Associations of neuroimaging markers with depressive symptoms over time in middle-aged and elderly persons.

BACKGROUND: Cerebrovascular disease is regarded as a potential cause of late-life depression. Yet, evidence for associations of neuroimaging markers of vascular brain disease with depressive symptoms is inconclusive. We examined the associations of neuroimaging markers and depressive symptoms in a large population-based study of middle-aged and elderly persons over time. METHODS: A total of 4943 participants (mean age = 64.6 ± 11.1 years, 55.7% women) from the Rotterdam Study were included. At baseline, total brain volume, gray matter volume, white matter volume, white matter hyperintensities volume, cortical infarcts, lacunar infarcts, microbleeds, white matter fractional anisotropy, and mean diffusivity (MD) were measured with a brain MRI (1.5T). Depressive symptoms were assessed twice with the Center for Epidemiologic Studies Depression scale (median follow-up time: 5.5 years, IQR = 0.9). To assess temporal associations of neuroimaging markers and depressive symptoms, linear mixed models were used. RESULTS: A smaller total brain volume (ß = -0.107, 95% CI -0.192 to -0.022), larger white matter hyperintensities volume (ß = 0.047, 95% CI 0.010-0.084), presence of cortical infarcts (ß = 0.194, 95% CI 0.047-0.341), and higher MD levels (ß = 0.060, 95% CI 0.022-0.098) were cross-sectionally associated with more depressive symptoms. Longitudinal analyses showed that small total brain volume (ß = -0.091, 95% CI -0.167 to -0.015) and presence of cortical infarcts (ß = 0.168, 95% CI 0.022-0.314) were associated with increasing depressive symptoms over time. After stratification on age, effect sizes were more pronounced at older ages. CONCLUSIONS: Neuroimaging markers of white matter microstructural damage were associated with depressive symptoms longitudinally in this study of middle-aged and elderly persons. These associations were more pronounced at older ages, providing evidence for the role of white matter structure in late-life depressive symptomatology.

Bivariate genome-wide association analyses of the broad depression phenotype combined with major depressive disorder, bipolar disorder or schizophrenia reveal eight novel genetic loci for depression.

Although a genetic basis of depression has been well established in twin studies, identification of genome-wide significant loci has been difficult. We hypothesized that bivariate analyses of findings from a meta-analysis of genome-wide association studies (meta-GWASs) of the broad depression phenotype with those from meta-GWASs of self-reported and recurrent major depressive disorder (MDD), bipolar disorder and schizophrenia would enhance statistical power to identify novel genetic loci for depression. LD score regression analyses were first used to estimate the genetic correlations of broad depression with self-reported MDD, recurrent MDD, bipolar disorder and schizophrenia. Then, we performed four bivariate GWAS analyses. The genetic correlations (rg ± SE) of broad depression with self-reported MDD, recurrent MDD, bipolar disorder and schizophrenia were 0.79 ± 0.07, 0.24 ± 0.08, 0.53 ± 0.09 and 0.57 ± 0.05, respectively. From a total of 20 independent genome-wide significant loci, 13 loci replicated of which 8 were novel for depression. These were MUC21 for the broad depression phenotype with self-reported MDD and ZNF804A, MIR3143, PSORS1C2, STK19, SPATA31D1, RTN1 and TCF4 for the broad depression phenotype with schizophrenia. Post-GWAS functional analyses of these loci revealed their potential biological involvement in psychiatric disorders. Our results emphasize the genetic similarities among different psychiatric disorders and indicate that cross-disorder analyses may be the best way forward to accelerate gene finding for depression, or psychiatric disorders in general.

Prolonged Grief and Cognitive Decline: A Prospective Population-Based Study in Middle-Aged and Older Persons.

OBJECTIVE: Bereavement can result in unresolved and prolonged grief, often termed prolonged grief disorder (PGD). The impact of PGD on cognitive functioning is poorly understood. The aim of the study was to compare the cognitive decline, assessed by repeated measures of different cognition domains, between persons with normal and PGD and a non-grieving reference population in a 7-year follow-up study. METHODS: The study sample comprised 3126 non-demented persons, mean age: 64 years, of the Rotterdam Study. Participants were classified into three groups: no grief (reference group, N = 2,582), normal grief (N = 418), and prolonged grief disorder (N = 126). Participants were assessed with the Complicated Grief Inventory and underwent cognitive testing (Mini-Mental State Examination [MMSE], Letter-Digit Substitution test, Stroop test, Word fluency task, Word learning test). Analyses were adjusted for baseline cognition and depressive symptoms; persons with major depressive disorders were excluded. RESULTS: Compared with the reference group, participants with PGD showed a decrease in global cognitive function, MMSE scores, and World learning test (immediate and delayed) over time. Participants with normal grief did not show a stronger cognitive decline in any of cognitive tests than the reference group. CONCLUSIONS: Participants with PGD showed a stronger cognitive decline than the reference group during 7 years of follow-up. This suggests that PGD is a risk factor for cognitive decline, but this study cannot detect the psychobiological mechanism underlying this longitudinal association.

The Impact of Complicated Grief on Diurnal Cortisol Levels Two Years After Loss: A Population-Based Study.

OBJECTIVE: Few studies have focused on the effect of complicated grief-unresolved and prolonged grief-on the neuroendocrine systems. The present study examined the association of complicated grief and normal grief with the diurnal cortisol patterns in a large population-based study. METHODS: This study was set in the Rotterdam Study and comprised 2084 persons aged older than 55 years (mean [SD] age, 64.9 [5.5] years). Participants were assessed with the Complicated Grief Inventory and classified into no grief (n = 1922), normal grief (n = 131), or complicated grief (n = 31) if they experienced the loss in the past 2 years. Saliva samples were collected to measure cortisol levels. Morning cortisol and summary measures (area under the curve and the slope) were studied to account for the diurnal pattern of cortisol. Persons with depressive disorders were excluded, and analyses were additionally adjusted for depressive symptoms. RESULTS: Compared to normal grievers, participants with complicated grief showed lower levels of morning cortisol (11.26 vs 15.51 nmol/L; difference, -4.24; 95% confidence interval [CI] = -7.87 to -0.62; p = .022), and lower levels of overall diurnal cortisol (6.89 vs 8.98 nmol/L; difference, -2.09; 95% CI = -3.81 to -0.37; p = .017). No difference was observed in slope between both groups. Participants with complicated grief also showed lower levels of morning cortisol than the nongrievers (11.26 vs 14.71; difference, -3.46; 95% CI = -6.78 to -0.13; p = .042). In contrast, cortisol secretion patterns did not differ between persons with normal grief and nongrieving controls. CONCLUSIONS: Participants with complicated grief showed low levels of morning cortisol and low overall diurnal cortisol levels characteristic for a chronic stress reaction.

Sexual Activity and Physical Tenderness in Older Adults: Cross-Sectional Prevalence and Associated Characteristics.

BACKGROUND: Despite a common misconception, older adults engage in sexual behavior. However, there is limited sexual behavior research in older adults, which is often restricted to small samples, to cohorts recruiting adults from 45 years old, and to questions regarding only sexual intercourse. AIM: To assess the cross-sectional prevalence of and characteristics associated with sexual activity and physical tenderness in community-dwelling older adults. METHODS: From the Rotterdam Study, sexual activity and physical tenderness were assessed in 2,374 dementia-free, community-dwelling men and women at least 65 years old from 2009 through 2012 in the Netherlands. Analyses were stratified by sex and partner status. OUTCOMES: Sexual activity and physical tenderness (eg, fondling or kissing) in the last 6 months. Potential associated characteristics included measurements of demographics, socioeconomic position, health behavior, and health status. RESULTS: The vast majority of partnered participants (men, n = 858; women, n = 724) had experienced physical tenderness in the previous 6 months (83.7% of men and 82.9% of women) and nearly half had engaged in sexual activity (49.5% and 40.4% respectively). Very few unpartnered women (n = 675) had engaged in sexual activity (1.3%) or physical tenderness (5.2%), whereas prevalence rates were slightly higher for unpartnered men (n = 117; 13.7% or 17.1%). Engaging in sexual behavior was generally associated with younger age, greater social support, healthier behaviors, and better physical and psychological health. CLINICAL IMPLICATIONS: Findings show that older adults engage in sexual activity. It is important not to assume that an older person is not interested in sexual pleasure or that an older person is unhappy with not having a sexual partner. Offering an opportunity for open discussion of sexuality and medical assistance without imposing is a difficult balance. We encourage health care professionals to proactively address sexuality and extend knowledge about safe sex and sexual function to older adults. STRENGTHS AND LIMITATIONS: Thus far, this is one of the largest samples of sexual behavior assessment in adults older than 60 years. Limitations of this study are common in sexual behavior research, including low sexual behavior engagement among unpartnered older adults and a small sample of unpartnered men, which restricted sex- and age-specific implications. CONCLUSION: Almost half of partnered older adults engaged in sexual activity and more than two thirds engaged in physical tenderness, but very few unpartnered older adults engaged in these behaviors. The greatest barrier to being sexually active at an older age is lack of a partner, which particularly affects women. Sexuality is an important aspect of active aging. Freak-Poli R, Kirkman M, De Castro Lima G, et al. Sexual Activity and Physical Tenderness in Older Adults: Cross-Sectional Prevalence and Associated Characteristics. J Sex Med 2017;14:918-927.

Happiness, rather than depression, is associated with sexual behaviour in partnered older adults.

Background: The relation between positive psychological well-being (PPWB) and sexual behaviour is understudied in older adult groups. Objective: To examine the relation between PPWB (positive affect and life satisfaction) and sexual behaviour (sexual activity and physical tenderness) in older adults, and whether it is independent from depressive symptoms and uniform across older age groups. Design: Cross-sectional. Setting: Community-dwelling adults aged 65 years or older, Rotterdam, The Netherlands. Methods: Sexual behaviour, the Cantril Self-Anchoring Striving Scale, the Center for Epidemiological Studies Depression (CES-D) scale and partner status were assessed in 2,373 dementia-free older adults from the Rotterdam Study. Results: For partnered participants, greater positive affect and life satisfaction was associated with more sexual activity and physical tenderness. Although CES-D was negatively associated with sexual behaviour within partnered older adults, there was no association between the negative affect sub-scale and sexual behaviour. The relations were independent of depressive symptoms, physical health and chronic disease status and were observed for both sexes at all older ages. For unpartnered participants, greater life satisfaction and was associated with more physical tenderness. There was low prevalence of sexual behaviour in unpartnered participants, limiting further stratification. Conclusion: Greater PPWB was associated with more sexual behaviour in partnered, community-dwelling older adults. We are the first to demonstrate that sexual behaviour is associated with PPWB, rather than lack of depressive symptoms; and that the association was present at all ages for partnered older adults. Limited conclusions can be drawn for unpartnered older adults as their sexual behaviour was infrequent.

Genome wide association identifies common variants at the SERPINA6/SERPINA1 locus influencing plasma cortisol and corticosteroid binding globulin.

Variation in plasma levels of cortisol, an essential hormone in the stress response, is associated in population-based studies with cardio-metabolic, inflammatory and neuro-cognitive traits and diseases. Heritability of plasma cortisol is estimated at 30-60% but no common genetic contribution has been identified. The CORtisol NETwork (CORNET) consortium undertook genome wide association meta-analysis for plasma cortisol in 12,597 Caucasian participants, replicated in 2,795 participants. The results indicate that <1% of variance in plasma cortisol is accounted for by genetic variation in a single region of chromosome 14. This locus spans SERPINA6, encoding corticosteroid binding globulin (CBG, the major cortisol-binding protein in plasma), and SERPINA1, encoding α1-antitrypsin (which inhibits cleavage of the reactive centre loop that releases cortisol from CBG). Three partially independent signals were identified within the region, represented by common SNPs; detailed biochemical investigation in a nested sub-cohort showed all these SNPs were associated with variation in total cortisol binding activity in plasma, but some variants influenced total CBG concentrations while the top hit (rs12589136) influenced the immunoreactivity of the reactive centre loop of CBG. Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants. These findings reveal a novel common genetic source of variation in binding of cortisol by CBG, and reinforce the key role of CBG in determining plasma cortisol levels. In turn this genetic variation may contribute to cortisol-associated degenerative diseases.

24-HOUR ACTIVITY RHYTHM AND SLEEP DISTURBANCES IN DEPRESSION AND ANXIETY: A POPULATION-BASED STUDY OF MIDDLE-AGED AND OLDER PERSONS.

BACKGROUND: Disturbed circadian rhythms have been associated with depression and anxiety, but it is unclear if disturbances in the 24-hr activity rhythm and sleep are independently and specifically related to these disorders. METHODS: In 1,714 middle-aged and elderly participants of the Rotterdam Study, we collected actigraphy recordings of at least 96 hr (138 ± 14 hr, mean ± standard deviation). Activity rhythms were quantified calculating the fragmentation of the rhythm, stability of the rhythm over days, and timing of the rhythm. Total sleep time, sleep onset latency, and wake after sleep onset were also estimated with actigraphy. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression scale, persons with clinically relevant depressive symptoms were interviewed to diagnose DSM-IV-depressive disorder. Anxiety disorders were determined with the Munich version of the Composite International Diagnostic Interview. RESULTS: More fragmented rhythms were associated with clinically relevant depressive symptoms (odds ratio (OR): 1.27, 95% confidence interval (CI): 1.04;1.54) and anxiety disorders (OR: 1.39, 95% CI: 1.14;1.70) after covariate adjustment. Less stable rhythms, longer sleep onset latency, and more wake after sleep onset were related to clinically relevant depressive symptoms or anxiety disorders only if not adjusted for covariates and other activity rhythm and sleep indicators. CONCLUSIONS: Our study in middle-aged and elderly persons suggests that fragmentation of the 24-hr activity rhythm is associated with depression and anxiety. Moreover, this association also largely accounts for the effect of disturbed sleep on these psychiatric disorders.

Genetic diversity is a predictor of mortality in humans.

BACKGROUND: It has been well-established, both by population genetics theory and direct observation in many organisms, that increased genetic diversity provides a survival advantage. However, given the limitations of both sample size and genome-wide metrics, this hypothesis has not been comprehensively tested in human populations. Moreover, the presence of numerous segregating small effect alleles that influence traits that directly impact health directly raises the question as to whether global measures of genomic variation are themselves associated with human health and disease. RESULTS: We performed a meta-analysis of 17 cohorts followed prospectively, with a combined sample size of 46,716 individuals, including a total of 15,234 deaths. We find a significant association between increased heterozygosity and survival (P = 0.03). We estimate that within a single population, every standard deviation of heterozygosity an individual has over the mean decreases that person's risk of death by 1.57%. CONCLUSIONS: This effect was consistent between European and African ancestry cohorts, men and women, and major causes of death (cancer and cardiovascular disease), demonstrating the broad positive impact of genomic diversity on human survival.

Anxiety is not associated with the risk of dementia or cognitive decline: the Rotterdam Study.

OBJECTIVE: Anxiety and depression frequently co-occur in the elderly and in patients with dementia. Prior research has shown that depression is related to the risk of dementia, but the effect of anxiety on dementia remains unclear. We studied whether anxiety symptoms and anxiety disorders are associated with the risk of dementia and cognition. METHODS: We studied 2,708 nondemented participants from the prospective, population-based Rotterdam Study who underwent the Hospital Anxiety and Depression Scale (HADS) (sample I, baseline 1993-1995) and 3,069 nondemented participants who underwent screening for anxiety disorders (sample II, baseline 2002-2004). In 1993-1995, anxiety symptoms were assessed using the HADS. In 2002-2004, anxiety disorders were assessed using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. In both study samples, participants were continuously monitored for dementia until January 1, 2011. Cognition was tested in 2002-2004 and at a follow-up visit in 2009-2011 in sample II only. RESULTS: In sample I, 358 persons developed dementia, and in sample II, 248 persons developed dementia. We did not find an association with the risk of dementia for anxiety symptoms (hazard ratio 1.05, 95% confidence interval: 0.77-1.43, Wald statistic 0.08, p = 0.77, df = 1) or for anxiety disorders (hazard ratio 0.92, 95% confidence interval: 0.58-1.45, Wald statistic 0.14, p = 0.71, df = 1). We could demonstrate an association of anxiety disorders with poor cognition cross-sectionally, but this attenuated after additional adjustments. CONCLUSION: Our findings do not offer evidence for an association between anxiety symptoms or anxiety disorders with the risk of dementia or with cognition. This suggests that anxiety is not a risk factor nor a prodrome of dementia in an elderly, community-dwelling population.

Depressive symptoms predict incident dementia during short- but not long-term follow-up period.

BACKGROUND: Whether depression is a long-term risk factor for dementia or represents a dementia prodrome is unclear. Therefore, we examined the relationship between depressive symptoms and dementia during short and long follow-up in a population-based cohort. METHODS: In the Rotterdam Study, 4393 nondemented individuals were followed for incident dementia for 13.7 years by continuous monitoring. Cox proportional hazards models for different time intervals were used to estimate the risk of incident dementia. RESULTS: Five-hundred eighty-two participants developed dementia during 13.7 years. Persons with depressive symptoms had an 8% increased risk of dementia compared with those without depressive symptoms during the overall follow-up. The risk was highest in the short and intermediate follow-up, particularly in men. We did not find an association in the follow-up period beyond 10 years. CONCLUSION: Our results suggest that late-life depressive symptoms are part of a dementia prodrome rather than an independent risk factor of dementia.

Associations Between Blood Levels of NLRP3 Inflammasome Components and Obsessive Compulsive Disorder.

Introduction: Even though the effect of inflammation on pathogenesis of obsessive compulsive disorder (OCD) is known, information regarding the underlying mechanisms are yet to be revealed. The NLRP3 inflammasome complex is an important component of the innate immune system that initiates and mediates inflammatory response to a variety of stimuli. This study aims to inquire into a possible association between NLRP3 inflammasome complex and OCD. Methods: This case-control study included 103 participants (51 cases with OCD and 52 healthy controls). All participants were evaluated with the Yale Brown Obsessive Compulsive Scale, Hamilton Depression Scale, and Hewitt Multidimensional Perfectionism Scale. RNA and proteins were extracted from peripheral blood mononuclear cells. Expression of NLRP3 inflammasome components were determined using quantitative real-time polymerase chain reaction (PCR) and Western blotting. Levels of Serum IL-1beta and IL-18 cytokine were determined by ELISA. Results: NEK7 and CASP1 mRNA levels were significantly higher in OCD patients, compared to controls. Pro-caspase-1 protein levels were elevated, as well. Regression analysis showed that NEK7 mRNA and pro-caspase-1 protein levels can differentiate OCD and healthy control groups. Conclusion: Our results provide insight into the molecular alterations that could explain the inflammation-OCD association.

The Relationship Between Cardiovascular Disease Risk and Major Depression.

Introduction: Cardiovascular risk in depression has been investigated in small clinical samples and population-based studies revealing inconclusive results. However, cardiovascular risk in drug-naive depressed patients has not been tested extensively. Methods: Body mass index-based Framingham Cardiovascular Risk Scores and soluble intercellular adhesion molecule-1 (sICAM-1) levels were used to assess the risk of cardiovascular disease in drug-naive depressed patients and healthy volunteers. Conclusion: There were no significant differences in Framingham Cardiovascular Risk Scores and individually assessed risk variables between patients and healthy controls (HC). Both groups were comparable in terms of sICAM-1. Results: The widely recognized association between cardiovascular risk and major depression might be more prominent in older depressed patients and patients with recurring episodes.

Endocrinological Approach to Adolescents with Gender Dysphoria: Experience of a Pediatric Endocrinology Department in a Tertiary Center in Turkey

Objective: A significant rise in the number of trans adolescents seeking medical interventions has been reported in recent years. The aim of this study was to report the clinical features, treatment, and follow-up of adolescents with gender dysphoria (GD) with our increased experience. Methods: Twenty-six male-to-female (MTF) and twenty-seven female-to-male (FTM) adolescents who were referred to the GD-outpatient clinic between 2016 and 2022 were reviewed. The clinical and laboratory findings of thirty transgender adolescents (15 FTM /15 MTF) who received medical intervention were evaluated retrospectively. Results: Most individuals (60.4%) were admitted between 2020 and 2022, and the remaining (39.6%) were admitted between 2016 and 2019. At the time of referral, median age was 16.3 years [interquartile range (IQR) 1.53; range 13.2-19.4] in 26 MTF, and 16.4 years (IQR 1.74; range 11.7-21.6) in 27 FTM adolescents. The median age at pubertal blockage with gonadotropin-releasing hormone analog and androgen receptor blocker was 16.4 years (IQR 1.4; range 11.7-17.8) in 22 adolescents (9 MTF, 13 FTM), and 17.4 years (IQR 1.4; range 15.5-19.4) in 6 MTF individuals, respectively. Cross-sex hormone therapy was commenced in 21 adolescents (12 MTF, 9 FTM) at the median age of 17.7 years (IQR 0.61; range 16-19.5). Fifteen individuals (8 MTF, 7 FTM) have been transferred to the adult endocrinology department in transition clinics. Conclusion: All treatments were generally well tolerated and effective, including bicalutamide, and no significant side effects were observed. Transition clinics played an important role in the better management of gender reassignment processes.

Using personality disorders to distinguish between patients with psychogenic nonepileptic seizures and those with epileptic seizures.

Identifying psychiatric disorders rather than psychiatric symptoms might help to distinguish patients with psychogenic nonepileptic seizures (PNES) from those with epileptic seizures (ES). Patients with PNES (n=35), patients with ES (n=35), and healthy controls (n=37) were compared with respect to the prevalence of psychiatric disorders in this study. We tested the predictive power of having axis I psychiatric disorders, as well as personality disorders, in distinguishing ES from PNES. There was no significant difference between the patient groups in the prevalence of axis I psychiatric disorders. Personality disorders were more prevalent in the PNES group than in the ES group (P<0.05). Having a personality disorder was the only predictor for the PNES group. Having a personality disorder seems to be a more significant predictor for PNES than having an axis I psychiatric disorder. Greater attention should be paid to personality disorders in the differentiation of PNES and ES and the provision of effective treatment.

Relationship of negative symptom severity with cognitive symptoms and functioning in subjects at ultra-high risk for psychosis.

AIM: Negative symptoms and cognition are related with functioning in schizophrenia. However, it is not clear whether they have a similar effect in individuals at ultra-high risk (UHR) for psychosis. In this study, we aimed to explore relationship of negative symptoms with cognition and functioning cross-sectionally in people with UHR for psychosis. METHODS: In total, 107 people participated in this study. We assessed negative symptoms with Scale for Negative Symptoms (SANS). We applied a cognitive battery including seven tests. We evaluated functioning by using Global Assessment of Functioning Scale and work/study status as an indicator of role functioning. RESULTS: SANS scores were correlated to global functioning cross-sectionally. SANS total score was correlated to cognitive test scores related to cognitive flexibility and attention. Only Trail Making Test B (TMT B) was negatively correlated to global functioning. SANS-affective blunting and SANS-avolition scores were independently related to global functioning. There was a significant indirect effect of the TMT B and composite attention scores on global functioning through negative symptoms indicating a complete mediation. CONCLUSION: Our findings suggest that negative symptoms, particularly avolition have an impact on functioning and the association of cognition with functioning was mediated by negative symptoms in UHR.

Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression.

BACKGROUND: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression. METHODS: We fine-mapped the classical MHC (chr6: 29.6-33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10-6) and a candidate threshold (1.6 × 10-4). RESULTS: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97-0.99). CONCLUSIONS: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.

Self-management plans for asthma control and predictors of patient compliance.

OBJECTIVE: To evaluate the impact of peak flow or symptom-based self-management plans on asthma control and patients' quality of life and to determine the main psychosocial factors that affect compliance with these plans. METHODS: The study sample consisted of 63 patients with persistent asthma outpatients. Data collection included demographics, pulmonary functions, symptom scores, and asthma control parameters recorded over the previous 2 consecutive years. A standard asthma self-management education program including personal action plans was given to the patients who were randomly divided into peak flow meter (PFM) (n = 31) or symptom-based (n = 32) action plan groups. Patients were then assessed prospectively for various study outcomes including symptoms, drug compliance, psychiatric co-morbidities, quality of life, and asthma control over the next 12 months. Psychiatric co-morbidities were assessed using Rotter's Internal and External Locus of Control Scale (RIELCS), Beck Depression Inventory (BDI), Structured Clinical Interview for DSM-IV (SCID-I), Spielberger State-Trait-Anxiety Inventory (STAI), and Short Form-36 (SF-36). RESULTS: Of the 63 patients (79% female; mean age 43), 85% of them had moderately or severely persistent asthma. Baseline demographics, clinical parameters, psychiatric diagnosis, and quality of life were not different between groups. Personal asthma plans increased optimal asthma control significantly. Emergency visits, antibiotic treatments, systemic corticosteroid treatments, and unscheduled visits were fewer than the previous year. Control parameters were better in the PFM group. After the self-management education, the quality of life dimensions, i.e., vitality, total mental and general scores of both groups increased. Frequency of psychiatric co-morbidities decreased from 61.9% to 49.2%. However, state anxiety levels were increased in both groups. These increases were statistically significant in the PFM group. Compliance with the action plans was better in the PFM group. Higher BDI scores were associated with worse compliance. No statistically significant association was found between demographic parameters and the compliance. Although the compliance had decreased in both groups after 6 months, this decrease was greater in the symptom group. Higher RIELCS and mental health scores were associated with better compliance. CONCLUSION: Introduction of self-management plans improved illness control and quality of life in asthma patients. Use of the PFM and the presence of higher RIELCS and lower BDI scores can be used to predict compliance with the action plans.

Schizophrenia in microcephalic osteodysplastic primordial dwarfism type II syndrome: supporting evidence for an association between the PCNT gene and schizophrenia.

Schizophrenia is a genetically complex disease that is related to neurodevelopmental abnormalities. Several genetic polymorphisms and genetic syndromes associated with neurodevelopmental processes have been linked to schizophrenia. In this case report, we present a case with an association between microcephalic osteodysplastic primordial dwarfism type II and schizophrenia. Microcephalic osteodysplastic primordial dwarfism type II syndrome is a rare, autosomal recessive disease that occurs as a result of the mutations in the pericentrin (PCNT) gene that are responsible for cell cycle and division. In this report, we discuss the possible association between the PCNT gene and schizophrenia.