual twins from Missouri. The potential for comorbidity with conduct disorder (CD), oppositional defiant disorder (ODD), or major depression (MD) to increase impairment in specific ADHD subtypes was also examined. CBCL profiles confirm differences in severity, with more severe classes having increased syndrome scale and decreased competency scale CBCL scores. Clinically significant impairment was found for severe inattentive and combined subtypes and the mild combined subtype. Overall, the presence of comorbid CD, ODD, or MD did not result in increased ADHD subtype impairment. CBCL scores distinguish impairment in ADHD subtypes created through LCA. Comorbidity with CD, ODD, or MD does not significantly increase impairment among ADHD subtypes. The mild combined ADHD subtype represents a clinically significant but under-studied form of ADHD.

Estimation of prevalence of DSM-IV and latent class-defined ADHD subtypes in a population-based sample of child and adolescent twins.

The goal of this study is to determine the prevalence and age of onset of Diagnostic and Statistical Manual of Mental Disorders and latent class-derived attention deficit/hyperactivity disorder (ADHD) subtypes in a population-based twin sample of boys and girls. Missouri birth records identified families with a twin pair 7 to 18 years of age. Telephone screening interviews for ADHD symptoms were completed for 5007 families. Diagnostic assessments were administered to 564 families with at least one twin meeting screening criteria, plus 183 control families. Prevalence and age of onset for both ADHD nosologies were calculated by sex and zygosity from parent report data. The prevalence of any DSM-IV ADHD was 6.2% overall, 7.4% in boys and 3.9% in girls. The inattentive subtype was most common in boys; the combined subtype was most common in girls. The mean age of onset of symptoms in children with any DSM-IV ADHD was 3.5 years, with no significant differences between boys and girls. Prevalences of latent class defined ADHD subtypes also varied by sex with the severe inattentive and combined classes more common in boys than girls. The age of onset of symptoms did not differ between boys and girls but were higher than in the DSM-IV subtypes. Findings in this twin sample showed that clinically significant ADHD, defined by either DSM-IV or latent class criterion, has an early age of onset and is more common in boys than girls. As clinical samples are most commonly composed of male combined subtypes, the inattentive subtype of both sexes in the general population is an under-treated segment of the general population.