Liability Factors Research Articles

Cognition and social cognition in non-psychotic siblings of patients with schizophrenia

Introduction. Deficits in Social Cognition are common in people with schizophrenia. However, it is not clear if these deficits are a vulnerability marker and whether they are independent to cognitive difficulties. This study investigates these two issues in individuals with a genetic liability to psychosis.Methods. Twenty-one healthy siblings of patients with schizophrenia were compared with 21 healthy individuals on a range of cognitive and social cognitive measures. Significant differences in cognitive domains were controlled for when comparing the two groups on measures of social cognition.Results. Siblings of people with schizophrenia performed significantly worst on tests of theory of mind and social perception but not on affect recognition. Scores on tests of executive function, processing speed and general IQ were also lower in the sibling group. When controlled for differences in cognitive tests, the two groups still retained significant differences in theory of mind and social perception. However, executive function significantly contributed to theory of mind and processing speed to social perception differences.Conclusions. These results further suggest that difficulties in some domains of social cognition are associated with a genetic vulnerability for schizophrenia. In these areas, cognitive difficulties account only partially for social cognition problems suggesting that these two domains may represent relatively independent liability factors.

SWI/SNF chromatin remodeling regulates alcohol response behaviors in Caenorhabditis elegans and is associated with alcohol dependence in humans

Alcohol abuse is a widespread and serious problem. Understanding the factors that influence the likelihood of abuse is important for the development of effective therapies. There are both genetic and environmental influences on the development of abuse, but it has been difficult to identify specific liability factors, in part because of both the complex genetic architecture of liability and the influences of environmental stimuli on the expression of that genetic liability. Epigenetic modification of gene expression can underlie both genetic and environmentally sensitive variation in expression, and epigenetic regulation has been implicated in the progression to addiction. Here, we identify a role for the switching defective/sucrose nonfermenting (SWI/SNF) chromatin-remodeling complex in regulating the behavioral response to alcohol in the nematode Caenorhabditis elegans. We found that SWI/SNF components are required in adults for the normal behavioral response to ethanol and that different SWI/SNF complexes regulate different aspects of the acute response to ethanol. We showed that the SWI/SNF subunits SWSN-9 and SWSN-7 are required in neurons and muscle for the development of acute functional tolerance to ethanol. Examination of the members of the SWI/SNF complex for association with a diagnosis of alcohol dependence in a human population identified allelic variation in a member of the SWI/SNF complex, suggesting that variation in the regulation of SWI/SNF targets may influence the propensity to develop abuse disorders. Together, these data strongly implicate the chromatin remodeling associated with SWI/SNF complex members in the behavioral responses to alcohol across phyla.

Hippocampal dysfunction during declarative memory encoding in schizophrenia and effects of genetic liability

Declarative memory (DM) impairments are reported in schizophrenia and in unaffected biological relatives of patients. However, the neural correlates of successful and unsuccessful encoding, mediated by the medial temporal lobe (MTL) memory system, and the influence of disease-related genetic liability remain under explored. This study employed an event-related functional MRI paradigm to compare activations for successfully and unsuccessfully encoded associative face-name stimuli between 26 schizophrenia patients (mean age: 33, 19m/7f), 30 controls (mean age: 29, 24m/6f), and 14 unaffected relatives of patients (mean age: 40, 5m/9f). Compared to controls or unaffected relatives, patients showed hyper-activations in ventral visual stream and temporo-parietal cortical association areas when contrasting successfully encoded events to fixation. Follow-up hippocampal regions-of-interest analysis revealed schizophrenia-related hyper-activations in the right anterior hippocampus during successful encoding; contrasting successful versus unsuccessful events produced schizophrenia-related hypo-activations in the left anterior hippocampus. Similar hippocampal hypo-activations were observed in unaffected relatives during successful versus unsuccessful encoding. Post hoc analyses of hippocampal volume showed reductions in patients, but not in unaffected relatives compared to controls. Findings suggest that DM encoding deficits are attributable to both disease-specific and genetic liability factors that impact different components of the MTL memory system. Hyper-activations in temporo-occipital and parietal regions observed only in patients suggest the influence of disease-related factors. Regional hyper- and hypo-activations attributable to successful encoding occurring in both patients and unaffected relatives suggest the influence of schizophrenia-related genetic liability factors.

Electronic cigarette effectiveness and abuse liability: predicting and regulating nicotine flux.

Electronic cigarettes (ECIGs) comprise an aerosolized nicotine delivery product category that provides consumers with probably unprecedented control over extensive features and operating conditions, allowing a wide range of nicotine yields to be obtained. Depending on the combination of such ECIG variables as electrical power input, geometry, liquid composition, and puff behavior, ECIG users can extract in a few puffs far more or far less nicotine than with a conventional combustible cigarette. These features of ECIG design and use present challenges for public health policy, central among which is the question of how to regulate nicotine delivery. In this commentary, we propose a conceptual framework intended to provide a convenient approach for evaluating and regulating the nicotine emitted from ECIGs. This framework employs nicotine flux to account for the total dose and rate at which nicotine reaches the user, 2 key factors in drug abuse liability. The nicotine flux is the nicotine emitted per puff second (e.g., mg/s) by a given ECIG design under given use conditions, and it can be predicted accurately using physical principles. We speculate that if the flux is too low, users likely will abandon the device and maintain conventional tobacco product use. Also, we speculate that if the flux is too high, individuals may suffer toxic side effects and/or the device may have higher-than-necessary abuse liability. By considering ECIG design, operation conditions, liquid composition, and puff behavior variables in combination, we illustrate how ECIG specifications can be realistically mandated to result in a target flux range.

The Structure of Genetic and Environmental Risk Factors for Dimensional Representations ofDSM-5Obsessive-Compulsive Spectrum Disorders

The new DSM-5 "Obsessive-Compulsive and Related Disorders" chapter contains a series of conditions thought to be etiologically related to obsessive-compulsive disorder (OCD). However, the evidence to support this relatedness remains incomplete. To estimate the degree to which genetic and environmental risk factors are shared and/or unique to dimensionally scored OCD, body dysmorphic disorder (BDD), hoarding disorder (HD), trichotillomania (hair-pulling disorder) (TTM), and excoriation (skin-picking) disorder (SPD). Multivariate twin modeling methods involving 5409 female members of the TwinsUK adult population-based twin register. Scores on the Obsessive-Compulsive Inventory-Revised, the Dysmorphic Concern Questionnaire, the Hoarding Rating Scale, the Massachusetts General Hospital Hairpulling Scale, and the Skin Picking Scale. A 2-latent factor common pathway model fitted the data best; the first latent factor loaded on all 5 phenotypes, particularly on OCD, BDD, and HD. A second factor loaded exclusively on TTM and SPD. Disorder-specific genetic (for OCD, BDD, and HD only) and particularly nonshared environmental risk factors were also evident. Shared environmental influences were negligible. Obsessive-compulsive and related disorders may be influenced by 2 distinct liability factors rather than a single liability factor. One of these factors was common to all disorders, and another was exclusive to TTM and SPD. Disorder-specific genetic factors unique to OCD, BDD, and HD were also apparent, whereas TTM and SPD were largely influenced by the same latent genetic factor. Environmental influences were largely disorder specific. The results help explain the apparent similarities as well as some important differences between the disorders included in the new Obsessive-Compulsive and Related Disorders chapter.

The contribution of familial internalizing and externalizing liability factors to borderline personality disorder

Individuals with borderline personality disorder (BPD) frequently display co-morbid mental disorders. These disorders include 'internalizing' disorders (such as major depressive disorder and anxiety disorders) and 'externalizing' disorders (such as substance use disorders and antisocial personality disorder). It is hypothesized that these disorders may arise from latent 'internalizing' and 'externalizing' liability factors. Factor analytic studies suggest that internalizing and externalizing factors both contribute to BPD, but the extent to which such contributions are familial is unknown. Participants were 368 probands (132 with BPD; 134 without BPD; and 102 with major depressive disorder) and 885 siblings and parents of probands. Participants were administered the Diagnostic Interview for DSM-IV Personality Disorders, the Revised Diagnostic Interview for Borderlines, and the Structured Clinical Interview for DSM-IV. On confirmatory factor analysis of within-person associations of disorders, BPD loaded moderately on internalizing (factor loading 0.53, S.E. = 0.10, p < 0.001) and externalizing latent variables (0.48, S.E. = 0.10, p < 0.001). Within-family associations were assessed using structural equation models of familial and non-familial factors for BPD, internalizing disorders, and externalizing disorders. In a Cholesky decomposition model, 84% (S.E. = 17%, p < 0.001) of the association of BPD with internalizing and externalizing factors was accounted for by familial contributions. Familial internalizing and externalizing liability factors are both associated with, and therefore may mutually contribute to, BPD. These familial contributions account largely for the pattern of co-morbidity between BPD and internalizing and externalizing disorders.

Structure of Genetic and Environmental Risk Factors for Symptoms ofDSM-IVBorderline Personality Disorder

Previous studies have indicated that the psychopathological dimensions of borderline personality disorder (BPD) are influenced by a unitary liability factor. However, to our knowledge, the underlying etiological nature of the individual criteria for BPD as defined by the DSM-IV has not been explored. To determine the structure of genetic and environmental risk factors for the symptoms of BPD. Multivariate twin study with BPD criteria assessed by personal interview within a general community setting. Participants included 2794 young adults from the Norwegian Institute of Public Health Twin Panel. The 9 criteria for BPD assessed by the Structured Interview for DSM-IV Personality. A common pathway model dominated by 1 highly heritable (55%) general BPD factor that strongly influenced all 9 BPD criteria (standardized path coefficients, 0.53-0.79) fit the data best. The model also included 2 additional common liability factors, mainly influencing criteria reflecting the affective and interpersonal dimensions. Both of these were mostly influenced by environmental liability factors (heritability, 29.3% and 2.2%). With 1 exception (criterion 2, unstable and intense relationships), the specific criteria were strongly influenced by environmental factors. Five of the 9 criterion-specific genetic effects were either 0 or negligible. These results indicate that most of the genetic effects on the individual BPD criteria derive from 1 highly heritable general BPD factor, whereas the environmental influences were mostly criterion specific.

Synergism Between a Serotonin 5-HT2A Receptor (5-HT2AR) Antagonist and 5-HT2CR Agonist Suggests New Pharmacotherapeutics for Cocaine Addiction

Relapse to cocaine dependence, even after extended abstinence, involves a number of liability factors including impulsivity (predisposition toward rapid, unplanned reactions to stimuli without regard to negative consequences) and cue reactivity (sensitivity to cues associated with cocaine-taking which can promote cocaine-seeking). These factors have been mechanistically linked to serotonin (5-hydroxytryptamine, 5-HT) signaling through the 5-HT(2A) receptor (5-HT(2A)R) and 5-HT(2C)R; either a selective 5-HT(2A)R antagonist or a 5-HT(2C)R agonist suppresses impulsivity and cocaine-seeking in preclinical models. We conducted proof-of-concept analyses to evaluate whether a combination of 5-HT(2A)R antagonist plus 5-HT(2C)R agonist would have synergistic effects over these liability factors for relapse as measured in a 1-choice serial reaction time task and cocaine self-administration/reinstatement assay. Combined administration of a dose of the selective 5-HT(2A)R antagonist M100907 plus the 5-HT(2C)R agonist WAY163909, each ineffective alone, synergistically suppressed cocaine-induced hyperactivity, inherent and cocaine-evoked impulsive action, as well as cue- and cocaine-primed reinstatement of cocaine-seeking behavior. The identification of synergism between a 5-HT(2A)R antagonist plus a 5-HT(2C)R agonist to attenuate these factors important in relapse indicates the promise of a bifunctional ligand as an anti-addiction pharmacotherapeutic, setting the stage to develop new ligands with improved efficacy, potency, selectivity, and in vivo profiles over the individual molecules.

Updating the mild encephalitis hypothesis of schizophrenia

Schizophrenia seems to be a heterogeneous disorder. Emerging evidence indicates that low level neuroinflammation (LLNI) may not occur infrequently. Many infectious agents with low overall pathogenicity are risk factors for psychoses including schizophrenia and for autoimmune disorders. According to the mild encephalitis (ME) hypothesis, LLNI represents the core pathogenetic mechanism in a schizophrenia subgroup that has syndromal overlap with other psychiatric disorders. ME may be triggered by infections, autoimmunity, toxicity, or trauma. A 'late hit' and gene-environment interaction are required to explain major findings about schizophrenia, and both aspects would be consistent with the ME hypothesis. Schizophrenia risk genes stay rather constant within populations despite a resulting low number of progeny; this may result from advantages associated with risk genes, e.g., an improved immune response, which may act protectively within changing environments, although they are associated with the disadvantage of increased susceptibility to psychotic disorders. Specific schizophrenic symptoms may arise with instances of LLNI when certain brain functional systems are involved, in addition to being shaped by pre-existing liability factors. Prodrome phase and the transition to a diseased status may be related to LLNI processes emerging and varying over time. The variability in the course of schizophrenia resembles the varying courses of autoimmune disorders, which result from three required factors: genes, the environment, and the immune system. Preliminary criteria for subgrouping neurodevelopmental, genetic, ME, and other types of schizophrenias are provided. A rare example of ME schizophrenia may be observed in Borna disease virus infection. Neurodevelopmental schizophrenia due to early infections has been estimated by others to explain approximately 30% of cases, but the underlying pathomechanisms of transition to disease remain in question. LLNI (e.g. from reactivation related to persistent infection) may be involved and other pathomechanisms including dysfunction of the blood-brain barrier or the blood-CSF barrier, CNS-endogenous immunity and the volume transmission mode balancing wiring transmission (the latter represented mainly by synaptic transmission, which is often described as being disturbed in schizophrenia). Volume transmission is linked to CSF signaling; and together could represent a common pathogenetic link for the distributed brain dysfunction, dysconnectivity, and brain structural abnormalities observed in schizophrenia. In addition, CSF signaling may extend into peripheral tissues via the CSF outflow pathway along brain nerves and peripheral nerves, and it may explain the peripheral topology of neuronal dysfunctions found, like in olfactory dysfunction, dysautonomia, and even in peripheral tissues, i.e., the muscle lesions that were found in 50% of cases. Modulating factors in schizophrenia, such as stress, hormones, and diet, are also modulating factors in the immune response. Considering recent investigations of CSF, the ME schizophrenia subgroup may constitute approximately 40% of cases.

A Population-Based Study of Familial and Individual-Specific Environmental Contributions to Traumatic Event Exposure and Posttraumatic Stress Disorder Symptoms in a Norwegian Twin Sample

Posttraumatic stress disorder (PTSD) is one of the only disorders in the Diagnostic and Statistical Manual of Mental Disorders that requires an environmental exposure. The relationship between liability factors for trauma exposure and those for PTSD symptoms following exposure are unclear. Exposure to a trauma and resulting PTSD symptoms were assessed in a sample of 2,794 members of the Norwegian Institute of Public Health Twin Panel. In the full sample, 737 twins experienced a trauma. A modified causal, contingent, common pathway model was used to examine trauma exposure and liability for PTSD. Genetic and common environmental factors could not be distinguished, so a model that included only familial and individual specific components was fit. The best-fitting model suggested that familial factors played an important role in liability for trauma exposure and for resulting PTSD symptoms, and that there was a modest transmission between trauma exposure and subsequent PTSD symptoms. One third of the variance in liability of PTSD symptoms is due to familial factors, and of this, approximately one fifth overlaps with the familial liability for trauma exposure while the other four fifths of the variance is specific to the risk of PTSD symptoms following exposure. The hypothesis that PTSD is etiologically similar to exposures to a traumatic event is not supported, suggesting that the factors that confer risk for trauma do not overlap completely with those that confer risk for PTSD.

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

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

The structure of genetic and environmental risk factors for phobias in women

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.

Tort Liability Law of the People's Republic of China

The book provides a comprehensive analysis of the Tort Liability Law of the People's Republic of China (GdH). For many years, Chinese Tort Law has been a controversial issue among Chinese legal scholars. This book examines the status quo of the discourse in the literature and provides specific illustrations of how general Tort principles such as causation, negligence and damages are applied in Chinese courts. Since the availability of Chinese case law is limited and many opinions lack reasoning, the book analyses representative cases to provide a basic understanding of how Tort Law functions within the Chinese legal system.This book has seven chapters. First (chapter A), this book presents an overview of the GdH in context of the civil law reform of China and summarizes the most important disputes within the legislative procedure. Second (chapter B), the book addresses the conflicts between the GdH and the General Principles of Civil Law in the PR China and special tort laws. Third (chapter C), the book examines in detail the scope of GdH’s protection. In this chapter, 'General Principles' such as causation, justification, intention/negligence and damages are discussed. In addition, this chapter presents the concept of the joint and several liability factors that reduce and eliminate liability and general injunctive relief. To conclude the general part of the book, questions concerning the burden of proof and the limitation of liability are discussed due to their importance in court proceedings. To follow the general part of the book, chapter D introduces the general liability clauses. Chapter E analyses the liability of special legal persons and individuals. Part E of this book provides an overview concerning product liability, liability for traffic accidents, liability for medical malpractice, environmental liability, liability for high risks, liability for animals and liability for special items. The book concludes with a discussion of the overarching themes of Chinese Tort Law that emerge from the above analysis.

The genetic epidemiology of personality disorders

Genetic epidemiologic studies indicate that all ten personality disorders (PDs) classified on the DSM-IV axis II are modestly to moderately heritable. Shared environmental and nonadditive genetic factors are of minor or no importance. No sex differences have been identified, Multivariate studies suggest that the extensive comorbidity between the PDs can be explained by three common genetic and environmental risk factors. The genetic factors do not reflect the DSM-IV cluster structure, but rather: i) broad vulnerability to PD pathology or negative emotionality; ii) high impulsivity/low agreeableness; and iii) introversion. Common genetic and environmental liability factors contribute to comorbidity between pairs or clusters of axis I and axis II disorders. Molecular genetic studies of PDs, mostly candidate gene association studies, indicate that genes linked to neurotransmitter pathways, especially in the serotonergic and dopaminergic systems, are involved. Future studies, using newer methods like genome-wide association, might take advantage of the use of endophenotypes.

Major depression and dimensional representations of DSM-IV personality disorders: a population-based twin study

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.

Factors associated with dropout from treatment for eating disorders: a comprehensive literature review

BackgroundDropout (DO) is common in the treatment of eating disorders (EDs), but the reasons for this phenomenon remain unclear. This study is an extensive review of the literature regarding DO predictors in EDs.MethodsAll papers in PubMed, PsycINFO and Cochrane Library (1980-2009) were considered. Methodological issues and detailed results were analysed for each paper. After selection according to inclusion criteria, 26 studies were reviewed.ResultsThe dropout rates ranged from 20.2% to 51% (inpatient) and from 29% to 73% (outpatient). Predictors of dropout were inconsistent due to methodological flaws and limited sample sizes. There is no evidence that baseline ED clinical severity, psychiatric comorbidity or treatment issues affect dropout. The most consistent predictor is the binge-purging subtype of anorexia nervosa. Good evidence exists that two psychological traits (high maturity fear and impulsivity) and two personality dimensions (low self-directedness, low cooperativeness) are related to dropout.ConclusionImplications for clinical practice and areas for further research are discussed. Particularly, these results highlight the need for a shared definition of dropout in the treatment of eating disorders for both inpatient and outpatient settings. Moreover, the assessment of personality dimensions (impulse control, self-efficacy, maturity fear and others) as liability factors for dropout seems an important issue for creating specific strategies to reduce the dropout phenomenon in eating disorders.

Decanalization and the origin of complex disease

Complex genetic disease is caused by the interaction between genetic and environmental variables and is the predominant cause of mortality globally. Recognition that susceptibility arises through the combination of multiple genetic pathways that influence liability factors in a nonlinear manner suggests that a process of 'decanalization' contributes to the epidemic nature of common genetic diseases. The rapid evolution of the human genome combined with marked environmental and cultural perturbation in the past two generations might lead to the uncovering of cryptic genetic variation that is a major source of disease susceptibility.

Early detection and intervention of psychosis. A review

The vulnerability and hybrid models for the onset of psychosis are presented. Familial liability, perinatal and developmental factors, and decreased cognitive performance associate with psychosis in adolescence and young adulthood. Genetic predisposition connected with behavioural deviances and/or mental symptoms associate with psychotic development so strongly that monitoring and intervention are indicated. Especially, in families where one or both parents or other family members are severely mentally ill, early family-centred assessments and interventions is needed. Together with familial psychosis, deficits in adolescent and young adult social development indicate thorough assessment, intensive monitoring and often also preventive interventions. During the prodromal phase of psychosis, patients often display unspecific symptoms, such as anxiety and depression, personality disorders, abuse of alcohol or drugs. Social decline, possibly associated with neurocognitive deficits, frequently occurs in the prodromal phase or in the early course of schizophrenia. Among help-seeking patients, occurrence of the Basic Symptoms represent the early initial prodromal state, while the late initial prodome state includes attenuated psychotic symptoms, brief limited intermittent psychotic symptoms, and a first degree relative with psychotic disorder, or a schizotypal personality disorder, together with decrease global functioning. These patients suffer also from other mental symptoms and functional decline, and are clearly in need of psychiatric assessment and treatment. Intervention trials have shown that patients suffering from prodromal syndromes can be successfully treated, and onset of psychosis prevented or delayed. However, more large-scale studies and clinical case descriptions of treatment of patients with sub-threshold psychotic symptoms are needed.

The role of internalizing and externalizing liability factors in accounting for gender differences in the prevalence of common psychopathological syndromes

We hypothesized that gender differences in average levels on the internalizing and externalizing factors that account for co-morbidity among common psychopathological syndromes in both men and women account for gender differences in the prevalence of specific syndromes. The latent structure of 11 syndromes was examined in a middle-aged (mean age=52.66 years, s.d.=5.82) sample of 2992 (37% men) members of the community-based Minnesota Twin Registry (MTR) assessed using 10 scales of the Psychiatric Diagnostic Screening Questionnaire (PDSQ) and an adult antisocial behavior scale. Confirmatory factorial invariance models were applied to a best-fitting, internalizing-externalizing model. A 'strong gender invariance model' fit best, indicating that gender differences in the means of individual syndromes were well accounted for by gender differences in mean levels of internalizing and externalizing. Women exhibited higher mean levels of internalizing (d=0.23) and lower mean levels of externalizing (d=-0.52) than men. These findings suggest that risk factors for common mental disorders exhibiting gender differences may influence prevalence at the latent factor level. Future research may benefit from focusing on both the latent factor and individual syndrome levels in explaining gender differences in psychopathology.

Polymorphisms in dopamine receptor DRD1 and DRD2 genes and psychopathological and extrapyramidal symptoms in patients on long‐term antipsychotic treatment

DRD(1) and DRD(2) receptor gene variants have been associated with clinical aspects of schizophrenia; however only specific features were analyzed in different samples. To assess the complex interaction between genetic and clinical factors, we studied the possible cross-interactions between DRD1 and DRD2 dopamine receptor gene polymorphisms, symptomatology of schizophrenia and schizoaffective disorders, and the occurrence of treatment induced side effects taking into consideration possible clinical confounding variables. One hundred thirty one outpatients in stable remission meeting the DSMIV criteria for schizophrenia spectrum disorders and receiving long-term maintenance therapy with haloperidol, fluphenazine, zuclopenthixole, or risperidone were genotyped for DRD1 A-48G, DRD2 Ins-141CDel, and DRD2 Ser311Cys polymorphisms. Psychopathological symptoms were assessed with the positive and negative syndrome scale for schizophrenia (PANSS). Extrapyramidal side effects were assessed with the Simpson-Angus extrapyramidal side effects scale (EPS), the Barnes Akathisia scale (BARS), and the abnormal involuntary movement scale (AIMS). Drug dosage was included as covariant because it was associated with the severity of symptomatology, akathisia, and parkinsonism. No association was observed for DRD1 and DRD2 polymorphisms and extrapyramidal side effects, or with the other clinical variables considered. Our study suggests that DRD1 and DRD2 variants are not liability factors for tardive dyskinesia.