Bipolar unspecified (BP-U) is an important cause of morbidity and mortality in hospitalized patients. While BP-U has been extensively studied in the past, the contemporary data for impact of BP-U on cost of hospitalization are largely lacking.

We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (HCUP-NIS) dataset between 1998–2011 using the ICD-9 codes. Severity of comorbid conditions was defined by Deyo modification of Charlson comorbidity index. Primary outcome was in-hospital mortality and secondary outcome was total charges for hospitalization. Using SAS 9.2, Chi2 test, t-test and Cochran-Armitage test were used to test significance.

A total of 711,147 patients were analyzed; 61.33% were female and 38.67% were male (P < 0.0001); 77.63% were white, 13.17% black and 9.2% of other race (P < 0.0001). Rate of hospitalization increased from 2,310.28/million to 74,908.88/million from 1998–2011. Overall mortality was 0.81% and mean cost of hospitalization was $25,152.02. The in-hospital mortality reduced from 1.24% to 0.97% (P < 0.0001) and mean cost of hospitalization increased from 11,308.05$ to 32,211.67$. Total yearly spending on BP-U related admissions have increased from $207 million/year to $19.15 billion/year.

While mortality has slightly decreased from 1998 to 2011, the cost has significantly increased from $0.21 billion/year $19.15 billion/year, which leads to an estimated $18.94 billion/year additional burden to US health care system. In the era of cost conscious care, preventing BP-U related hospitalization could save billions of dollars every year. Focused efforts are needed to establish preventive measures for BP-U related hospitalization.

The authors have not supplied their declaration of competing interest.

Bipolar I most recent episode-manic (BP-I-M) is an important cause of morbidity and mortality in hospitalized patients. While BP-I-M has been extensively studied in the past, the contemporary data for impact of BP-I-M on cost of hospitalization are largely lacking.

We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (HCUP-NIS) dataset between 1998–2011 using the ICD-9 codes. Severity of comorbid conditions was defined by Deyo modification of Charlson comorbidity index. Primary outcome was in-hospital mortality and secondary outcome was total charges for hospitalization. Using SAS 9.2, Chi2 test, t-test and Cochran-Armitage test were used to test significance.

A total of 10,875 patients were analyzed; 57.13% were female and 42.87% were male (P < 0.0001); 74.78% were white, 14.51% black and 10.71% of other race (P < 0.0001). Rate of hospitalization increased from 528.71/million to 588.76/million from 1998–2011. Overall mortality was 0.42% and mean cost of hospitalization was 22,215.77$. The in-hospital mortality increased from 0.37% to 0.82% (P < 0.0001) and mean cost of hospitalization increased from 10,580.54$ to 40,737.65$. Total spending on BP-I-M related admissions have increased from $44.24 million/year to $187.00 million/year.

While mortality has slightly decreased from 1998 to 2011, the cost has significantly increased from $44.24 million/year to $187.00 million/year, which leads to an estimated $ 142.76 million/year additional burden to US health care system from. In the era of cost conscious care, preventing BP-I-M related hospitalization could save billions of dollars every year. Focused efforts are needed to establish preventive measures for BP-I-M related hospitalization.

The authors have not supplied their declaration of competing interest.

Guanfacine extended release (GXR) is a non-stimulant treatment for attention-deficit/hyperactivity disorder (ADHD).

To separate efficacy and sedative treatment-emergent adverse events (TEAEs) associated with GXR in four randomized, controlled trials in children (6–12 years) and adolescents (13–17 years) with ADHD.

SPD503-301 (n = 345) and SPD503-304 (n = 324) were 8 and 9 week studies of fixed-dose GXR (≤ 4 mg/day). SPD503-312 (n = 314; adolescents only) and SPD503-316 (n = 338) were 10–13 week studies of dose-optimized GXR (1–7 mg/day).

In fixed-dose studies, pooled incidences of sedative TEAEs with GXR were highest at week 1 (GXR, 13.9–18.7%; placebo, 8.7%) and decreased to placebo levels at week 8 (0–1.4%; placebo, 0%). In contrast, proportions of responders (≥ 30% reduction from baseline in ADHD Rating Scale IV [ADHD-RS-IV] total score) increased from week 1 (GXR, 29.6–34.8%; placebo, 25.0%) through endpoint (GXR, 66.7–72.2%; placebo, 42.6%). Incidences of sedative TEAEs, but not proportions of responders, increased with GXR dosing. GXR was associated with a statistically significant reduction in ADHD-RS-IV total score from baseline to endpoint in patients without sedative TEAEs in both fixed-dose and dose-optimized studies (GXR versus placebo, effect size = 0.49 and 0.67, respectively; P < 0.001). GXR was associated with statistically significant improvements compared with placebo in both ADHD-RS-IV Hyperactivity/Impulsivity and Inattentiveness subscale scores (P < 0.001).

These data from pooled GXR clinical trials indicate that incident sedative TEAEs do not contribute to increased treatment response over time, and that sedation and symptomatic improvement are distinct effects of GXR.

The authors have not supplied their declaration of competing interest.

To evaluate the effect of comorbid psychiatric disorders (PD) on the association between childhood ADHD and suicidality and the effect of gender on the association between PDs and suicidality among adults with childhood ADHD.

Subjects were recruited from a birth cohort of all children born 1976–1982 remaining in Rochester, MN after five years of age. Participating subjects with research-identified childhood ADHD (n = 232; mean age 27.0 years; 72% men) and non-ADHD controls (n = 335; mean age 28.6 years; 63% men) were administered a structured psychiatric interview (MINI International Neuropsychiatric Interview) to assess suicidality and psychiatric comorbidities.

Compared to controls, ADHD cases were significantly more likely to meet criteria for suicidality [odds ratio (OR) = 2.7, 95% CI 1.7–4.5]. Although this association was not moderated by the presence of PDs (P = 0.63 for interaction effect), the association between ADHD and suicidality was partially mediated by the presence of PDs [OR decreased from 2.7 to 2.1 (95% CI 1.2–3.5)]. Among adults with childhood ADHD, there was no significant moderating effect of gender on the association between suicidality and PD (P = 0.26 for interaction effect). However, the odds of suicidality was 6.1 (95% CI, 2.3–15.9) times higher among males with both externalizing and internalizing PDs compared to males with no disorders; among females the corresponding odds ratio was 3.4 (95% CI, 0.7–16.6).

Childhood ADHD is significantly associated with adult suicidal risk. Among those with ADHD, associations between suicidality and comorbid psychiatric disorders are more apparent in men among those with comorbid externalizing and internalizing disorders.

The authors have not supplied their declaration of competing interest.

Methods for measuring cognitive reserve (CR) are limited and controversial. Dual task cost (DTC) paradigms, assessing links between gait and cognition, are increasingly regarded as robust measures of CR.

Here, we aimed to validate a simplified methodology for a DTC paradigm in healthy volunteers for application in clinical settings as a measurement of CR.

We tested if subtracting by 7's (cognitive task) while walking (motor task) induced a DTC in a sample of 39 healthy young adults. For the cognitive task, we recorded the number of correct and incorrect subtractions, as well as the latency between subtractions. Gait parameters were recorded on a tri-axial accelerometer fixed to the left ankle. Both tasks were performed separately (single task) and simultaneously (double task) to assess the DTC. A battery for neuropsychological assessment and questionnaires to assess quality of life and affective symptoms were also applied, to measure possible correlations with the DTC.

Subtracting 7's while walking caused significant changes in gait parameters and in cognitive task performance. A significant decrease in the autocorrelation of the accelerometer signal during the dual task was also found (DTC = 37.92 ± 7.56%; P < 0.0001). This measure has not been previously used and may be a more sensitive measure of the dual task induced disturbance of the gait periodic signal pattern. Correlations between DTC and quality of life, affective or cognitive measures were not significant.

Our study provides an effective, portable and non-intrusive DTC experimental protocol that can be easily applied in clinical settings.

The authors have not supplied their declaration of competing interest.

Older people are particularly exposed to stressful events, known to activate the hypothalamus-pituitary-adrenal axis. Many studies highlighted the possible deleterious effects of elevated cortisol on cognition, assuming a likely role of stressful events. Yet, very few studies actually examined these assumed links between life events, cortisol and cognition.

To examine associations between salivary cortisol, cognition and life events in a population of non-demented old individuals.

A cross-sectional analysis was conducted using data from Colaus/PsyColaus, a longitudinal population-based study involving 6733 Lausanne residents. Salivary cortisol samples (upon waking, 30 minutes after waking, at 11 am and at 8 pm) were obtained from 799 non-demented participants aged at least 60.

Life events, activities of daily life along with depressive symptoms were assessed using a standardized questionnaire. A comprehensive neuropsychological test battery was used to determine the Clinical Dementia Rating (CDR).

For multiple comparisons, P values were adjusted (P′) according to Holm-Bonferroni's method.

Cortisol at 11 am and cortisol area under the curve (AUC) were positively correlated with CDR sum of boxes (CDRSOB) scores (P′ = 0.035; Rho = 0.097 and P′ = 0.024; Rho = 0.110, respectively). The association between cortisol AUC and CDRSOB remained significant after controlling for age, sex, body mass index, education, smoking and depression (P = 0.001; β = 0.001; R2 change = 0.016).

The number and the total impact of life events were associated neither with cortisol nor with CDRSOB.

Elevated cortisol was associated with poorer cognitive functioning yet independently of life events. This suggests that the increased cortisol associated with poorer cognition might be not a mere reflection of stressful events but rather explained by other factors, yet to be elucidated.

The authors have not supplied their declaration of competing interest.

The authors have not supplied their declaration of competing interest.

Premorbid adjustment (PA) is one of the main prognostic indicators of schizophrenia. Both social and cognitive deficits observed during the premorbid period hold a predictive value for the onset of schizophrenia.

To investigate how cognitive functions are related to aspects of PA.

To examine the relationship of each PA domain (academic and social) at each of the three developmental stages (childhood, early adolescence and late adolescence), as well as their course with the cognitive functions in schizophrenia patients.

PA, intellectual quotient (IQ), verbal learning, memory, processing speed, executive functions and verbal fluency were assessed using PAS, WAIS, RAVLT, TMT, WCST and COWAT measures respectively in a sample of 85 clinically stabilized male schizophrenia inpatients.

Negative correlations emerged between academic PA during adolescence and both verbal IQ and processing speed, while positive correlations were found with working memory. Negative correlations emerged between deterioration in academic PA during adolescence and both processing speed and immediate auditory verbal recall, while correlations with verbal learning were positive. There was no relationship between cognitive functions and either social PA or its deterioration.

Our findings revealed significant associations between both academic PA and its course with cognitive functions in schizophrenia patients. In summary, deficits in several fields of cognitive functions seem to follow a different path long before and after the onset of the disease, but further investigation is necessary.

The authors have not supplied their declaration of competing interest.

Pro-inflammatory states of the large bowel have a multifactorial aetiology, including metabolism, atherogenesis, and psychological determinants. Inflammation plays a role in depressive and anxiety disorders, is tightly associated with early pro-atherogenetic alterations and metabolic dysregulation, and is also a key factor for the development of colorectal cancer.

To investigate the association between pro-atherogenetic factors, metabolic status, psychological assessment and presence of colorectal adenomas.

Case-control study, approved by the local Ethic Committee. Patients aged 40 or more and undergoing colonoscopy for positive faecal blood test and/or abdominal symptoms, with a negative history for neoplasia or inflammatory bowel diseases, were enrolled. For each patient the following data were collected: waist and hip circumferences, BMI, arterial pressure, fasten serum glycemia, current medications. Beside colonoscopy, carotid intima-media thickness (IMT) was assessed by means of echographic evaluation. Psychometric assessment included HADS, TCI, IMSA, SF-36. Statistics performed with SigmaPlot v.12 Platform.

Preliminary results are available for 18 patients (male/female 8/10) Mean age 62.6 ± 8.4. Ten patients had at least one adenoma, 8 patients had no lesions. The following differences were noticeable: HADS-depression (mean ± SD) adenoma vs. no-adenoma: 4.9 ± 3.2 vs. 1.7 ± 1.8 (P < .01); IMT median value adenoma vs. no-adenoma: 793 vs. 638 micrometers (P = .04); Body weight (mean ± SD) adenoma vs. no-adenoma: 66.4 ± 8.7 kg vs. 80.9 ± 15.3 kg (P = .03); waist circumference (mean ± SD) adenoma vs. no-adenoma: 105.2 ± 13.4 cm vs. 89.5 ± 4.7 cm (P < .01).

Preliminary data from PNEI-MO Research Group support the relation between systemic inflammation, psychological status and development of precancerous colorectal cancer lesions. Depression seems associated with the presence of colorectal adenomas.

The authors have not supplied their declaration of competing interest.

Despite the fact that depression has an estimated heritability around 40%, there is no definitive candidate gene contributing to its etiology. The lack of an identified genetic component for high-heritability disorders, like depression, gave rise to the concept of missing heritability. The epigenetics’ field has pushed forward new hypotheses to fill this gap since transgenerational inheritance of epigenetic patterns has been described both in animal models and, more recently, in humans. Depression is usually associated with an abnormal stress response and an altered hypothalamic-pituitary-adrenal axis, regulated by the glucocorticoid receptor (coded by NR3C1 gene). Therefore, NR3C1 has been widely investigated as a functional candidate gene involved in anxious-depressive spectrum disorders (ADSD) although a more comprehensive study of its methylation is further required (Palma-Gudiel et al., 2015).

To analyze NR3C1 promoter's methylation and to study its association with anxious-depressive spectrum disorders.

The sample consisted of 48 pairs of monozygotic twins, from the UB twin register, grouped as concordant, discordant and healthy pairs depending on whether both, one or none of the co-twins of each pair were affected by a lifetime ADSD, according to DSM-IV criteria (SCID). DNA methylation was assessed by bisulfite conversion and subsequent pyrosequencing.

Hypermethylation at specific CpG sites, not previously reported, was detected in concordant twin pairs as compared with discordant and healthy groups (P = 0.03).

The epigenetic pattern newly described in NR3C1 gene may be contributing to the familial component of depression and thus could be putatively explained by transgenerational inheritance of epigenetic phenomena.

The authors have not supplied their declaration of competing interest.

The authors have not supplied their declaration of competing interest.

Treatment with pegylated interferon alpha (PEG-IFN-α) is associated with depression more frequently in chronic hepatitis C (CHC) patients than with other inflammatory diseases.

To prospectively asses sex differences in the prevalence of depression in CHC patients during the PEG-IFN-α, as well as in the CHC group with no therapy.

Sample consisted of 103 subjects with CHC on the PEG-IFN-α and 103 subjects with CHC without interferon therapy. The diagnosis of depressive disorder was established by using Structured Clinical Interview and Criteria of International Classification Disorder. The severity of depression was assessed by using Hamilton Depression Rating Scale (HAMD ≥ 8) prior to PEG-IFN-α (baseline) and at the follow-up visits (4th, 12th, 24th, 48th, 72nd week).

During the course of PEG-IFN-α, 49.5% of subjects showed depressive symptomatology (HAMD ≥ 8). Except at baseline and in the 72nd week, on the all other follow-up visits the prevalence of depression was significantly higher in female subjects (*all Ps < 0.05). The strongest difference was observed in the 12th week: of all the subjects with HAMD ≥ 8, 68.8% were female and 32.7% were male (P < 0.001). The multivariate logistic regression model showed that female sex is a very strong predictor for the development of depression during the interferon treatment [Exp (B) = 6.729]. There were no significant sex differences in the prevalence of depression in the control group.

Our study (the longest study in this area) indicate that the prevalence of depression is significantly higher in female subjects with CHC during antiviral treatment.

The authors have not supplied their declaration of competing interest.

The authors have not supplied their declaration of competing interest.

The authors have not supplied their declaration of competing interest.

The authors have not supplied their declaration of competing interest.

There is only limited literature concerning haematological abnormalities in anorexia nervosa (AN), with little past investigation into these abnormalities in adult AN patients admitted to inpatient eating disorder (ED) units.

This study sought to determine the prevalence and severity of haematological abnormalities in admitted AN patients, and to examine correlates of these abnormalities.

All adult patients with a clinical diagnosis of AN admitted to the Cotswold House specialist ED inpatient unit between November 2013 and December 2014 were included in the study. Demographic, anthropometric and haematological parameters were systematically recorded for the duration of each admission. The proportions of patients affected by haematological abnormalities (anaemia, leucocytopaenia, neutropaenia, thrombocytopaenia and pancytopaenia) were selected as primary outcomes, and binary logistic regression was performed using SPSS 22.0.

A total of 37 AN patients (91.9% female; mean age: 29.7 years) were included in this study, with a mean admission BMI of 13.7 kg/m2 (SD: 1.8) and a mean admission duration of 128 days; 54.1% of patients were anaemic, 64.9% of patients experienced leucocytopaenia, 56.8% of patients developed neutropaenia, 16.2% of patients suffered thrombocytopaenia, and 8.1% of patients were pancytopaenic. Logistic regression identified low admission BMI (P = 0.009) and low serum albumin level (P = 0.017) as significant correlates of anaemia, and isolated increased age (P = 0.034) as a significant associate of leucocytopaenia.

Haematological abnormalities occur frequently in AN inpatients. Given the frequency at which abnormalities occurred in this cohort, further large-scale and prospective studies examining haematological abnormalities in inpatient AN populations are warranted.

The authors have not supplied their declaration of competing interest.

Multi-attribute utility instruments (MAUIs) are generic health-related quality of life (HRQoL) measures that enable valuation of health states relative to death (0.0) and full health (1.0). The usefulness of MAUIs in people with psychosis has been questioned, with the EQ-5D considered “insensitive”, the 15D “problematic” and the SF-6D “unsuitable”.

Confirm the Assessment of Quality of Life (AQoL)-4D MAUI is useful and meaningful in people with psychosis.

Assess utility values across demographic, general and disease-specific health categorisations for a large nationally-representative sample with psychosis (n = 1825).

Participants underwent a comprehensive 32 module interview encompassing psychopathology to service use. Utility values were calculated by applying a standard algorithm to responses to each of 12 items of the AQoL-4D.

Utility values were assessed for 1793 participants (98.2%). No ceiling effect was observed and only 6.6% of participants scored in the top decile of HRQoL [0.9–10.0]. In contrast, 10.8% scored in the lowest decile [−0.04–0.10], a floor effect observed in 0.4%. The mean utility value was 0.49 (95% CI: 0.48–0.51), significantly lower than the Australian population norm of 0.81 (95% CI: 0.81–0.82). Greatest impacts on HRQoL were for diminishing global independent functioning as measured by the MSIF (ESMSIF: 0.68–2.24), self-rated current mental health (ESMH: 0.15–1.65) and physical health status (ESPH: 0.11–1.21). Strong effects also observed for course of disorder (ESCoD: 0.08–1.13), current suicidal ideation (ESCSI1: 0.76–1.08), and labor force participation (ESLFP: 0.11–0.97).

The AQoL-4D had good lower end sensitivity in a large sample of people with a psychotic illness, and demonstrated responsiveness across subjective, objective and symptom measures.

The authors have not supplied their declaration of competing interest.

Loneliness is a common emotional distress experience and there is increasing evidence of associations with unhealthy lifestyle and adverse health-related factors. Little is known about age and sex as potential effect modifiers, and about the prevalence of loneliness.

To assess the associations of loneliness with behavioral, physical and mental health factors, taking sex and age into account and to examine the prevalence of loneliness in individuals aged 15+ years.

Data from 20,007 participants of the cross-sectional population-based Swiss Health Survey 2012 were analyzed. The association of loneliness with lifestyle and health-related factors were assessed with logistic regression analyses. Wald tests were used to test for age and sex differences.

Loneliness was reported by 64.1% of individuals, and was associated with smoking (OR 1.13, 95% CI 1.05–1.23), physical inactivity (1.20, 1.10–1.31), non-adherence to the 5-a-day recommendation for fruit and vegetable consumption (1.21, 1.07–1.37), and more visits to a physician within the last year (1.29, 1.17–1.42). Loneliness was also associated with high cholesterol levels (1.31, 1.18–1.45), diabetes (1.40, 1.16–1.67), self-reported chronic diseases (1.41, 1.30–1.54), impaired self-perceived health (1.94, 1.74–2.16), moderate and high psychological distress (3.74, 3.37–4.16), and depression (2.78, 2.22–3.48). Age modulated the associations in BMI, smoking, visiting a physician within the past year, and self-perceived health. Sex did generally not modulate the associations.

Loneliness is associated with unhealthy lifestyle, and poorer physical and mental health. Associations were modulated by age, but not sex. Further longitudinal studies are needed to elucidate the causal relationships of these associations.

The authors have not supplied their declaration of competing interest.

Postpartum psychosis (PP) is the most severe psychiatric disorder associated with childbirth. Previous evidence has shown gene expression alterations in immune profile in women with PP when compared with healthy postpartum women. However, no study has ever evaluated women at risk who do not develop the disorder.

We conducted an exploratory analysis of a gene expression profile that could distinguish women with PP episode (PPE) from women at risk who do not develop PP (NPPE) after delivery.

The sample was characterised by 24 women at risk of PP of which n = 12 with PPE and n = 12 with NPPE and 21 healthy women in the same postpartum period. Following Microarray analysis, we assessed gene expression signature across the 3 groups using ANOVA. We then studied Pathway analysis of genes differently expressed in PPE and PPE exploring canonical pathways and upstream regulators using Ingenuity Pathway Analysis software.

Following an exploratory gene expression analysis we identified 719 genes that are differently expressed across PPE and NPPE. The PPE presented upregulation of several genes involved in the inflammatory pathway and increased gene expression levels of GRIA4, AKT3, SP4 and NRG1 genes, which have been previously described in psychotic disorders. Moreover, 5 differently expressed canonical pathways were identified including ones relevant to development, mitochondrial formation and immune system.

These preliminary results reveal the presence of an immuno-neuro-endocrine dysregulation in postpartum psychosis, with an upregulation of the immune system specific to those women at risk who actually develop postpartum psychosis episodes.

The author has not supplied his declaration of competing interest.

Gene × environment (G × E) interactions in eating pathology have been increasingly investigated, however studies have been limited by sample size due to the difficulty of obtaining genetic data.

To synthesize existing G × E research in the eating disorders (ED) field and provide a clear picture of the current state of knowledge with analyses of larger samples.

Complete data from seven studies investigating community (n = 1750, 64.5% female) and clinical (n = 426, 100% female) populations, identified via systematic review, were included. Data were combined to perform five analyses: 5-HTTLPR × Traumatic Life Events (0–17 events) to predict ED status (n = 909), 5-HTTLPR × Sexual and Physical Abuse (n = 1097) to predict bulimic symptoms, 5-HTLPR × Depression to predict bulimic symptoms (n = 1256), and 5-HTTLPR × Impulsivity to predict disordered eating (n = 1149).

The low function (s) allele of 5-HTTLPR interacted with number of traumatic life events (P < .01) and sexual and physical abuse (P < .05) to predict increased likelihood of an ED in females but not males (Fig. 1). No other G × E interactions were significant, possibly due to the medium to low compatibility between datasets (Fig. 1).

Early promising results suggest that increased knowledge of G × E interactions could be achieved if studies increased uniformity of measuring ED and environmental variables, allowing for continued collaboration to overcome the restrictions of obtaining genetic samples.

The authors have not supplied their declaration of competing interest.