There are no clinically useful biomarkers for the prediction of treatment response in bipolar depression (BD). One of the best-documented markers of response to an antidepressant therapy in patients with unipolar depression is a decrease in quantitative electroencephalography measure of prefrontal cordance in theta frequency band (Leuchter et al., 2010).

The aim of our study was to examine whether the change of theta prefrontal cordance after one week of various antidepressive interventions predicts response to a 4-week treatment in patients with BD.

We enrolled 24 inpatients into the study. Theta prefrontal cordance was computed at baseline and after 1 week of treatment. Depressive symptoms were evaluated using the Montgomery and Åsberg Depression Rating Scale.

Twenty patients finished the study. Seven of 8 responders and only 2 of 12 non-responders showed a decrease in prefrontal theta cordance after the first week of drug administration (p = 0.02). Using the decrease of prefrontal cordance value as a predictor of treatment response yielded Positive Predictive value of 0.78 and Negative Predictive Value of 0.91. We also found higher baseline theta cordance in responders. Nevertheless when baseline cordance and cordance change entered into the logistic regression model, only the latter emerged as a predictor of response (p = 0.007; correctly classified 85% cases).

The change in prefrontal theta cordance was associated with subsequent change in depressive symptoms and potentially might be a useful marker of response to antidepressive interventions in BD patients (Bares et al., 2011). Supported by a grant MSMT 1M0517.

This comparative study investigated consumption patterns, comorbidity and treatment utilization of opioid addicts in six European cities (Athens, Essen, London, Padua, Stockholm, Zurich).

Data were collected by structured face-to-face interviews. The representative sample comprises 599 addicts (100 patients per centre, 99 in London) at the start of a treatment episode.

Patients were dependent on opioids for about 10 years. Regional differences were significant regarding the patients’ drug consumption pattern and their method of heroin administration (up to a fourth of the patients in Essen, London and Zurich usually smoke heroin). Concomitant use of benzodiazepines, cannabis and alcohol was common in all regions with the German and English samples showing the highest level of polydrug use. The prevalence of major depression was high in all regions (50%). Stockholm and London patients worry most about their physical health. Differences in the amount of needle sharing and especially in the use of public health service were prominent between the sites. Opioid addiction was a long-term disorder associated with a high burden of comorbidity and social problems in all cities.

The results of the study show significant interregional differences of opioid addicts which might require different treatment strategies in European countries to handle the problem.

We considered that completed opiate detoxification resulted in increased life expectancy and earning capacity as compared to non-completed detoxification.

The cohort study sample included pure opioid or poly-substance addicts admitted for voluntary in-patient detoxification between 1997 and 2004. Of 404 patients, 58.7% completed the detoxification program and 41.3% did not. The Austrian Social Security Institution supplied data on survival and employment records for every single day in the individual observation period between discharge and December 2007. Statistical analyses included the calculation of standardized mortality rates for the follow-up period of up to 11 years.

The standardized mortality ratios (SMRs) were between 13.5 and 17.9 during the first five years after discharge, thereafter they fell clearly with time. Mortality did not differ statistically significantly between completers and non-completers. The median employment rate was insignificantly higher in completers (12.0%) than in non-completers (5.5%). The odds for being employed were higher in pure opioid addicts than in poly-substance addicts (p = 0.003).

The assumption that completers of detoxification treatment have a better outcome than non-completers has not been confirmed. The decrease in mortality with time elapsed since detoxification is interesting. Pure opioid addicts had better employment prospects than poly-substance addicts.

Previous studies on the impact of cannabis use disorders (CU) on outcome in psychosis were predominantly based on non representative samples, often have not controlled for confounders and rarely focused on adolescent patients. Thus, the aims of the present study were to assess: (i) prevalence of CU; (ii) baseline and pretreatment differences between CU and those without CU (NCU); (iii) the impact of baseline and course of CU on 18-month outcomes in a representative cohort of adolescents with early onset first episode psychosis (EOP).

The sample comprised 99 adolescents (age 14 to 18) with EOP (onset age 14 to 17), admitted to the Early Psychosis Prevention and Intervention Centre in Australia. Data were collected from medical files using a standardized questionnaire.

Prevalence of lifetime CU was 65.7%, of current CU at baseline 53.5%, and of persistent CU throughout treatment 26.3%. Baseline CU compared to NCU had significantly higher illness-severity, lower psychosocial functioning, less insight, lower premorbid functioning and longer duration of untreated psychosis. Compared to all other groups, only persistent CU was linked to worse outcomes and more service disengagement. Effect sizes were medium controlling for relevant confounders. Medication non-adherence did not explain the association between persistent CU and worse outcome.

Baseline CU was associated with worse baseline characteristics, but only persistent CU was linked with worse outcome. About half of those with baseline CU reduced cannabis during treatment. For these, effectively treating the psychotic disorder may already be beneficial. However, future research is necessary on the reasons for persistent CU in EOP and its treatment.

Neuroprotective effects of lithium have been well documented in tissue cultures and animal models. The evidence for lithium related neuroprotection in human subjects is limited and inconsistent, likely due to methodological heterogeneity.

To investigate the effects of lithium on brain chemistry and structure, we recruited bipolar patients selected for substantial illness burden and varied the exposure to lithium by using strict inclusion criteria.

We obtained 1.5T magnetic resonance imaging data from 27 bipolar patients with at least 2 years of ongoing lithium treatment (Li group), 16 subjects with < 3 months lifetime exposure to lithium >2 years ago (non-Li group) and 21 healthy controls. Patient groups had to have at least 10 years of illness and 5 episodes.

The non-Li group had significantly lower hippocampal volumes (t = 4.68,corrected p < 0.05) and prefrontal cortex N-acetyl aspartate (NAA) levels (t = −2.91,corrected p < 0.05) than controls, who showed comparable hippocampal volumes and NAA levels to the Li treated subjects. Duration of illness was negatively associated with NAA levels only in the non-Li, but not the Li group.

Among patients selected for substantial illness burden, only those with no or minimal lifetime Li exposure had significantly lower prefrontal NAA levels and hippocampal volumes than controls. Patients with at least 2 years of ongoing Li treatment showed no such changes, despite substantial burden of illness. These findings provide indirect support for neuroprotective effects of lithium and negative effects of illness burden on brain chemistry and structure in patients with bipolar disorders.

To evaluate the effectiveness and tolerability of pregabalin in the management of the discontinuation of benzodiazepines in long-term users.

We performed a 12-week, prospective, uncontrolled, non-interventional, and observational study in patients aged 18 years old or above, who met DSM-IV-TR criteria for benzodiazepine dependence without other major psychiatry disorder. Evaluations included the Benzodiazepine Withdrawal Symptom Questionnaire, the Hamilton Anxiety Rating Scale, the Clinical Global Impression Scale, and the Sheehan Disability Scale. A urine drug screen for benzodiazepines was performed at baseline and every 4 weeks thereafter. The primary effectiveness variable was success rate, defined as achievement of benzodiazepine-free status at week 12 according to the urine drug screen.

The mean dose at week 12 was 315 (±166) mg/day. The success rate of the benzodiazepine taper in the primary efficacy population (n = 282) was 52% (95% confidence interval [CI], 46–58). Success rates for women and men were 58% (95% CI, 49–67) and 46% (95% CI, 38–55), respectively. The success rates did not differ according to either the benzodiazepine of abuse or the presence of other substance use disorders. Significant and clinically relevant improvements were observed in withdrawal and anxiety symptoms, as well as in patients’ functioning. At week 12, tolerability was rated as good or excellent by 90% and 83% of the clinicians and patients, respectively.

Our results suggest that pregabalin is an efficacious and well-tolerated adjunctive treatment for benzodiazepine withdrawal.

This study sought to determine the clinical correlates of adolescents with cannabis use and no additional drug use (CU) compared to adolescents with no drug use (NDU) among a group of adolescent psychiatric inpatients in Israel.

Two hundred and thirty-six patients consecutively admitted to an adolescent inpatient unit at a university-affiliated mental health center in Israel during a 3-year period were screened. Individuals with polydrug use were excluded from the study.

Prevalence of cannabis use was 13%. In the CU group, 39% were diagnosed with attention deficit and disruptive behavior disorders compared with 16% in the NDU group. Antipsychotics were the most common medications prescribed in both groups. Mood stabilizers were more frequently prescribed to CU than to NDU patients (39% vs 16%, respectively). A higher prevalence of alcohol abuse and criminal behaviors was found among CU compared to NDU patients (61% and 39% vs 6% and 4%, respectively).

The high prevalence of disruptive behaviors and frequent treatment with antipsychotics and mood stabilizers in the CU group may be related to the strong association between externalizing behavior and cannabis use and the non-specific pharmacological treatment of disruptive behaviors. Formal screening for cannabis use should be considered in psychiatric facilities. Specifically, adolescents with disruptive behaviors could benefit from early interventions, before and after cannabis initiation.

Converging evidence from neuroimaging studies indicates that white matter abnormalities may be involved in bipolar disorder (BP). One most consistent finding, though not universal, has been the increased occurrence of white matter hyperintensities (WMH) in BP patients. The role of hyperintensities in the pathogenesis, and treatment of mood disorders remains unclear. However, the diffusion tensor imaging (DTI) has expanded somewhat our understanding of white matter in BP.

During this presentation I will give the overview of the white matter pathology in BP. In addition, I will introduce the results of our study concerning WMH, affective disorders, and neuropsychological functioning.

We have studied 13 BPI, 15 BPII, 16 major depressive patients, and 21 controls at baseline, and at 5-year follow-up. Besides clinical interviews, further detailed investigation comprised a neuropsychological test battery and structural brain imaging with DTI. WMH were calculated manually, and DTI will be analyzed using tract based statistical methods.

BPI patient group had increased risk for DWMH contrary to BPII and MDD patients when compared to controls. Increased DWMH grade together with age and BDI score predicted decreased capability of visual attention measured by visual span forward subtest of the WMS-R.

While suicidal behavior is frequently accompanied by serotonergic system alterations, specific associations with variants of the serotonin 2A receptor gene (HTR2A) have been inconsistent.

To confirm and extend previous associations of HTR2A with suicidal behavior.

To study genetic effects, as well as gene-environment interaction (GxE) and parent-of-origin effects (POE) that may further contribute to association.

Using a family-based study design of 660 offspring who have made a suicide attempt (SA) and both parents, we conducted an association and linkage analysis of single nucleotide polymorphisms (SNPs) with extensive gene coverage. We included the study of GxE with physical and sexual assault (with a cutoff age of 18 years), as well as cumulative types of stressful life events (lifetime SLEs). We also studied POE at SNP rs6313.

The main finding was a GxE between rs6313 and exposure to lifetime SLEs in the total sample, driven by overtransmission of CT and undertransmission of TT. Further exploratory analysis revealed a significant POE in this GxE in females which followed a polar overdominant imprinting pattern. In addition, several nominally significant findings were observed with other SNPs, many of which had previously reported and/or hypothesized functional effects.

This study found multiple associations of HTR2A with SA, and strongest statistical evidence for a GxE involving rs6313. It further suggested the importance of taking into account different genetic models of inheritance and GxEs with regard to HTR2A.