White matter (WM) abnormalities are considered integral to the pathophysiology of Schizophrenia (SZ) and Bipolar Disorder (BD), but there is ongoing uncertainty about the contribution of medication to these findings.

Diffusion Tensor Imaging (DTI) is a neuroimaging technique that provides quantitative indices of the structural and orientational characteristics of WM. These indices include mean diffusivity (MD), which is a directionally averaged measure of the apparent diffusion coefficient, and fractional anisotropy (FA), which summarizes the orientational dependence of diffusivity. We wanted to determine if these indices are affected by antipsychotic medication.

Our aim was to examine the available literature in order to differentiate antipsychotic effects from disorder-specific WM abnormalities on DTI measures.

We conducted a systematic qualitative review of the DTI literature in Bipolar Disorder (BD) and Schizophrenia (SZ), between 1998 and 2010 and included only studies where the relationship between DTI measures and antipsychotic medication was explicitly examined and reported.

We identified 40 studies in SZ and 8 in BD. All studies were cross-sectional and involved relatively small patient samples. 32 studies (80%) did not find any relationship between antipsychotic medication (dose, cumulative exposure) and FA or MD.

Current evidence does not indicate a major impact of antipsychotic treatment on DTI indices of WM integrity. However, the lack of longitudinal, within-subject designs is a major gap in the current literature.

Evaluate efficacy and tolerability of quetiapine and paroxetine monotherapy for major depressive episodes in bipolar disorder during an acute 8-week period and up to 52-week continuation phase.

740 patients (478 bipolar I, 262 bipolar II) were randomized to quetiapine 300mg/d (n=245), quetiapine 600mg/d (n=247), paroxetine 20mg/d (n=122), or placebo (n=126) for 8 weeks. Primary endpoint was change from baseline to 8 weeks in MADRS total score. After 8 weeks, patients with MADRS ≤12 and YMRS ≤12 entered a 26- to 52-week continuation phase of quetiapine (300mg/d or 600mg/d) or placebo. Patients on paroxetine received 300mg/d of quetiapine (continuation phase results not included here and to be presented separately).

LSM MADRS score change at 8 weeks was -16.19 (quetiapine 300mg/d),-16.31 (quetiapine 600mg/d), -13.76 (paroxetine), and -12.60 (placebo; P<0.001 for both quetiapine doses, P=0.313 for paroxetine, versus placebo; LOCF ANCOVA). Quetiapine (both doses)-treated patients showed significantly greater improvements (P≤0.05) in MADRS response rate, HAM-D, CGI-BP-S, CGI-BP-Change, HAM-A, and MADRS item 10 (suicidal thoughts) at Week 8 versus placebo; MADRS remission rates improved with quetiapine 600mg/d versus placebo (P=0.012). Paroxetine improved HAM-A scores versus placebo (P=0.033).

Most common adverse events considered drug-related included dry mouth, somnolence, sedation, and dizziness with quetiapine (both doses); dry mouth, sedation, headache, insomnia, and nausea with paroxetine.

Quetiapine (300mg/d or 600mg/d) was more effective than placebo for the treatment of acute depressive episodes in bipolar I and II disorder. Quetiapine treatment was generally well tolerated.

Supported by funding from AstraZeneca Pharmaceuticals LP.

Risk of psychosis is defined by the presence of positive psychotic-like symptoms, by subtle self-perceived cognitive and perceptual deficiencies, or by decreased functioning with familial risk of psychosis. We studied the associations of psychiatric outpatients' self-reported functioning and interpersonal relationships with vulnerability to and risk of psychosis.

A total of 790 young patients attending psychiatric outpatient care completed the PROD screen [Heinimaa M, Salokangas RKR, Ristkari T, Plathin M, Huttunen J, Ilonen T, et al. PROD-screen – a screen for prodromal symptoms of psychosis. Int J Meth Psychiatr Res 2003;12:92–04.], including questions on functioning, interpersonal relationships and subtle specific (psychotic-like) and non-specific symptoms. Vulnerability to psychosis was assessed employing the patient's written descriptions of specific symptoms. Of the patients vulnerable to psychosis, those at current risk of psychosis were assessed using the Bonn Scale for Assessment of Basic Symptoms [Schultze-Lutter F, Klosterkötter J. Bonn scale for assessment of basic symptoms – prediction list, BSABS-P. Cologne: University of Cologne; 2002] and the Structured Interview for Positive symptoms [Miller TJ, McGlashan TH, Rosen JL, Somjee L, Markovich PJ, Stein K, et al. Prospective diagnosis of the initial prodrome for schizophrenia based on the structured interview for prodromal syndromes: preliminary evidence of interrater reliability and predictive validity. Am J Psychiatry 2002;159:863–65.].

In all, 219 patients vulnerable to and 55 patients at current risk of psychosis were identified. Vulnerability to psychosis was associated with all items of functioning and interpersonal relationships. Current risk of psychosis, however, was associated only with the subjectively reported negative attitude of others. Negative attitude of others was also associated with feelings of reference at both vulnerability and risk levels.

The subjective experience of negative attitude of others towards oneself may be an early indicator of psychotic development.

Substantial literature supports clinically important associations between anxiety and chronic medical conditions. Diabetes is among the most psychologically and behaviorally demanding chronic medical illnesses. Anxiety has been associated with poor glycemic control, regimen adherence, and with accelerated rates of coronary heart disease in diabetic patients.

The aim of this study is to provide an overview of the role of clinically significant anxiety in patients with diabetes mellitus.

MEDLINE, EMBASE and PSYCINFO databases were searched using the combined search terms diabetes, diabetes mellitus, anxiety symptoms and anxiety disorders. Published reference lists were also examined. In total 25 studies were identified that fulfilled the inclusion criteria.

Anxiety was present in 41.7% of diabetic patients. There was no significant difference between those with Types 1 and types 2 diabetes. The rate of elevated symptoms was significantly higher in diabetic women than in diabetic men. General anxiety disorder was the most prevalent of the clinical disorders and was found in 13.2% of the diabetic patients. The rates of the other anxiety disorders were within the range of those reported in community studies. Treatment of anxiety was associated with improved glycemic control, particularly in the subgroup of patients with severe anxiety.

Emerging data offer a strong argument for the role of anxiety in diabetes. Psychological interventions and/ or pharmacological treatments in patients with diabetes are needed, in order to increase treatment adherence and control of the disease and improve patients’ functioning and quality of life.

BackgroundThe aim of this study was to characterize mood instability (MI) in Bipolar Disorder (BD) and to investigate potential differences between subtype I and II.

MethodsLife-charts from weekly mood ratings of 90 patients were used to compute: weeks spent with symptoms, number of episodes, and MI. Regression analyses were conducted to assess the relationship between BD subtype and MI adjusting by all potential confounding factors. Hierarchical cluster analysis was performed to determine the appropriate number of clusters that described the data and to assign subjects to a specific cluster based on their MI. We then compared clusters on clinical and psychosocial outcomes.

ResultsMedian follow-up was 5 years (IQR: 3.6–7.9). Patients spent 15.2%, 5%, and 3% of follow-up with depressive, manic, and mixed symptoms, respectively. BD type II presented higher MI (β = 1.83, 95% CI: 0.66–3.00) and subsydromal symptoms than BD type I patients. No differences in functioning or recurrences were found between subtypes. Differences in MI between the two clusters mimicked those between type I and II but enhanced (β = 3.86, 95%CI -4.72, -2.66). High MI (n = 43) patients presented poorer functioning and higher recurrences compared to Low MI patients (n = 43).

ConclusionBD type II presented higher MI and subsyndromal symptoms than BD type I patients. However, these differences did not translate into clinically relevant outcomes. A classification based on MI may provide useful clinical insights.

The authors have not supplied their declaration of competing interest.

There is consistent evidence that theory of mind (ToM) is impaired in schizophrenia (SZ); however, it remains unclear whether such deficits are trait- or state-dependent. We evaluated ToM in patients with schizophrenia spectrum disorders (SSDs), their healthy first-degree relatives, and controls to test its suitability as an endophenotypic marker. We also studied the modifying effect of markers of clinical and genetic liability to SZ (schizotypy and genetic variability in the oxytocin receptor gene: OXTR) on ToM in healthy individuals.

The sample included 38 stable SSD patients, 80 unaffected first-degree relatives, and 81 controls. ToM was assessed using the Hinting Task (HT) and schizotypy via the Schizotypal Personality Questionnaire-Brief (SPQ-B), which generates interpersonal (SPQ-IP), cognitive-perceptual (SPQ-CP), and disorganization (SPQ-D) scores. The polymorphism rs53576 of OXTR was genotyped.

Patients presented poorer HT performance than relatives and controls (p = 0.003 and p < 0.001). High SPQ-IP and SPQ-CP scores correlated with poorer ToM performance in relatives (p = 0.010 and p = 0.030), but not in controls. OXTR was not associated with HT scores, but it showed a modifying effect within controls; high SPQ-CP was related to HT poorer performance conditional to GG genotype (p = 0.007).

ToM deficits were present in patients but not in unaffected relatives or controls. However, our data indicate the usefulness of clinical and genetic liability markers to characterize differences in ToM abilities within healthy individuals. Then, the observed link between ToM and SZ liability suggests the putative role of ToM as an endophenotypic marker. Nevertheless, new analyses in larger samples are needed.

The aim of the present study is to evaluate the role of individual affective temperaments as clinical predictors of bipolarity in the clinical setting.

The affective temperaments of 1723 consecutive adult outpatients presenting for various symptoms to a university-based mental health clinical setting were assessed. Patients were administered the Hypomania Checklist-32 and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego – Auto-questionnaire (TEMPS-A) and were diagnosed by psychiatrists according to the DSM-5 criteria. TEMPS-A scores were studied as both continuous and normalized categorical z-scores from a previously established nationwide study on the general population of Lebanon. Simple and multiple binary logistic regressions were done on patients who have any of the DSM-5 defined bipolar types, as a combined group or separately, versus patients without any bipolar diagnosis.

At the multivariable level and taking into account all temperaments, the irritable temperament is a consistent predictor of bipolar I and bipolar II disorders. Cyclothymic temperament also played a strong role in bipolarity but more decisively so in bipolar II and substance-induced bipolarity. The hyperthymic temperament had no role in bipolar I or bipolar II disorder.

Whether non-genetic prognostic factors significantly influence the variable prognosis of antipsychotic-induced weight gain (AIWG) has not yet been systematically explored.

Searches for both randomized and non-randomized studies were undertaken using four electronic databases, two trial registers, and via supplemental searching methods. Unadjusted and adjusted estimates were extracted. Meta-analyses were undertaken using a random-effects generic inverse model. Risk of bias and quality assessments were undertaken using Quality in Prognosis Studies (QUIPS) and Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively.

Seventy-two prognostic factors were assessed across 27 studies involving 4426 participants. Only age, baseline body mass index (BMI), and sex were suitable for meta-analysis. Age (b=−0.044, 95%CI −0.157–0.069), sex (b=0.236, 95%CI −0.086–0.558), and baseline BMI (b=−0.013 95%CI −0.225–0.200) were associated with nonsignificant effects on AIWG prognosis. The highest quality GRADE rating was moderate in support of age, trend of early BMI increase, antipsychotic treatment response, unemployment, and antipsychotic plasma concentration. Trend of early BMI increase was identified as the most clinically significant prognostic factor influencing long-term AIWG prognosis.

The strong prognostic information provided by BMI trend change within 12 weeks of antipsychotic initiation should be included within AIWG management guidance to highlight those at highest risk of worse long-term prognosis. Antipsychotic switching and resource-intensive lifestyle interventions should be targeted toward this cohort. Our results challenge previous research that several clinical variables significantly influence AIWG prognosis. We provide the first mapping and statistical synthesis of studies examining non-genetic prognostic factors of AIWG and highlight practice, policy, and research implications.

To identify some of the main features of bipolar disorder for both first-episode (FE) mania and the preceding prodromal phase, in order to increase earlier recognition.

One thousand and ninety manic patients (FE=81, multiple-episodes [ME]=1009) were assessed for clinical and temperamental characteristics.

Compared to ME, FE patients reported more psychotic and less depressive symptoms but were comparable with respect to temperamental measures and comorbid anxiety. The following independent variables were associated with FE mania: a shorter delay before correct diagnosis, greater substance use, being not divorced, greater stressors before current mania, a prior diagnosis of an anxiety disorder, lower levels of depression during index manic episode, and more suicide attempts in the past year.

In FE patients, the diagnosis of mania may be overlooked, as they present with more psychotic symptoms than ME patients. The prodromal phase is characterised by high levels of stress, suicide attempts, anxiety disorders and alcohol or substance abuse. Data suggest to consider these prodromes as harmful consequences of temperamental predispositions to bipolar disorder that may concur to precipitate mania onset. Their occurrence should therefore incite clinicians to screen for the presence of such predispositions, in order to identify patients at risk of FE mania.

Our previous study (Salokangas et al., 2009) suggested that the subjective experience of negative attitude of others (NAO) towards oneself is an early indicator of psychotic development. The aim of this prospective follow-up study was to test this hypothesis.

A total of 55 young psychiatric outpatients assessed as being at current risk of psychosis (CROP) were followed for up to 60 months and rates of transition to psychosis (TTP) identified. CROP was assessed employing the Bonn Scale for assessment of basic symptoms (Schultze-Lutter and Klosterkötter, 2002) and the Structured Interview for prodromal symptoms (Miller et al., 2002). TTP was defined by a psychotic episode lasting for more than one week. Associations between NAO at baseline and TTP were analyzed by a Cox regression survival analysis.

Eight (14.5%) TTP were identified: four (57.1%) within seven NAO patients and four (8.7%) within forty-six non-NAO patients. In the multivariate Cox regression analysis, NAO at baseline significantly (P = 0.007) predicted TTP.

The prospective follow-up results support our hypothesis that subjective experience of NAO is an early indicator of psychotic in development.