Strength training integrated in long term collaborative care of patients with schizophrenia.

INTRODUCTION: Skeletal muscle strength is reduced in patients with schizophrenia, contributing to their impaired physical health, functional performance, and potentially mental health challenges. Although short-term training programs have shown promising results, improving muscle strength and functional performance, it is unknown how exercise can be successfully integrated into the long-term clinical care of outpatients with schizophrenia. OBJECTIVE: To investigate effects of strength training with adherence support in a collaborative care model. METHODS: We randomized 28 men and 20 women (mean ± SD, 35 ± 11 years) to leg press maximal strength training (MST) with 4 sets at 90 % of one repetition maximum (1RM) 2 × week, facilitated by municipal service and professional supervision (TG), or a control group (CG). RESULTS: The TG increased scaled leg press 1RM (0-3 months: 19 %; 0-6 months: 31 %, 0-12 months: 40 %, all p < .001, and 3-12 months: 18 %, p < .05) and power (0-3 months, 11 %; 0-6 months: 22 %, 0-12 months: 26 %, all p < .001, and 3-12 months: 13 %, p < .05) throughout the 1-year period compared to the CG. The increased muscle strength was accompanied by improved sit-to-stand performance (20 %) after 12 months (p < .001). Both groups also exhibited within-group improvements in walking work efficiency after 6 months (TG: 13 %; CG: 23 %) and 1 year (TG: 11 %; CG: 21 %, p < .01-0.05), but with no evident differences between the groups. Stair climbing performance remained unchanged. CONCLUSION: Our results reveal that strength training can successfully be integrated as a part of long-term clinical care of outpatients with schizophrenia, contributing to improved functional performance.

Essential Oil Content, Antioxidative Characteristics and Enzyme Inhibitory Activity of Sideritis akmanii Aytaç, Ekici & Dönmez

Objectives: Our research measures the essential oil analysis mineral substance profiles, total phenolic substance content, free radical scavenger properties, antioxidant capacity, and enzyme inhibitory activity of Sideritis akmanii Aytaç, Ekici & Dönmez, 1996. Materials and Methods: A mixture of S. akmanii plant roots and stems were used. Essential fatty acid components of S. akmanii were determined by gas chromatography-mass spectrometry and bioelement concentrations by inductively coupled plasma optical emission spectrometry. The antioxidant activity of extracts was screened by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities, total phenolic content, total antioxidant status (TAS), total oxidant status (TOS) analysis. Cholinesterase (ChE), α-glucosidase, α-amylase, and tyrosinase inhibitory activity was determined. Results: The results demonstrated that the phenolic substance content was higher in methanol extract (144.08±2.01 µg gallic acid equivalent/mg extract). DPPH scavenging effect of S. akmanii methanol extract (73.2%) was higher than acetone extract (60.1%). TAS values of extract methanol and acetone were 2.32±0.4 and 2.38±0.2 µmol trolox Eq /g, TOS values were 4.88±0.6 and 5.04±0.5 µmol H2O2 Eq/g, and oxidative stress index values were 2.1±0.3 and 2.11±0.24 arbitrary units, respectively. Hexadecanoic acid (17.9%) was found as the main component in the plant essential oil. S. akmanii species was prominent with high Mg and Al concentrations. Anti-ChE activity was determined that acetone extract (42.95%±0.90; 217.37±0.81 mg galantamine equivalents [(GALAEs)/g] exhibited higher than methanol (33.33%±1.81; 208.76±1.62 mg GALAE/g). α-Amylase inhibition was high in methanol extract [53.62±1.85 mmol angiotensin converting enzymes (ACEs)/g extract] compared to acetone (47.73±0.92 mmol ACEs/g extract). The tyrosinase inhibitory activity of S. akmanii was determined very low inhibition of the reference compound. Conclusion: It has been determined that S. akmanii Aytaç, Ekici & Dönmez extracts have antioxidant properties and can inhibit acetylcholinesterase, α-glucosidase, α-amylase enzymes. This study is informative on future studies on S. akmanii a highly bioavailable species and very extensive studies should be carried out.

Kynurenine metabolites and ratios differ between Chronic Fatigue Syndrome, Fibromyalgia, and healthy controls.

BACKGROUND: There is growing evidence that the kynurenine pathway is involved in the pathology of diseases related to the central nervous system (CNS), because of the neuroprotective or neurotoxic properties of certain metabolites, yet the role of each metabolite is not clear. The pathology of Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM) is currently under investigation, and the overlapping symptoms such as depression suggest that the CNS may be involved. These symptoms may be driven by enhanced neurotoxicity and/or diminished neuroprotection. However, the kynurenine metabolite status has not been well studied in these two possible related disorders of CFS and FM. The objective of this study was to investigate the metabolites and ratios of the kynurenine pathway in CFS and FM compared to healthy controls and examine the possible correlations with symptoms of anxiety and depression. METHOD: In this study, females aged 18-60 were included: 49 CFS patients; 57 FM patients; and 54 healthy controls. Blood plasma was analysed for the following metabolites involved in the kynurenine pathway: Tryptophan, kynurenine, kynurenic acid (KA), 3-hydroxykykynurenine (HK), anthranilic acid, xanthurenic acid (XA), 3-hydroxyanthranilic acid, quinolinic acid (QA) and picolinic acid. The concentrations of these metabolites, as well as the ratios of different metabolites indicating enzymatic activity, were compared between the groups. Findings were controlled for age, body mass index (BMI), and symptoms of anxiety and depression. RESULTS: QA differed between CFS and FM patients (ß = .144, p = .036) and was related to higher levels of BMI (ß = .017, p = .002). The neuroprotective ratio given by KA/QA was lower for CFS patients compared to healthy controls (ß = -.211, p = .016). The neuroprotective ratio given by KA/HK was lower for FM patients compared to healthy controls, and this lower neuroprotective ratio was associated with increased symptoms of pain. The kynurenine aminotransferase II (KAT II) enzymatic activity given by XA/HK was lower for FM patients compared to healthy controls (ß = -.236, p = .013). In addition, BMI was negatively associated with enhanced KAT II enzymatic activity (ß = -.015, p = .039). Symptoms of anxiety and depression were not associated with the metabolites or ratios studied. CONCLUSION: Our study indicates associations between kynurenine metabolism and CFS and FM as well as characteristic symptoms like fatigue and pain. Forthcoming studies indicating a causative effect may place kynurenine metabolites as a target for treatment as well as prevention of these conditions in the future.

Test-Retest Reliability of the Patient Activation Measure-13 in Adults with Substance Use Disorders and Schizophrenia Spectrum Disorders.

Patient Activation Measure-13 (PAM-13) is a valid and widely used questionnaire that assess an individual's knowledge, confidence, and skills for self-management of their chronic illness. Although there is some evidence regarding its reliability, the test-retest reliability has not been investigated among patients with substance use disorders (SUDs) or schizophrenia spectrum disorders. We investigated the internal consistency and test-retest reliability of PAM-13 in these populations. Test-retest reliability was analysed using data from 29 patients with SUDs and 28 with schizophrenia spectrum disorders. Cronbach's α and Intraclass Correlation Coefficient (ICC) scores were used to examine internal consistency and test-retest reliability, respectively. Of the 60 collected test-retest questionnaires, 57 were included in the analyses. No mean differences between time one (T1) and time two (T2) were observed in either patient group, except for item 12 in schizophrenia spectrum disorders patients (p < 0.05). Internal consistency for T1 and T2 was 0.75 and 0.84 in SUDs patients and 0.87 and 0.81 in schizophrenia spectrum disorders patients, respectively. The ICC was r = 0.86 in patients with SUDs and r = 0.93 in patients with schizophrenia spectrum disorders. To conclude, PAM-13 showed good internal consistency and test-retest reliability in SUDs and schizophrenia spectrum disorders patients.

Strength training restores force-generating capacity in patients with schizophrenia.

Patients with schizophrenia spectrum disorders have impaired skeletal muscle force-generating capacity (FGC) of the lower extremities, that is, one repetition maximum (1RM) and rapid force development, and poor functional performance. We therefore investigated whether 12 weeks of maximal strength training (MST) could (a) restore FGC and functional performance to the level of healthy references, (b) increase patient activation and quality of life, and (c) explore associations between symptom severity, defined daily dose of medication, illness duration, level of patient activation, and improvements in FGC and functional performance. Forty-eight outpatients were randomized to a training group (TG) or control group (CG). TG performed leg press MST 2 day/week at ~ 90% 1RM. The CG received two introductory training sessions and encouragement to train independently. Leg press 1RM, rapid force development, a battery of functional performance tests, Patient Activation Measure-13, and 36-Item Short Form Health Survey were tested. Healthy references performed baseline tests of FGC and functional performance. Thirty-six patients completed the study (TG: 17, CG: 19). TG improved 1RM (28%) and rapid force development (20%, both P < .01) to a level similar to healthy references, while no change was apparent in the CG. TG's improvement in rapid force development was negatively associated with defined daily dose of medication (r = -0.5, P = .05). Both TG and CG improved 30-second sit-to-stand test performance (P < .05) which was associated with improved rapid force development (r = 0.6, P < .05). In conclusion, 12 weeks of MST restored patients' lower extremity FGC to a level similar to healthy references and improved 30-second sit-to-stand test performance.

One-year aerobic interval training in outpatients with schizophrenia: A randomized controlled trial.

Although aerobic interval training (AIT) is recognized to attenuate the risk of cardiovascular disease (CVD) and premature mortality, it appears that it rarely arrives at patients' doorsteps. Thus, this study investigated 1-year effects and feasibility of AIT delivered with adherence support in collaborative care of outpatients with schizophrenia. Forty-eight outpatients (28 men, 35 [31-38] (mean [95% confidence intervals]) years; 20 women, 36 [30-41] years) with schizophrenia spectrum disorders (ICD-10) were randomized to either a collaborative care group provided with municipal transportation service and training supervision (walking/running 4 × 4 minutes at ~90% of peak heart rate; HRpeak ) 2 d wk-1 at the clinic (TG) or a control group (CG) given 2 introductory AIT sessions and advised to continue training. Directly assessed peak oxygen uptake ( V ˙ O 2 peak ) increased in the TG after 3 months (2.3 [0.6-4.4] mL kg-1  min-1 , Cohen's d = 0.33[-4.63 to 4.30], P = 0.04), 6 months (2.7 [0.5-4.8] mL kg-1  min-1 , Cohen's d = 0.42[-4.73 to 4.11], P = 0.02) and 1 year (4.6 [2.3-6.8] mL kg-1  min-1 , Cohen's d = 0.70[-4.31 to 4.10], P < 0.001) compared to the CG. One-year cardiac effects revealed higher HRpeak (7 [2-11] b min-1 , Cohen's d = 0.34[-8.48 to 8.65], P = 0.01), while peak stroke volume tended to be higher (0.9 [-0.2 to 2.0] mL b-1 , Cohen's d = 0.35[-1.62 to 2.01], P = 0.11) in the TG compared to the CG. Conventional risk factors (body weight, waist circumference, blood pressure, and lipids/glucose) remained unaltered in both groups. One-year AIT adherence rates were 15/25 (TG; different from CG: P < 0.001) and 0/23 (CG). AIT was successfully included in long-term collaborative care of outpatients with schizophrenia and yielded improved V ˙ O 2 peak , advocating this model for aerobic capacity improvement and CVD risk reduction in future treatment.

Genetic polymorphisms associated with sleep-related phenotypes; relationships with individual nocturnal symptoms of insomnia in the HUNT study.

BACKGROUND: In recent years, several GWAS (genome wide association studies) of sleep-related traits have identified a number of SNPs (single nucleotides polymorphism) but their relationships with symptoms of insomnia are not known. The aim of this study was to investigate whether SNPs, previously reported in association with sleep-related phenotypes, are associated with individual symptoms of insomnia. METHODS: We selected participants from the HUNT study (Norway) who reported at least one symptom of insomnia consisting of sleep onset, maintenance or early morning awakening difficulties, (cases, N = 2563) compared to participants who presented no symptoms at all (controls, N = 3665). Cases were further divided in seven subgroups according to different combinations of these three symptoms. We used multinomial logistic regressions to test the association among different patterns of symptoms and 59 SNPs identified in past GWAS studies. RESULTS: Although 16 SNPS were significantly associated (p < 0.05) with at least one symptom subgroup, none of the investigated SNPs remained significant after correction for multiple testing using the false discovery rate (FDR) method. CONCLUSIONS: SNPs associated with sleep-related traits do not replicate on any pattern of insomnia symptoms after multiple tests correction. However, correction in this case may be overly conservative.

Differences in anxiety levels among symptoms of insomnia. The HUNT study.

OBJECTIVES: This study aim is to compare anxiety levels among individuals experiencing different symptoms of insomnia. DESIGN: Case-control study. SETTING: The Nord-Trøndelag Health Study (the HUNT3 study, Norway). PARTICIPANTS: Of the 50,802 individuals taking part in the HUNT3 study, the current sample comprised 7933 individuals, including 4317 cases with insomnia and 3616 controls. MEASUREMENTS: Symptoms of anxiety were assessed using Hospital Anxiety and Depression Scale, whereas insomnia symptoms were assessed according to the core Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, nocturnal symptoms. Anxiety levels of the 4317 individuals reporting at least 1 insomnia symptom were compared with the 3616 controls reporting no symptoms. Level of anxiety among participants experiencing combinations of insomnia symptoms was also investigated. RESULTS: Anxiety levels were significantly higher in individuals reporting insomnia symptoms (M = 2.5, SD = 2.4) compared to controls (5.5, SD = 3.7, P < .001). Anxiety levels also differed significantly between different insomnia symptoms (P < .001). Participants reporting all 3 insomnia symptoms had the highest anxiety score (M = 6.8, SD = 4.3), followed in decreasing order by sleep onset insomnia with terminal insomnia (M = 6.7, SD = 4.0), sleep onset insomnia with sleep maintenance insomnia (M = 6.3, SD = 3.8), sleep onset insomnia only (M = 5.8, SD = 3.7), sleep maintenance insomnia with terminal insomnia (M = 5.6, SD = SD = 3.4), terminal insomnia (M = 5.2, SD = 3.4), and sleep maintenance insomnia only (M = 4.5, SD = 3). CONCLUSIONS: Difficulties initiating sleep, both alone and in combination with 1 or 2 of the other symptoms, seem to play a key role in rising anxiety levels.

Patients with schizophrenia have impaired muscle force-generating capacity and functional performance.

Patients with schizophrenia have impaired physical health. However, evidence of how skeletal muscle force-generating capacity (FGC), a key component of functional performance, may contribute to the impairment is scarce. Thus, the aim of this study was to investigate the patient groups' skeletal muscle FGC and its association with functional performance. Leg-press FGC was assessed along with a battery of functional performance tests in 48 outpatients (28 men, 34 ± 10 years; 20 women, 36 ± 12 years) with schizophrenia spectrum disorder (ICD-10, F20-29), and compared with 48 healthy age- and gender-matched references. Results revealed reduced one-repetition maximum (1RM) in men (-19%, P < .01) and a trend toward reduction in women (-13%, P = .067). The ability to develop force rapidly was also impaired (men: -30%; women: -25%, both P < .01). Patients scored worse than healthy references on all physical performance tests (stair climbing: -63%; 30-second sit-to-stand (30sSTS): -48%; six-minute walk test (6MWT): -22%; walking efficiency: -14%; and unipedal stance eyes open: -20% and closed: -73%, all P < .01). 1RM correlated with 6MWT (r = .45), stair climbing (r = -.44), 30sSTS (r = .43), walking efficiency (r = .26), and stance eyes open (r = .33) and closed (r = .45), all P < .01. Rapid force development correlated with 6MWT (r = .54), stair climbing (r = -.49), 30sSTS (r = .45), walking efficiency (r = .26), and stance eyes open (r = .44) and closed (r = .51), all P < .01. In conclusion, skeletal muscle FGC and functional performance are reduced in patients with schizophrenia and should be recognized as important aspects of the patient groups' impaired health. Resistance training aiming to improve these components should be considered an important part of clinical treatment.

The Predictive Properties of Violence Risk Instruments May Increase by Adding Items Assessing Sleep.

Background: The psychometric instruments developed for short-term prediction of violence in psychiatric inpatients do not include variables assessing sleep. Disturbances in sleep may precede aggression in this setting. We investigated whether adding information on sleep improved the predictive properties of the Brøset Violence Checklist (BVC). Methods: The study population consists of all patients admitted to a psychiatric intensive care unit (PICU) over a 6-month period who were hospitalized for at least one night (n = 50). Sleep observed by staff (521 nights), behavior assessed with the BVC (433 days), and aggressive incidents recorded by the Staff Observation Scale-Revised (n = 14) were included in the analysis. Results: The ability of the BVC to predict aggressive incidents improved from AUCROC 0.757 to AUCROC 0.873 when a combined sleep variable including both sleep duration and night-to-night variations of sleep duration was added to the BVC recordings. The combined sleep variable did not significantly predict aggressive incidents (AUCROC 0.653, p = 0.051). Conclusions: A sleep disturbance variable improves the predictive properties of the BVC in PICUs. Further studies of sleep duration, night-to-night variations in duration of sleep, and aggression are needed.

Variations in circadian genes and individual nocturnal symptoms of insomnia. The HUNT study.

Insomnia is a condition characterized by three nocturnal symptoms: problems with sleep onset or maintenance and early morning awakenings (terminal insomnia). Affected individuals may present one or more of these symptoms. Several studies have shown that insomnia is moderately heritable and that proxy phenotypes for the three insomnia symptoms show different heritabilities. This suggests that different nocturnal symptoms of insomnia may arise from different genetic and biological backgrounds. Circadian genes are good candidates to account for these differences as they regulate the periodicity of several physiological functions including sleep. Evidence from studies in animals and humans have suggested that circadian genes might be involved in sleep disturbances such as insomnia. In this study, we investigated the association between Single Nucleotide Polymorphisms (SNPs) in circadian genes and individual symptoms of insomnia and their combinations using data from the Nord-Trøndelag Health Study 3 (the HUNT3 study, N = 50807). Participants (N = 6029) provided information about sleep onset insomnia, maintenance insomnia, and terminal insomnia. Participants who responded "several times a week" to at least one question regarding the mentioned symptoms were classified as cases (N = 3577) and categorized in seven subgroups according to possible symptom combinations. Controls (N = 2452) answered "Never/Seldom" to all sleep-related questions. Using multinomial regression, we assessed 73 SNPs in nine circadian genes (PER1, 2, 3, CRY1, 2, TIMELESS, CLOCK, REV-ERBα, ARNTL) for differences among symptoms subgroups. Twenty-five SNPs showed significant p-values and supportive odds-ratios. All significant SNPs in PER3 were associated with reporting all three symptoms simultaneously. SNPs in CRY genes were associated with terminal insomnia alone or in combination with other symptoms. Genes PER1 and two were mostly associated with sleep maintenance insomnia. However, none of the SNPs remained significant after False Discovery Rate (FDR) correction for multiple statistical testing. In conclusion, even though none of the SNPs remained significant after FDR correction, the clustering of some genes around specific symptoms points to the need for additional research on these relationships.

A comprehensive cardiovascular disease risk profile in patients with schizophrenia.

Patients with schizophrenia are physically inactive and have high prevalence of cardiovascular disease (CVD). Peak oxygen uptake (V̇O2peak ) is one of the strongest predictors for CVD, yet is rarely investigated in this patient population, and how V̇O2peak relates to other conventional CVD risk measures in this population is unclear. We measured treadmill V̇O2peak along with daily physical activity assessed by triaxial accelerometry, body mass index (BMI), waist circumference, blood pressure, lipid profiles, and glucose in 48 outpatients (28 men, 35 ± 10 (SD) years; 20 women, 35 ± 12 years), diagnosed with schizophrenia, schizotypal, or delusional disorders (ICD-10; F20-29). The patients were compared with 48 age- and sex-matched healthy references (±2 years) and normative data from the population. V̇O2peak was 34.5 ± 8.7 mL/kg/min (men) and 26.4 ± 7.0 mL/kg/min (women), which was 27% and 30% lower than healthy references, respectively (both P < 0.01). V̇O2peak was not associated with daily physical activity in men while a weak association was seen in women (steps per day: r2  = 0.26; counts per minute: r2  = 0.25; P < 0.05). BMI (26.0 ± 6.1 kg/m2 ) revealed that patients were moderately overweight with a waist circumference of 103 ± 17 cm. Lipid- and glucose levels, and blood pressure were all within normative range. Our data advocate the utilization of V̇O2peak assessment for CVD risk profile determination in patients with schizophrenia. Daily physical activity was poorly and inconsistently related to V̇O2peak, suggesting increased daily physical activity might not translate into improved V̇O2peak and CVD risk reduction.

Three-Week Inpatient Treatment of Obsessive-Compulsive Disorder: A 6-Month Follow-Up Study.

Background: Specialized inpatient or residential treatment might be an alternative treatment approach for patients with obsessive-compulsive disorder (OCD) that do not respond satisfactorily to the standard outpatient treatment formats. Method: The aim of this open trial was to investigate the 6-month effectiveness of a 3-week inpatient treatment of OCD, where exposure with response prevention (ERP) was the main treatment intervention. The sample consisted of 187 adult patients with OCD, all with previous treatment attempts for OCD. Results: The sample showed significant reductions in symptoms of OCD and depression. The effect sizes were large for obsessive-compulsive symptoms and moderate to large for depressive symptoms. At discharge, 79.7% of the intent-to-treat (ITT) group were classified as treatment responders (≥35% reduction in Y-BOCS scores). However, some participants experienced relapse, as 61.5% of the ITT group were classified as treatment responders at 6-month follow-up. Antidepressant use appeared not to influence the outcome. Only pre-treatment levels of obsessive-compulsive symptoms emerged as a significant predictor of relapse. Conclusion: The 3-week inpatient programme produced similar treatment effects as previous inpatient and residential studies of longer duration (2 - 3 months). The results suggest that patients with severe OCD can be treated efficiently using this brief inpatient format. However, better relapse prevention interventions are needed.

Serum N-Desmethylcitalopram Concentrations are Associated with the Clinical Response to Citalopram of Patients with Major Depression.

OBJECTIVE: Citalopram (CITA) is a widely used and well-tolerated selective serotonin reuptake inhibitor. The aim of the study was to evaluate the possible influences of serum concentrations of CITA and its major metabolite n-desmethylcitalopram (NDCITA) on the efficacy and tolerability of CITA in patients with major depressive disorder. METHODS: The study included 46 outpatients with major depressive disorder who received CITA. The efficacy and tolerability were assessed for 6 weeks. Serum CITA and NDCITA levels were measured at the 4th week. RESULTS: The HDRS17 total scores of the patients with high NDCITA and CITA & NDCITA concentrations showed a more significant reduction compared to the patients with expected and low serum NDCITA and CITA & NDCITA concentrations. However, we did not observe a correlation between the serum concentrations and the side effects of CITA, NDCITA, and CITA & NDCITA. CONCLUSION: Our results suggested the potential contribution of NDCITA to the antidepressant effect of CITA. Further studies involving larger clinical samples are required to confirm the impact of serum NDCITA concentrations on the efficacy of CITA.

Peer Problems and Hyperactivity-Impulsivity Among Norwegian and American Children: The Role of 5-HTTLPR.

Peer problems are linked to attention deficit hyperactivity disorder (ADHD) symptoms and the serotonin system is thought to be involved in ADHD-related behavior. Hence, from a Gene × Environment perspective, the serotonin transporter 5-HTTLPR may play a moderating role. In two large community samples, the moderating role of 5-HTTLPR was examined related to more hyperactivity-impulsivity symptoms (HI symptoms) predicted by more peer problems. In Study 1, involving 642 Norwegian children, results indicated that for s-allele carriers only, caregiver-reported peer problems at age 4 predicted more parent-reported HI symptoms at age 6. In Study 2, similar results emerged involving 482 American children. Discussion focuses on differential sensitivity to the adverse effects of poor peer relations.

Change in parenting, change in student-teacher relationships, and oxytocin receptor gene (OXTR): Testing a gene-×-environment (G×E) hypothesis in two samples.

Prior research suggests that parenting affects children's relationships, including those with teachers, although there is variation across individuals in such effects. Given evidence suggesting that oxytocin may be particularly important for the quality of social relationships, we tested the hypotheses (a) that change in parenting from 4 to 6 years of age influences and predicts change in the student-teacher relationship from 6 to 8 years of age and (b) that this effect is moderated by a polymorphism related to the child's oxytocin receptor gene (OXTR), rs53576. In 2 studies, participants included, respectively, 652 socioeconomically diverse Norwegian children from a community sample (50.8% male; mean age of 54.9 months at first assessment) and 559 such children from 8 different U.S. locales (49.0% male; approximately 54 months at the first assessment). Norwegian results showed that change in parenting predicted change in student-teacher relationships, but only in the case of children homozygous for the A allele of rs53576 and in a manner consistent with differential-susceptibility theory: for AA carriers, when parenting changed for the worse, so did children's relationship with teachers, whereas when parenting changed for the better, the teacher-child relationships improved accordingly. Such G×E findings could not be replicated in the American sample. Results are discussed in terms of 2 contrasting models of Person-×-Environment interaction (differential susceptibility and diathesis stress) and potential reasons for failure to replicate. (PsycINFO Database Record

Influence of ABCB1 polymorphisms and serum concentrations on venlafaxine response in patients with major depressive disorder.

BACKGROUND: The pharmacokinetics and the pharmacodynamics of antidepressants show large inter-individual variations which result in unpredictable clinical responses. AIM: The aim of the study was to examine the effect of ABCB1 polymorphisms and the serum concentrations on the efficacy and tolerability of venlafaxine in patients with major depressive disorder (MDD). METHODS: Fifty-two outpatients who met the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for MDD were recruited for the study. The severity of depression was assessed using the 17-item Hamilton Rating Scale for Depression scale (HDRS17) and tolerability was assessed based on a query regarding side-effects for 6 weeks. The ABCB1 C3435T/A and G2677T/A polymorphisms were genotyped by PCR/RFLP and steady-state serum venlafaxine concentrations were measured by high-performance liquid chromatography. RESULTS: Patients with the TT genotype for the C3435T and the TT/TA genotype for the G2677T/A polymorphism showed significantly higher frequencies in venlafaxine-induced akathisia. This relationship was not observed for efficacy. As regards serum venlafaxine concentrations, patient groups showed no significant differences in efficacy and tolerability. CONCLUSION: The results suggest that individuals with the TT-TT/TA genotypes for the C3435T-G2677T/A polymorphisms of ABCB1 may be pre-disposed to a risk of akathisia.

Challenges in detecting and diagnosing substance use in women in the acute psychiatric department: a naturalistic cohort study.

BACKGROUND: This study examines sex differences in substance use and substance use disorder in the acute psychiatric department, and possible interactions between sex and clinical and social factors associated with this phenomenon. METHODS: Data concerning substance use were collected in a naturalistic cohort study (n = 384, 51.6% male, 48.4% female) in an acute psychiatric department. Recent intake of substances at admission, diagnosis of substance use disorder and demographic and socioeconomic information were recorded. At admission, serum and urine samples were analysed for substance use and breath analysis was performed for alcohol levels. RESULTS: Twice as many men as women were diagnosed with substance use disorder, whereas there were no gender differences in the number of positive toxicology screenings. Toxicology screening revealed the use of non-prescribed medication with addiction potential in 40% of both female and male patients many of whom did not report this in the admission interview. A low level of education in men and absence of parental responsibility in women showed a statistically significant interaction with a current diagnosis of substance use disorder. CONCLUSIONS: Despite no sex differences in positive toxicology screenings in the acute psychiatric department, twice as many men as women are diagnosed with substance use disorders. The use of prescription drugs with addiction potential was widely under-reported by both sexes, in patients with no prescriptions for the medications. Women with no parental responsibility are overrepresented among those diagnosed with substance use disorder, as are men with a low level of education. TRIAL REGISTRATION: The study is registered with the ClinicalTrials.gov identifier NCT01415323.

Incidence of violent behavior among patients in psychiatric intensive care units

Background and Objectives: Both psychiatric acute units and psychiatric intensive care units (PICUs) focus on acute treatment of behavioral disturbances such as violence and aggressive threats and acts. The aim of the present study is to describe the frequency of violent behavior; such as verbal or physical threats and physical attacks, among patients admitted to psychiatric intensive care unit (PICU). In addition the relationship between the episodes of threats and/or attacks in relation to time of the day, days of the week, and their seasonal variations was explored. Methods: All violent behavior was continuously assessed at the psychiatric emergency department. Data were collected during the period from May 2010 to May 2012. Results: Patients with only one hospitalization were less violent than those who have had two hospitalizations. There was a statistically significant difference in violence among patients without formal secondary education and those who have not formal education. Violent behavior showed two peaks during the day; the first occurring at 1 pm and the second at 8 pm. In regard to seasonality, summer had a higher incidence of violence. The most peaceful seasons of the year were spring and autumn. Conclusions: Violent behavior shows variation in daytime, days of the week and season in acute psychiatric intensive care. Daytime variation shows two peaks of violence at 1 pm and 8 pm, Sundays and Wednesdays being the quietest days regarding violence both in winter and summer. Patient`s level of education and hospitalization status partially explain the variation (AU)

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Polygenic Risk, Appetite Traits, and Weight Gain in Middle Childhood: A Longitudinal Study.

IMPORTANCE: Genome-wide association studies have identified genetic risks for obesity. These genetic risks influence development of obesity partly by accelerating weight gain in childhood. Research is needed to identify mechanisms to inform intervention. Cross-sectional studies suggest appetite traits as a candidate mechanism. Longitudinal studies are needed to test whether appetite traits mediate genetic influences on children's weight gain. OBJECTIVE: To test whether genetic risk for obesity predicts accelerated weight gain in middle childhood (ages 4-8 years) and whether genetic association with accelerated weight gain is mediated by appetite traits. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal study of a representative birth cohort at the Trondheim Early Secure Study, Trondheim, Norway, enrolled at age 4 years during 2007 to 2008, with follow-ups at ages 6 and 8 years. Participants were sampled from all children born in 2003 or 2004 who attended regular community health checkups for 4-year-olds (97.2% attendance; 82.0% consent rate, n = 2475). Nine hundred ninety-five children participated at age 4 years, 795 at age 6 years, and 699 at age 8 years. Analyses included 652 children with genotype, adiposity, and appetite data. MAIN OUTCOMES AND MEASURES: Outcomes were body mass index and body-fat phenotypes measured from anthropometry (ages 4, 6, and 8 years) and bioelectrical impedance (ages 6 and 8 years). Genetic risk for obesity was measured using a genetic risk score composed of 32 single-nucleotide polymorphisms previously discovered in genome-wide association studies of adult body mass index. Appetite traits were measured at age 6 years with the Children's Eating Behavior Questionnaire. RESULTS: Of the 652 genotyped child participants, 323 (49.5%) were female, 58 (8.9%) were overweight, and 1 (0.2%) was obese. Children at higher genetic risk for obesity had higher baseline body mass index and fat mass compared with lower genetic risk peers, and they gained weight and fat mass more rapidly during follow-up. Each SD increase in genetic risk score was associated with a 0.22-point increase in BMI at age-4 baseline (for the intercept, unstandardized path coefficient B = 0.22 [95% CI, 0.06-0.38]; P = .008. Children with higher genetic risk scores also gained BMI points more rapidly from ages 4 to 6 years (B = 0.11 [95% CI, 0.03-0.20]; P = .01 ; ß = 0.12) and from 6 to 8 years (B = 0.09 [95% CI, 0.00-0.19]; P = .05; ß = 0.10), compared with their lower genetic risk peers. Children at higher genetic risk had higher levels of alleged obesogenic appetite traits than peers with lower genetic risk at age 6 years, but appetite traits did not mediate genetic associations with weight gain. The sum of the 5 indirect effects was B = -0.001 (95% CI, -0.02 -0.01); P = .86; ß = 0.00. CONCLUSIONS AND RELEVANCE: Genetic risk for obesity is associated with accelerated childhood weight gain. Interventions targeting childhood weight gain may provide one path to mitigating genetic risk. However, middle childhood appetite traits may not be a promising target for such interventions. Studies of early-childhood samples are needed to test whether appetite traits explain how genetic risks accelerate growth earlier in development.