Dysregulation of the hypothalamic-pituitary-adrenal (HPA-)axis is hypothesized to play a role in the pathogenesis of bipolar disorder (BD). Conflicting results have been reported when saliva or serum was used to measure cortisol levels. A recently developed method is to measure cortisol in scalp hair, with one cm of scalp hair representing one month. We studied whether there are differences in long-term hair cortisol levels between BD patients and healthy individuals and whether there are associations between hair cortisol, life events and disease characteristics.

Hair samples were collected in 100 BD patients and 195 healthy controls. Long-term cortisol levels were determined in 3 cm hair segments. Saliva samples were collected on two consecutive evenings. Documented disease characteristics were disease state, age of onset, psychiatric co-morbidity, and life events.

Hair cortisol levels were not statistically different in BD patients compared to healthy controls (p=0.233) and were not associated with the disease state at the moment of sample collection (p=0.978). Clinical characteristics, such as age of onset ≥30 years (p=0.004) and psychiatric co-morbidity (44.87 versus 31.41 pg/mg hair; p=.021), appeared to associate with higher hair cortisol levels. Panic disorder associated with decreased cortisol levels (22.13 versus 34.67 pg/mg hair; p=0.019). The occurrence of recent negative major life events, but not of positive major life events, was associated with an increase in HCC in BD patients.

Major depressive disorder (MDD) has harmful effects on an individual's personal life. In the European Union, in any given year, about 7% of all adults suffer from it. Primary choice of medical management is pharmacotherapy - second generation antidepressants (SGA). Some SGA are available as both immediate-release (IR), and extended-release formulations. Advantages of extended-release formulations may be the potentially improved adherence, and tolerability.

The objective of this systematic review was to assess the comparative efficacy, risk of harms, and adherence of IR- and extendedrelease antidepressants for the treatment of MDD.

To systematically review the evidence on differences between IR and extended-release formulations to provide an objective basis for clinical decision-making.

Abstracts were retrieved from PubMed, EMBASE, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to October 2012 as well as from hand search. We dually reviewed abstracts and full-texts and assessed quality ratings. We conducted network meta-analyses using Bayesian methods, due to the lack of head-to-head trials. Response on the Hamilton Depression Rating Scale (HAM-D) was our outcome measure.

We located seven head-to-head trials and 94 placebo and active controlled trials for network meta-analysis. Overall, our analyses show that IR and extended-release formulations of bupropion, trazodone, venlafaxine and paroxetine have similar efficacy. However, evidence suggests that there might be a difference between formulations based on adverse events and adherence.

Current evidence couldn’t prove a significant difference in the efficacy of IR- and extended-release formulations.

To review the role of the precuneus in major depression

We will review the literature involving the precuneus in the pathophysiology of depression. We will also report a recent study of our group using structural MRI and VBM analyses to assess the role of precuneus in Autobiographical Memory (AM). Visual perspective during AM retrieval was assessed in two independent datasets of 45 and 20 healthy young adults with two different AM retrieval tasks.

Precuneus, a medial part of the parietal cortex, is a central component of the default mode network. Results from our VBM study show that the precuneus volume in healthy subjects is correlated with the ability to retrieve autobiographical memories with a first-person perspective. Consistent with its role in integration of self-relevant mental simulations with past experiences and visuo-spatial processes during AM retrieval, the precuneus may subserve emotion regulation processes in healthy subjects and depressed patients. The precuneus and the default mode network show abnormal connectivity in depressed patients that may indicate abnormal self-processing in depression.

Abnormal activity and connectivity of the precuneus within the default mode network is associated with impairment in self-processing in depression and may be related to the tendency of depressed patients to retrieve AM using third-person perspective. Further studies are needed to evaluate if impaired function or structure of the precuneus may predict the clinical response to antidepressant treatment.

Antipsychotic drugs (APDs) are the first-line pharmacological treatments for schizophrenia. Recent human studies have found that myelin integrity could be improved by APD treatment in schizophrenia patients. Previous studies indicated that regulation of oligodendrocyte development and function may be a novel target for APDs.

The aim of this current study was to examine the possible effects of the antipsychotic drugs (APDs) haloperidol (HAL), olanzapine (OLA), and quetiapine (QUE) on the development of oligodendroglial lineage cells.

CG4 cells, an oligodendrocyte progenitor cell line, were treated with various concentrations of HAL, OLA, or QUE for specific periods. The proliferation and differentiation of the CG4 cells were measured. The regulation of CG4 cell differentiation by oligodendrocyte lineage transcription factors 1 and 2 (Olig1 and Olig2) was examined.

The APDs used in this study had no effect on the proliferation of CG4 cells. The APDs elevated the expression of 2’,3’-cyclic nucleotide 3’-phosphodiesterase (CNP), a specific marker of oligodendrocytes, and promoted the CG4 cells to differentiate into CNP positive oligodendrocytes. QUE and OLA increased the expression of Olig1 and Olig2 whereas HAL only increased the expression of Olig2.

Our findings suggest that oligodendrocyte development is a target of HAL, OLA, and QUE and provide further evidence of the important role of oligodendrocytes in the pathophysiology and treatment of schizophrenia. They also indicate that the expression level of oligodendrocyte/myelinrelated genes could be profoundly affected by APDs.

Planning ability as a critical component of executive function has been used to investigate prefrontal cortex (PFC) function in Schizophrenia patients by several neuroimaging studies. However, the changes of PFC activation after effective antipsychotic treatment are still unclear.

The aim of this study is to explore whether there is any variation in the prefrontal hemodynamic response during Tower of London test after 6 weeks’ antipsychotic treatment in schizophrenia patients, and the relationship between the changes in PFC activation and some demographic factors as well as the severity of the patients’ psychiatric symptoms.

40 patients with first-episode schizophrenia were recruited for the present study. 28-channel NIRS (near infrared spectroscopy) was used to measure changes in hemoglobin concentration in the prefrontal cortical surface area during Tower of London (TOL) test—a classic neuropsychological test for planning abilities. The patients were examined before treatment and after six weeks’ treatment with second-generation antipsychotic medicines.

After the short-term treatment, the patients’ TOL test performance and the activations in PFC during the task period did not differ from baseline (P>0.05), although the psychiatric symptoms of the patients were improved significantly(positive subscale score 18.25±2.86 & 12.75±2.60; general psychopathology 33.67±3.65 & 27.00±3.67; PANSS total score 72.25±7.07 & 55.42±7.53; P<0.001).

It suggests that the impairment of cognitive function and the function of the PFC of schizophrenia patients would not be improved with the improvement of psychiatric symptoms, as further support the hypothesis that PFC damage is a durable impairment for schizophrenia.

It is well known that medical students are subjected to different levels of stressors during various stages of their study. Exposure to severe and prolonged stressors may cause serious psychological distress that may hinder students’ academic performance and may affect their mental and physical health as well. Therefore, this study aimed to determine the prevalence of psychological distress among medical undergraduate students throughout the different stages of their study.

A sample of 551 undergraduate medical students from Kulliyyah (Faculty) of Medicine, International Islamic University Malaysia participated in this study (First year 141, Second 119, Third 109, Fourth 101, Fifth 81), the psychological distress was assessed using the 12-item General Health Questionnaire (GHQ-12), which is the short version developed by David Goldberg and Paul Williams. A binary scoring method was used to evaluate responses (i.e. 0-0-1-1). The rate was compared between different stages of the academic programme.

The overall prevalence of psychological distress among medical students was found to be 31.2% and the rate was higher during clinical than preclinical phases (33.7% and 28.5% respectively). Gender wise, it was found that the rate of psychological distress was significantly higher among female (35.5%) than male students (24.3%).

Psychological distress is common among medical students, it is higher among female than male students, and the rate is higher during clinical phase than preclinical phase.

Depression and pain symptoms are often comorbid and share common neurobiological and psychological background.

To find out the prevalence of painful physical symptoms (PPS) in otherwise healthy patients hospitalized due to recurrent unipolar (UD) and bipolar depression (BD) and to compare socio-demographic and illness related characteristics.

180 somatically healthy patients were recruited in the study. Symptoms of depression were evaluated with standard clinical tools. The presence of somatic illness was excluded. Visual Analogue Scale was used to evaluate the intensity and location of painful symptoms. Sociodemographic, illness and therapy related data, substance use, and suicidality were recorded as well.

41 patients met criteria for BD and 139 for UD. The average age was 50 years (75% females). Higher prevalence of PPS in group of UD (72.6%) in comparison to BD (58.5%) was found. The average intensity of painful symptoms was high. Patients with UD+PPS had higher total number of PPS and scored higher on HAM-D21 and Zung Self Rating Depression Scale than patients with BD+PPS. Use of analgesics and anxiolytics was high.

The study offers an insight in the high prevalence of PPS in patients with acute severe unipolar and bipolar depression and the results warn of possible over prescribing of analgesics and anxiolytics. Lower prevalence of PPS in BD might be explained with less severe depression symptoms. The results offer new information on PPS in acute bipolar depression since there is very little research data on this topic.

Symptoms that are linked to schizophrenia and other psychotic disorders, such as auditory verbal hallucinations (AVH), are also commonly reported by individuals who function well in society. These individuals are not in need for care, do not suffer from schizotypal personality disorder or other psychotic disorders, and provide the opportunity to investigate the relationship between nonclinical psychotic symptoms and brain morphology.

Fifty individuals with nonclinical AVH, 50 patients with a psychotic disorder and AVH, and 50 healthy controls underwent structural magnetic resonance imaging. The three groups were matched for age, gender, handedness and years of parental education. Cortical thickness was assessed using the FreeSurfer software suite.

Cortical thickness in the left pars orbitalis, left paracentral gyrus, right fusiform gyrus and right inferior temporal gyrus was lowest in patients, intermediate in the nonclinical AVH group, and highest in controls. The patients also showed additional cortical thinning in widespread frontal, temporal and parietal areas compared to both other groups. In additional analysis, ranking the levels of cortical thickness per brain region across groups revealed that for the large majority of brain regions (88%), the patients had the lowest cortical thickness, the nonclinical individuals with AVH were in between, and the control subjects had the highest cortical thickness.

Individuals with nonclinical psychotic symptoms show a similar but less pronounced pattern of cortical thinning as patients with a psychotic disorder, which is suggestive of a similar, but milder underlying pathophysiology in the nonclinical hallucinating group compared to the psychosis group.

Various psychological factors (personality traits, acute stressors, etc.). are involved in development of psychiatric disorders after acute coronary syndrome (ACS).

More passive personality traits might have protective effect in development of particular type of ACS [ST-segment elevation (STEACS) or non–ST-segment elevation (NSTE-ACS)].

To investigate the development of psychiatric disorders and dimensions of personality in the subjects with ACS, and their changes retesting them after one month and after 6 months.

Research has been conducted in three phases: the 1st after stabilization of ACS, the 2nd after one month and the 3rd after six months. The first phase of the study included 121 subjects, the second phase included 80 subjects and the third phase 56 subjects. Dimensions of personality were measured by Emotions Profile Index (EPI). Psychiatric disorders were diagnosed using the Mini International Neuropsychiatric Inventory (MINI).

A group profile of subjects matches the profile of the normal population. The dimensions of personality were stable over 3 phases of research. In the first phase dimension of impulsiveness was more prominent in subjects with STE-ACS, while dimension of deprivation was more prominent in subjects with NSTE-ACS. NSTE-ACS patients who develop PTSD manifest personal dimension of deprivation.

It is important to consider potentially negative personality traits, especially in chronic diseases such as cardiovascular disease, since personality traits determines the behavior of the patients that consequently affects the adhesiveness to therapy and positive outcome of the treatment.

The objective of our study is to describe the prevalence of insomnia during active consumption and hospitalisation for detoxification, and its influence on relapses at 3 and 6 months in drug-dependent patients.

We conducted a prospective study of drug-dependence inpatients admitted to the hospital detoxification unit between June 2008 and November 2012, and performed psychiatric follow-up on an outpatient basis over the six months following discharge. Insomnia prior to admission was measured by clinical interview from the patient concerning sleep habits, and during hospital stay using a sleep log filled out by nurse team. Demographic, clinical and diagnostic variables were recorded and a structured clinical interview (SCID) was conducted to assess psychiatric diagnoses. Relapse was deemed to be renewed use of the substance that brought about admission, which was assessed by alcohol testing and/or urinalysis.

We included 434 patients. Insomnia during consumption was reported by 64.3% of patients and 66.1% reported insomnia during hospital stay. Of the patients with preadmission insomnia, 68.3% relapsed at 3 months from discharge, as did 71% of patients with insomnia during hospital stay. Patients who relapsed at 3 months of follow-up showed significantly greater sleep initiation dysfunction prior to and during hospitalisation. Of the patients with preadmission insomnia, 69.2% had relapsed at 6 months from discharge. Patients who relapsed at 6 months of follow-up showed significantly greater sleep initiation dysfunction and global insomnia prior to and during hospitalisation.

Sleep disorders should be study as a prognostic factor in drugdependent patients.

Narrative, unsystematic reviews revealed no differences in terms of efficacy between the various first-generation antipsychotics (FGAs) resulting in the psychopharmacological assumption of comparable efficacy between the different FGAs. Because this assumption contrasts with the clinical impression a high-quality systematic evaluation of this issue appeared highly necessary.

A systematic literature survey was applied to identify all randomized controlled trials (RCTs) that compared oral haloperidol with another oral FGA in schizophrenia. Primary outcome was clinically important response to treatment and secondary outcomes were overall acceptability, efficacy, tolerability, and specific adverse effects. Study selection and data extraction were carried out independently by at least two authors. All analyses were based on a random-effects model.

We included 63 RCTs with 2819 participants in our meta-analysis. In short term studies (up to 12 weeks) there was no statistically significant difference between haloperidol and the other FGAs in achieving response to treatment (40 RCTs, n=2132, RR 0.93 CI 0.87-1.00). In medium term trials haloperidol was significantly less effective than the other FGAs (1 RCT, n=80, RR 0.51 CI 0.37-0.69). There were no significant between-group differences regarding the other outcomes with the exception that haloperidol produced less akathisia in the medium term.

The findings of this meta-analysis support the statements of previous narrative, unsystematic reviews suggesting comparable efficacy of FGAs. Additionally, we demonstrated that haloperidol is characterized by a similar risk profile compared to the other FGAs. The results were limited by the low methodological quality in many of the included original studies.

Individuals with serious mental illnesses experience poor physical health, particularly increased rates of cardiometabolic disorders. There are corresponding increases in premature mortality.

To assess the nature and extent of cardiometabolic risk factors and comorbidities in bipolar disorder and depression compared to controls.

Cross-sectional analysis of records for 502,602 participants within the UK Biobank database. Mood disorder was identified using an internally developed algorithm. Presence of cardiometabolic conditions and risk factors was examined. Multinomial logistic regression analyses were applied.

Compared to controls, individuals with bipolar and depression were significantly more likely to smoke. Rates of smoking were particularly elevated in the bipolar group, with a RRR of 3.18 (95% CI 2.790–3.632) compared to controls.

Individuals with bipolar disorder or severe recurrent depression were significantly more likely to be underweight, and have classes I, II and III obesity. All mood disorders were significantly associated with Class II and Class III obesity.

Bipolar disorder was significantly associated with increased rates of hypertension, diabetes, MI, angina and stroke. Severe depression was also associated with an increased risk of hypertension, diabetes, angina and stroke and individuals with moderate depressive disorder showed increased rates of MI, angina and stroke. Rates of ‘no cardiovascular illness’ were significantly reduced across the mood disorder spectrum.

Individuals with mood disorder have significantly increased rates of both cardiovascular risk factors and cardiometabolic illness. These findings using a large and extensive national dataset highlight a significant health inequality.

To establish the prevalence of metabolic syndrome and its parameters in group of patients with schizophrenia in polypharmacy – receiving first generation antipsychotics versus clozapine alone treated group.

48 outpatients with schizophrenia divided into two groups: the first group of 21 patients in polypharmacy with first generation antipsychotics, and the second group of 27 patients treated with clozapine alone were assessed for the presence of metabolic syndrome. We used logistic regression models to assess the relationship between metabolic syndrome and antipsychotic therapy, gender and age.

metabolic syndrome was found in 52.1% of all subjects. Compared to first generation antipsychotics polypharmacy, the monopharmacy with clozapine was associated with elevated rates of metabolic syndrome (28.6% vs. 70.4%, p= 0.004). With regard to particular parameters of metabolic syndrome, the elevated plasma triglycerides were significantly more present in subjects within Clozapine group (p=0.03). Logistic regression analysis showed that female gender (p= 0.004), older age (p=0.56), and clozapine treatment (p= 0.005) were significantly associated with metabolic syndrome.

Results of this study are consistent with other studies, which showed that patients receiving Clozapine are at higher risk for metabolic abnormalities.

Compared to polypharmacy with first generation antipsychotics, the higher prevalence of metabolic syndrome is found in patients treated with Clozapine alone. The most prevalent metabolic disorder is dyslipidemia. Female gender, older age, clozapine treatment are significantly associated with metabolic syndrome.

Aim of this study was to investigate whether agomelatine relieves both symptoms of depression and physical symptoms in women in the perimenopausal transition

This study is an open, randomized, non-controlled pilot study. Agomelatine was administered at the single daily dose of 25mg over 6 weeks to 50 women with first-onset perimenopausal depression (mean age 52-SD 4.8-years). Perimenopause was determined by subjetcs’ reports and hormonal assessment. Outcome measures included MINI (once for assessment of DSM-IV diagnosis of depression) at the beginning of the study and Hamilton Depression Rating Scale (HAMD), Montgomery Asberg Depression Scale (MADRS), Pittsburgh Sleep Quality Index (PSQI) as well as Menopause Rating Scale II, which were assessed weekly. Adverse drug reactions (ADRs) were documented at every visit.

At inclusion, women had moderate depression with a mean HAM-D-score of 17 and a mean MADRS-score of 19. Over the study period, agomelatine significantly improved depression and perimenopausal physical symptoms in all women. This was particularly evident for hot flashes, decreased performance, sexual problems, heartaches and joint/muscle pain. In addition, anxiety, irritability and disordered sleep improved as well. At the end of the study, women reported to be basically free of both physical and psychological symptoms of perimenopause. Agomelatine showed good tolerability, majority of the women reported no side-effects. Only in the first 2 weeks tiredness was reported by about 10% of the subjects.

The findings demonstrated that agomelatine significantly improved symptoms of depression and physical symptoms related to perimenopause over 6 weeks. Further, good tolerability was observed.

Emotional dysregulation represents a typical trait of many psychiatric disorders. One aspect of emotional regulation deficiencies are acceptance and suppression of negative and/or positive emotions. Changes of acceptance and suppression during the course of illness have not been investigated yet.

Investigation of the course of emotional regulation strategies.

The purpose of this study was to investigate,

1. 1. whether acceptance and suppression are related to positive and negative emotions;

2. 2. if there is any change of acceptance and suppression over time;

3. 3. whether depressive patients and healthy controls differ regarding acceptance and suppression levels.

Subjects were 40 patients with depression and 29 healthy controls. The study was conducted in the Clinic of Psychiatry and Psychotherapy Bethel, Bielefeld, Germany. The patients were diagnosed according to DSM–IV criteria. BDI was used to assess the level of depressive symptoms. For the assessment of acceptance and suppression of negative and positive emotions the questionnaire FrAGe (Questionnaire of the acceptance of emotions) was used at the begin (T1) and at the end (T2) of inpatient treatment.

Depressive patients reported reduced acceptance of positive and negative emotions. Although the level of acceptance was higher at T2, they still accepted their emotions less than the healthy controls. Patients also suppressed emotions more intensively than controls.

There are significant differences between depressive and healthy subject in terms of the acceptance and suppression of negative and positive emotions. Nevertheless, the suppression and acceptance of emotions are changing during treatment towards a more adaptive level.