Global cross-cultural validation of a brief measure for identifying potential suicide risk in 42 countries.

OBJECTIVES: This study aimed to examine the psychometric properties of the P4 suicide screener in a multinational sample. The primary goal was to evaluate the reliability and validity of the scale and investigate its convergent validity by analyzing its correlation with depression, anxiety, and substance use. STUDY DESIGN: The study design is a cross-sectional self-report study conducted across 42 countries. METHODS: A cross-sectional, self-report study was conducted in 42 countries, with a total of 82,243 participants included in the final data set. RESULTS: The study provides an overview of suicide ideation rates across 42 countries and confirms the structural validity of the P4 screener. The findings indicated that sexual and gender minority individuals exhibited higher rates of suicidal ideation. The P4 screener showed adequate reliability, convergence, and discriminant validity, and a cutoff score of 1 is recommended to identify individuals at risk of suicidal behavior. CONCLUSIONS: The study supports the reliability and validity of the P4 suicide screener across 42 diverse countries, highlighting the importance of using a cross-cultural suicide risk assessment to standardize the identification of high-risk individuals and tailoring culturally sensitive suicide prevention strategies.

A translational approach to the genetics of anxiety disorders.

There have been important advances in our understanding of the genetic architecture of anxiety disorders. At the same time, relatively few genes have reached genome wide significance in anxiety disorders, and there is relatively little work on how exposure to an adverse environment impacts on gene expression in either animal models or human clinical populations. Here we assessed differential expression of genes of the dorsal striatum involved in synaptic transmission in an animal models of early adversity (maternal separation followed by restraint stress), and investigated whether variants in these genes were associated with risk for anxiety disorders, particularly in the presence of environmental stressors. Fifty-two male Sprague Dawley rats underwent maternal separation, and gene expression was studied using array technology. The human homologues of the differentially expressed genes were screened and analysed in a DSM-IV anxiety disorders cohort, and healthy controls (patients, n = 92; controls, n = 194), using blood. Two candidate genes (Mmp9 and Bdnf) were aberrantly expressed in the experimental rodent group relative to controls. Four single nucleotide polymorphisms (SNPs) in the human homologues of these genes were significantly associated with susceptibility for anxiety disorders (MMP9: rs3918242 and BDNF: rs6265, rs10835210 and rs11030107). Three of these (BDNF: rs6265, rs10835210, rs11030107) were found to interact significantly with childhood trauma severity resulting in increased likelihood of an anxiety disorder diagnosis. This study provides insights into the utility of rat models for identifying molecular candidates for anxiety disorders in humans.

Obsessive-compulsive disorder in the elderly: A report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS).

INTRODUCTION: Obsessive-compulsive disorder (OCD) is a highly disabling condition, with frequent early onset. Adult/adolescent OCD has been extensively investigated, but little is known about prevalence and clinical characterization of geriatric patients with OCD (G-OCD≥65years). The present study aimed to assess prevalence of G-OCD and associated socio-demographic and clinical correlates in a large international sample. METHODS: Data from 416 outpatients, participating in the ICOCS network, were assessed and categorized into 2 groups, age

Comorbidity, age of onset and suicidality in obsessive-compulsive disorder (OCD): An international collaboration.

OBJECTIVES: To collate data from multiple obsessive-compulsive disorder (OCD) treatment centers across seven countries and five continents, and to report findings in relation to OCD comorbidity, age of onset of OCD and comorbid disorders, and suicidality, in a large clinical and ethnically diverse sample, with the aim of investigating cultural variation and the utility of the psychiatric diagnostic classification of obsessive-compulsive and related disorders. METHODS: Researchers in the field of OCD were invited to contribute summary statistics on current and lifetime psychiatric comorbidity, age of onset of OCD and comorbid disorders and suicidality in their patients with OCD. RESULTS: Data from 3711 adult patients with primary OCD came from Brazil (n=955), India (n=802), Italy (n=750), South Africa (n=565), Japan (n=322), Australia (n=219), and Spain (n=98). The most common current comorbid disorders were major depressive disorder (28.4%; n=1055), obsessive-compulsive personality disorder (24.5%, n=478), generalized anxiety disorder (19.3%, n=716), specific phobia (19.2%, n=714) and social phobia (18.5%, n=686). Major depression was also the most commonly co-occurring lifetime diagnosis, with a rate of 50.5% (n=1874). OCD generally had an age of onset in late adolescence (mean=17.9years, SD=1.9). Social phobia, specific phobia and body dysmorphic disorder also had an early age of onset. Co-occurring major depressive disorder, generalized anxiety disorder and psychotic disorders tended to have a later age of onset than OCD. Suicidal ideation within the last month was reported by 6.4% (n=200) of patients with OCD and 9.0% (n=314) reported a lifetime history of suicide attempt. CONCLUSIONS: In this large cross-continental study, comorbidity in OCD was common. The high rates of comorbid major depression and anxiety disorders emphasize the need for clinicians to assess and monitor for these disorders. Earlier ages of onset of OCD, specific phobia and social phobia may indicate some relatedness between these disorders, but this requires further study. Although there do not appear to be significant cultural variations in rates or patterns of comorbidity and suicidality, further research using similar recruitment strategies and controlling for demographic and clinical variables may help to determine whether any sociocultural factors protect against suicidal ideation or psychiatric comorbidity in patients with OCD.

Modification of the association between early adversity and obsessive-compulsive disorder by polymorphisms in the MAOA, MAOB and COMT genes.

The monoamine oxidases (MAOA/B) and catechol-O-methyltransferase (COMT) enzymes break down regulatory components within serotonin and dopamine pathways, and polymorphisms within these genes are candidates for OCD susceptibility. Childhood trauma has been linked OCD psychopathology, but little attention has been paid to the interactions between genes and environment in OCD aetiology. This pilot study investigated gene-by-environment interactions between childhood trauma and polymorphisms in the MAOA, MAOB and COMT genes in OCD. Ten polymorphisms (MAOA: 3 variants, MAOB: 4 variants, COMT: 3 variants) were genotyped in a cohort of OCD patients and controls. Early-life trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Gene-by-gene (GxG) and gene-by-environment interactions (GxE) of the variants and childhood trauma were assessed using logistic regression models. Significant GxG interactions were found between rs362204 (COMT) and two independent polymorphisms in the MAOB gene (rs1799836 and rs6651806). Haplotype associations for OCD susceptibility were found for MAOB. Investigation of GxE interactions indicated that the sexual abuse sub-category was significantly associated with all three genes in haplotype x environment interaction analyses. Preliminary findings indicate that polymorphisms within the MAOB and COMT genes interact resulting in risk for OCD. Childhood trauma interacts with haplotypes in COMT, MAOA and MAOB, increasing risk for OCD.

Polymorphisms within the neuronal cadherin (CDH2) gene are associated with obsessive-compulsive disorder (OCD) in a South African cohort.

OCD is characterised by recurrent obsessions and compulsions that result in severe distress and increased risk for comorbidity. Recently published findings have indicated that the neuronal cadherin gene (CDH2) plays a role in the development of canine OCD, and led us to investigate the human ortholog, CDH2, in a human OCD cohort. Seven CDH2 polymorphisms were selected and genotyped in a South African Caucasian cohort of 234 OCD patients and 180 healthy controls using TaqMan assays. Polymorphisms were analysed in a single-locus and haplotypic context. Of the seven polymorphisms, two reached statistical significance for OCD under additive and codominant models of inheritance (rs1120154 and rs12605662). CDH2 SNP, rs1120154, C-allele carriers were found to be significantly associated with lower risk to develop OCD compared to TT-homozygotes (OR = 0.49; 95% CI: 0.32-0.75; p < 0.001), and rs12605662 G-allele carriers were significantly associated with reduced risk OCD compared to TT-homozygotes (OR = 0.46; 95% CI: 0.30-0.71; p < 0.001), Furthermore, a single haplotype was found to infer an increased risk for OCD diagnosis (*rs8087457-rs1148374: A-T). Polymorphisms within the CDH2 gene are associated with susceptibility to OCD in a South African cohort.

Predictors of distress and anxiety during pregnancy.

OBJECTIVE: There is a high incidence of distressing psychological symptoms including anxiety in pregnancy. Nevertheless, predictors of distress and anxiety during pregnancy have not been well characterized. We determined whether temperament and character, trait anxiety, resilience, and social support predicted distress and anxiety symptoms in pregnancy. METHOD: Pregnant women (n=105) with low risk singleton pregnancies were recruited from Midwife Obstetric Units. Assessments of distress (using the K-10) and anxiety (using the Spielberger State Inventory) were undertaken in trimester 2 and 3. Measures of temperament and character, trait anxiety, resilience and social support were undertaken at the same time points. Regression analyses were used to determine predictors of distress and anxiety at each trimester. RESULTS: Predictors of distress and anxiety were lower selfdirectedness, higher harm avoidance, higher trait anxiety, lower resilience, and lower social support, at each time point. CONCLUSION: Understanding predictors of distress and anxiety in pregnancy may be useful in developing interventions for addressing such symptoms, as well as perhaps in preventing potential sequelae such as anxiety and mood disorders.

Genome-wide association study of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two P-values were located within DLGAP1 (P=2.49 × 10(-6) and P=3.44 × 10(-6)), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value=3.84 × 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 × 10(-5), losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation QTLs (P<0.001) and frontal lobe expression quantitative trait loci (eQTLs) (P=0.001) was observed within the top-ranked SNPs (P<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.

Dopamine transporter binding in social anxiety disorder: the effect of treatment with escitalopram.

Social anxiety disorder (SAD) is characterised by fear of social or performance situations where the individual is exposed to unfamiliar people or to possible scrutiny by others. The literature on dopamine ligands and dopamine genotypes in SAD is however inconsistent. In this study we measured the effects of SSRI pharmacotherapy on dopamine transporter (DAT) binding in patients with SAD, also addressing variability in DAT genotype. Adult subjects meeting DSM-IV criteria for generalised SAD were studied before and after 12 weeks of pharmacotherapy with the selective serotonin reuptake inhibitor (SSRI) escitalopram. DAT single photon emission computed tomography (SPECT) using (123)I-FP-CIT was performed at baseline, and repeated at 12 weeks. Striatal DAT binding was analysed for changes following therapy, and for correlations with clinical efficacy, in the whole group as well as for a subgroup with the A10/A10 DAT genotype. The study included 14 subjects (9 male, 5 female) with a mean (SD) age of 41 (±13) years. The subjects' Liebowitz Social Anxiety Scale (LSAS) score was significantly decreased following pharmacotherapy. In the combined group the left caudate and left putamen showed clusters of increased DAT binding after therapy. The left caudate changes were also observed in the subgroup of 9 A10/A10 homozygotes. However no correlation was found between improved symptoms and DAT binding. The changes found in DAT binding in the caudate and putamen may be due to serotonergic activation of dopamine function by SSRI therapy. This is consistent with previous work indicating decreased DAT binding in SAD, and increased DAT binding after SSRI administration.

Functional magnetic resonance imaging during emotion recognition in social anxiety disorder: an activation likelihood meta-analysis.

BACKGROUND: Social anxiety disorder (SAD) is characterized by abnormal fear and anxiety in social situations. Functional magnetic resonance imaging (fMRI) is a brain imaging technique that can be used to demonstrate neural activation to emotionally salient stimuli. However, no attempt has yet been made to statistically collate fMRI studies of brain activation, using the activation likelihood-estimate (ALE) technique, in response to emotion recognition tasks in individuals with SAD. METHODS: A systematic search of fMRI studies of neural responses to socially emotive cues in SAD was undertaken. ALE meta-analysis, a voxel-based meta-analytic technique, was used to estimate the most significant activations during emotional recognition. RESULTS: Seven studies were eligible for inclusion in the meta-analysis, constituting a total of 91 subjects with SAD, and 93 healthy controls. The most significant areas of activation during emotional vs. neutral stimuli in individuals with SAD compared to controls were: bilateral amygdala, left medial temporal lobe encompassing the entorhinal cortex, left medial aspect of the inferior temporal lobe encompassing perirhinal cortex and parahippocampus, right anterior cingulate, right globus pallidus, and distal tip of right postcentral gyrus. CONCLUSION: The results are consistent with neuroanatomic models of the role of the amygdala in fear conditioning, and the importance of the limbic circuitry in mediating anxiety symptoms.

Childhood trauma in adults with social anxiety disorder and panic disorder: a cross-national study.

OBJECTIVES: The influence of childhood trauma as a specific environmental factor on the development of adult psychopathology is far from being elucidated. As part of a collaborative project between research groups from South Africa (SA) and Sweden focusing on genetic and environmental factors contributing to anxiety disorders, this study specifically investigated rates of childhood trauma in South African and Swedish patients respectively, and whether, in the sample as a whole, different traumatic experiences in childhood are predictive of social anxiety (SAD) or panic disorder (PD) in adulthood. METHOD: Participants with SAD or PD (85 from SA, 135 from Sweden) completed the Childhood Trauma Questionnaire (CTQ). Logistic regression was performed with data from the two countries separately, and from the sample as a whole, with primary diagnoses as dependent variables, gender, age, and country as covariates, and the CTQ subscale totals as independent variables. The study also investigated the internal consistency (Cronbach alpha) of the CTQ subscales. RESULTS: SA patients showed higher levels of childhood trauma than Swedish patients. When data from both countries were combined, SAD patients reported higher rates of childhood emotional abuse compared to those with PD. Moreover, emotional abuse in childhood was found to play a predictive role in SAD/PD in adulthood in the Swedish and the combined samples, and the same trend was found in the SA sample. The psychometric qualities of the CTQ subscales were adequate, with the exception of the physical neglect subscale. CONCLUSION: Our findings suggest that anxiety disorder patients may differ across countries in terms of childhood trauma. Certain forms of childhood abuse may contribute specific vulnerability to different types of psychopathology. Longitudinal studies should focus on the potential sequential development of SAD/PD among individuals with childhood emotional abuse.

Childhood trauma in adults with social anxiety disorder and panic disorder: a cross-national study

Objectives: The influence of childhood trauma as a specific environmental factor on the development of adult psychopathology is far from being elucidated. As part of a collaborative project between research groups from South Africa (SA) and Sweden focusing on genetic and environmental factors contributing to anxiety disorders; this study specifically investigated rates of childhood trauma in South African and Swedish patients respectively; and whether; in the sample as a whole; different traumatic experiences in childhood are predictive of social anxiety (SAD) or panic disorder (PD) in adulthood. Method: Participants with SAD or PD (85 from SA; 135 from Sweden) completed the Childhood Trauma Questionnaire (CTQ). Logistic regression was performed with data from the two countries separately; and from the sample as a whole; with primary diagnoses as dependent variables; gender; age; and country as covariates; and the CTQ subscale totals as independent variables. The study also investigated the internal consistency (Cronbach alpha) of the CTQ subscales. Results: SA patients showed higher levels of childhood trauma than Swedish patients. When data from both countries were combined; SAD patients reported higher rates of childhood emotional abuse compared to those with PD. Moreover; emotional abuse in childhood was found to play a predictive role in SAD/PD in adulthood in the Swedish and the combined samples; and the same trend was found in the SA sample. The psychometric qualities of the CTQ subscales were adequate; with the exception of the physical neglect subscale. Conclusion: Our findings suggest that anxiety disorder patients may differ across countries in terms of childhood trauma. Certain forms of childhood abuse may contribute specific vulnerability to different types of psychopathology. Longitudinal studies should focus on the potential sequential development of SAD/PD among individuals with childhood emotional abuse

A culture-bound syndrome 'amafufunyana' and a culture-specific event 'ukuthwasa': differentiated by a family history of schizophrenia and other psychiatric disorders.

BACKGROUND: 'Amafufunyana' and 'ukuthwasa' are two culture-specific descriptive terms used by Xhosa traditional healers to explain aberrant behavioral and psychological phenomena. Some overlap between these conditions and schizophrenia (DSM-IV) is apparent. The aim of this study was to determine the extent to which amafufunyana and ukuthwasa were used as cultural explanatory models by traditional healers for DSM-IV-defined schizophrenia and whether there were significant phenomenological differences in schizophrenia symptoms in patients with the diagnosis of amafufunyana rather than ukuthwasa. SAMPLING AND METHODS: Xhosa patients with schizophrenia underwent a structured clinical diagnostic interview (Diagnostic Interview for Genetic Studies). The use of traditional diagnostic and treatment methods was assessed by structured open-ended interviewer-rated questions. The sample was then stratified for the presence/absence of a past/current diagnosis of amafufunyana and/or ukuthwasa. The clinical parameters were compared across groups by means of the chi2 or Student t tests. RESULTS: 247 adult subjects participated in the study. 106 (53%) patients reported a previous diagnosis of amafufunyana, and 9 (4.5%) reported a diagnosis of ukuthwasa. A family history of schizophrenia (p = 0.004) or any psychiatric disorder (p = 0.008) was more common in the ukuthwasa group. Subjects with a primary diagnosis other than amafufunyana or ukuthwasa were more likely to be married (p = 0.004), to have a history of stressor(s) prior to illness onset (p = 0.026), to be from a rural environment (p = 0.007) or to have a history of cannabis abuse/dependency (p = 0.015). CONCLUSION: The culture-bound syndrome amafufunyana and the culture-specific phenomenon of ukuthwasa are both used to explain symptoms in patients with schizophrenia (DSM-IV). Identification of cases as amafufunyana and ukuthwasa may correlate with a distinction between familial and sporadic cases of schizophrenia. Whether the positive connotations associated with ukuthwasa, as opposed to the more negative connotations associated with amafufunyana, hold any implications for the treatment or prognosis of schizophrenia remains to be clarified.

Olfactory reference syndrome: diagnostic criteria and differential diagnosis.

Olfactory reference syndrome (ORS) has been defined as a psychiatric condition characterized by persistent preoccupation about body odour accompanied by shame, embarrassment, significant distress, avoidance behaviour and social isolation. ORS has however not been included in the Diagnostic and Statistical Manual of Mental Disorders (4th edition) (DSM-IV) and, given that its primary symptoms may be found in various other disorders, differential diagnosis can be problematic. Using an illustrative case of ORS, we propose diagnostic criteria for ORS. We also argue that ORS represents a unique cluster of symptoms that can be delineated as a separate diagnostic entity, and that ORS falls on a spectrum of social anxiety disorders that includes social anxiety disorder, taijin kyofusho, and body dysmorphic disorder.

Role of cholecystokinin in the regulation of gastric emptying and pancreatic enzyme secretion in humans. Studies with the cholecystokinin-receptor antagonist loxiglumide.

The role of cholecystokinin (CCK) in the regulation of gastric emptying and pancreatic enzyme secretion was evaluated by infusing the CCK-receptor antagonist loxiglumide. Gastric emptying rates and pancreatic secretory outputs were measured in five healthy volunteers by the double-indicator perfusion technique using a multiple-lumen tube in the duodenum. Placebo or loxiglumide (22 mumol.kg-1.h-1) was infused throughout each experiment. Five hundred-milliliter liquid intragastric meals of (a) fat, protein, and glucose (Ensure; Abbott, Chicago, IL); (b) glucose, 20 g/dL; and (c) guar gum, 1.1 g/dL, were given in random order. In addition, the effect of a physiologic CCK-8 dose (20 pmol.kg-1.h-1) after an intragastric 500-mL saline meal (0.154 mol/L) was tested. Intravenous CCK-8 induced a marked retardation of the gastric emptying rate of the saline solution (P less than 0.05) while stimulating pancreatic secretory outputs; both effects were completely abolished by the infusion of loxiglumide. Loxiglumide markedly accelerated the gastric emptying rates (by approximately 40%) and simultaneously diminished lipase (by approximately 75%) and trypsin (by approximately 50%) outputs of both the mixed meal (P less than 0.01) and the pure glucose meal (P less than 0.05). Additional experiments using gamma camera scintigraphy confirmed the accelerating effect of loxiglumide on gastric emptying of the mixed meal (P less than 0.01). The gastric emptying rate of the guar meal, which did not release CCK, was not influenced by the infusion of loxiglumide. Loxiglumide distinctly augmented plasma CCK levels after the mixed (2.6 times) and the pure glucose (2.1 times) meals while markedly reducing (approximately 76%) pancreatic polypeptide release (P less than 0.02). It is concluded that endogeneous CCK exerts a major role in the regulation of both gastric liquid emptying and pancreatic secretion in humans.

Lead and sudden infant death. Investigations on blood samples of SID babies.

To investigate a potential relationship between an elevated lead burden and sudden infant death (SID), the lead concentrations (Pb-B) were determined in 41 blood samples from SID babies and compared with the Pb-B of 5 babies who died traumatically and 77 living control babies. Several factors that may influence the Pb-B were taken into consideration, especially a dependence of the Pb-B on age and social class. Moreover, a post-mortem water shift occurs in the blood. Even taking these factors into consideration the distribution of the Pb-B's of the SID group was found to differ on a highly significant level (greater than 99.9%) from the control group. Five Pb-B's of the SID group were higher than the highest lead concentration found in blood from the control babies. Negative influences of lead on the pre- and postnatal maturation of the brain are discussed in the search for a possible causal connection between an elevated lead burden and the occurrence of SID.

[Phagocytosis of blood cells in pleural effusions]. / Zytophagozytose von Blutzellen in Pleuraergüssen.

Macrophages can be found in pleural effusions in varying number according to etiology and duration of the underlying pleural disease. These phagocytes are able to ingest different particles and cells: morphologically intact white and red blood cells or degradation products (such as, for instance, specific granules of granulocytes) are detectable in up to 10% of pleural macrophages. Little is known about the significance and mechanisms of cytophagocytosis of blood cells by macrophages in pleural effusions. To learn more about it we studied the phenomenon of endocytosis in 105 patients with pleural effusions of various etiologies. Cytophagocytosis can be observed in all pleural effusions independently of underlying pleural processes. The nature of ingested cells in macrophages corresponds to free blood cells in effusions and a similar ratio can be shown. The results indicate that white and red blood cells which enter the pleural space may be eliminated by macrophages by a similar mechanism to the well known cytohemolysis of blood cells in the reticulo-endothelium of the body.