Genome-wide association study of co-occurring anxiety in major depression.

OBJECTIVES: Co-morbidity between depression and anxiety disorders is common. In this study we define a quantitative measure of anxiety by summating four anxiety items from the SCAN interview in a large collection of major depression (MDD) cases to identify genes contributing to this complex phenotype. METHODS: A total of 1522 MDD cases dichotomised according to those with at least one anxiety item scored (n = 1080) and those without anxiety (n = 442) were analysed, and also compared to 1588 healthy controls at a genome-wide level, to identify genes that may contribute to anxiety in MDD. RESULTS: For the quantitative trait, suggestive evidence of association was detected for two SNPs, and for the dichotomous anxiety present/absent ratings for three SNPs at genome-wide level. In the genome-wide analysis of MDD cases with co-morbid anxiety and healthy controls, two SNPs attained P values of < 5 × 10⁻⁶. Analysing candidate genes, P values ≤ 0.0005 were found with three SNPs for the quantitative trait and three SNPs for the dichotomous trait. CONCLUSIONS: This study provides an initial genome-wide assessment of possible genetic contribution to anxiety in MDD. Although suggestive evidence of association was found for several SNPs, our findings suggest that there are no common variants strongly associated with anxious depression.

Addition of aripiprazole to the clozapine may be useful in reducing anxiety in treatment-resistant schizophrenia.

There exist many case reports and studies on the antipsychotic augmentation by aripirazole in partial responders to clozapine, the most seem to be finding a slight difference in the PANSS and CGI scores after the aripirazole addition. The results of our report are compatible with those of other studies but, we have found a considerable antianxiety action in both of the cases. The 5HT1A agonism of aripirazole could be hypothesized as mechanism contributing to this effect.

Quetiapine affects neuropeptide Y and corticotropin-releasing hormone in cerebrospinal fluid from schizophrenia patients: relationship to depression and anxiety symptoms and to treatment response.

Cumulative evidence indicates that neuropeptides play a role in the pathophysiology of schizophrenia. Early data showed increased neuropeptide Y (NPY) in cerebrospinal fluid (CSF) from schizophrenia patients and data from rodents show that antipsychotic drugs modulate NPY levels in and release from selected rat brain regions. In view of these findings we investigated whether the atypical antipsychotic quetiapine, originally used as an antipsychotic but subsequently shown to be efficient also in major depressive disorder and in both poles of bipolar disorder, would affect NPY-like immunoreactivity (-LI), and corticotropin-releasing hormone (CRH)-LI levels in CSF of schizophrenia patients. NPY-LI and CRH-LI in CSF were determined in 22 patients with schizophrenia. Lumbar puncture was performed at baseline and again after 4 wk of quetiapine treatment (600 mg/d). Patients were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at weekly intervals. Quetiapine treatment was associated with a significant increase in NPY-LI (p<0.001) and decrease in CRH-LI (p<0.01). Stepwise multiple regression analysis revealed that ΔNPY-LI and ΔCRH-LI levels predicted 63% (p<0.001) of the variability of the ΔPANSS total score, ΔNPY-LI 42% (p<0.05) of the ΔPANSS anxiety items (G2) and ΔCRH-LI 40% (p=0.05) of the ΔPANSS depression items (G6). These results suggest that while quetiapine's effects on monoamines are probably related to its antipsychotic properties, the modulation of NPY and CRH accounts for its antidepressant and anxiolytic effects and can be markers of response.

Cardio respiratory activity in high-anxious vs. low-anxious professional music students before and during performance

Questionnaire studies indicate that high-anxious musicians may suffer from hyperventilation symptoms before and/or during performance. Reported symptoms include amongst others shortness of breath, fast or deep breathing, dizziness and thumping heart. However, no study has yet tested if these self-reported symptoms reflect actual cardio respiratory changes. Disturbances in breathing patterns and hyperventilation may contribute to the often observed poorer performance of anxious musicians under stressful performance situations. The main goal of this study is to determine if music performance anxiety is manifest physiologically in specific correlates of cardio respiratory activity. We studied 74 professional music students divided into two groups (i.e. high-anxious and lowanxious) based on their self-reported performance anxiety in three distinct situations: baseline, private performance (without audience), public performance (with audience). We measured a) breathing patterns, end-tidal carbon dioxide (EtCO2, a good non-invasive estimator for hyperventilation), ECG and b) self-perceived emotions and self-perceived physiological activation. The poster will concentrate on the preliminary results of this study. The focus will be a) on differences between high-anxious and low-anxious musicians regarding breaths per minute and heart rate and b) on the response coherence between self-perceived palpitations and actual heart rate.

Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium.

OBJECTIVES: To investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach. DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and observational meta-analyses of the associations of smoking status and smoking heaviness with depression, anxiety and psychological distress. PARTICIPANTS: Current, former and never smokers of European ancestry aged ≥16 years from 25 studies in the Consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). PRIMARY OUTCOME MEASURES: Binary definitions of depression, anxiety and psychological distress assessed by clinical interview, symptom scales or self-reported recall of clinician diagnosis. RESULTS: The analytic sample included up to 58 176 never smokers, 37 428 former smokers and 32 028 current smokers (total N=127 632). In observational analyses, current smokers had 1.85 times greater odds of depression (95% CI 1.65 to 2.07), 1.71 times greater odds of anxiety (95% CI 1.54 to 1.90) and 1.69 times greater odds of psychological distress (95% CI 1.56 to 1.83) than never smokers. Former smokers also had greater odds of depression, anxiety and psychological distress than never smokers. There was evidence for positive associations of smoking heaviness with depression, anxiety and psychological distress (ORs per cigarette per day: 1.03 (95% CI 1.02 to 1.04), 1.03 (95% CI 1.02 to 1.04) and 1.02 (95% CI 1.02 to 1.03) respectively). In Mendelian randomisation analyses, there was no strong evidence that the minor allele of rs16969968/rs1051730 was associated with depression (OR=1.00, 95% CI 0.95 to 1.05), anxiety (OR=1.02, 95% CI 0.97 to 1.07) or psychological distress (OR=1.02, 95% CI 0.98 to 1.06) in current smokers. Results were similar for former smokers. CONCLUSIONS: Findings from Mendelian randomisation analyses do not support a causal role of smoking heaviness in the development of depression and anxiety.

Anxiety, depression and school absenteeism in youth with chronic or episodic headache.

BACKGROUND: Chronic daily headache (CDH) in children has been documented in general and clinical populations. Comorbid psychological conditions, risk factors and functional outcomes of CDH in children are not well understood. OBJECTIVES: To examine anxiety and depression, associated risk factors and school outcomes in a clinical population of youth with CDH compared with youth with episodic headache (EH). METHODS: Data regarding headache characteristics, anxiety, depression and missed school days were collected from 368 consecutive patients eight to 17 years of age, who presented with primary headache at a specialized pediatric headache centre. RESULTS: A total of 297 patients (81%) were diagnosed with EH and 71 were diagnosed with CDH. Among those with CDH, 78.9% presented with chronic tension-type headache and 21.1% with chronic migraine (CM). Children with CDH had a higher depression score than the standardized reference population. No difference was observed for anxiety or depression scores between children with CDH and those with EH. However, children with CM were more anxious and more depressed than those with chronic tension-type headache. Youth experiencing migraine with aura were three times as likely to have clinically significant anxiety scores. Headache frequency and history were not associated with psychopathological symptoms. Children with CDH missed school more often and for longer periods of time. CONCLUSIONS: These findings document the prevalence of anxiety, depression and school absenteeism in youth with CDH or EH. The present research also extends recent studies examining the impact of aura on psychiatric comorbidity and the debate on CM criteria.

Associations of Serum Uric Acid and SLC2A9 Variant with Depressive and Anxiety Disorders: A Population-Based Study.

BACKGROUND: Limited information exists regarding the association between serum uric acid (SUA) and psychiatric disorders. We explored the relationship between SUA and subtypes of major depressive disorder (MDD) and specific anxiety disorders. Additionally, we examined the association of SLC2A9 rs6855911 variant with anxiety disorders. METHODS: We conducted a cross-sectional analysis on 3,716 individuals aged 35-66 years previously selected for the population-based CoLaus survey and who agreed to undergo further psychiatric evaluation. SUA was measured using uricase-PAP method. The French translation of the semi-structured Diagnostic Interview for Genetic Studies was used to establish lifetime and current diagnoses of depression and anxiety disorders according to the DSM-IV criteria. RESULTS: Men reported significantly higher levels of SUA compared to women (357±74 µmol/L vs. 263±64 µmol/L). The prevalence of lifetime and current MDD was 44% and 18% respectively while the corresponding estimates for any anxiety disorders were 18% and 10% respectively. A quadratic hockey-stick shaped curve explained the relationship between SUA and social phobia better than a linear trend. However, with regards to the other specific anxiety disorders and other subtypes of MDD, there was no consistent pattern of association. Further analyses using SLC2A9 rs6855911 variant, known to be strongly associated with SUA, supported the quadratic relationship observed between SUA phenotype and social phobia. CONCLUSIONS: A quadratic relationship between SUA and social phobia was observed consistent with a protective effect of moderately elevated SUA on social phobia, which disappears at higher concentrations. Further studies are needed to confirm our observations.

Anxiety and severity of illicit substance use in adolescence: Evaluating the mediating role of perceived coping styles

The purpose of this study was to examine whether coping styles (Active coping, Internal coping and Withdrawal coping) mediated the relationships between anxiety and severity of illicit substance use among a sample of 110 Swiss adolescents ages 12-19 (M=16.3, SD=1.66). The current study tested two competing models of anxiety on severity of illicit substance use. In the first model, we tested the direct effect of trait anxiety (STAI-Y anxiety score) on severity of illicit substance use (ADAD drug use severity rating), while in the second models we examined the mediating role of coping styles in the link between trait anxiety and severity of illicit substance use. Path models indicated that the associations between trait anxiety and severity of illicit substance use are partially mediated by active and withdrawal coping styles. Limitations of the findings and implications for prevention of substance use in adolescence are discussed.

Transgenerational transmission of trauma in families of Holocaust survivors: The consequences of extreme family functioning on resilience, Sense of Coherence, anxiety and depression.

BACKGROUND: The psychological transmission of the noxious effects of a major trauma from one generation to the next remains unclear. The present study aims to identify possible mechanisms explaining this transmission among families of Holocaust Survivors (HS). We hypothesized that the high level of depressive and anxiety disorders (DAD) among HS impairs family systems, which results in damaging coping strategies of their children (CHS) yielding a higher level of DAD. METHODS: 49 CHS completed the Resilience Scale for Adults, the Hopkins Symptom Check List-25, the 13-Item Sense of Coherence (SOC) scale, and the Family Adaptability and Cohesion Scale. We test a mediation model with Family types as the predictor; coping strategies (i.e. Resilience or SOC) as the mediator; and DAD as the outcome variable. RESULTS: Results confirm that the CHS׳ family types are more often damaged than in general population. Moreover, growing in a damaged family seems to impede development of coping strategies and, therefore, enhances the occurrence of DAD. LIMITATIONS: The present investigation is correlational and should be confirmed by other prospective investigations. CONCLUSIONS: At a theoretical level we propose a mechanism of transmission of the noxious effects of a major trauma from one generation to the next through family structure and coping strategies. At a clinical level, our results suggest to investigate the occurrence of trauma among parents of patients consulting for DAD and to reinforce their coping strategies.

The effectiveness of a standardised preoperative preparation in reducing child and parent anxiety: a single-blind randomised controlled trial.

AIMS: To evaluate the effect of a structured preoperative preparation on child and parent state anxiety, child behavioural change and parent satisfaction. BACKGROUND: It is estimated that around 50-70% of hospitalised children experience severe anxiety and distress prior to surgery. Children who are highly anxious and distressed preoperatively are likely to be distressed on awakening and have negative postoperative behaviour. Although education before surgery has been found to be useful mostly in North America, the effectiveness of preoperative preparation programme adapted to the Australian context remains to be tested. DESIGN: This single-blind randomised controlled study was conducted at a tertiary referral hospital for children in Western Australia. METHODS: Following ethics approval and parental consent, 73 children and one of their carers (usually a parent) were randomly assigned into two groups. The control group had standard practice with no specific preoperative education and the experimental group received a preoperative preparation, including a photo file, demonstration of equipment using a role-modelling approach and a tour. RESULTS: The preoperative preparation reduced parent state anxiety significantly (-2·32, CI -4·06 to -0·56, p = 0·009), but not child anxiety (-0·59, CI -1·23 to 0·06, p = 0·07). There was no significant difference in child postoperative behaviour or parent satisfaction between the groups. There was a significant two-point pain score reduction in the preoperative preparation group, when compared with the control group median 2 (IQR 5) and 4 (IQR 4), respectively (p = 0·001).¦CONCLUSIONS: Preoperative preparation was more efficient on parent than child. Although the preoperative preparation had limited effect on child anxiety, it permitted to decrease pain experience in the postoperative period.¦RELEVANCE TO CLINICAL PRACTICE: Parents should be actively involved in their child preoperative preparation.

Defensive flexibility and its relation to symptom severity, depression, and anxiety.

Numerous studies have examined which individual defense mechanisms are related with mental health, and which are linked with psychopathology. However, the idea that a flexible use of defensive mechanisms is related to psychological wellbeing remained a clinical assumption, which this study sought to test empirically. A total of 62 (N = 62) outpatients participated in the study and were assessed with the Symptom Checklist-90R and the Social Adjustment Self-rated Scale. A subsample of 40 participants was further assessed using the Hamilton Depression (HAMD-21) and Anxiety scales (HAMA-21). The first therapy session of all participants was transcribed and rated using the Defense Mechanisms Ratings Scales (), and the Overall Defensive Functioning (ODF) score, which indicates the maturity of one's defensive functioning, was computed. An indicator of flexible use of defenses was also calculated based on the Gini Concentration C measure. Results showed that defensive flexibility, but not ODF, could predict anxiety scores. Symptom severity was predicted by both ODF and defensive flexibility, although in directions opposite to our predictions. Results suggest that defensive flexibility captures another aspect of an individual's functioning not assessed by the ODF, and that it is a promising new way of documenting defensive functioning.