BDNF and NGF Signalling in Early Phases of Psychosis: Relationship With Inflammation and Response to Antipsychotics After 1 Year.

Previous studies have indicated systemic deregulation of the proinflammatory or anti-inflammatory balance in individuals with first-episode psychosis (FEP) that persists 12 months later. To identify potential risk/protective factors and associations with symptom severity, we assessed possible changes in plasma levels of neurotrophins (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) and their receptors in peripheral blood mononuclear cells (PBMCs). Expression of the 2 forms of BDNF receptors (active TrkB-FL and inactiveTrkB-T1) in PBMCs of FEP patients changed over time, TrkB-FL expression increasing by 1 year after diagnosis, while TrkB-T1 expression decreased. The TrkB-FL/TrkB-T1 ratio (hereafter FL/T1 ratio) increased during follow-up in the nonaffective psychosis group only, suggesting different underlying pathophysiological mechanisms in subgroups of FEP patients. Further, the expression of the main NGF receptor, TrkA, generally increased in patients at follow-up. After adjusting for potential confounders, baseline levels of inducible isoforms of nitric oxide synthase, cyclooxygenase, and nuclear transcription factor were significantly associated with the FL/T1 ratio, suggesting that more inflammation is associated with higher values of this ratio. Interestingly, the FL/T1 ratio might have a role as a predictor of functioning, a regression model of functioning at 1 year suggesting that the effect of the FL/T1 ratio at baseline on functioning at 1 year depended on whether patients were treated with antipsychotics. These findings may have translational relevance; specifically, it might be useful to assess the expression of TrkB receptor isoforms before initiating antipsychotic treatment in FEPs.

Influence of birth cohort on age of onset cluster analysis in bipolar I disorder.

PURPOSE: Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database. METHODS: The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared. RESULTS: There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups. CONCLUSION: These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.

Affective dimensions as a diagnostic tool for bipolar disorder in first psychotic episodes.

OBJECTIVE: To examine the predictive diagnostic value of affective symptomatology in a first-episode psychosis (FEP) sample with 5 years' follow-up. METHOD: Affective dimensions (depressive, manic, activation, dysphoric) were measured at baseline and 5 years in 112 FEP patients based on a factor structure analysis using the Young Mania Rating Scale and Hamilton Depression Rating Scale. Patients were classified as having a diagnosis of bipolar disorder at baseline (BDi), bipolar disorder at 5 years (BDf), or "other psychosis". The ability of affective dimensions to discriminate between these diagnostic groups and to predict a bipolar disorder diagnosis was analysed. RESULTS: Manic dimension score was higher in BDi vs. BDf, and both groups had higher manic and activation scores vs. "other psychosis". Activation dimension predicted a bipolar diagnosis at 5 years (odds ratio=1.383; 95% confidence interval, 1.205-1.587; P=0.000), and showed high levels of sensitivity (86.2%), specificity (71.7%), positive (57.8%) and negative predictive value (90.5%). Absence of the manic dimension and presence of the depressive dimension were both significant predictors of an early misdiagnosis. CONCLUSION: The activation dimension is a diagnostic predictor for bipolar disorder in FEP. The manic dimension contributes to a bipolar diagnosis and its absence can lead to early misdiagnosis.

Cognitive function in 6- to 12-year-old offspring of women with Type 1 diabetes.

AIMS: Maternal diabetes is a recognized risk factor for congenital malformation, perinatal morbidity and obesity in later childhood. The aim of this study is to assess the impact of maternal diabetes on cognitive function in offspring. METHODS: Participants were 6- to 12-year-old offspring of women with Type 1 diabetes. All women received their antenatal care and delivered at one university hospital. HbA(1c) was monitored monthly throughout pregnancy and cognitive function was assessed using the Wechsler Intelligence Scale for Children, version 4. RESULTS: We present results in 40 offspring. There was no difference in overall full-scale IQ compared with UK normative data. However, working memory was poorer than other parts of the Wechsler Intelligence Scale for Children version 4 test and significantly lower compared with UK normative data [8.4 (2.2) vs. 10.1 (3.2), P < 0.01]. We found no correlation between measurement of digit span or HbA(1c) at any stage during pregnancy (r = -0.225 to 0.002), gestational age at delivery (r = -0.178) or infant birthweight ratio (r = -0.176). There was no relationship between working memory score and maternal hypoglycaemia episodes or maternal duration of diabetes. Comparing infants born before (n = 9) or after 37 weeks' gestation, digit span was non-significantly lower [7.9 (1.8) vs. 8.6 (2.4)]. DISCUSSION: These results suggest offspring of women with Type 1 diabetes have normal overall cognitive function but poorer working memory. We have been unable to identify specific risk factors. Further larger studies are required to increase the understanding of this memory defect and identify any modifiable risk factors.