Parsing the familiality of oppositional defiant disorder from that of conduct disorder: a familial risk analysis

Background

Family risk analysis can provide an improved understanding of the association between attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), attending to the comorbidity with conduct disorder (CD).

Methods

We compared rates of psychiatric disorders in relatives of 78 control probands without ODD and CD (Control, N = 265), relatives of 10 control probands with ODD and without CD (ODD, N = 37), relatives of 19 ADHD probands without ODD and CD (ADHD, N = 71), relatives of 38 ADHD probands with ODD and without CD (ADHD + ODD, N = 130), and relatives of 50 ADHD probands with ODD and CD (ADHD + ODD + CD, N = 170).

Results

Rates of ADHD were significantly higher in all three ADHD groups compared to the Control group, while rates of ODD were significantly higher in all three ODD groups compared to the Control group. Evidence for co-segregation was found in the ADHD + ODD group. Rates of mood disorders, anxiety disorders, and addictions in the relatives were significantly elevated only in the ADHD + ODD + CD group.

Conclusions

ADHD and ODD are familial disorders, and ADHD plus ODD outside the context of CD may mark a familial subtype of ADHD. ODD and CD confer different familial risks, providing further support for the hypothesis that ODD and CD are separate disorders.     

Family history of alcohol use disorders among adults with panic disorder in the community

Objective

Clinical studies suggest a familial association between panic disorder and alcohol use disorders but this relationship has not been examined in a representative community sample. The objective of this study is to examine the familial association between panic disorder and alcohol use disorders among adults in the community.

Method

Data were drawn from the NESARC, a nationally representative sample of over 43,000 adults in the United States. Rates of alcohol use disorders were examined using the family history method in first-degree relatives (FDRs) of adults with panic disorder. Analyses were adjusted for demographics, alcohol use disorders in the proband, and anxiety disorders in the FDRs.

Results

First-degree relatives of adults with panic disorder have significantly higher odds of alcohol use disorders, compared with FDRs of adults without panic disorder. These associations persist after adjusting for demographic characteristics, alcohol use disorders in the proband, and anxiety disorders in the FDR’s.

Conclusions

Consistent with findings from clinical studies, this is the first population-based study to show a familial link between panic disorder and alcohol use disorders. This association appears independent of the influence of comorbidity of alcohol use disorders and anxiety disorders, suggesting a potential familial and/or genetic pathway. Future longitudinal studies will be needed to further understand the mechanism of this observed association.     

Validation of the Peritraumatic Dissociative Experiences Questionnaire and Peritraumatic Distress Inventory in school-aged victims of road traffic accidents

Background

Although the reliable and valid Peritraumatic Distress Inventory (PDI-C) and Peritraumatic Dissociative Experiences Questionnaire (PDEQ) are useful for identifying adults at risk of developing acute and chronic posttraumatic stress disorder (PTSD), they have not been validated in school-aged children and their predictive values remain unknown in this population. This study aims to assess the psychometric properties of the children versions of these two measures (PDI-C and PDEQ-C) in a sample of French-speaking school-children.

Methods

One-hundred and thirty-three consecutive victims of road traffic accidents, aged 8-15 years, were recruited into this longitudinal study via the emergency room. The peritraumatic reactions were assessed at baseline and PTSD symptoms were assessed 1 month later.

Results

Cronbach's alpha coefficients were 0.8 and 0.77 for the PDI-C and PDEQ-C, respectively. The 1-month test-retest correlation coefficient (n = 33) was 0.77 for both measures. The PDI-C demonstrated a two-factor structure while the PDEQ-C displayed a one-factor structure. As with adults, the two measures were intercorrelated (r = 0.52) and correlated with subsequent PTSD symptoms and diagnosis (r = 0.21-0.56; P < 0.05).

Conclusions

The children versions of the PDI and PDEQ are reliable and valid in children.     

Simvastatin and rosuvastatin mobilize Endothelial Progenitor Cells but do not prevent their acute decrease during systemic inflammation

Introduction

Endothelial Progenitor Cells (EPCs) are a specific subtype of haematopoietic stem cells that contribute to the repair of injured endothelium. Treatment with atorvastatin has been shown to increase EPC counts in patients with stable coronary artery disease. Numbers of circulating EPCs decrease in various inflammatory diseases. Thus, we hypothesized that short term statin pre-treatment may alter the acute change in EPC levels during systemic inflammation.

Objectives

To explore the effect of statin pretreatment and low grade experimental endotoxemia on endothelial progenitor cells in humans.

Materials and Methods

Randomized, double-blind, placebo-controlled three way cross-over trial in six healthy male volunteers. Each volunteer received three treatments consisting of 5 days of oral simvastatin (80 mg/day), rosuvastatin (40 mg/day) or placebo. On Day 5 of each study period, subjects received lipopolysaccharide (LPS; 2 ng/kg i.v.). This trial has been registered with Clinical.Trials.gov, trial number NCT00309374.

Results

Statin pre-treatment led to a significant increase in circulating EPCs (1.9-3.5 fold, depending on statin and analytic method; P < 0.05) but could not suppress the endotoxemia induced EPC decrease (∼ − 75%; P < 0.05) during the observation period.

Conclusions

Statin therapy significantly increases EPCs within 96 hours and this may be a class effect. However, statins could not counteract the acute decrease in circulating EPCs after LPS infusion.     

Sex-specific cortisol levels in bipolar disorder and schizophrenia during mental challenge--relationship to clinical characteristics and medication

Objective

Our objective was to examine the cortisol release during a mental challenge in severe mental disorders versus healthy controls (HC), analyzing effects of sex, clinical characteristics and medication, and comparing Bipolar Disorder (BD) to Schizophrenia (SCZ).

Methods

Patients with BD and SCZ (n = 151) were recruited from a catchment area. HC (n = 98) were randomly selected from the same area. Salivary samples were collected before and after a mental challenge and cortisol levels determined.

Results

During the challenge there was an interaction between group and sex (P = 0.015) with male patients having a blunted cortisol release compared to male HC (P = 0.037). Cortisol change did not differ significantly between BD and SCZ. In all patients, the cortisol change correlated with number of psychotic episodes (r = − 0.23, P = 0.025), and in females patients, with number of depressive episodes (r = − 0.33, P = 0.015). Patients using antidepressants had a greater cortisol release during challenge than those not using antidepressants (P = 0.043).

Conclusions

Male patients with severe mental disorders seem to have a uniform abnormal cortisol release during mental challenges which associates with clinical course, and with beneficial effects of antidepressants.     

Health care costs in persons with asthma and comorbid mental disorders : A systematic review

Objective

The aim of this study was to systematically review the impact of comorbid mental disorders on health care costs in adult persons with asthma.

Method

A comprehensive search for studies investigating adult persons (≥18 years) with asthma was conducted. All studies were included, which allowed a comparison of health care utilization and costs between asthma patients with mental disorders and asthma patients without.

Results

The literature search revealed 1977 potentially relevant studies. Eighteen primary studies (20 publications) fulfilled the inclusion criteria. Mood disorders (n=14) and anxiety disorders (n=9) were studied most often. Increased rates of hospitalizations (odds ratio range, 0.9-6.1; n=7), emergency department visits (odds ratio range, 1.8-17.2; n=7) and general practitioner visits (standardized mean difference range, 0.1-1.1; n=6) were found in asthma patients with mental comorbidity. Indirect costs of work absence were investigated in two studies pointing in the same direction of increased costs. Evidence is sparse regarding other outcomes due to a lack of primary studies.

Conclusion

The present systematic review highlights a meaningful impact of comorbid mental disorders on health care utilization and costs in adult patients with asthma. Thus, psychodiagnostic routines and appropriate mental health treatments are needed to reduce health care costs in asthma care.     

Early-age clinical and developmental features associated to Substance Use Disorders in Attention-Deficit/Hyperactivity Disorder in Adults

Objective

The main objective was to explore early-age conditions associated to Substance Use Disorders (SUD) in adults with Attention Deficit/Hyperactivity Disorder (ADHD); secondly, to determine which of those conditions are specific to ADHD subjects; and finally, to compare ADHD and non-ADHD subjects in terms of SUD lifetime prevalence and professional, social and personal adjustment.

Method

Comparison between ADHD adults with (n = 236) and without lifetime SUD (n = 309) regarding clinical characteristics of ADHD, externalization disorders, temperamental traits, environmental factors, academic history and family psychiatric history; secondly, ADHD subjects were compared to a non-ADHD group (n = 177) concerning those variables.

Results

The following variables were found to be positively associated to SUD in ADHD subjects: ADHD severity, CD and ODD comorbidities, temperamental characteristics (“fearful”, “accident prone” and “frequent temper tantrums”), “sexual abuse”, “be suspended from school”, family history of SUD and ADHD, and male gender; ADHD inattentive subtype and “fearful” were inversely associated to SUD. From those variables, “frequent temper tantrums” was also associated to SUD in non-ADHD subjects. ADHD subjects had higher prevalence of lifetime SUD and greater professional, social and personal impairment than non-ADHD subjects.

Conclusion

Findings suggest a significant association between ADHD, SUD and early-age conditions, such as CD and ODD comorbidity; other variables from childhood, namely, ADHD subtype, temper characteristics (“fearful”, “accident prone”), “sexual abuse”, “be suspended from school” and family history of ADHD are associated to SUD in ADHD subjects, but not in non-ADHD subjects. Moreover, this study confirms both the higher prevalence of lifetime SUD and greater professional, social and personal impairment in ADHD subjects than in non-ADHD subjects.     

Psychopathology in offspring from families of alcohol dependent female probands: A prospective study

Background

Despite the importance of understanding the long-term outcome for children of alcohol dependent (AD) women, the available literature is largely based on offspring of AD fathers and few have utilized prospective designs that include child, adolescent and young adult assessments. Multiplex AD families in which multiple cases of AD are present provide an ideal setting for understanding developmental variants of the adult phenotype.

Method

Offspring from multiplex AD families identified through the mother or control families were evaluated multiple times during childhood and followed to young adulthood. Familial risk status and the presence of specific child/adolescent disorders were used as predictors of substance use disorder outcome by young adulthood.

Results

Offspring who were members of maternal multiplex families had elevated rates of child and young adulthood disorders. High risk offspring of alcohol dependent women were at increased risk for externalizing (Conduct Disorder and ADHD) and internalizing disorders (Major Depressive Disorder (MDD) and Anxiety Disorders). By young adulthood, offspring from these multiplex families had significantly greater odds of developing alcohol abuse or dependence (odds ratio [OR] = 3.63 [CI 1.36-9.64]) and drug abuse or dependence (OR = 4.23 [CI 1.73-10.32]). The prospective design of the study revealed that specific childhood disorders (Conduct Disorder, ADHD, MDD) increased the odds of subsequent development of substance use disorder (SUD).

Conclusions

Multiplex familial risk for alcohol dependence is a significant predictor of substance use disorders by young adulthood. Familial risk and an earlier childhood disorder may set the stage for later development of SUD.     

The burden of mental disorders in primary care

Objectives

To describe and compare the prevalence of mental disorders across primary care populations, and estimate their impact on quality of life.

Methods

Cross-sectional multilevel analysis of a systematic sample of 2539 attendees to eight primary care centres in different regions of Spain, assessed with the WHO Composite International Diagnostic Interview (CIDI 1.1), the Short Form Health Survey (SF-36) quality of life questionnaire and the SF-6D utility index.

Results

The 12-month prevalence of any mental disorder was 23% (95% confidence interval: 21-24%), 10% had mood, 9% anxiety, 5% organic, 4% somatoform, and 1% alcohol use disorders, with a significant between-centre variability (P < 0.001). People with mental disorders had one standard deviation lower mental quality of life than the general population. We estimated that 1831 quality-adjusted life-years (QALYs) are lost annually per 100,000 patients due to mental disorders, without considering mortality. Mood disorders have the worst impact with an annual loss of 1124 QALYs per 100,000 patients, excluding mortality (95% confidence interval: 912-1351).

Conclusions

Prevalence rates were similar to those obtained in international studies using the same diagnostic instrument and, given the significant between-centre variability found, it is recommended that mental health statistics be considered at small area level. Mental disorders, and especially mood disorders, are associated with very poor quality of life and higher scores on disability indexes than other common chronic conditions.     

Mental disorders and cardiovascular disease among adults in the United States

Objective

Numerous population-based studies have found an association between major depression and CVD, though these studies did not assess anxiety disorders. Patient samples have shown associations between anxiety disorders and cardiovascular disease (CVD), but without consideration of depressive disorders. Therefore, it remains unclear whether: (a) both anxiety and depressive disorder are associated with CVD; (b) these associations are generalizable to adults in the community.

Materials and Methods

Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative sample of 43,093 civilian non-institutionalized participants aged 18 and older.

Results

CVD (total prevalence 3.3%) was associated with increased likelihood of any anxiety disorder (OR = 1.43, (1.20, 1.71)), after adjusting for depressive disorders, as well as Generalized Anxiety Disorder (OR = 1.48 (1.09, 2.01)), Panic disorder (OR = 1.46 (1.12, 1.91)), and specific phobia (OR = 1.29 (1.04, 1.59)). CVD was significantly associated with any mood disorder (OR = 1.34 (1.13, 1.58)) after adjusting for anxiety disorders, though neither the link with major depression, nor other specific mood disorders remained significant after adjustment.

Conclusions

Our findings suggest that anxiety disorders, mood disorders, and CVD are highly comorbid among adults in the United States, and demonstrate the importance of including anxiety disorder assessment in studies of mental and physical comorbidity. These results reveal how the lack of investigation into specific relationships between CVD and the range of mental disorders in population-based studies of risk factors for CVD may obscure important relationships.     

Childhood adversity and personality disorders: results from a nationally representative population-based study

Background

Although, a large population-based literature exists on the relationship between childhood adversity and Axis I mental disorders, research on the link between childhood adversity and Axis II personality disorders (PDs) relies mainly on clinical samples. The purpose of the current study was to examine the relationship between a range of childhood adversities and PDs in a nationally representative sample while adjusting for Axis I mental disorders.

Methods

Data were from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; n = 34,653; data collection 2004-2005); a nationally representative sample of the United States population aged 20 years and older.

Results

The results indicated that many types of childhood adversity were highly prevalent among individuals with PDs in the general population and childhood adversity was most consistently associated with schizotypal, antisocial, borderline, and narcissistic PDs. The most robust childhood adversity findings were for child abuse and neglect with cluster A and cluster B PDs after adjusting for all other types of childhood adversity, mood disorders, anxiety disorders, substance use disorders, other PD clusters, and sociodemographic variables (Odd Ratios ranging from 1.22 to 1.63). In these models, mood disorders, anxiety disorders, and substance use disorders also remained significantly associated with PD clusters (Odds Ratios ranging from 1.26 to 2.38).

Conclusions

Further research is necessary to understand whether such exposure has a causal role in the association with PDs. In addition to preventing child maltreatment, it is important to determine ways to prevent impairment among those exposed to adversity, as this may reduce the development of PDs.     

Antisocial personality disorder is on a continuum with psychopathy

Background

Antisocial personality disorder (ASPD) and psychopathy are different diagnostic constructs. It is unclear whether they are separate clinical syndromes or whether psychopathy is a severe form of ASPD.

Methods

A representative sample of 496 prisoners in England and Wales was interviewed in the second phase of a survey carried out in 1997 using the Schedules for Clinical Assessment in Neuropsychiatry, the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis II personality disorders, and the Psychopathy Checklist-Revised.

Results

Among those 18 years and older (n = 470), 211 (44.9%) received a diagnosis of ASPD, of whom 67 (31.8%) were classified as psychopaths, indicated by Psychopathy Checklist-Revised scores of 25 and above. Symptoms of ASPD and psychopathy both demonstrated low diagnostic contrast when comparing subgroups of ASPD above and below the cutoff for psychopathy. There were no differences in demography, Axis I comorbidity, and treatment-seeking behavior. Psychopathic individuals with ASPD demonstrated comorbid schizoid and narcissistic personality disorder, more severe conduct disorder and adult antisocial symptoms, and more violent convictions.

Conclusions

Psychopathy and ASPD are not separate diagnostic entities, but psychopathic ASPD is a more severe form than ASPD alone with greater risk of violence. Dimensional scores of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition personality disorders (other than ASPD) may be helpful in identifying this specific subgroup.     

Difficulty in resuming or inability to resume sleep and the links to daytime impairment: Definition, prevalence and comorbidity

Objectives

To assess the chronicity and severity of nocturnal awakenings with difficulty resuming sleep (DRS), its value as an indicator of an ongoing sleep and/or mental disorder and, finally, how it affects on daytime functioning.

Methods

A cross-sectional telephone study was performed in the non-institutionalized general population of France, the United Kingdom, Germany, Italy and Spain. This representative sample of 22,740 non-institutionalized individuals aged 15 or over was interviewed on their sleeping habits, health, sleep and mental disorders. These five European countries totaled 245.1 million inhabitants. The evaluation of nocturnal awakenings with DRS included duration, frequency (per night, per week and in the previous months) and assessment scale of daytime functioning. DRS was defined as a complaint of difficulty in resuming or inability to resume sleep occurring at least three nights per week and lasting for at least one month.

Results

A total of 16.1% [95% CI: 15.6-16.6] of the sample had DRS. Prevalence was higher in women and increased with age. The average duration of DRS was 40 months. DRS individuals slept on average 30 min less than other subjects with insomnia symptoms and 60 min less than the rest of the sample. Painful physical conditions, anxiety and mood disorders were the most discriminative factors for individuals with DRS distinguishing them from other insomnia subjects and the rest of the sample. Daytime impairment was observed in 52.2% of DRS individuals compared to 32.8% in individuals with classical insomnia symptoms (p < 0.0001).

Conclusions

(1) DRS affect a large segment of the population; (2) it is a good indicator of an ongoing sleep or mental disorder; (3) it has a stronger impact on daytime functioning than classical insomnia symptoms (OR: 4.7).     

Etiology and neuropsychology of comorbidity between RD and ADHD: The case for multiple-deficit models

Introduction

Attention-deficit/hyperactivity disorder (ADHD) and reading disability (RD) are complex childhood disorders that frequently co-occur, but the etiology of this comorbidity remains unknown.

Method

Participants were 457 twin pairs from the Colorado Learning Disabilities Research Center (CLDRC) twin study, an ongoing study of the etiology of RD, ADHD, and related disorders. Phenotypic analyses compared groups with and without RD and ADHD on composite measures of six cognitive domains. Twin analyses were then used to test the etiology of the relations between the disorders and any cognitive weaknesses.

Results

Phenotypic analyses supported the hypothesis that both RD and ADHD arise from multiple cognitive deficits rather than a single primary cognitive deficit. RD was associated independently with weaknesses on measures of phoneme awareness, verbal reasoning, and working memory, whereas ADHD was independently associated with a heritable weakness in inhibitory control. RD and ADHD share a common cognitive deficit in processing speed, and twin analyses indicated that this shared weakness is primarily due to common genetic influences that increase susceptibility to both disorders.

Conclusions

Individual differences in processing speed are influenced by genes that also increase risk for RD, ADHD, and their comorbidity. These results suggest that processing speed measures may be useful for future molecular genetic studies of the etiology of comorbidity between RD and ADHD.     

Low anxiety disorder comorbidity rate in bipolar disorders in Han Chinese in Taiwan

Objectives

Studies report high comorbidity of lifetime anxiety disorders with bipolar disorders in Western patients, but it is unclear in Taiwan. The authors explored the comorbidity of anxiety disorders in different bipolar disorder subtypes in Han Chinese in Taiwan.

Methods

Three hundred twenty-five patients with bipolar disorder (bipolar I: 120; bipolar II: 205) disorder were recruited from two general medical outpatient services. They were evaluated and their diagnoses confirmed by a psychiatrist using the Chinese version of the Modified Schedule of Affective Disorder and Schizophrenia-Lifetime. The exclusion criteria were: any DSM-IV-TR Axis I diagnosis, other than bipolar disorder, being outside the 18-65-year-old age range, any other major and minor mental illnesses except anxiety disorder, any neurological disorders or organic mental disorders.

Results

Thirty-two (26.7%) of patients were comorbid with lifetime anxiety disorder and bipolar I, 80 (39.0%) with lifetime anxiety disorder and bipolar II, 7 (5.8%) were comorbid with two or more anxiety disorders and bipolar I, and 27 (13.2%) with two or more anxiety disorders and bipolar II.

Conclusion

That more than twice as many bipolar II than bipolar I patients reported two or more anxiety disorders implies that the complication is more prevalent in bipolar II patients.     

Cortical activity patterns in ADHD during arousal, activation and sustained attention

Objective

The goal of the present study is to test whether there are Attention-Deficit Hyperactivity Disorder (ADHD)-related differences in brain electrical activity patterns across arousal, activation and vigilance states.

Method

The sample consists of 80 adults (38 with ADHD and 42 non-ADHD controls) who were recruited for a family study on the genetics of ADHD. Patterns of cortical activity were measured using electroencephalography (EEG) during baseline and sustained attention conditions and compared according to ADHD diagnostic status. Cortical activity was examined separately for the first, middle, and last 5-min of the sustained attention task to assess whether patterns differed over time and according to ADHD status.

Results

In frontal and parietal regions, patterns of activation in the alpha (8-10 Hz) range differed according to ADHD status, indicating increased cortical arousal among ADHD subjects. Beta power (13-14 and 17-18 Hz) also differed between ADHD and controls, indicating increased cortical activation is associated with ADHD. Behavioral performance on the sustained attention task did not differ significantly by diagnosis. EEG correlates of cognitive performance differed significantly ADHD diagnosis and were primarily in frontal regions. Brain activation patterns recorded during the sustained attention task suggest that the ADHD group exhibited significantly increased cortical activation at the end of the task when compared to controls.

Conclusions

Adults with ADHD may have different neural organization primarily in frontal regions which results in the need for continually high levels of cortical activation to maintain sustained attention.     

Predictors of persistent ADHD: An 11-year follow-up study

Objective

Despite the existence of several follow-up studies of children with ADHD followed up into adulthood, there is limited information on whether patterns of persistence and remission in ADHD can be predicted over the long term. The main aim of this study was to evaluate predictors of persistence of ADHD in a large sample of boys with and without ADHD followed prospectively for 11 years into young adulthood.

Method

Subjects were Caucasian, non-Hispanic boys with (N = 110) and without (N = 105) ADHD who were 6-17 years old at the baseline assessment (mean age 11 years) and 15 to 31 years old at the follow-up assessment (mean age 22 years). Subjects were comprehensively and blindly assessed with structured diagnostic interviews and assessments of cognitive, social, school, and family functioning.

Results

At the 11-year follow-up, 78% of children with ADHD continued to have a full (35%) or a partial persistence (subsyndromal (22%), impaired functioning (15%), or remitted but treated (6%)). Predictors of persistence were severe impairment of ADHD, psychiatric comorbidity, and exposure to maternal psychopathology at baseline.

Conclusions

These findings prospectively confirm that persistence of ADHD over the long term is predictable from psychosocial adversity and psychiatric comorbidity ascertained 11 years earlier.     

Late-onset ADHD in adults: Milder, but still dysfunctional

Objective

The requirement in classificatory systems that some impairment from attention-deficit/hyperactivity disorder (ADHD) symptoms starts before 7 years of age (age of onset of impairment criteria - AOC) has been harshly criticized. Although there is evidence that late-onset ADHD is a valid diagnosis, little is known about the role of age of onset of impairment on the clinical profile of adult patients.

Methods

The diagnoses of 349 adults with ADHD followed DSM-IV criteria. ADHD and oppositional defiant disorder (ODD) were evaluated with the K-SADS-E, and other comorbidities with the SCID-IV and the MINI. Subjects were divided in early and late-onset groups (age of onset of impairment between 7 and 12 years old). The effect of age of onset over clinical and demographic characteristics was tested by regression models.

Results

Late-onset subjects were diagnosed later (P = 0.04), had a lower frequency of problems with authority and discipline (P = 0.004), and lower scores in SNAP-IV (P < 0.001) and in Barkley’s scale for problems in areas of life activities (P = 0.03). On the other hand, late-onset patients presented a higher prevalence of comorbid general anxiety disorder (GAD) (P = 0.01). Both groups had a similar profile in the remaining comorbidities and sociodemographic characteristics.

Conclusions

This study provides initial evidence that adults with late-onset ADHD have less severity, lower frequency of externalizing symptoms and increased comorbidity with GAD, but similar profile in other comorbidities. In addition, the data suggest that late-onset patients have a higher probability of delayed diagnosis despite the significant impairment of their condition.     

Prevalence of liver disease in veterans with bipolar disorder or schizophrenia

Objective

To assess the prevalence of three liver diseases [hepatitis C virus (HCV), nonalcoholic fatty liver disease and alcohol-induced cirrhosis] in patients (veterans) with/without schizophrenia/schizoaffective disorder and bipolar disorder.

Methods

A retrospective electronic chart review of Veterans Integrated Services Network 20 facilities from January 1, 2001 to December 21, 2006 selected patients to one of two groups: schizophrenia/schizoaffective disorder or bipolar disorder. Patients in both groups were compared with veterans in an equal-sized random sample from the same data set of veterans without psychiatric diagnoses. Logistic regression models evaluated risk for overall liver diseases as well as HCV, nonalcoholic fatty liver disease and alcoholic-induced cirrhosis.

Results

Patients with schizophrenia (n=6521) had a higher prevalence of liver disease [22.4% versus 3.2%; odds ratio (OR)=8.73]; HCV (16.5% versus 1.9%; OR=10.21); and alcohol-related cirrhosis (1.6% versus 0.4%; OR=4.09) than matched controls. Patients with bipolar disorder (n=5319) had a higher prevalence of liver disease (21.5% versus 3.5%; OR=7.58); HCV (15.5% versus 2.1%; OR=8.60); and alcohol-related cirrhosis (1.6% versus 0.4%; OR=3.82) than matched controls. Risk factors for liver disease in patients with schizophrenia (versus matched controls) included diabetes (OR=1.29), hypertension (OR=1.27), HIV (OR=3.54), substance use disorder (SUD) (OR=2.28), alcohol use disorder (OR=3.05) and schizophrenia (OR=2.74). Risk factors for development of liver disease for patients with bipolar disorder: diabetes (OR=1.40), HIV (OR=3.66), SUD (OR=2.68), alcohol use disorder (OR=3.22) and bipolar disorder (OR=2.27).

Conclusions

This study in veterans shows that the presence of mental illness and its comorbidities represents a significant risk factor for the diagnosis of liver disease, including HCV and alcohol-related cirrhosis.     

Genome-wide association study of blood pressure response to methylphenidate treatment of attention-deficit/hyperactivity disorder

Objective

We conducted a genome-wide association study of blood pressure in an open-label study of the methylphenidate transdermal system (MTS) for the treatment of attention-deficit/hyperactivity disorder (ADHD).

Method

Genotyping was conducted with the Affymetrix Genome-Wide Human SNP Array 6.0. Multivariate association analyses were conducted using the software package PLINK. After data cleaning and quality control we tested 316,934 SNPs in 140 children with ADHD.

Results

We observed no genome-wide statistically significant findings, but a SNP in a K⁺-dependent Na⁺/Ca²⁺ exchanger expressed in vascular smooth muscle (SLC24A3) was included in our top associations at p < 1E-04. Genetic enrichment analyses of genes with ≥ 1 SNP significant at p < 0.01, implicated several functional categories (FERM domain, p = 5.0E-07; immunoglobulin domain, p = 8.1E-06; the transmembrane region, p = 4.4E-05; channel activity, p = 2.0E-04; and type-III fibronectins, p = 2.7E-05) harboring genes previously associated with related cardiovascular phenotypes.

Conclusions

The hypothesis generating results from this study suggests that polymorphisms in several genes consistently associated with cardiovascular diseases may impact changes in blood pressure observed with methylphenidate pharmacotherapy in children with ADHD.