[What is adult ADHD after all?]

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset mental disorder, demonstrates genetical effects, and is characterized by attention deficit, hyperactivity, and impulsivity. While ADHD was previously only considered a childhood disorder, longitudinal studies over the past decades have proven that in a significant number of cases, the symptoms of the disorder can also be detected in adulthood, and therefore affects 2-4% of the adult population. In Hungary, adult ADHD programs started about 20 years ago and has been able to provide help to many adults living with ADHD. However, this form of care needs further development in many aspects and suffers from capacity deficits at the national level. On July 4-6, 2023 we organized a CME course on adult ADHD at the Department of Psychiatry and Psychotherapy Semmelweis University. The objective of this course was to deepen the knowledge of participants and alleviate care difficulties in the long term through the sharing of information and good practices. As part of this, a narrative review was written, which touches on the current issues of diagnosing and treating ADHD in adults.

Differential neurocognitive profiles in adult attention-deficit/hyperactivity disorder subtypes revealed by the Cambridge Neuropsychological Test Automated Battery.

Adult attention-deficit/hyperactivity disorder (aADHD) represents a heterogeneous entity incorporating different subgroups in terms of symptomatology, course, and neurocognition. Although neurocognitive dysfunction is generally associated with aADHD, its severity, association with self-reported symptoms, and differences between subtypes remain unclear. We investigated 61 outpatients (65.6% male, mean age 31.5 ± 9.5) diagnosed using DSM-5 criteria together with age-, sex-, and education-matched healthy controls (HC) (n = 58, 63.8% male, mean age 32.3 ± 9.6). Neurocognitive alterations were assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and compared between groups using the generalized linear model (GLM) method. Multivariate effects were tested by principal component analysis combined with multivariate pattern analysis. Self-reported symptom severity was tested for correlations with neurocognitive performance. GLM analyses revealed nominally significant differences between the aADHD and HC groups in several domains, however, only the Rapid Visual Information Processing measures survived correction, indicating impaired sustained attention and response inhibition in the aADHD group. Comparison of the predominantly inattentive and the hyperactive-impulsive/combined subtypes yielded nominally significant differences with higher levels of dysfunction in the inattentive group. In the stepwise discriminant analysis aADHD and HC groups were best separated with 2 factors representing sustained attention and reaction time. We found only weak correlations between symptom severity and CANTAB factors. aADHD patients are neuropsychologically heterogeneous and subtypes show different neurocognitive profiles. Differences between the aADHD and HC groups were driven primarily by the inattentive subtype. Sustained attention and its factor derivative showed the most significant alterations in aADHD patients.

[New directions in psychiatric genetics: Genome-wide association studies, polygenic risk score and cross-disorder analysis].

The field of psychiatric genetics investigates the genetic background of psychiatric disorders. In a broader sense, this discipline aims to understand the molecular pathways underlying psychopathology, therefore, it is also referred to as molecular psychiatry. The most important question of this field was originally the following: What type of inheritance is responsible for the overrepresentation of psychiatric disorders in certain families, and which variants of the human genome account for the heritability of these disorders? Moreover, can we get closer to understanding the biological mechanisms of psychiatric disorders by studying and identifying such genetic variants? Technological development during the past decades has enabled us to collect, analyze and compare genetic data from large sample sets of patients and healthy control individuals. Genome-wide association studies (GWAS) have identified common variants that convey increased risk of small effect for the development of different psychiatric disorders. Furthermore, we are now able to compose polygenic risk scores (PRS) from these disease-causing variants and quantify the overall genetic risk of individuals. The implementation of this method supports the polygenic nature of psychiatric disorders. Finally, cross-disorder analyses have the potential to compare the genetic background of different psychiatric disorders and to determine overlapping and distinct marker sets between disorders. These new research methods are described in our review paper through the examples of schizophrenia and attention deficit-hyperactivity disorder (ADHD). Psychiatric genetics has not yet entered the everyday clinical practice in psychiatry, however, it informs us about the biological underpinnings and genetic architecture of psychiatric disorders.

[Multilocus genetic analysis implicates neurodevelopment and immune system in the etiology of schizophrenia]. / A szkizofrénia multilókusz genetikai vizsgálata az idegfejlodés és az immunrendszer zavarának oki szerepére utal(hat).

BACKGROUND AND PURPOSE: Schizophrenia is a severe psychiatric disorder of poorly understood etiology, characterized by high heritability, multifactorial inheritance and high heterogeneity. Multilocus associaton methods may reduce the genetic heterogeneity and improve the probability of replication between analyses. The aims of our study were twofold: 1. To analyse genetic risk factors of schizophrenia by using multilocus genetic tests. 2. To assess the replication probability attributable to the various multilocus tests. METHODS: Subjects - Discovery set: case-parent trios of unaffected parents and affected probands with a DSM-IV schizophrenia diagnosis (n=16); replication set: schizophrenia cases and unaffected controls (n=5337). Associations of single nucleotide and indel markers were transferred to gene- and geneset-based associations, furthermore to geneset-enrichment tests and functional annotation cluster analyses in a two-staged designs. Associations with p<0.1 from the discovery set were tested in the replication sample. Familywise p-value correction for multiple comparisons were performed during the replication step. RESULTS: After correction for multiplicity, no significant association or enrichment were detected for gene-based nor canonical pathway analyses, but significant association of the 14q31 cytoband and enrichments of the 5q31 and Xq13 cytobands were found (p_corr: 0.002, 0.006 and 0.048, respectively). Functional annotation clustering yielded statistically significant enrichment scores for clusters of splicing/alternative splicing, neurodevelopment and embryonic development. Improvements in replication probability were found with increased test complexity (P_rep: 0, 0.015, 0.21). CONCLUSION: Our results corroborate the involvement of neurodevelopment, synaptic plasticity and immune mechanisms in the etiology of schizophrenia. Also, our findings indicated improvement of replication probability by using multilocus genetic analyses.

[Investigation of CNTF, COMT, DDR1, DISC1, DRD2, DRD3, and DTNBP1 candidate genes in schizophrenia: Results from the Hungarian SCHIZOBANK Consortium]. / CNTF, COMT, DDR1, DISC1, DRD2, DRD3 és DTNBP1 kandidáns gének vizsgálata szkizofréniában: eredmények a Magyar SCHIZOBANK Konzorcium vizsgálatából.

Schizophrenia is a chronic, debilitating psychiatric disorder characterized by heterogeneous clinical symptoms. Although the pathogenesis of this disorder is poorly understood, several lines of evidence support the role of both common and rare genetic variants in the etiology of schizophrenia. Common variants, single nucleotide polymorphisms can be investigated by candidate gene association studies or genome-wide association studies, while rare variants, single nucleotide variants are assessable by means of candidate gene resequencing or whole-exome and genome sequencing using next generation sequencing. In this study we investigated polymorphisms of 7 candidate genes in a Hungarian schizophrenia cohort. Candidate genes were chosen on the basis of previous results and biological plausibility. 390 patients were recruited in 5 centers in the framework of the Hungarian SCHIZOBANK Consortium, the schizophrenia sample was contrasted to 1069 healthy control individuals. In this sample SNPs of DDR1 and DRD2 genes demonstrated significant association with schizophrenia. The role of DDR1 and DRD2 genes in the etiology of schizophrenia warrant further investigation, based on their genomic localization and biological functions.

Multimarker analysis suggests the involvement of BDNF signaling and microRNA biosynthesis in suicidal behavior.

Despite moderate heritability estimates the genetics of suicidal behavior remains unclear, genome-wide association and candidate gene studies focusing on single nucleotide associations reported inconsistent findings. Our study explored biologically informed, multimarker candidate gene associations with suicidal behavior in mood disorders. We analyzed the GAIN Whole Genome Association Study of Bipolar Disorder version 3 (n = 999, suicidal n = 358) and the GAIN Major Depression: Stage 1 Genomewide Association in Population-Based Samples (n = 1,753, suicidal n = 245) datasets. Suicidal behavior was defined as severe suicidal ideation or attempt. Candidate genes were selected based on literature search (Geneset1, n = 35), gene expression data of microRNA genes, (Geneset2, n = 68) and their target genes (Geneset3, n = 11,259). Quality control, dosage analyses were carried out with PLINK. Gene-based associations of Geneset1 were analyzed with KGG. Polygenic profile scores of suicidal behavior were computed in the major depression dataset both with PRSice and LDpred and validated in the bipolar disorder data. Several nominally significant gene-based associations were detected, but only DICER1 associated with suicidal behavior in both samples, while only the associations of NTRK2 in the depression sample reached family wise and experiment wise significance. Polygenic profile scores negatively predicted suicidal behavior in the bipolar sample for only Geneset2, with the strongest prediction by PRSice at Pt < 0.03 (Nagelkerke R(2) = 0.01, P < 0.007). Gene-based association results confirmed the potential involvement of the BDNF-NTRK2-CREB pathway in the pathogenesis of suicide and the cross-disorder association of DICER1. Polygenic risk prediction of the selected miRNA genes indicates that the miRNA system may play a mediating role, but with considerable pleiotropy. © 2016 Wiley Periodicals, Inc.

Epidemiology and Treatment Guidelines of Negative Symptoms in Schizo-phrenia in Central and Eastern Europe: A Literature Review.

AIM: To gather and review data describing the epidemiology of schizophrenia and clinical guidelines for schizophrenia therapy in seven Central and Eastern European countries, with a focus on negative symptoms. Methods : A literature search was conducted which included publications from 1995 to 2012 that were indexed in key databases. Results : Reports of mean annual incidence of schizophrenia varied greatly, from 0.04 to 0.58 per 1,000 population. Lifetime prevalence varied from 0.4% to 1.4%. One study reported that at least one negative symptom was present in 57.6% of patients with schizophrenia and in 50-90% of individuals experiencing their first episode of schizophrenia. Primary negative symptoms were observed in 10-30% of patients. Mortality in patients with schizophrenia was greater than in the general population, with a standardized mortality ratio of 2.58-4.30. Reasons for higher risk of mortality in the schizophrenia population included increased suicide risk, effect of schizophrenia on lifestyle and environment, and presence of comorbidities. Clinical guidelines overall supported the use of second-generation antipsychotics in managing negative symptoms of schizophrenia, although improved therapeutic approaches are needed. Conclusion : Schizophrenia is one of the most common mental illnesses and poses a considerable burden on patients and healthcare resources alike. Negative symptoms are present in many patients and there is an unmet need to improve treatment offerings for negative symptoms beyond the use of second-generation antipsychotics and overall patient outcomes.

Genetics in the ADHD Clinic: How Can Genetic Testing Support the Current Clinical Practice?

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a childhood prevalence of 5%. In about two-thirds of the cases, ADHD symptoms persist into adulthood and often cause significant functional impairment. Based on the results of family and twin studies, the estimated heritability of ADHD approximates 80%, suggests a significant genetic component in the etiological background of the disorder; however, the potential genetic effects on disease risk, symptom severity, and persistence are unclear. This article provides a brief review of the genome-wide and candidate gene association studies with a focus on the clinical aspects, summarizing findings of ADHD disease risk, ADHD core symptoms as dimensional traits, and other traits frequently associated with ADHD, which may contribute to the susceptibility to other comorbid psychiatric disorders. Furthermore, neuropsychological impairment and measures from neuroimaging and electrophysiological paradigms, emerging as potential biomarkers, also provide a prominent target for molecular genetic studies, since they lie in the pathway from genes to behavior; therefore, they can contribute to the understanding of the underlying neurobiological mechanisms and the interindividual heterogeneity of clinical symptoms. Beyond the aforementioned aspects, throughout the review, we also give a brief summary of the genetic results, including polygenic risk scores that can potentially predict individual response to different treatment options and may offer a possibility for personalized treatment for the therapy of ADHD in the future.

A comparison of two single-item screeners for hazardous drinking and alcohol use disorder.

BACKGROUND: There is increasing interest in and physician support for the use of single-item screeners for problem drinking. METHODS: In a representative sample of U.S. adults (n = 43,093) and within selected subgroups, past-year frequency of drinking 5+/4+ drinks and maximum drinks consumed on any day were evaluated as screeners for past-year alcohol dependence, any alcohol use disorder (AUD), and any AUD or hazardous drinking, using standard measures of screening performance. AUDs were defined according to DSM-IV criteria. Hazardous drinking was defined as consuming >14 drinks/wk or 5+ drinks on any day for men and >7 drinks/wk or 4+ drinks on any day for women. RESULTS: Optimal cutpoints for both screeners varied across population subgroups, and these variations should be taken into account in order to maximize screening performance. At the optimal cutpoints for the total population, the sensitivity and specificity of maximum drinks were 89% and 82% for dependence at > or =5 drinks, 90% and 79% for any AUD at > or =4 drinks, and 90% and 96% for any AUD or hazardous drinking at > or =4 drinks. Comparable values of sensitivity and specificity for 5+/4+ frequency were 90% and 83% at > or =3 times a year, 87% and 82% at > or =once a year, and 88% and 100% at > or =once a year, respectively. Specificity was lower when only past-year drinkers were considered. The 5+/4+ frequency screener yielded fairly low sensitivity in predicting alcohol problems among the elderly and among Blacks. Results supported a past-year reference period for frequency of 5+/4+ drinks and substantiated gender- and age-specific thresholds for defining risk drinking. CONCLUSIONS: Both of the single-item screeners performed nearly on a par with the AUDIT-C and have potential for use in primary and emergency care settings.

Prevalence, correlates, disability, and comorbidity of DSM-IV schizotypal personality disorder: results from the wave 2 national epidemiologic survey on alcohol and related conditions.

OBJECTIVE: To present nationally representative findings on the prevalence, correlates, and comorbidity of and disability associated with DSM-IV schizotypal personality disorder (SPD). METHOD: This study used the 2004-2005 Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions, which targeted a nationally representative sample of the adult civilian population of the United States aged 18 years and older and residing in households and group quarters. In Wave 2, attempts were made to conduct face-to-face reinterviews with all respondents to the Wave 1 interview. RESULTS: Lifetime prevalence of SPD was 3.9%, with significantly greater rates among men (4.2%) than women (3.7%) (p < .01). Odds for SPD were significantly greater among black women, individuals with lower incomes, and those who were separated, divorced, or widowed; odds were significantly lower among Asian men (all p < .01). Schizotypal personality disorder was associated with substantial mental disability in both sexes. Co-occurrence rates of Axis I and other Axis II disorders among respondents with SPD were much higher than rates of co-occurrence of SPD among respondents with other disorders. After adjustment for sociodemographic characteristics and additional comorbidity, associations remained significant in both sexes between SPD and 12-month and lifetime bipolar I disorder, social and specific phobias, and posttraumatic stress disorder, as well as 12-month bipolar II disorder, lifetime generalized anxiety disorder, and borderline and narcissistic personality disorders (all p < .01). CONCLUSIONS: Common and unique factors may underlie associations of SPD with narcissistic and borderline personality disorders, whereas much of the comorbidity between SPD and most mood and anxiety disorders appears to reflect factors common to these disorders. Some of the associations with SPD were sex specific. Schizotypal personality disorder and dependent, avoidant, and borderline personality disorders were associated with the occurrence of schizophrenia or psychotic episode. Schizotypal personality disorder is a prevalent, fairly stable, highly disabling disorder in the general population. Sex differences in associations of SPD with other specific Axis I and II disorders can inform more focused, hypothesis-driven investigations of factors underlying the comorbid relationships. Schizotypal as well as borderline, dependent, and avoidant personality disorders may be components of the schizophrenia spectrum.

ADHD: a hidden comorbidity in adult psychiatric patients.

Adult attention-deficit/hyperactivity disorder (aADHD) has recently been better recognized and treated in many European countries. In spite of this development, aADHD still features as a "hidden" comorbidity, often not diagnosed even in patients under psychiatric treatment for other psychiatric disorders. The aim of this study was to establish the prevalence rates of unrecognized aADHD in academic centers providing regular psychiatric services in the Czech Republic and Hungary. In a population of psychiatric in-and outpatients, Adult ADHD Self-Report Scale was administered. All positively and about half of the negatively screened subjects were clinically interviewed and the DSM diagnosis of ADHD was determined based on the symptom list and Conners' Adult ADHD Rating Scale. The estimated point prevalence rate of unrecognized comorbid aADHD among psychiatric in-and out patients was 6.99% (95% lower CI: 5.11, 95% upper CI 8.86) according to the DSM-IV-TR criteria and 9.27% (95% lower CI: 7.13, 95% upper CI 11.40) according to the DSM-5 criteria. Current suicide risk was significantly associated with the presence of undiagnosed aADHD; however, life time suicide attempts, depression, dysthymia, alcohol and substance dependence, anxiety and stress related disorders were not. Further educational efforts are needed to improve the recognition and treatment of aADHD in adults.

Genome-wide association analysis reveals KCTD12 and miR-383-binding genes in the background of rumination.

Ruminative response style is a passive and repetitive way of responding to stress, associated with several disorders. Although twin and candidate gene studies have proven the genetic underpinnings of rumination, no genome-wide association study (GWAS) has been conducted yet. We performed a GWAS on ruminative response style and its two subtypes, brooding and reflection, among 1758 European adults recruited in the general population of Budapest, Hungary, and Manchester, United Kingdom. We evaluated single-nucleotide polymorphism (SNP)-based, gene-based and gene set-based tests, together with inferences on genes regulated by our most significant SNPs. While no genome-wide significant hit emerged at the SNP level, the association of rumination survived correction for multiple testing with KCTD12 at the gene level, and with the set of genes binding miR-383 at the gene set level. SNP-level results were concordant between the Budapest and Manchester subsamples for all three rumination phenotypes. SNP-level results and their links to brain expression levels based on external databases supported the role of KCTD12, SRGAP3, and SETD5 in rumination, CDH12 in brooding, and DPYSL5, MAPRE3, KCNK3, ATXN7L3B, and TPH2 in reflection, among others. The relatively low sample size is a limitation of our study. Results of the first GWAS on rumination identified genes previously implicated in psychiatric disorders underscoring the transdiagnostic nature of rumination, and pointed to the possible role of the dorsolateral prefrontal cortex, hippocampus, and cerebellum in this cognitive process.

The relationship of impairment to personality disorder severity among individuals with specific axis I disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

The present study examined one dimensional approach to personality disorders (PDs) in a large (n = 43,093), nationally representative sample of the U.S. population. Respondents were classified in four personality severity categories (no PD, subthreshold PD, simple PD, complex PD). Linear regression analyses were conducted to examine mental disability by PD severity for major DSM-IV substance use, mood and anxiety disorders. Significant increases in disability were observed between no PD and simple PD and between simple PD and complex PD for each Axis I disorder except drug dependence, but few differences in disability were found between no PD and subthreshold PD. This study found support for the clinical utility of the dimensional classification of PD severity with regard to the distinction between simple and complex PD and for a combined no PD-subthreshold PD level of severity. Future planned analyses will address the clinical utility of the classification prospectively, with a full battery of all Axis II PDs.

[Problems occurring in the application of cytogenetic biomarkers for alcoholics with and without malignant diseases]. / Biomarkerek alkalmazása során felmerülo problémák malignus és nem malignus betegségben szenvedo alkoholisták esetében.

Applicability of alcohol- and smoking-related cancer-risk biomarkers might be modified by several factors. Among those, reality of self-reports on alcohol consumption of alcoholic patients with different diseases and extreme high mutagen hypersensitivity of Hungarians, as well as the immunologic role of peripheral lymphocytes as experimental objects of cytogenetic biomarkers seem to be new viewpoints of interest. To clarify these problems, 432 head and neck cancer patients (HNCP), 62 alcoholics with alcoholic hepatitis (ALCL), and 101 disease-free chronic alcoholics (ALC) were examined. Despite clinically confirmed alcohol-related diagnoses (and GGT and MCV values) only about half of HNCPs and ALCLs reported about any alcohol consumption, in contrast to the realistic self-reports of ALCs. In cytogenetic case control investigations no difference between the spontaneous rate of chromosomal aberrations (CAs) of healthy controls and ALCs was found, however, genetic instability expressed as a 40-50% elevation rate of CAs in HNCPs and ALCLs might be associated with systemic inflammatory reaction of lymphocytes. Bleomycin sensitivity assay showed the highest break/cell (b/c) values not in HNCPs (1.06 b/c) as it was reported earlier, but in "healthy" ALCs (1.52 b/c). This phenomenon can be related to the local effect of genotoxins (alcohol, smoking, and in particular the diet), which probably reflects merely a reaction of mucosal immune system. Nearly 50% of mutagen-hypersensitive Hungarian controls, in contrary to the expected 10-20% ones, might also be explained by this. Similarly, HNCPs with oral cancer, where the local mutagen effect was the most intensive, had the highest b/c values. In conclusion, when cytogenetic biomarkers of alcoholism are examined, the subjective character of self-reports at epidemiologic level and immunologic role of lymphocyte subpopulations as genetic confounders must also be taken into consideration.

Antisocial behavioral syndromes and DSM-IV drug use disorders in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

BACKGROUND: Antisocial behavioral syndromes, including antisocial personality disorder (ASPD), syndromal adult antisocial behavior (AABS) without conduct disorder (CD) before age 15, and CD without progression to ASPD ("CD only") are highly comorbid with drug use disorders (DUDs). Among patients in DUD treatment, antisocial syndromes are associated with greater severity and poorer outcomes. Comparative data concerning associations of antisocial syndromes with clinical characteristics of DUDs among general population adults have not previously been available. This study describes associations of antisocial syndromes with clinical characteristics of lifetime Diagnostic and Statistical Manual-Version IV DUDs in the general U.S. adult population. METHODS: This report is based on the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (n=43,093, response rate=81%). Respondents (n=4068) with lifetime DUDs were classified according to whether they met criteria for ASPD, AABS, "CD only," or no antisocial syndrome. Associations of antisocial syndromes with clinical characteristics of DUDs were examined using logistic regression. RESULTS: Antisocial syndromes were significantly associated with the phenomenology of DUDs, particularly ASPD with the most severe clinical presentations. Associations with AABS were similar to those with ASPD; those with "CD only" were weak, inconsistent, and not statistically significant. Patterns of associations differed little between men and women. CONCLUSIONS: Both ASPD and AABS, but not "CD only," appear to identify greater clinical severity of DUDs among adults in the general U.S. population.

Dimensionality of hallucinogen and inhalant/solvent abuse and dependence criteria: implications for the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition.

BACKGROUND: Prior research has demonstrated the dimensionality of Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) alcohol, nicotine, cannabis, cocaine and amphetamine abuse and dependence criteria. The purpose of this study was to examine the dimensionality of hallucinogen and inhalant/solvent abuse and dependence criteria. In addition, we assessed the impact of elimination of the legal problems abuse criterion on the information value of the aggregate abuse and dependence criteria, another proposed change for DSM-IV currently lacking empirical justification. METHODS: Factor analyses and item response theory (IRT) analyses were used to explore the unidimisionality and psychometric properties of hallucinogen and inhalant/solvent abuse and dependence criteria using a large representative sample of the United States (U.S.) general population. RESULTS: Hallucinogen and inhalant/solvent abuse and dependence criteria formed unidimensional latent traits. For both substances, IRT models without the legal problems abuse criterion demonstrated better fit than the corresponding model with the legal problem abuse criterion. Further, there were no differences in the information value of the IRT models with and without the legal problems abuse criterion, supporting the elimination of that criterion. No bias in the new diagnoses was observed by sex, age and race-ethnicity. CONCLUSION: Consistent with findings for alcohol, nicotine, cannabis, cocaine and amphetamine abuse and dependence criteria, hallucinogen and inhalant/solvent criteria reflect underlying dimensions of severity. The legal problems criterion associated with each of these substance use disorders can be eliminated with no loss in informational value and an advantage of parsimony. Taken together, these findings support the changes to substance use disorder diagnoses recommended by the DSM-V Substance and Related Disorders Workgroup, that is, combining DSM-IV abuse and dependence criteria and eliminating the legal problems abuse criterion.

Temporal relationships between overweight and obesity and DSM-IV substance use, mood, and anxiety disorders: results from a prospective study, the National Epidemiologic Survey on Alcohol and Related Conditions.

OBJECTIVE: To present nationally representative findings on the prospective relationships between overweight and obesity and DSM-IV substance use, mood, and anxiety disorders. METHOD: A nationally representative sample of 34,653 US adults was interviewed in Wave 1 (2001-2002) and Wave 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. The target population was the civilian population residing in households and group quarters, with gathered data adjusted to be representative of the civilian population of the United States on the basis of the 2000 Decennial Census. The main outcome measures were the incidence of DSM-IV substance use, mood, and anxiety disorders and changes in body mass index status during the 3-year follow-up period. RESULTS: Regression analyses that controlled for a wide array of covariates showed that overweight and obese women were at increased risk (P < .05) for incident major depressive disorder during the follow-up period (adjusted OR [AOR] = 1.3 [95% CI, 1.02-1.56] and AOR = 1.2 [95% CI, 1.02-1.51], respectively). Overweight men and obese men were at decreased risk (P < .05) of incident drug abuse and alcohol dependence (AOR = 0.7 [95% CI, 0.44-0.96] and AOR = 0.7 [95% CI, 0.52-0.97]), respectively. Obese women had a decreased risk (P < .05) of incident alcohol abuse and drug dependence (AOR = 0.6 [95% CI, 0.45-0.88] and AOR = 0.4 [95% CI, 0.21-0.91], respectively). Men with drug dependence and women with specific phobia had a decreased risk (P < .05) of becoming overweight or obese during the follow-up period (AOR = 0.4 [95% CI, 0.19-0.99] and AOR = 0.8 [95% CI, 0.66-0.95], respectively). CONCLUSIONS: Increased risk of major depressive disorder among overweight and obese women could be attributed to stigma and greater body dissatisfaction among women in Western cultures. Overweight and obesity may serve as protective factors against developing incident substance use disorders, possibly due to shared neural functions in the brain underlying addictions to numerous substances. Results are discussed in terms of their clinical implications, including the need to update treatment guidelines for the management of overweight, obesity, and major depressive disorder.

Association of SOD2, a mitochondrial antioxidant enzyme, with gray matter volume shrinkage in alcoholics.

Chronic alcoholism leads to gray matter shrinkage and induces the formation of superoxide anions (O(2)(-)) that can cause neuronal cell death. The mitochondrial superoxide dismutase 2 (SOD2) enzyme is critical in the metabolism of superoxide. An Ala16Val polymorphism putatively affects SOD2 enzyme activity in vivo. Brain volumes of 76 treatment-seeking alcohol-dependent individuals were measured with a 1.5T MRI. Intracranial tissue margins were manually outlined on coronal sections. Gray matter, white matter, sulcal, and ventricular CSF volumes were estimated using intensity-based K-means clustering. Ala16Val (rs4880) and a second haplotype tagging SNP, rs10370, were genotyped. The q-value package was used to correct for multiple comparisons. In the alcoholics, cerebrospinal fluid and intra-cranial volumes showed significant differences across the six diplotype categories. The homozygous Ala16-containing diplotype rs10370TT-rs4880GG was associated with lowest gray matter ratio (greater shrinkage; p=0.005). Presence of one or two copies of the low activity Ala16 allele was a risk factor for lower gray matter volume in alcoholics below the median alcohol consumption (p=0.03) but not in alcoholics above this level. White matter ratio was associated with sex (p=0.002) and lifetime total alcohol consumption (p=0.01) but not with diplotypes. In this exploratory analysis, a putative functional missense variant of SOD2 appears to influence gray matter loss in alcoholics. This may be due to impaired clearance of reactive oxygen species formed as a result of alcohol exposure. The risk/protective effect was observed in alcoholics with lower levels of lifetime alcohol consumption. Highest levels of exposure may overwhelm the protective action of the SOD2 enzyme.

The relationship of DSM-IV personality disorders to nicotine dependence-results from a national survey.

This study examined the prevalence of nicotine dependence (ND) and its associations with DSM-IV personality disorders (PDs) among current smokers (n=7078), controlling for sociodemographic characteristics and comorbid Axis I and II disorders. Data were derived from a nationally representative sample of the U.S. population. Although all PDs were significantly associated with ND when sociodemographic factors were controlled, only schizotypal, borderline, narcissistic and obsessive-compulsive PDs were associated with ND after adding controls for Axis I and other Axis II disorders. These associations remained significant after controlling for degree of smoking exposure. The results suggest that both shared and PD-specific pathogenetic factors underlie these PD-ND associations. Implications are also discussed in terms of the relationship between personality features of schizotypal, borderline, narcissistic and obsessive-compulsive PDs and the self-medication hypothesis and the role of neurotransmission.

Dimensionality of DSM-IV nicotine dependence in a national sample: an item response theory application.

BACKGROUND: Research focusing on the development of a dimensional representation of DSM-IV nicotine dependence is scarce and prior research has not assessed the role of nicotine use criteria in that a dimensional representation, nor the invariance of the DSM-IV nicotine dependence criteria across important population subgroups. METHODS: Using a large, representative sample of the U.S. population, this study utilized item response theory (IRT) analyses to explore the dimensionality of DSM-IV nicotine dependence criteria and several candidate criteria for cigarette use among past-year cigarette smokers (n=10,163). RESULTS: Factor analyses demonstrated the unidimensionality of nicotine dependence criteria and IRT analyses demonstrated good fit of the observed responses and the underlying, unobserved latent trait of dependence severity. The model containing all seven DSM-IV dependence criteria, along with the consumption criterion of smoking at least a quarter of a pack of cigarettes in a day in the past year, was identified as the best-fitting model. No differential criterion functioning was shown across sex, race-ethnicity, and age subgroups. DISCUSSION: Major implications of this study are discussed in terms of the addition of a dimensional representation of nicotine dependence to pre-existing categorical representations of the disorder in the DSM-V, and the need for a nicotine consumption criterion to improve representations of nicotine dependence severity.