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The aim of this study was to identify independent risk and protective factors associated with self-reported suicidal thoughts and behaviors (STB) among young adolescents by examining self-report data on mental health, substance abuse, violence involvement, social and economic challenges and supports, physical health and demographics in relation to STB. Data from nearly 27,000 students who completed the 2018-19 Maryland Middle School Youth Risk Behavior Survey/Youth Tobacco Survey (YRBS/YTS) were used to identify independent risk and protective factors associated with STB among middle school students (grades 6-8; ages 11-14). Twenty-three percent of students reported lifetime suicidal ideation and nine percent reported lifetime attempt(s). Independent risk factors associated with STB include depression, substance abuse or misuse, violence involvement, bullying victimization at school or electronically, sexual activity, and sleep deprivation. Protective factors include having an adult outside of school to confide in and feeling that teachers care and provide encouragement. Interactive effects by gender and/or race/ethnicity were observed for some factors in relation to STB. These results suggest that evidence-based programs and policies at the universal and selective/indicated levels in school settings are needed and should be introduced earlier on to address the widespread prevalence of STB in young adolescents. Program planners should take into consideration social, cultural and language needs when implementing and developing intervention strategies., Supplementary Information: The online version contains supplementary material available at 10.1007/s12310-022-09521-6., Competing Interests: Conflicts of interestThe authors have no conflicts of interest to report., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022.)

The disaster of the COVID-19 pandemic has fundamentally changed the norms of psychiatric practice: from its methods of care delivery to its methods of practice. Traditional methods of care delivery using in-person visits became impractical or unsafe. Meanwhile, the pandemic has resulted in an increased demand for services. The resulting pivot to telepsychiatry required a skillset that was not a part of traditional psychiatry training. To meet the demand for services, many providers needed to join collaborative models of care to help scale their expertise. Although many innovative collaborative models of care exist, providers remain in their traditional consultative roles within many of those models. In a disaster, when there is an expanding mental health care need in the population, psychiatrists need to adapt their practice to meet expanded roles that naturally build on their usual ones. We explore the expanded roles that psychiatrists will need to fill based on what is known about the field of disaster mental health and principles from Psychological First Aid (PFA). In preparation for a new normal, in what George Everly describes as a 'disaster of uncertainty,' we propose evolutions in the way psychiatrists are trained. Specific training on telepsychiatry best practices will prepare psychiatrists to use this method most effectively and appropriately. Additional training should focus on the core competencies of disaster psychiatry: effective crisis leadership and strategic planning, disaster surveillance, knowledge of benign vs. concerning symptoms, psychological triage, implementation of crisis interventions, resource facilitation, crisis communication, and self and peer care. Developing and integrating these competencies into psychiatry training programs will best prepare psychiatrists for the expanding mental health care needs of the community in this ongoing disaster and future ones.

Unhealthy preteen behaviors are associated with adolescent depression. However, little is known about preteen factors among sexual minority young people, a group at increased risk for teen depression and suicide. We completed weighted multivariate logistic regression analyses on data from the national 2015 and 2017 Youth Risk Behavior Survey of 30 389 high school students in the United States. Preteen sex, cigarette smoking, and alcohol and marijuana use were significantly more prevalent among lesbian, gay, or bisexual (LGB) and questioning students who reported depressive symptoms than among their heterosexual peers (adjusted prevalence ratio [APR] range, 1.33-2.34; all significant at P < .05). The only exception was that marijuana use among questioning students was not significantly different from use among heterosexual peers (APR = 1.34; P = .11). Assessment of preteen sex and substance use-especially among LGB and questioning young people, who are more prone to depressive symptoms and more likely to initiate risky preteen behaviors than their heterosexual counterparts-will facilitate a life course approach to sexual minority mental health that should begin by early adolescence.

Background: Suicidal thoughts and behaviors (STBs) are increasing among adolescents in the United States and are challenging to predict and prevent.  The current study identifies subtypes of youth at risk for suicidal thoughts and behaviors (STBs) in school-based settings., Method: Data are from the CDC's 2015 and 2017 National Youth Risk Behavior Survey of US high school students. Among students reporting depression symptoms, latent class analysis is used to identify subtypes at risk for STBs based on personal characteristics, risk behaviors and environments., Results: Two distinct subtypes of youth were found to be at high risk for STBs: The first, larger subtype (22%) is predominately females in early high school, many of whom identify as bisexual, experienced past-year bullying, and are likely to have experienced sexual victimization.  These students have low levels of externalizing risk behaviors making them difficult to detect.  The second high-risk subtype (7%) is characterized by students with significant social integration challenges, with extremely high levels of substance abuse, fighting, physical and sexual victimization and poor academic performance.  Many of these students have low English fluency, and identify as sexual minority., Limitations: Due to attrition or language barriers, experiences of some students at high-risk for STBs may not have been captured by this survey., Conclusion: Universal screening in clinical settings, and universally focused suicide prevention programs in school-based settings are needed and should be introduced early on. Interventions should be tailored to reach high-risk students with language, cultural and social integration challenges., Competing Interests: Declarations of Competing Interest None, (Copyright © 2020. Published by Elsevier B.V.)

E2F-2 is a retinoblastoma (Rb)-regulated transcription factor induced during terminal erythroid maturation. Cyclin E-mediated Rb hyperphosphorylation induces E2F transcriptional activator functions. We previously reported that deregulated cyclin E activity causes defective terminal maturation of nucleated erythroblasts in vivo Here, we found that these defects are normalized by E2F-2 deletion; however, anemia in mice with deregulated cyclin E is not improved by E2F-2-loss, which itself causes reduced peripheral red blood cell (RBC) counts without altering relative abundances of erythroblast subpopulations. To determine how E2F-2 regulates RBC production, we comprehensively studied erythropoiesis using knockout mice and hematopoietic progenitors. We found that efficient stress erythropoiesis in vivo requires E2F-2, and we also identified an unappreciated role for E2F-2 in erythroblast enucleation. In particular, E2F-2 deletion impairs nuclear condensation, a morphological feature of maturing erythroblasts. Transcriptome profiling of E2F-2-null, mature erythroblasts demonstrated widespread changes in gene expression. Notably, we identified citron Rho-interacting kinase (CRIK), which has known functions in mitosis and cytokinesis, as induced in erythroblasts in an E2F-2-dependent manner, and we found that CRIK activity promotes efficient erythroblast enucleation and nuclear condensation. Together, our data reveal novel, lineage-specific functions for E2F-2 and suggest that some mitotic kinases have specialized roles supporting enucleation of maturing erythroblasts., (Copyright © 2016 American Society for Microbiology.)

Mental health literacy appears to be an important target for prevention and intervention efforts. However, limitations exist in this literature base, including the lack of a validated measure to assess this construct. The Adolescent Depression Knowledge Questionnaire (ADKQ) was created to assess knowledge of depression and attitudes about seeking help (i.e., depression literacy) for mental health issues before and after introduction of a universal, school-based intervention, the Adolescent Depression Awareness Program (ADAP). The ADKQ measured depression knowledge and attitudes in 8,216 high school students immediately before ADAP was implemented and 6 weeks after. The latent structure of the Knowledge section was examined with attention to measurement invariance between males and females and type of instructor, as well as pre- to post-test. Categories were developed for the open-ended questions of the Attitudes section. A one-factor (General Knowledge) latent structure was the best fit to the data. The latent structure of the ADKQ did not differ by student's gender or type of instructor, nor did it differ based on pre- or post-test. Categories for the Attitudes portion of the ADKQ were developed. Psychometric evidence supports the ADKQ as a measure to evaluate adolescent depression literacy pre- to post-test and within several groups of interest (e.g., gender, facilitator). Categories for the Attitudes section of the ADKQ will allow for easier evaluation of this measure with quantitative data.

The Fbw7 ubiquitin ligase critically regulates hematopoietic stem cell (HSC) function, though the precise contribution of individual substrate ubiquitination pathways to HSC homeostasis is unknown. In the work reported here, we used a mouse model in which we introduced two knock-in mutations (T74A and T393A [changes of T to A at positions 74 and 393]) to disrupt Fbw7-dependent regulation of cyclin E, its prototypic substrate, and to examine the consequences of cyclin E dysregulation for HSC function. Serial transplantation revealed that cyclin E(T74A T393A) HSCs self-renewed normally; however, we identified defects in their multilineage reconstituting capacity. By inducing hematologic stress, we exposed an impaired self-renewal phenotype in cyclin E knock-in HSCs that was associated with defective cell cycle exit and the emergence of chromosome instability (CIN). Importantly, p53 deletion induced both defects in self-renewal and multilineage reconstitution in cyclin E knock-in HSCs with serial transplantation and CIN in hematopoietic stem and progenitor cells. Moreover, CIN was a feature of fatal T-cell malignancies that ultimately developed in recipients of cyclin E(T74A T393A); p53-null HSCs. Together, our findings demonstrate the importance of Fbw7-dependent cyclin E control to the hematopoietic system and highlight CIN as a characteristic feature of HSC dysfunction and malignancy induced by deregulated cyclin E., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

The mechanisms that coordinate the final mitotic divisions of terminally differentiated bone marrow (BM) erythroid cells with components of their structural and functional maturation program remain largely undefined. We previously identified phenotypes resembling those found in early-stage myelodysplastic syndromes (MDS), including ineffective erythropoiesis, morphologic dysplasia and BM hyper-cellularity, in a knock-in mouse model in which cyclin E mutations were introduced at its two Cdc4 phosphodegrons (CPDs) to ablate Fbw7-dependent ubiquitination and degradation. Here, we have examined the physiologic consequences of cyclin E dysregulation in BM erythroid cells during terminal maturation in vivo. We found that cyclin E protein levels in BM erythroid cells are dynamically regulated in a CPD-dependent manner and that disruption of Fbw7-dependent cyclin E regulation impairs terminal erythroid cell maturation at a discrete stage before enucleation. At this stage of erythroid cell maturation, CPD phosphorylation of cyclin E regulates both cell-cycle arrest and survival. We also found that normal regulation of cyclin E restrains mitochondrial reactive oxygen species (ROS) accumulation and expression of genes that promote mitochondrial biogenesis and oxidative metabolism during terminal erythroid maturation. In the setting of dysregulated cyclin E expression, p53 is activated in BM erythroid cells as part of a DNA damage response-type pathway, which mitigates ineffective erythropoiesis, in contrast to the role of p53 induction in other models of dyserythropoiesis. Finally, cyclin E dysregulation and ROS accumulation induce histone H3 lysine 9 hyper-methylation and disrupt components of the normal terminal erythroid maturation gene expression program. Thus, ubiquitin-proteasome pathway control of G1-to-S-phase progression is intrinsically linked to regulation of metabolism and gene expression in terminally differentiating BM erythroid cells.

Introduction: Central aortic systolic pressure (CASP) strongly predicts cardiovascular outcomes. We undertook to measure ambulatory CASP in 74 prevalent dialysis patients using the BPro (HealthStats, Singapore) device. We also determined whether coronary or abdominal aortic calcification was associated with changes in CASP and whether interdialytic CASP predicted ambulatory measurement., Methods: All patients underwent computed tomography for coronary calcium score, lateral abdominal radiography for aortic calcium score, echocardiography for left ventricular mass index and ambulatory blood pressure measurement using BPro calibrated to brachial blood pressure. HealthStats was able to convert standard BPro SOFT(®) data into ambulatory CASP., Results: Ambulatory CASP was not different in those without and with coronary (137.6 vs 141.8 mmHg, respectively, p = 0.6) or aortic (136.6 vs 145.6 mmHg, respectively, p = 0.2) calcification. Furthermore, when expressed as a percentage of brachial systolic blood pressure to control for peripheral blood pressure, any difference in CASP was abolished: CASP: brachial systolic blood pressure ratio = 0.9 across all categories regardless of the presence of coronary or aortic calcification (p = 0.2 and 0.4, respectively). Supporting this finding, left ventricular mass index was also not different in those with or without vascular calcification (p = 0.7 and 0.8 for coronary and aortic calcification). Inter-dialytic office blood pressure and CASP correlated excellently with ambulatory measurements (r = 0.9 for both)., Conclusion: Vascular calcification was not associated with changes in ambulatory central aortic systolic pressure in this cohort of prevalent dialysis patients. Inter-dialytic blood pressure and CASP correlated very well with ambulatory measurement.

Background: Major depression is a common disorder among teenagers and is associated with significant morbidity and mortality. Suicide is the third leading cause of death among 15-24 year olds. Early identification and treatment is essential to prevent suicide. Depression education is a potential intervention for improving knowledge about depression and help-seeking behavior., Methods: The Adolescent Depression Awareness Program (ADAP) is a school-based depression education intervention with a core message that depression is a treatable medical illness. 710 high school students from six schools in Tulsa, OK participated in the study comparing changes in knowledge about depression and attitudes toward treatment-seeking between students receiving the intervention and those who did not. Changes in depression knowledge and attitude toward help-seeking were measured using the ADAP Depression Knowledge Questionnaire (ADKQ)., Results: There was a significant positive change in ADKQ score for students receiving the intervention but not in the control group. The intervention group also demonstrated a significant difference in willingness to "tell someone" if concerned about depression in a peer, which was not present in the control group., Limitations: The students were not randomized to the intervention and control groups. The ADKQ evaluates attitudes about help-seeking but not behavior., Conclusions: A school-based educational intervention improved knowledge about depression and attitudes toward help-seeking in adolescents. Future studies should investigate if such change in knowledge results in help-seeking behaviors., (© 2013 Elsevier B.V. All rights reserved.)

In an effort to decrease the suicide rate in adolescents, many interventions have focused on school-based suicide prevention programs. Alternatively, depression education in schools might be effective in decreasing the morbidity, mortality, and stigma associated with adolescent depression. The Adolescent Depression Awareness Program (ADAP) developed a 3-hour curriculum to teach high school students about the illness of depression. The purpose of this study was to assess the effectiveness of the ADAP curriculum in improving high school students' knowledge about depression. From 2001 to 2005, 3,538 students were surveyed on their knowledge about depression before and after exposure to the ADAP curriculum. The number of students scoring 80% or higher on the assessment tool more than tripled from pretest to posttest (701 to 2,180), suggesting the effectiveness of the ADAP curriculum. Further study and replication are required to determine if improved knowledge translates into increased treatment-seeking behavior.

We sought to determine whether premenstrual mood symptoms exhibit familial aggregation in bipolar disorder or major depression pedigrees. Two thousand eight hundred seventy-six women were interviewed with the Diagnostic Interview for Genetic Studies as part of either the NIMH Genetics Initiative Bipolar Disorder Collaborative study or the Genetics of Early Onset Major Depression (GenRED) study and asked whether they had experienced severe mood symptoms premenstrually. In families with two or more female siblings with bipolar disorder (BP) or major depressive disorder (MDD), we examined the odds of having premenstrual mood symptoms given one or more siblings with these symptoms. For the GenRED MDD sample we also assessed the impact of personality as measured by the NEO-FFI. Premenstrual mood symptoms did not exhibit familial aggregation in families with BP or MDD. We unexpectedly found an association between high NEO openness scores and premenstrual mood symptoms, but neither this factor, nor NEO neuroticism influenced evidence for familial aggregation of symptoms. Limitations include the retrospective interview, the lack of data on premenstrual dysphoric disorder, and the inability to control for factors such as medication use.

Background: We sought to determine the prevalence of, and association between, reproductive cycle-associated mood symptoms in women with affective disorders. We hypothesized that symptoms would correlate with each other across a woman's reproductive life span in both major depression (MDD) and bipolar I disorder (BP)., Methods: 2412 women with, MDD or BP were asked standardized questions about mood symptoms prior to menstruation, within a month of childbirth and during perimenopause. Lifetime rates for each of these symptom types were determined and an odds ratio was calculated correlating each of the types with the others., Results: Of 2524 women with mood disorders, 67.7% reported premenstrual symptoms. Of those at risk, 20.9% reported postpartum symptoms and 26.4% reported perimenopausal symptoms. The rates did not differ between women with MDD and BP but were significantly different from women who were never ill. The symptoms were significantly correlated in women with MDD with odds ratios from 1.66 to 1.82, but were not in women with BP., Limitations: This is a secondary analysis of a sample that was collected for other purposes and is based upon retrospective reporting., Conclusions: Reproductive cycle-associated mood symptoms were commonly reported in women with mood disorders and did not differ based on diagnosis. In MDD, but not BP, the occurrence of these symptoms was trait-like as the presence of one predicted the occurrence of the others. Further prospective study is required to clarify the determinants of this trait.

Adolescent depression and suicide are major public health concerns. Best practices for suicide prevention and education in high schools are not well understood. The Adolescent Depression Awareness Program (ADAP) was developed to address depression education as an effective means towards decreasing the morbidity and mortality associated with adolescent depression. Adolescents' baseline knowledge about depression was assessed to enhance curriculum development. The survey was administered to 5,645 high school students between 1999 and 2003. Results indicated that students had a cursory knowledge of depression facts but had gaps in knowledge about treatment and symptom identification.

Alcohol misuse among women is an important and growing problem. There is epidemiological and metabolic evidence that risk factors for and consequences of alcohol misuse are significantly different for women than for men. Understanding these differences is imperative if effective preventative and treatment interventions are to be undertaken. This article reviews the epidemiology of alcohol misuse by women, effects of alcohol misuse on women, fetuses, and relationships, and assessment and treatment strategies. We then suggest directions for future research in this field.

Objective: No previous research has investigated whether there is an association between anxiety disorders and urinary incontinence. We hypothesized that anxiety disorders would be associated with increased urinary incontinence related disability., Method: Continuing participants who were aged 50 years and older in a longitudinal study of community-dwelling adults who were initially living in East Baltimore in 1981 (n = 787). Participants were classified as incontinent if any uncontrolled urine loss within the 12 months prior to the interview was reported. Urinary incontinence related functional loss was further assessed based on a series of questions relating directly to participants' inability to engage in certain activities due to their urinary incontinence. Anxiety disorders were assessed with standardized interviews., Results: Persons meeting criteria for an anxiety disorder were no more likely to have urinary incontinence than were persons without anxiety disorders (unadjusted odds ratio (OR) = 1.36,95 percent confidence interval (CI) [0.96, 1.93]). Among people with urinary incontinence (n = 159), persons meeting criteria for anxiety disorders in 1981 and in 1994 were much more likely to report urinary incontinence relatedfunctional impairment in 1994(adjusted OR = 6.51, 95 percent CI [1.42, 29.86])., Conclusions: Individuals with changes in day-to-day routines or activities secondary to urinary incontinence were more likely to meet criteria for an anxiety disorder than were other older adults. Further studies must tease out the temporal relationship and whether early detection of urinary incontinence and associated anxiety improves quality of life and functioning.

Information from multiple genome scans and collaborative efforts suggests that schizophrenia is a heterogeneous, complex disorder with polygenic and environmental antecedents. In a previous paper we demonstrated that stratification of families on the basis of co-segregating phenotypes (psychotic affective disorders (PAD) and schizophrenia spectrum personality disorders (SSPD) in first-degree relatives of schizophrenic probands increased linkage evidence in the chromosome 8p21 region (D8S1771) among families with co-segregating SSPD. We have now applied a method of conditional analysis of sib-pairs affected with schizophrenia, examining shared alleles identical-by-descent (IBD) at multiple loci. The method yields enhanced evidence for linkage to the chromosome 8p21 region conditioned upon increased allele sharing at a chromosome 14 region. The method produces a more refined estimate of the putative disease locus on chromosome 8p21, narrowing the region from 18 cM (95% confidence interval) in our previous genome scan, to approximately 9.6 cM. We have also shown that the affected siblings sharing two alleles IBD at the chromosome 8p21 region and one allele IBD at the chromosome 14 region differ significantly in clinical symptoms from non-sharing affected siblings. Thus the analysis of allele sharing at a putative schizophrenia susceptibility locus conditioned on allele sharing at other loci provides another important method for dealing with heterogeneity.

The patient with chronic dizziness should never be labeled with psychogenic dizziness. Chronic does not mean psychogenic. Chronic means that health care has been unsuccessful. A systematic approach that yields a comprehensive formulation and rational treatment plan will increase the probability of a successful outcome and return to health. The four perspectives of diseases, life stories, dimensions, and behaviors provide a comprehensive yet flexible methodology for the evaluation of the patient in distress with chronic and disabling dizziness. The design of a comprehensive treatment plan involves the determination of each perspective's contribution to the patient's distress and to what relative degree. This process recognizes that the perspectives are distinct from one another but complementary in illuminating the various reasons for a patient's distress. The perspectives come together as the formulation of the patient's case and offer a recipe for treatment rather than just a list of ingredients such as bio, psycho, and social.

Despite considerable effort to identify susceptibility loci for schizophrenia, none have been localized. Multiple genome scans and collaborative efforts have shown evidence for linkage to regions on chromosomes 1q, 5q, 6q, 8p, 13q, 10p and 22q.(1-9) Heterogeneity is likely. We previously mapped schizophrenia susceptibility loci (SSL) to chromosomes 13q32 (P = 0.00002) and 8p21-22 (P= 0.0001) using 54 multiplex pedigrees and suggested linkage heterogeneity. We have now stratified these families based on co-segregating phenotypes in non-schizophrenic first degree relatives (schizophrenia spectrum personality disorders (SSPD); psychotic affective disorders (PAD)). Genome scans were conducted for these phenotypic subgroups of families and broadened affected phenotypes were tested. The SSPD group provided its strongest genome-wide linkage support for the chromosome 8p21 region (D8S1771) using either narrow (non-parametric lod (NPL) P= 0.000002) or broadened phenotypes (NPL P = 0.0000008) and a new region of interest on 1p was identified (P = 0.006). For PAD families, the peak NPL in the genome scan occurred on chromosome 3p26-p24 (P = 0.008). The identification of multiple susceptibility loci for schizophrenia may be enhanced by stratification of families using psychiatric diagnoses of the non-schizophrenic relatives.

Background: The cross-sectional relation between migraine headaches and affective disorders has been demonstrated in studies of clinical and community populations. Few studies have investigated the prospective relation between psychiatric disorders and migraine headaches., Methods: A prospective follow-up of the Baltimore, Md, cohort of the Epidemiologic Catchment Area Study assessed psychopathologic features in 1981 and again between 1993 and 1996. Interviews included a history of headaches at baseline and self-reported assessment of migraine headaches at follow-up. Risk estimates for incident migraine headaches by 1981 demographic variables and psychopathologic features were calculated. The cross-sectional association between prevalent migraine and lifetime psychiatric diagnoses was estimated., Results: In the at-risk population of 1343, there were 118 incident cases of migraine headaches. The age- and sex-specific incident rates of migraine headaches followed the expected patterns, with younger age and female sex identified as risk factors. In cross-sectional analyses, major depression (odds ratio, 3.14; 95% confidence interval, 2.03-4. 84) and panic disorder (odds ratio, 5.09; 95% confidence interval, 2. 65-9.79) had the strongest associations, and alcohol and other substance abuse were not associated. In logistic regression models including age, sex, and psychiatric illness in 1981, only phobia was predictive of incident migraines (odds ratio, 1.70; 95% confidence interval, 1.11-2.58). Affective disorders were not predictive of incident migraine headaches. Including a history of tricyclic antidepressant use did not change the results., Conclusions: There is a strong cross-sectional relation between affective disorders and migraine headaches in this cohort. However, there is no association between antecedent affective disorders and incident migraine headaches in this population-based prospective study.

Objective: The aim of the study was to estimate the incidence of social phobia in the general population., Method: The Baltimore cohort of 3481 subjects, sampled during the 1981 Epidemiologic Catchment Area study, was traced. A total of 1920 subjects were re-interviewed from 1993 to 1996 using the Diagnostic Interview Schedule (DIS). A subsample of 349 subjects was interviewed by psychiatrists using the Schedules for Clinical Assessment in Neuropsychiatry., Results: The estimated incidence of DIS/DSM-IV social phobia is 4-5/1000/year. New cases were found in all age groups, with the highest rates in subjects with baseline depressive and panic disorders. Psychiatric evaluations showed broad diagnostic concordance with DIS diagnoses in incident cases. However, validity indices were highly dependent on diagnostic thresholds. None of the psychiatrist-ascertained social phobics had received treatment for the disorder, although the majority were considered likely to benefit from treatment., Conclusion: New cases of social phobia occur in adults of all age groups, and are often secondary to other psychiatric conditions.

Schizophrenia is a common disorder characterized by psychotic symptoms; diagnostic criteria have been established. Family, twin and adoption studies suggest that both genetic and environmental factors influence susceptibility (heritability is approximately 71%; ref. 2), however, little is known about the aetiology of schizophrenia. Clinical and family studies suggest aetiological heterogeneity. Previously, we reported that regions on chromosomes 22, 3 and 8 may be associated with susceptibility to schizophrenia, and collaborations provided some support for regions on chromosomes 8 and 22 (refs 9-13). We present here a genome-wide scan for schizophrenia susceptibility loci (SSL) using 452 microsatellite markers on 54 multiplex pedigrees. Non-parametric linkage (NPL) analysis provided significant evidence for an SSL on chromosome 13q32 (NPL score=4.18; P=0.00002), and suggestive evidence for another SSL on chromosome 8p21-22 (NPL=3.64; P=0.0001). Parametric linkage analysis provided additional support for these SSL. Linkage evidence at chromosome 8 is weaker than that at chromosome 13, so it is more probable that chromosome 8 may be a false positive linkage. Additional putative SSL were noted on chromosomes 14q13 (NPL=2.57; P=0.005), 7q11 (NPL=2.50, P=0.007) and 22q11 (NPL=2.42, P=0.009). Verification of suggestive SSL on chromosomes 13q and 8p was attempted in a follow-up sample of 51 multiplex pedigrees. This analysis confirmed the SSL in 13q14-q33 (NPL=2.36, P=0.007) and supported the SSL in 8p22-p21 (NPL=1.95, P=0.023).

A variety of analogues of stearic acid in which one of the methylene groups was replaced by a sulfur atom were examined as inhibitors of growth and fatty acid biosynthesis in the trypanosomatid protozoan Crithidia fasciculata. The 8-, 9-, 10-, and 11-thiastearic acids were found to suppress the synthesis of the cyclopropane-containing fatty acid dihydrosterculic acid (9,10-methyleneoctadecanoic acid) at micromolar concentrations in the growth medium, and all but the 9-thiastearate were found to inhibit the growth of the protozoa at concentrations. The most potent inhibitor, 8-thiastearic acid (I50 for growth = 0.8 microM; I50 dihydrosterculate synthesis = 0.4 microM), was also observed to inhibit the synthesis of gamma-linolenic acid at a similar concentration. The sulfoxide derivatives of the 9- and 10-thiastearates were found to have little effect on growth or fatty acid synthesis, and several long-chain amides of 3-amino-1,2-propanediol were found to have effects similar to those of the fatty acids from which they were derived.

Despite the overt nature of most motor and phonic tic phenomena, the development of valid and reliable scales to rate tic severity has been an elusive goal. The Yale Global Tic Severity Scale (YGTSS) is a new clinical rating instrument that was designed for use in studies of Tourette's syndrome and other tic disorders. The YGTSS provides an evaluation of the number, frequency, intensity, complexity, and interference of motor and phonic symptoms. Data from 105 subjects, aged 5 to 51 years, support the construct, convergent, and discriminant validity of the instrument. These results indicate that the YGTSS is a promising instrument for the assessment of tic severity in children, adolescents and adults.