Childhood adversity is a major risk factor for life-time various psychiatric disorders. The vulnerability for psychiatric disorders appears to be modulated by cognitive reserve (CR).

We wanted to examine the impact of childhood adversity on lifetime suicidal behavior and major depression and its modulation by education, a CR proxy.

1494 non-institutionalized individuals without dementia from a cohort of community-dwelling persons aged over 65 years (the ESPRIT study) were randomly selected from electoral rolls and rated for childhood adversity (e.g., emotional abuse and neglect). Life-time major depression and suicidal behavior were assessed according to DSM-IV criteria.

Exposure to adversity in childhood increased the risk of life-time suicidal behavior and major depression (p< 0.0001 OR=1.75 [1.34-2.28]) but there was no significant effect of education alone (p=0.276). Subjects with a low level of education were observed to be at higher risk (p< 0.005; OR=2.19 [1.26-3.80]) and subjects with the higher level of education showed a non significant risk (p=0.244).

Our results suggest high education level as a protective factor to counteract the effects of childhood adversity on the onset of mental disorders in adulthood.

Patients with chronic kidney disease (CKD) have more cognitive impairments. However, the etiologies are not fully clear. Plasma homocysteine levels and vascular burden rise in CKD; meanwhile, high homocysteine levels and vascular factors are known risk factors of dementia in non-CKD patients. Thus, we aimed to investigate the association between homocysteine, vascular burden and cognitive impairment in CKD and to see if the effect of elevated homocysteine on cognitive impairment mediated by vascular factor.

146 patients with CKD and 69 normal comparisons were recruited. Cognitive function was evaluated by comprehensive neuropsychological tests assessing processing speed, executive function, language, visuospatial function, memory, and attention domains. Vascular burden was assessed by Framinghan cardiovascular risk scale (FCRS) which indicates risk of atherosclerotic diseases including stroke.

In controlled analysis, patients with CKD had lower scores in all cognitive domains, and had higher homocysteine levels (18.5±6.4 vs. 9.8±2.9, p< 0.0001) and FCRS(17.0±4.7 vs. 14.0±4.7, p< 0.0001). Among patients with CKD, higher homocysteine levels (p=0.026) were associated with lower score on digit symbol task which is related to processing speed and executive function with controlling for age, sex, education and stage of CKD. The association persisted (p=0.047) after controlling for vascular risks.

Patients with CKD had extensive cognitive impairments. Elevated homocysteine levels may be an risk factor, which is independent of vascular burden, of cognitive impairment on processing speed and executive function. Further studies to investigate if normalization of homocysteine can improve cognitive function will be suggested.

The impact of cannabis use on brain structure, particularly white matter (WM), is poorly understood. The CC is the largest WM structure in the brain. Abnormalities revealed in the CC may underlie functional anomalies of cannabis use. This is the largest study to explore the effect of cannabis on callosal WM connectivity among first episode psychosis (FEP) and controls.

To investigate the relationship between cannabis use and WM micro-structural integrity of the CC, in FEP and healthy controls.

We evaluated 56 FEP patients (67% current cannabis users), and 43 healthy controls (44% current cannabis users). We used Diffusion Tensor Imaging combined with a WM mapping-tractography technique to investigate the microstructural integrity of the CC.

Total CC Fractional anisotropy (FA) was lower in patients than controls (p=0.05). Cannabis-using patients had lower FA of the total CC than cannabis-using controls (p=0.04). There were no differences in FA between cannabis-using patients and those who had never used. However, cannabis-using patients had higher mean diffusivity (MD) of total CC (p= 0.02), Rostral-Body (p=0.003), Anterior Mid-Body (p=0.03) and the Splenium (p=0.06) than patients who never used cannabis. There were no differences in MD between patient users who started before the age of 16 and those who started later.

Cannabis is associated with a significant effect on callosal WM integrity only in patients with psychosis. Disturbed callosal connectivity may explain some of the abnormalities with regard to the functional and clinical outcomes in FEP cannabis users, including measures of cognitive impairment.

Follow up periods of up to 48 months after the time of initial admission to the program was conducted and the frequency of re-offense was observed. Comparisons for the significance of risk factors were analyzed using t-tests and Chisquare tests.

191 clients were admitted to the Mount Sinai Hospital Court Support Program between September 2001 and June 2007. At first admission, the mean ± s.d. age was 35.8 ± 9.8 years (range=18-74 years; n=184). The median age was 35 years. The modal age was 34 years. Of the 191 clients, 16 (8.4%) reoffended. Two of them (12.5%) had a third offense; and 1 (6.3%) had a total of four offenses within this tracking period. it appears that re-offense is more likely between 13 and 24 months. No re-offense was noted beyond the 48 months. The gender distribution was not significantly different between reoffenders and non-reoffenders. The mean age at first admission also did not differ between reoffenders and non-reoffenders. The distribution of ethnic groups among reoffenders and non-reoffenders did not differ.

The findings seem to indicate that recidivism has no relationship with gender, age and ethnic groups. The comprehensive and length of support services seem more important in preventing recidivism.

Agomelatine is a novel antidepressant which was licensed in the United Kingdom in February 2009, but has not yet been included in national prescribing guidelines in the UK. The cost of Agomelatine and the need for monitoring of liver function during treatment have informed the development of strict local guidelines in respect of the initiation of Agomelatine.

To assess the use of Agomelatine following introduction in a district general hospital outpatient setting.

To determine whether Agomelatine use is in accordance with recently formulated local guidelines and to explore prescribing patterns for Agomelatine.

Case notes were reviewed for consecutive patients prescribed Agomelatine over a 3 month study period. Using a specifically designed proforma, prescribing data, laboratory indices, outcome data and patient feedback were assessed against standards derived by consensus based on new prescribing guidelines.

27 patients were studied. Agomelatine was initiated in 93% of cases for major depressive disorder as third-line treatment. 89% of patients completed baseline liver function tests and 63% had these reviewed at all of 3 time-points as recommended. 14% did not require an increment to the 50mg dose. 33% discontinued Agomelatine. 44% experienced mild side-effects such as headaches and nausea. 56% did not require an additional anxiolytic and 14% were successfully discharged. Positive feedback was obtained verbally and with rating scales.

Initiation of agomelatine in accordance with recommended standards proved possible in a district general hospital setting. Agomelatine was well tolerated and positive patient feedback was received.

To investigate the relationships between work environmental factors and the risk of major depressive disorder (MDD) over one year and to identify factors associated with the outcomes of individuals with MDD.

We conducted a population-based longitudinal study of employees who were randomly selected in Alberta (n = 4239). MDD was assessed using the World Health Organization's Composite International Diagnostic Interview - Auto 2.1.

The one-year incidence of MDD was 3.6% (95% CI: 2.8%-4.6%) overall. It was 2.9% (95% CI: 1.9% - 4.2%) in men and 4.5% (95% CI: 3.3% - 6.2%) in women. The relationships between work environmental factors and MDD differed by sex. In men, high job strain increased the risk of MDD in those who worked 35-40 hours per week; job insecurity and family-work conflict were predictive of MDD. Women who worked 35-40 hours, who reported job insecurity, high effort-reward imbalance and work-family conflict were at higher risk of MDD. Long working hours, negative thinking and having comorbid social phobia were predictive of MDD. Perceived work-family conflict, severity of major depressive episode and symptom of depressed mood were significantly associated with recurrence of MDD.

Job strain, effort-reward imbalance, job insecurity and work-family conflicts are important risk factors for the onset of MDD, and should be targets of primary prevention. However, these work environmental factors appear to operate differently in men and in women. Clinical and psychosocial factors are important in the prognosis of MDD. The factors associated with persistence and recurrence of MDD may be different.

Little is known about long-term effects of psychotherapy on depressive or anxiety disorders.

To compare the effectiveness of three psychotherapies of different length in a clinical trial with a 5-year follow-up.

In the Helsinki Psychotherapy Study, 326 outpatients with mood or anxiety disorder were randomly assigned to longterm psychodynamic psychotherapy (LPP), short-term psychodynamic psychotherapy (SPP), and solution-focused therapy (SFT), and were followed up for 5 years from start of treatment. Depressive, anxiety and general psychiatric symptoms (BDI, SCL-90-Anx, and SCL-90-GSI), working ability (WAI), and recovery (based on changes in psychiatric symptoms and use of auxiliary treatment) were used as outcome measures.

For patients with depressive disorder LPP was more effective than SPP or SFT in reducing symptoms, improving work ability and leading to recovery during the 3 last years of follow-up. For patients with anxiety disorder effectiveness of LPP was less pronounced with no differences between short-term and long-term therapy in recovery from anxiety symptoms. No differences were found between the effectiveness of the short-term therapies.

Long-term psychotherapy is more effective than short-term therapy during a long follow-up especially in the treatment of depressive disorder. More research especially considering different anxiety disorders is still needed.

Analgesics are easily obtainable and frequently used as a means of suicide. Elderly persons are high consumers of analgesics, notably opiods and also have a high suicide risk.

To determine whether elderly persons with a history of suicide attempts have higher rates of analgesic use compared to depressed and normal controls.

857 non-institutionalized individuals without dementia from a cohort of community-dwelling persons aged over 65 years (the ESPRIT study) were randomly selected from electoral rolls and divided into three groups: 41 subjects with a lifetime history of suicide attempts (SA), 410 affective controls (AC) with a history of depression without suicide attempts, and 406 healthy controls (HC). Data on socio-demographic and clinical characteristics including analgesic use (based on data from the national healthcare insurance scheme over 3 year follow up) were collected. Logistic regression was used to compare analgesic consumption by grade (I: non opioid drugs; II: opioid drugs) in the three groups.

After controlling for gender, age, education, chronic disease, hospitalization, living alone and subjective health, opioid consumption was observed to be significantly higher in both SA and AC in comparison to HC (respectively: OR=2.33 [1.15-4.73] and OR=1.39 [1.01-1.91]). After exclusion of cancer cases, the relationship remained significant only for the SA group.

Our findings suggest that suicidal vulnerability may be associated with an increased sensitivity to pain.

In a European, phase 3 study (SPD489-325), lisdexamfetamine dimesylate (LDX) and osmotic-release oral system methylphenidate (OROS-MPH) were more effective than placebo in improving core symptoms in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).

To compare post hoc the efficacy of LDX and OROS-MPH in study SPD489-325.

This 7-week, randomized, double-blind, parallel-group, dose-optimized, placebo-controlled trial enrolled patients aged 6-17 years with ADHD of at least moderate severity. Patients were randomized (1:1:1) to receive a once-daily dose of LDX (30, 50, 70 mg/day), OROS-MPH (18, 36, 54 mg/day) or placebo. Efficacy was assessed using the ADHD Rating Scale version IV (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) scale. Endpoint was defined as the last ontherapy treatment visit with a valid assessment.

The full analysis set comprised 317 patients (LDX, n=104; placebo, n=106; OROS-MPH, n=107). The difference between LDX and OROS-MPH in least squares mean change (95% confidence interval [CI]) in ADHD-RS-IV total score from baseline to endpoint was statistically significant in favour of LDX (-5.6 [-8.4, -2.7]; p < 0.001; effect size, 0.541). The difference (LDX minus OROS-MPH) in the percentage of patients (95% CI) with an improved CGI-I score at endpoint was also statistically significant in favour of LDX (17.4 [5.0, 29.8]; p < 0.05).

This post hoc analysis indicated that LDX is significantly more effective than OROS-MPH in improving core symptoms and global functioning in children and adolescents with ADHD.

Supported by: Funding from Shire Development LLC.

In a European, phase 3 study (SPD489-325), lisdexamfetamine dimesylate (LDX) was more effective than placebo in improving symptoms and global functioning in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).

To evaluate the impact of age, sex and baseline disease severity on efficacy outcomes in SPD489- 325.

This 7-week, double-blind, parallel-group, dose-optimized study enrolled patients aged 6-17 years with ADHD. Patients were randomized (1:1:1) to once-daily LDX (30, 50 or 70mg/day), osmotic-release oral system methylphenidate (OROS-MPH; 18, 36 or 54mg/day) or placebo. Efficacy outcomes were analysed in patients dichotomized by age (6-12 years [n=229] or 13-17 years [n=88]), sex (male [n=255] or female [n=62]) and baseline ADHD Rating Scale version IV (ADHD-RSIV) total score (28-41 [n=161] or 42-54 [n=152]). Endpoint was the last on-treatment visit with a valid assessment.

At endpoint, differences (active-placebo) in least-squares mean changes from baseline in ADHD-RS-IV total scores were statistically significant in all age, sex and ADHD-RS-IV total score subgroups for LDX (p< 0.001; effect sizes, 1.68-2.26) and OROS-MPH (p< 0.01; effect sizes, 0.88-1.46). Proportions of patients with a Clinical Global Impressions-Improvement rating of 1 (very much improved) or 2 (much improved) were statistically significantly greater than placebo at endpoint in all subgroups receiving LDX (p< 0.01) and in all subgroups except females receiving OROS-MPH (p< 0.05).

LDX showed greater efficacy than placebo in children and adolescents with ADHD, regardless of their age, sex or baseline disease severity.

Supported by: Funding from Shire Development LLC.

In the diagnosis of functional states of the brain are bursts deviation from the normal pattern EEG. Also used registration of the scalp-recorded direct current (DC) potentials, which in the modern view is characteristic of indirect energy metabolism of the brain.

Studied 25 children 8, 5±3, 3 years of schizophrenia. Aims To assess the significance of electrographic parameters abnormal theta activity with characteristics of energy metabolism of the brain in schizophrenia.

Shifts in scalp-recorded DC potential were studied in relation to the changes of EEG recording such as abnormal prominent theta bursts. Standard EEG recordings were made during wakefulness. “Theta bursts” appeared in two frequency bands: 4-5 cps and 6-7 cps. DC potentials and their topographical distribution were investigated in schizophrenic patients with and without designated electroencephalogram characteristics. The mental state of children assessed psychopathological method and using the scale of PANSS. The obtained data were analyzed using software Statistica-7.

The presence of 6 - 7 Hz in the EEG theta activity, particularly in the temporal areas, combined with a higher level of permanent potentials. Fairly significant differences were observed for the left (p < 0,018) and right (p < 0,012) of the temporal lobes. Were observed higher ratings of positive syndromes scale PANSS (p < 0,014). The presence of 4-5-Hz activity was associated with a decline in constant potentials, and a decrease in mean scores of positive syndromes PANSS.

It was concluded that DC measurement reflects changes in brain state associated with pathophysiology of schizophrenia.

Menopause is characterized by a decline in ovarian function resulting in vasomotor symptoms. Vasomotor symptoms include hot flashes and night sweats.The purpose of this study was to examine the effect of SSRIs on hot flashes in perimenopausal women with depression.

Sixty five perimenopausal women participated in this study. The subjects included 41 perimenopausal women with depression and 24 healthy women. The diagnosis of depression was made by a psychiatric interview and with the help of Hamilton Depression Rating Scale 17 (HAM-D 17). Hot flashes were examined with the use of Menopause Rating Scale (MRS) and they were divided as absent, mild, moderate, severe and very severe.

Perimenopausal women were divided in three groups. The first group consisted of normal controls, the second of depressed perimenopausal women who were taking SSRIs and the third of depressed women not taking SSRIs. The control group had fewer hot flashes than the other two groups (p< 0.0001).The two groups of depressed women did not show any statistically significant difference in the presence and severity of hot flashes in relation to the use of SSRIs.

It was found that depression is associated with the presence of hot flashes in perimenopausal women. On the other hand the use of SSRIs did not relieve perimenopausal women with depression of hot flashes. Therefore, it seems that hormonal replacement therapy has the first role in the treatment of vasomotor symptoms in perimenopausal women.

To analyze the effect of adjunctive therapy with pregabalin versus usual care (UC) on healthcare costs and clinical consequences in generalized anxiety disorder (GAD) patients with partial response (PR) to previous SSRI.

Post-hoc analysis of patients enrolled in a prospective 6-month observational study. Patients with a PR [CGI score >3 and insufficient response with persistence of anxiety symptoms (HAM-A score ≥16)] to SSRI monotherapy were considered eligible for inclusion. Two groups (based on psychiatrist judgment) were analyzed 1) adding pregabalin (150-600 mg/day) to existing therapy; or 2) UC (switching to a different SSRI or adding another anxiolytic. Costs estimation used year-2009 prices for GAD related healthcare resources utilization. Measures of clinical consequences were, changes in total scores of anxiety in HAM-A (primary outcome) and GAD co-morbid depressive symptoms in MADRS (secondary outcome) scales.

Four-hundred-eighty-six newly prescribed pregabalin and 239 UC GAD patients [mean (SD) HAM-A 26.7 (6.9) and CGI 4.1 (0.5)] were analyzed. Adding pregabalin was associated with significantly higher adjusted mean changes (95% CI) vs. UC in HAM-A [-11.2 (-12.2;-10.2) vs. -14.9 (-15.6;-14.2), respectively; p< 0.001] and MADRS [-7.8 (-8.7;-6.8) vs. -11.6 (- 12.2;-10.9), respectively; p< 0.001]. Adjusted mean baseline healthcare costs were significantly reduced in both cohorts; -€487 (-652;-317) and -€531 (-648;-413), respectively (both p< 0.001), yielding to similar 6-month costs; €1543 (1375;1711) UC and €1497 (1380;1614) pregabalin, p=0.661.

In this post-hoc analysis, GAD patients with PR to SSRI experienced greater symptom improvement with adjunctive therapy with pregabalin versus UC without increasing healthcare cost.

The mortality among homeless people is linked to the presence of psychiatric disorders.

We compared the risk of specific death causes among clients of the Public Mental Health care (PMHc) in Utrecht with that of the general population, and assessed whether treatment at a local psychiatric service is associated with this risk.

To clarify the association between the presence of a mental disorder and mortality among the socially marginalized.

Out of 8,741 clients in the PMHc register, the records of 6,724 could be linked to the registries of Statistics Netherlands (CBS). Controls (N=66,247) from the population register were personally matched to a PMHc client. A Cox regression analysis was used to estimate hazard ratios (HR) of death.

An increased all-cause mortality among PMHc clients compared to controls was found (HR=2.99, 95%-CI: 2.63- 3.41), associated with a broad range of death causes.PMHc clients with record linkage to the Psychiatric Case Registry Middle Netherlands (’PMHc+’) had an increased risk of suicide (HR=2.63, 0.99-7.02), but a lower risk of death from natural causes (HR=0.71, 0.54-0.92), compared to PMHc clients without (‘PMHc-’). Compared to controls, however, ‘PMHc-’ clients experienced increased risks of suicide (HR=3.63, 1.42-9.26) and death due to mental & behavioural disorders (HR=7.85, 3.54- 17.43).

Among PMHc clients, a registered diagnosis at a local psychiatric service appears to be favourably associated with lower mortality due to natural death causes. The high risk of suicide among ‘PMHc-’ clients probably indicates a high prevalence of undiagnosed mental disorders among PMHc clients.

ADHD in adults is associated with a significant impairment in many life activities increasing the risk of chronic stress in everyday life. Previous studies reported normal cortisol awakening response (CAR) in children with ADHD without comorbidities, nevertheless there is a lack of studies in adults.

The aim of the present research is to examine CAR in adults with ADHD and to assess possible differences between the combine and inattentive subtypes.

Patients were recruited from the Program for adults with ADHD in the Department of Psychiatry of the Hospital Universitari Vall d’Hebron. The clinical sample consisted of 50 adults, age between 18 and 51 years (mean 35.24 ± 9.21) fulfilling current diagnostic criteria for ADHD (DSM-IV criteria). All patients were naïve to stimulant medication. Psychiatric and organic comorbid disorders were excluded. To assess CAR, four salivary cortisol samples were collected at 0, 30, 45 and 60 minutes after awakening.

The mean increase in CAR for the whole group of patients was 10.34±8.79 nmols/l. T-test comparisons showed no significant differences in the mean increase of CAR between the inattentive (mean: 9.47±9.04 nmols/l) and combine (mean: 11.25±8.67 nmols/l) subtypes (t=0.610; z=0.546).

Despite there were no significant differences in salivary CAR between ADHD subtypes in adults, the mean increase of CAR was higher in combine than in the inattentive subtype. Salivary CAR needs to be further explored as an index of vulnerability to stress in these patients.

There is a large mortality gap between patients with a non-affective psychotic disorder (NAPD) and the general population.

To assess whether mortality risks vary for different death causes according to duration since diagnosis and age in a large sample of NAPD patients.

To get insight into the risk of specific death causes along the treatment trajectory, important for interventions that are tailored to the patients' risk profile.

Data of NAPD patients (n=12,580) from three Dutch psychiatric registers were linked to the registers of Statistics Netherlands and compared to personally matched controls (n=124,143). Death rates were analysed by duration since the date of diagnosis of the (matched) patient and age using Poisson regression.

Among patients, the rates of all-cause death decreased with longer duration. This was explained by lower suicide rates. E.g., among those aged 40-60 years, the rate ratios (RRs) of suicide during 2-5 and >5 years compared to the early years after diagnosis were 0.52 and 0.46 (P=0.002). Compared with controls, patients experienced higher rates of natural death causes during all stages and in all age categories: RRs 2.35-5.04, P < 0.05. No increase in these RRs for patients compared to controls with increasing duration or increasing age was found.

The high risk of natural death causes among NAPD patients is not (only) an effect of accumulating risks induced by the chronic nature of the disorder and/or antipsychotic treatment, but is already present during the early stages of the treatment and at young age.