Personality disorders (PDs) have been shown to be modestly heritable. Accurate heritability estimates are, however, dependent on reliable measurement methods, as measurement error deflates heritability. The aim of this study was to estimate the heritability of DSM-IV avoidant and dependent personality disorder, by including two measures of the PDs at two time points.
Data were obtained from a population-based cohort of young adult Norwegian twins, of whom 8045 had completed a self-report questionnaire assessing PD traits. 2794 of these twins subsequently underwent a structured diagnostic interview for DSM-IV PDs. Questionnaire items predicting interview results were selected by multiple regression, and measurement models of the PDs were fitted in Mx.
The heritabilities of the PD factors were 0.64 for avoidant PD and 0.66 for dependent PD. No evidence of common environment, that is, environmental factors that are shared between twins and make them similar, was found. Genetic and environmental contributions to avoidant and dependent PD seemed to be the same across sexes.
The combination of both a questionnaire- and an interview assessment of avoidant and dependent PD results in substantially higher heritabilities than previously found using single-occasion interviews only.
twin studies; personality disorders; genetics
Drug abuse (DA) is a clinically heterogeneous syndrome. Using medical, legal, death and pharmacy records covering the entire population of Sweden, could we uncover meaningful subtypes of DA?
We performed a latent class analysis (LCA) on all individuals in Sweden born 1950–1993 who were registered with DA or its consequences (n=192 501) and then validated these classes using demographics, patterns of co-morbidity with alcohol use disorder (AUD), non-DA crime and psychiatric illness, and the pattern of aggregation and co-aggregation in sibling pairs.
The best-fit LCA had six classes: (1) low-frequency pure criminal, (2) high-frequency medical criminal, (3) low-frequency pure medical, (4) high-frequency medical, (5) prescription and (6) death. Each class had a distinct pattern of demographic features and co-morbidity and aggregated within sibling pairs with at least moderate specificity. For example, class 2 was characterized by early age at registration, low educational attainment, high male preponderance, high rates of AUDs, strong resemblance within sibling pairs [odds ratio (OR) 12.6] and crime and the highest risk for DA in siblings (20.0%). By contrast, class 5 had a female preponderance, late age at registration, low rates of crime and AUDs, high rates of psychiatric illness, high familiality within sibling pairs (OR 14.7) but the lowest observed risk for DA in siblings (8.9%).
DA as assessed by public records is a heterogeneous syndrome. Familial factors contribute substantially to this heterogeneity. Advances in our understanding of etiological processes leading to DA will be aided by a consideration of this heterogeneity.
Drug abuse; latent class analysis; siblings; Sweden
Alcohol consumption is influenced by genetic factors. Previous studies have examined the heritability of alcohol consumption, or related phenotypes, from adolescence into adulthood, frequently finding that total heritability changes over time. However, it remains unclear whether the same genes underlie liability to alcohol consumption across development versus whether novel risk genes become important over time.
A population-based study of adult male twins (n=1790) born in Virginia, USA, retrospectively reported on their average monthly alcohol consumption from early adolescence through adulthood. We used twin modeling methods to explore genetic and environmental influences on alcohol consumption over time.
One latent genetic factor accounted for the majority of the heritability in alcohol consumption during mid-to late adolescence, but its influence declined thereafter ; from young adulthood forward, heritability was largely attributable to a second genetic factor. The total heritability of alcohol consumption increased from 0 at ages 12–14 years to 0.40 by ages 18–21 years. Shared environmental factors declined in influence over time.
The heritability of alcohol consumption over time is dynamic both quantitatively and qualitatively. These results have important implications for gene identification endeavors. Furthermore, these findings could inform efforts to elucidate developmentally dynamic behaviors, such as antisocial behavior.
Adolescent-limited genetic factors; alcohol consumption; gene identification; genetic influences; genetic innovation; twin modeling
Previous research has shown that stressful life events (SLEs) influence the pattern of individual depressive symptoms. However, we do not know how these differences arise. Two theories about the nature of psychiatric disorders have different predictions about the source of these differences : (1) SLEs influence depressive symptoms and correlations between them indirectly, via an underlying acute liability to develop a dysphoric episode (DE; common cause hypothesis); and (2) SLEs influence depressive symptoms and correlations between them directly (network hypothesis). The present study investigates the predictions of these two theories.
We divided a population-based sample of 2096 Caucasian twins (49.9% female) who reported at least two aggregated depressive symptoms in the last year into four groups, based on the SLE they reported causing their symptoms. For these groups, we calculated tetrachoric correlations between the 14 disaggregated depressive symptoms and, subsequently, tested whether the resulting correlation patterns were significantly different and if those differences could be explained by underlying differences in a single acute liability to develop a DE.
The four SLE groups had markedly different correlation patterns between the depressive symptoms. These differences were significant and could not be explained by underlying differences in the acute liability to develop a DE.
Our results are not compatible with the common cause perspective but are consistent with the predictions of the network hypothesis. We elaborate on the implications of a conceptual shift to the network perspective for our diagnostic and philosophical approach to the concept of what constitutes a psychiatric disorder.
Common cause hypothesis; dysphoric episode; network hypothesis; stressful life events
Designed as state measures to monitor treatment response, symptoms of anxiety and depression (SxAnxDep) also have trait-like characteristics. No comprehensive etiologic model for SxAnxDep has illuminated the inter-relationship between their state- and trait-like characteristics, while including key predictor variables.
In a prospective three-wave study of 2395 female twins from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders (VATSPSUD), we examined, using structural equation modeling, how genes, childhood and past-year environmental stressors, personality and episodes of major depression (MD) and generalized anxiety disorder (GAD) influence SxAnxDep.
The best-fit model, which explained 68–74% of the variance in SxAnxDep, revealed two etiologic pathways. Stable levels of SxAnxDep resulted largely from neuroticism, which in turn was influenced by genetic and early environment risk factors. Occasion-specific influences resulted from stressful events mediated through episodes of MD or GAD. These two pathways, which had approximately equal influences on levels of SxAnxDep, were substantially correlated because the genetic, early environmental and personality factors that impacted on stable symptom levels also predisposed to event exposure and disorder onset. No significant interaction was seen between the two pathways.
SxAnxDep in women in the general population arise from two inter-related causal pathways. The first, the ‘trait-like’ pathway, reflects genetic and early environmental risk factors, and is mediated largely through personality. The second pathway is mediated through episodes of MD and GAD, and is the result of both recent environmental adversities and trait-like factors that influence event exposure and the probability of disorder onset.
Anxiety; depression; longitudinal model; neuroticism
Genetic and environmental factors are important in the etiology of substance use. However, little is known about the stability of these factors across development. We aimed to answer three crucial questions about this etiology that have never been addressed in a single study: (1) Is there a general vulnerability to substance consumption from early adolescence to young adulthood? (2) If so, do the genetic and environmental influences on this vulnerability change across development? (3) Do these developmental processes differ in males and females ?
Subjects included 1480 twin pairs from the Swedish Twin Study of Child and Adolescent Development who have been followed since 1994. Prospective, self-reported regular smoking, alcohol intoxication and illicit drug use were assessed at ages 13–14, 16–17 and 19–20 years. Structural modeling was performed with the program Mx.
An underlying common factor accounted for the association between smoking, alcohol and illicit drug consumption for the three age groups. Common genetic and shared environmental effects showed substantial continuity. In general, as participants aged, the influence of the shared environment decreased, and genetic effects became more substance specific in their effect.
The current report answers three important questions in the etiology of substance use. The genetic and environmental risk for substance consumption is partly mediated through a common factor and is partly substance specific. Developmentally, evidence was strongest for stability of common genetic effects, with less evidence for genetic innovation. These processes seem to be the same in males and females.
Adolescence; development; substance use; twin study
To explore the genetic and environmental factors underlying the co-occurrence of lifetime diagnoses of DSM-IV phobia.
Female twins (n = 1430) from the population-based Norwegian Institute of Public Health Twin Panel were assessed at personal interview for DSM-IV lifetime specific phobia, social phobia and agoraphobia. Comorbidity between the phobias were assessed by odds ratios (ORs) and polychoric correlations and multivariate twin models were fitted in Mx.
Phenotypic correlations of lifetime phobia diagnoses ranged from 0.55 (agoraphobia and social phobia, OR 10.95) to 0.06 (animal phobia and social phobia, OR 1.21). In the best fitting twin model, which did not include shared environmental factors, heritability estimates for the phobias ranged from 0.43 to 0.63. Comorbidity between the phobias was accounted for by two common liability factors. The first loaded principally on animal phobia and did not influence the complex phobias (agoraphobia and social phobia). The second liability factor strongly influenced the complex phobias, but also loaded weak to moderate on all the other phobias. Blood phobia was mainly influenced by a specific genetic factor, which accounted for 51% of the total and 81% of the genetic variance.
Phobias are highly co-morbid and heritable. Our results suggest that the co-morbidity between phobias is best explained by two distinct liability factors rather than a single factor, as has been assumed in most previous multivariate twin analyses. One of these factors was specific to the simple phobias, while the other was more general. Blood phobia was mainly influenced by disorder specific genetic factors.
Heritability; phobia; twin study
Alcohol consumption is influenced by specific genetic risk factors for alcohol use disorders (AUDs), non-specific genetic risk factors for externalizing behaviors and various environmental experiences. We have limited knowledge of how these risk factors inter-relate through development.
Retrospective assessments in 1796 adult male twins using a life history calendar of key environmental exposures and alcohol consumption from early adolescence to mid-adulthood. Analysis by linear mixed models.
The importance of non-specific genetic risk factors on maximal alcohol consumption rose rapidly in early to mid-adolescence, peaked at ages 15–17 years and then declined slowly. Alcohol-specific genetic risk factors increased slowly in influence through mid-adulthood. We detected robust evidence for environmental moderation of genetic effects on alcohol consumption that was more pronounced in early and mid-adolescence than in later periods. Alcohol availability, peer deviance and low prosocial behaviors showing the strongest moderation effects. More interactions with environmental risk factors were seen for the non-specific externalizing disorder risk than for specific genetic risk for AUDs.
The impact of specific and non-specific genetic influences on alcohol consumption have different development trajectories. Genetic effects on alcohol use are more pronounced when social constraints are minimized (e.g. low prosocial behaviors or parental monitoring) or when the environment permits easy access to alcohol and/or encourages its use (e.g. high alcohol availability or peer deviance). Gene–environment interactions influencing alcohol intake may be more robust at younger ages, indicating greater plasticity of genetic influences early in the development of drinking patterns.
Adolescence; alcohol; genetics; gene–environment interaction
To describe the structure of genetic and environmental risk factors for four dimensions of borderline personality disorder (BPD) and to understand the source of resemblance of these dimensions and normal personality.
A web-based sample (n = 44,112 including 542 twin pairs) completed items from 4 scales of the Dimensional Assessment of Personality Pathology Basic Questionnaire and the Big Five Inventory.
A one-factor common pathway model best fits the 4 BPD scales producing a highly heritable latent liability (heritability = 60%) and strong loadings on all 4 dimensions. Affective instability had the lowest trait-specific genetic loading, suggesting that it was a core feature of BPD. A complex pattern of genetic and environmental associations was found between the big five personality traits and BPD dimensions. The strongest genetic correlations with the BPD traits were generally seen for neuroticism (positive), followed by conscientiousness and agreeableness, both negative.
In the general population, these four BPD dimensions reflect one underlying highly heritable factor. The association between normative personality and dimensions of BPD is complex with high degrees of genetic correlation.
borderline personality disorder; twins; personality; genetics
Numerous epidemiological studies have reported a positive association between major depression (MD) and regular tobacco use (RU) or nicotine dependence (ND). However, few have used a genetically informative design to assess whether these traits share a common genetic and/or environmental liability.
We assessed MD, RU and ND in same-sex twins from the population-based Swedish Twin Registry. In males, we examined both cigarette use and snus (smokeless tobacco) use. We used structural equation modeling to examine the relationship between MD, RU, and ND given RU.
The results suggest modest correlations between MD and RU, and between MD and ND. In males, the liability shared between MD and RU is solely genetic for both cigarettes and snus, while MD and ND share both genetic and unique environmental influences. The continuation to ND given RU differed considerably between cigarette and snus users. In females, both MD–RU and MD–ND relationships are partially attributable to genetic and unique environmental correlations.
The relationship among MD, RU and ND is at least partially attributable to shared genetic and environmental risk factors. The genetic and environmental correlations between traits are modest. The nature of the shared liability differs by sex, and in males, by the type of tobacco product used. Differences between previous reports and results presented in the current study are suggestive of population differences in how MD and tobacco use inter-relate.
Genetic risk; shared liability; twin modeling
An association between childhood maltreatment and subsequent alcohol abuse and/or dependence (AAD) has been found in multiple studies of females. Less is known about the association between childhood maltreatment and AAD among males, and the mechanisms that underlie this association in either gender. One explanation is that childhood maltreatment increases risk for AAD. An alternative explanation is that the same genetic or environmental factors that increase a child's risk for being maltreated also contribute to risk for AAD in adulthood.
Lifetime diagnosis of AAD was assessed using structured clinical interviews in a sample of 3527 male participants aged 19–56 years from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. The sources of childhood maltreatment–AAD association were estimated using both a matched case–control analysis of twin pairs discordant for childhood maltreatment and bivariate twin modeling.
Approximately 9% of participants reported childhood maltreatment, defined as serious neglect, molestation, or physical abuse occurring before the age of 15 years. Those who experienced childhood maltreatment were 1.74 times as likely to meet AAD criteria compared with males who did not experience childhood maltreatment. The childhood maltreatment–AAD association largely reflected environmental factors in common to members of twin pairs. Additional exploratory analyses provided evidence that AAD risk associated with childhood maltreatment was significantly attenuated after adjusting for measured family-level risk factors.
Males who experienced childhood maltreatment had an increased risk for AAD. Our results suggest that the childhood maltreatment–AAD association is attributable to broader environmental adversity shared between twins.
Alcoholism; Child abuse; Child neglect; family environment; genetics
Recent behavioral genetic studies have emphasized the importance of investigating eating disorders at the level of individual symptoms, rather than as overall diagnoses. We examined the heritability of binge eating disorder (BED) using an item-factor analytic approach, which estimates contributions of additive genetic (A), common environmental (C), and unique environmental (E) influences on liability to BED as well as individual symptoms.
Participants were 614 monozygotic and 410 dizygotic same-sex female twins from the Mid-Atlantic Twin Registry who completed a self-report measure of BED symptoms based upon DSM-IV criteria. Genetic and environmental contributions to BED liability were assessed at the diagnostic and symptom levels, using an item-factor approach.
Liability to BED was moderately heritable; 45% of the variance was due to A, with smaller proportions due to C (13%), and E (42%). Additive genetic effects accounted for 29–43% of the variance in individual items, while only 8–14% was due to C.
Results highlight the relevance of examining eating disorders at the symptom level, rather than focusing on aggregate diagnoses.
Binge eating disorder; heritability; item-factor model; twins
Severity is an important characteristic of major depression (MD) and an ‘episode specifier’ in DSM-IV classifying depressive episodes as ‘mild’, ‘moderate’ or ‘severe’. These severity subtypes rely on three different measures of severity: number of criteria symptoms, severity of the symptoms and degree of functional disability. No prior empirical study has evaluated the coherence and validity of the DSM-IV definition of severity of MD.
In a sample of 1015 (518 males, 497 females) Caucasian twins from a population-based registry who met criteria for MD in the year prior to interview, factor analysis and logistic regression were conducted to examine the inter-relationships of the three severity measures and their associations with a wide range of potential validators including demographic factors, risk for future episodes, risk of MD in the co-twin, characteristics of the depressive episode, the pattern of co-morbidity, and personality traits.
Correlations between the three severity measures were significant but moderate. Factor analysis indicated the existence of a general severity factor, but the factor was not highly coherent. The three severity measures showed differential predictive ability for most of the validators.
Severity of MD as defined by the DSM-IV is a multifaceted and heterogeneous construct. The three proposed severity measures reflect partly overlapping but partly independent domains with differential validity as assessed by a wide range of clinical characteristics. Clinicians should probably use a combination of severity measures as proposed in DSM-IV rather than privileging one.
DSM-IV; major depression; psychiatric diagnosis; severity
The DSM-IV symptomatic criteria for major depression (MD) derive primarily from clinical experience with modest empirical support.
The sample studied included 1015 (518 males, 497 females) Caucasian twins from a population-based registry who met criteria for MD in the year prior to the interview. Logistic regression analyses were conducted to compare the associations of: (1) single symptomatic criterion, (2) two groups of criteria reflecting cognitive and neurovegetative symptoms, with a wide range of potential validators including demographic factors, risk for future episodes, risk of MD in the co-twin, characteristics of the depressive episode, the pattern of co-morbidity and personality traits.
The individual symptomatic criteria showed widely varying associations with the pattern of co-morbidity, personality traits, features of the depressive episode and demographic characteristics. When examined separately, these two criteria groups showed robust differences in their patterns of association, with the validators with the cognitive criteria generally producing stronger associations than the neurovegetative.
Among depressed individuals, individual DSM-IV symptomatic criteria differ substantially in their predictive relationship with a range of clinical validators. These results challenge the equivalence assumption for the symptomatic criteria for MD and suggest a more than expected degree of ‘ covert ’ heterogeneity among these criteria. Part of this heterogeneity is captured by the distinction between cognitive versus neurovegetative symptoms, with cognitive symptoms being more strongly associated with most clinically relevant characteristics. Detailed psychometric evaluation of DSM-IV criteria is overdue.
Criteria symptoms; DSM-IV; heterogeneity; major depression; psychiatric diagnosis
Major depressive disorder (MDD) co-occurs frequently with personality disorders (PDs). The extent to which this results from shared genetic or environmental risk factors remains uncertain.
Young adult twins (n=2801) from the population-based Norwegian Institute of Public Health Twin Panel were assessed at personal interview for DSM-IV lifetime MDD and the 10 Axis II PDs. The relationship between MDD and dimensional representations of all PDs was explored by stepwise logistic regression. Multivariate Cholesky twin models were fitted using the Mx program, and genetic and environmental correlations were estimated.
Dimensional representations of borderline (BPD), avoidant (AVPD) and paranoid personality disorder (PPD) were independently and significantly associated with increased risk for MDD. Multivariate twin modeling indicated that one latent factor accounted for the genetic covariance between MDD and the three PDs. The genetic correlations between MDD and dimensional representations of BPD, AVPD and PPD were +0.56, +0.22 and +0.40 respectively. No sex differences or shared environmental effects were found. The structure of the individual-specific environmental factors influencing MDD and the three PDs were similar to the genetic factors but the environmental correlations were lower: +0.39, +0.23 and +0.27 respectively.
There is substantial overlap between liability factors for MDD and BPD from cluster B, PPD from cluster A and AVPD from cluster C. The vulnerability to general PD pathology and MDD seem to be closely related. The patterns of co-morbidity observed between diverse psychiatric disorders might result from just a few liability factors.
Borderline personality disorder; depression; genetics; personality disorders; twin studies
Twin studies have suggested that additive genetic factors significantly contribute to liability to bulimia nervosa (BN). However, the diagnostic criteria for BN remain controversial. In this study, an item-factor model was used to examine the BN diagnostic criteria and the genetic and environmental contributions to BN in a population-based twin sample. The validity of the equal environment assumption (EEA) for BN was also tested.
Participants were 1024 female twins (MZ n=614, DZ n=410) from the population-based Mid-Atlantic Twin Registry. BN was assessed using symptom-level (self-report) items consistent with DSM-IV and ICD-10 diagnostic criteria. Items assessing BN were included in an item-factor model. The EEA was measured by items assessing similarity of childhood and adolescent environment, which have demonstrated construct validity. Scores on the EEA factor were used to specify the degree to which twins shared environmental experiences in this model.
The EEA was not violated for BN. Modeling results indicated that the majority of the variance in BN was due to additive genetic factors. There was substantial variability in additive genetic and environmental contributions to specific BN symptoms. Most notably, vomiting was very strongly influenced by additive genetic factors, while other symptoms were much less heritable, including the influence of weight on self-evaluation. These results highlight the importance of assessing eating disorders at the symptom level.
Refinement of eating disorder phenotypes could ultimately lead to improvements in treatment and targeted prevention, by clarifying sources of variation for specific components of symptomatology.
Bulimia nervosa; heritability; item-factor model; twins
Whether avoidant personality disorder symptoms are related to neurocognitive impairments that aggregate in relatives of schizophrenics is unknown. We report the relationship between avoidant personality disorder symptoms and neurocognitive performance in the first-degree relatives of probands with schizophrenia.
367 first degree relatives of probands with schizophrenia and 245 relatives of community controls were interviewed for the presence of avoidant personality symptoms and symptoms of paranoid and schizotypal personality disorders and administered neurocognitive measures. Relationships between neurocognitive measures and avoidant symptoms were analyzed using linear mixed models.
Avoidant dimensional scores predicted performance on the span of apprehension (SPAN), 3–7 Continuous Performance Test (3–7 CPT), and Trail Making Test (TMT-B) in schizophrenia relatives. These relationships remained significant on the SPAN even after adjustment for paranoid or schizoptypal dimensional scores and on the TMT-B after adjustment for paranoid dimensional scores. Moreover, in a second set of analyses comparing schizophrenia relatives to controls there were significant or trending differences in the degree of the relationship between avoidant symptoms and each of these neurocognitive measures even after adjustments for paranoid and schizotypal dimensional scores. The substantial correlation between avoidant and schizotypal symptoms suggests that these personality disorders are not independent.
Avoidant and in some cases schizotypal dimensional scores are significant predictors of variability in these neurocognitive measures. In all analyses, higher levels of avoidant symptoms were associated with worse performance on the neurocognitive measures in relatives of schizophrenia probands. These results support the hypothesis that avoidant personality disorder may be a schizophrenia spectrum phenotype.
Avoidant Personality Disorder; Schizotypal Personality Disorder; Schizophrenia; Genetics; Paranoid Personality Disorder; Neurocognition
SNAP25 occurs on chromosome 20p12.2, which has been linked to schizophrenia in some samples, and recently linked to latent classes of psychotic illness in our sample. SNAP25 is crucial to synaptic functioning, may be involved in axonal growth and dendritic sprouting, and its expression may be decreased in schizophrenia. We genotyped 18 haplotype-tagging SNPs in SNAP25 in a sample of 270 Irish high-density families. Single marker and haplotype analyses were performed in FBAT and PDT. We adjusted for multiple testing by computing q values. Association was followed up in an independent sample of 657 cases and 411 controls. We tested for allelic effects on the clinical phenotype by using the method of sequential addition and 5 factor-derived scores of the OPCRIT. Nine of 18 SNPs had P values <0.05 in either FBAT or PDT for one or more definitions of illness. Several two-marker haplotypes were also associated. Subjects inheriting the risk alleles of the most significantly associated two-marker haplotype were likely to have higher levels of hallucinations and delusions. The most significantly associated marker, rs6039820, was observed to perturb 12 transcription-factor binding sites in in silico analyses. An attempt to replicate association findings in the case–control sample resulted in no SNPs being significantly associated. We observed robust association in both single marker and haplotype-based analyses between SNAP25 and schizophrenia in an Irish family sample. Although we failed to replicate this in an independent sample, this gene should be further tested in other samples.
schizophrenia; SNAP25; polymorphism; association; clinical features
This essay, which seeks to provide an historical framework for our efforts to develop a scientific psychiatric nosology, begins by reviewing the classificatory approaches that arose in the early history of biological taxonomy. Initial attempts at species definition used top-down approaches advocated by experts and based on a few essential features of the organism chosen a priori. This approach was subsequently rejected on both conceptual and practical grounds and replaced by bottom-up approaches making use of a much wider array of features. Multiple parallels exist between the beginnings of biological taxonomy and psychiatric nosology. Like biological taxonomy, psychiatric nosology largely began with ‘expert’ classifications, typically influenced by a few essential features, articulated by one or more great 19th-century diagnosticians. Like biology, psychiatry is struggling toward more soundly based bottom-up approaches using diverse illness characteristics. The underemphasized historically contingent nature of our current psychiatric classification is illustrated by recounting the history of how ‘Schneiderian’ symptoms of schizophrenia entered into DSM-III. Given these historical contingencies, it is vital that our psychiatric nosologic enterprise be cumulative. This can be best achieved through a process of epistemic iteration. If we can develop a stable consensus in our theoretical orientation toward psychiatric illness, we can apply this approach, which has one crucial virtue. Regardless of the starting point, if each iteration (or revision) improves the performance of the nosology, the eventual success of the nosologic process, to optimally reflect the complex reality of psychiatric illness, is assured.
DSM; philosophy of science; psychiatric nosology; Schneiderian symptoms
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.
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.
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.
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.
DSM-IV borderline criteria; item analyses; measurement invariance
The serotonin neurotransmitter system in general, and the serotonin 1A receptor in particular, has been broadly implicated in the pathophysiology of mood and anxiety disorders, although the results of genetic association studies have been mixed. In this study, we examined the serotonin 1A receptor gene, HTR1A, for its association with shared genetic risk across a range of anxiety and depression-related phenotypes. Using multivariate structural equation modeling, we selected twin pairs from the population-based Virginia Adult Twin Study of Psychiatric and Substance Use Disorders scoring at the extremes of a latent genetic risk factor that underlies susceptibility to neuroticism, major depression, and several anxiety disorders. One member from each selected pair was entered into a 2-stage, case-control association study for the HTR1A gene. In the resulting sample of 589 cases and 539 controls, four SNPs spanning the HTR1A locus, including the C(−1019)G functional promoter polymorphism (rs6295), were screened in stage 1, the positive results of which were tested for replication in stage 2. While one marker met threshold significance criteria in stage 1, this association was not replicated in stage 2. Post-hoc analyses did not reveal association to any of the specific psychiatric phenotypes. Our data suggests that the HTR1A gene may not play a major role in the genetic susceptibility underlying depressive and anxiety-related phenotypes.
serotonin; depression; anxiety; personality; association study; genetics
Little is known about the pattern of genetic and environmental influences on symptoms of anxiety and depression (SxAnxDep) from childhood to early adulthood.
Parental- and self-reported levels of SxAnxDep were assessed at ages 8–9, 13–14, 16–17 and 19–20 years in 2508 twins from the Swedish Twin Study of Child and Adolescent Development (TCHAD). Analysis conducted using the Mx program included SxAnxDep by parental and self-report.
The best-fit model revealed one genetic risk factor for SxAnxDep acting at ages 8–9, 13–14, 16–17 and 19–20, and new sets of genetic risk factors ‘coming on line’ in early adolescence, late adolescence and early adulthood. Together, these genetic factors were very strong influences on the levels of SxAnxDep reported in common by parents and twins with heritability estimates, correcting for rater- and time-specific effects, ranging from 72% to 89%. The first genetic factor, which accounted for 72% of the variance in SxAnxDep at ages 8–9, attenuated sharply in influence, accounting for only 12% of the variance by ages 19–20. No evidence was found for shared environmental influences. Although not statistically significant, the correlation between genetic risk factors for SxAnxDep in males and females declined with advancing age.
Genetic effects on SxAnxDep are developmentally dynamic from middle childhood to young adulthood, demonstrating both genetic innovation and genetic attenuation. The attenuation might explain the low levels of continuity observed for anxiety and depressive disorders from childhood to adulthood. Differences in genetic risk factors for SxAnxDep in males and females may increase during development.
Anxiety; depression; development; genetic effects; twins
Structural magnetic resonance imaging data from 308 twins, 64 singleton siblings of twins, and 228 singletons were analyzed using structural equation modeling and selected multivariate methods to identify genetically mediated intracortical associations. Principal components analyses (PCA) of the genetic correlation matrix indicated a single factor accounting for over 60% of the genetic variability in cortical thickness. When covaried for mean global cortical thickness, PCA, cluster analyses, and graph models identified genetically mediated fronto-parietal and occipital networks. Graph theoretical models suggest that the observed genetically mediated relationships follow small world architectural rules. These findings are largely concordant with other multivariate studies of brain structure and function, the twin literature, and current understanding on the role of genes in cortical neurodevelopment.
child development; genetics; neuroanatomy; small world
It is unresolved whether avoidant personality disorder (APD) is an independent schizophrenia (Sz)-spectrum personality disorder (PD). Some studies find APD and social anxiety symptoms (Sxs) to be a separable dimension of psychopathology in relatives (Rels) of schizophrenics while other studies find avoidant Sxs to be correlated with schizotypal and paranoid Sxs.
Rates of APD among first degree Rels of Sz probands, attention-deficit/hyperactivity disorder (ADHD) probands, and community control (CC) probands were examined. Further analyses examined rates when controlling for the presence of schizotypal (SPD) and paranoid (PPD) personality disorders, differences in APD Sxs between relative groups, and whether APD in Rels of Szs reflects a near miss for another Sz-spectrum PD.
362 first degree Rels of Sz probands, 201 relatives of ADHD probands, and 245 Rels of CC probands were interviewed for the presence of DSM-III-R Axis I and II disorders. Diagnoses, integrating family history, interview information, and medical records, were determined.
APD occurred more frequently in Rels of Sz probands compared to CC probands (p<.001) and also when controlling for SPD and PPD (p<.005). Two Sxs of APD were most characteristic of the Rels of Sz probands: “avoids social or occupational activities…” and “exaggerates the potential difficulties…” 65% of the Rels of Sz probands who had diagnoses of APD were more than one criterion short of a DSM-III-R diagnosis of either SPD or PPD. This indicates that APD is a separate Sz-spectrum disorder, and not merely a sub-clinical form of SPD or PPD.
Avoidant Personality Disorder; Schizotypal Personality Disorder; Schizophrenia; Genetics; Paranoid Personality Disorder; Family Study
Studies in Western countries have repeatedly shown that women with a history of childhood sexual abuse (CSA) are at increased risk for developing major depression (MD). Would this relationship be found in China?
Three levels of CSA (non-genital, genital, and intercourse) were assessed by self-report in two groups of Han Chinese women: 1970 clinically ascertained with recurrent MD and 2597 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression and regression coefficients by linear or Poisson regression.
Any form of CSA was significantly associated with recurrent MD [OR 3.26, 95% confidence interval (CI) 1.95–5.45]. This association strengthened with increasing CSA severity: non-genital (OR 2.47, 95% CI 1.17–5.23), genital (OR 2.77, 95% CI 1.32–5.83) and intercourse (OR 13.35, 95% CI 1.83–97.42). The association between any form of CSA and MD remained significant after accounting for parental history of depression, childhood emotional neglect (CEN), childhood physical abuse (CPA) and parent–child relationship. Among the depressed women, those with CSA had an earlier age of onset, longer depressive episodes and an increased risk for generalized anxiety disorder (GAD; OR 1.92, 95% CI 1.39–2.66) and dysthymia (OR 2.16, 95% CI 1.52–3.09).
In Chinese women CSA is strongly associated with MD and this association increases with greater severity of CSA. Depressed women with CSA have an earlier age of onset, longer depressive episodes and increased co-morbidity with GAD and dysthymia. Although reporting biases cannot be ruled out, our results are consistent with the hypothesis that, as in Western countries, CSA substantially increases the risk for MD in China.
Childhood sexual abuse; co-morbidity; major depression