Age-of-onset (AO) seems to be a phenotypic variable with a strong genetic component and therefore useful in molecular analysis of bipolar disorder (BP). A debate about the cut-off point for defining early AO has developed over the last few years. Using an Expectation-Maximization algorithm Bellivier et al. (2001) found the best fit for a model with three onset-groups, proposing the age 20-21 as cut-off for early onset, while using the same algorithm Kennedy et al. (2005) found the best fit for a two onset-group model with age 40 as cut-off with an incidence peak for mania in the age-band 21-25. Based on segregation analysis, we proposed a two AO-group model with cut-off age 25 for early onset (Grigoroiu-Serbanescu et al. 2001). The present study aimed at investigating the best AO-model in 500 Romanian BPI and 1458 German BPI patients using commingling analysis (SAGEv6.01-software) (Elston et al, 2009). The best model was selected according to Akaike's Information Criterion (AIC).

The two AO-group and three AO-group models provided similar AIC-values both in the Romanian and the German sample. The Romanian early-onset group (40% cases) had means around 18 years, SDs=6-7, while in the German early-onset group the mean AO was around 20 years (SDs=9-11) (50% cases). Thus the cut-off for early-onset (X +1SD) was different.

Our results overlapped with the findings of Kennedy et al (2005) showing that two-curve and three-curve AO mixtures similarly fit the AO-distribution in BPI disorder and the cut-offs for early-onset differ by sample.

Neurocognitive impairments in depression have traditionally been regarded as epiphenomena of the illness. Increasing evidence for the stability of neurocognitive deficits outside of depressive episodes implicates their potential role as mechanisms for emotion dysregulation associated with depressive states. This study thus examined associations between neurocognition and emotion regulation in currently depressed patients.

Participants were thirty patients presenting with current DSM-IV major depression. Participants completed neurocognitive tasks assessing executive function, attention, working memory, and response control to emotional stimuli. The capacity to implement functional emotion regulation strategies was assessed using additive sub-scales from the ‘Cognitive Emotion Regulation Questionnaire’ (CERQ), while emotion regulation difficulties were assessed using the ‘Difficulties in Emotion Regulation Scale’ (DERS).

Neurocognitive performance was compared between sub-groups of patients identified via median split on combined CERQ and DERS items. Patients reporting greater difficulties in emotion regulation demonstrated impaired sustained attention and response control, and increased reaction time to negative stimuli, in comparison to those reporting fewer difficulties. In addition, patients with better access to functional strategies demonstrated better attentional performance and fewer errors of omission to positive stimuli on the response control task.

Neuropsychological impairments in attention and response inhibition may contribute to emotion dysregulation in depressive episodes. By implication, remediation of particular neurocognitive deficits may improve the capacity to implement context-appropriate emotion regulation strategies in affective disorders. Examination of associations between neurocognitive impairment and emotion dysregulation outside of acute illness episodes is necessary to determine the relevance of these associations for illness development.

Despite lithium has been used for the last 50 years as a maintenance treatment for bipolar disorder during pregnancy, there is limited information about perinatal clinical outcomes from fetal exposure to lithium.

1. 1. To quantify the rate of lithium placental passage

2. 2. To assess any association between plasma concentration of lithium at delivery and perinatal outcome.

Observational and prospective study. Subjects: Women in maintenance treatment with lithium, being attended during pregnancy at the Perinatal Psychiatry Programme of Hospital Clínic (Barcelona, Spain) between 2007 and 2009. Procedure: We assessed sociodemographical data; dose/day of lithium carbonate; other drugs doses; plasmatic concentration of lithium carbonate in maternal blood intrapartum and in the umbilical cord; obstetrical maternal complications; gestational age at delivery; weight at delivery; Apgar scores; congenital malformations; hospital stays, infant serum concetrations of thyroid-stimulating hormone.

Eight mother-child diads. Mean age of the mother (SD): 32.1 (4,7); 100% caucasian and married. Mean dose of maternal lithium (SD): 675mg (237,5mg). Premature rupture of membranes (%):25. Gestational mean age (in weeks) (SD): 39,9 (1). Birth weight (SD) : 3625gr (451,2gr); Mean Apgar1min (SD): 8,38 (1,1); Mean Apgar5min (SD): 9,75 (0,4). Loss of fetal intrapartum wellness (%): 12,5. Days of hospitalization (mean) (SD):9,5(16,6). Lithium plasmatic concentration (mEq/L), mean (SD): maternal 0,45(0,1), umbilical cord 0,33(0,1), lithium ratio uc/m 0,93 (0,3); infant TSH μU/mL mean (SD): 4,9(4,6).

Lithium placental passsage was 0,93 (0,63-1,07). ≤At umbilical cord lithium levels ≤ 0.60 mEq/L, we didn't have any preterm deliveries, low birth weight newborns, nor neonatal complications.

There is a substantial body of evidence that cognitive deficits in schizophrenia and bipolar disorder persist after the subsidence of active symptoms. The aim of the study was to assess and compare the cognitive functioning of patients with clinically stable schizophrenia and bipolar disorder.

Attention, memory, verbal learning ability, visuospatial ability, executive functions and social cognition were assessed in 21 patients with schizophrenia in remission, 23 euthymic bipolar-I patients, and 27 normal controls, using WAIS - Vocabulary, Block design, and Digit span, Stroop Test, Babcock Story Recall Test, Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test (Trails A and B), Wisconsin Card Sorting Test (WCST), and Faux Pas Recognition Test. The three groups were matched for gender, age and education. One-way ANOVA with post hoc Bonferroni corrections was used for the between groups comparisons.

Both bipolar disorder and schizophrenia patients were significantly impaired on tests of working memory, learning abilities, and executive functions compared to control subjects. Patients with schizophrenia performed significantly worse than patients with bipolar disorder on attention and verbal memory tasks, whereas the latter performed worse than normal controls on visuospatial ability tasks.

Table 1

Comparison of neuropsychological function

Our results indicate that stable schizophrenia and euthymic bipolar disorder exhibit different but overlapping profiles of cognitive impairment.

Cognitive function seems to be impaired during both the acute and euthymic phases of bipolar disorder. The aim of the study was to determine the effect of remission on cognitive functioning in bipolar disorder.

Attention, memory, verbal learning ability, visuospatial ability, executive functions and social cognition were assessed in 19 patients with bipolar-I patients during an episode of the illness and in remission as well as in 16 normal controls, using WAIS - Vocabulary, Block design, and Digit span, Stroop Test, Babcock Story Recall Test, Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test (Trails A and B), Wisconsin Card Sorting Test (WCST), and Faux Pas Recognition Test. The two groups were matched for gender, age and education. Paired t-test was used to compare patients’ neuropsycholigical performance in episode and euthimic states and one-way ANOVA with post hoc Bonferroni corrections for the between groups comparisons.

Patients showed cognitive dysfunction in verbal learning, visospatial ability, executive functions and social cognition during both the acute and the euthymic phases in relation to the comparison group. Poorer performance in attention and working memory tasks was observed only in the acute phase of the illness. Performance in verbal learning and executive function tasks was significantly improved but still impaired in remission.

Patients with bipolar disorder exhibit similar profiles of cognitive impairment during the acute and the euthymic phases of the illness.

To determine if utilization and expenditures differ between ADHD medication classes.

Prescription and medical claims for Texas Medicaid patients with an ADHD diagnosis newly initiated on an ADHD medication (no previous use for 180 days) between January 2006 and September 2007 were analyzed. Logistic and linear regression analyses were used to evaluate differences in adherence, persistence, switching, and expenditures during a 180-day post-initiation observation period across ADHD treatment classes [immediate-release methylphenidate (IR-M) and amphetamines (IR-A) and extended-release methylphenidate (ER-M) and amphetamines (ER-A)] with relevant demographic and pre-initiation period comorbidities, utilization, and expenditure variables as covariates. Because prior authorization was required, the non-stimulant medication atomoxetine was excluded.

The sample consisted of 15,055 subjects with 71% aged 6 to 12 years; 64.7% were initiated on ER-M and 25.4% on ER-A. Compared to the ER-A group, the IR-M (OR=0.56, 95%CI=0.45-0.69) and IRA (OR=0.60, 95%CI=0.46-0.78) groups were less likely to be adherent, more likely to discontinue therapy (OR=2.03, 95%CI=1.67-2.47; and OR=1.77, 95%CI=1.38-2.27; respectively) and more likely to switch medications (OR=2.44, 95%CI=2.05-2.90; and OR=2.85, 95%CI=2.28-3.56; respectively) (all p< 0.001). The ER-A group had significantly higher ADHD medication expenditures compared to other groups (all p≤0.001), but no significant differences in medical expenditures.

Utilization patterns differed across the ADHD medication classes. Most subjects were initiated on ER medications which demonstrated advantages in adherence, persistence, and less switching while the ER-A group, which included more complex patients as indicated by comorbidities, had higher ADHD medication expenditures but no difference in overall medical expenditures.

To determine if utilization and expenditures differ between a newly-marketed (at time of study) ADHD medication (lisdexamfetamine dimesylate [LDX]) and existing medications.

Prescription and medical claims for Texas Medicaid patients diagnosed with ADHD newly initiated on an ADHD medication (no previous use for 180 days) during August and September 2007 were analyzed. Logistic and linear regressions were used to evaluate differences in adherence, persistence, switching, and expenditures during a 180-day post-initiation period between the LDX group and existing medications (immediate-release methylphenidate [IR-M] and amphetamines [IR-A] and extended-release methylphenidate [ER-M] and amphetamines [ER-A, excluding LDX]) with relevant demographic and preinitiation period comorbidities, utilization, and expenditure variables as covariates. Because prior authorization was required, the non-stimulant atomoxetine was excluded.

The sample consisted of 1810 subjects with 69% aged 6 to 12 years; 58.0% were initiated on ER-M and 14.4% on LDX. Psychiatrists prescribed 60.5% of LDX prescriptions. A greater proportion of LDX patients had psychiatric-related comorbidities compared to the other medication groups. Logistic regression showed that compared to the LDX group, the IR-M group was more likely to discontinue therapy (OR=1.95, 95%CI=1.05-3.60, P=0.034), and the IR-A group was more likely to switch therapy (OR=2.39, 95%CI=1.22-4.69, P=0.012). ADHD medication expenditures were significantly lower for the LDX group than the ER groups (all P≤0.003). ADHD-related and total medical expenditures did not differ significantly.

Although used in more complex patients, LDX demonstrated advantages over IR-M on persistence, IR-A on therapy switching, and the ER groups on medication expenditures.

Rumination is a significant cognitive symptom of depression. As rumination is strongly related to altered memory function we selected two genes previously described as important candidates for both depression and memory processing to assess their contribution to rumination. Based on a possible functional role for cAMP-dependent protein kinase in the mechanism of action antidepressants, we studied the association between G protein-activated K+ channel 2 (GIRK2) and cAMP-response element binding (CREB) protein genes and rumination in two independent European samples.

We genotyped an exonic SNP (rs2070995) in GIRK2 gene and a promoter SNP (rs2253206) in CREB gene of 611 individuals from Budapest and 1174 individuals from Manchester. Rumination was measured by Ruminative Response Scale (RRS) of Response Style Questionnaire. Generalized linear models (GLMs) were performed for single marker associations. Likelihood ratio tests were used for interactions between genetic markers on RRS.

Single marker associations did not provide any significant individual effect of the two SNPs on rumination. However, interaction analyses revealed a strongly significant interaction between the rs2070995 and rs2253206 on RRS in both European samples (pBudapest=0.00099; pManchester=0.0027). Homozygous TT individuals for rs2070995 in interaction with homozygous GG for rs2253206 scored significantly higher on RRS compared with other genotypes.

Our results suggest that two key post-receptor signalling proteins, GIRK2 and CREB, interact with each other in regulating the process of rumination which may have relevance for depression and its treatment.

These studies were supported by the Sixth Framework Programme of the EU, LSHM-CT-2004-503474, HRF T03298/2000.

The safety and tolerability of aripiprazole as adjunctive treatment was examined in patients with major depressive disorder (MDD) without psychotic features who had a major depressive episode and who did not respond adequately to standard antidepressant therapy (ADT).

Data from three identical short-term, double-blind, placebo-controlled studies (CN138139, CN138163, CN138165) were pooled. After a prospective phase with placebo plus ADT, patients without adequate response entered a 6-week, double-blind phase with placebo or aripiprazole plus ADT. Safety endpoints included death, serious adverse events (SAEs), treatment-emergent adverse events (AEs), Simpson-Angus Scale (SAS), Barnes Akathisia Global Clinical Assessment, Abnormal Involuntary Movement Scale (AIMS), clinical laboratory tests, vital signs and electrocardiograms.

In total, 538 patients were randomized to adjunctive placebo and 547 to adjunctive aripiprazole. AEs with an incidence ≥5% and at least twice the rate of placebo were akathisia (adjunctive aripiprazole, 22.7%; adjunctive placebo, 4.1%), restlessness (12.4% vs 2.2%), fatigue (8.6% vs 4.3%), insomnia (8.2% vs 3.2%), vision blurred (6.2% vs 1.5%), somnolence (5.9% vs 2.6%), and constipation (4.9% vs 2.4%). AEs that had a treatment difference of ≥2% included akathisia, somnolence, sedation, dizziness, disturbance in attention, extrapyramidal disorder, restlessness, insomnia, constipation, dyspepsia, fatigue, feeling jittery, vision blurred, weight increased, and dyspnea. SAEs occurred in 0.7% of patients in each treatment group. There were no deaths during the studies.

In this pooled analysis of patients with MDD and an inadequate response to ADT, adjunctive aripiprazole showed consistently high study completion rates and low discontinuation rates resulting from adverse events.

Poor sleep is a common complaint in postpartum depression (PPD). Depression as well as sleep disturbances may affect parenting functions and mother-infant relationship. The purpose of this study was to examine the relationship between objective sleep data, parenting stress and bonding in PPD.

Forty-five mothers (age: 34.5 ± 5.4 years SD) suffering from PPD were examined 212 ± 156 days (SD) after parturition. Depression was measured by Hamilton Depression Rating Scale (HDRS-ADS) and Beck Depression Inventory (BDI). Parenting stress and bonding were assessed by self report scales, i.e. Parenting Stress Index (PSI) and Postpartum Bonding Questionnaire (PBQ). In a subsample of 10 participants sleep parameters were assessed by actigraphy and sleep logs during seven consecutive days. Actigraphic sleep parameters were put in relation to severity of depression, PSI and PBQ scores.

Poor sleep, i.e. low total sleep time (TST) was negatively correlated to depression (HRDS-ADS) (r = -.63; p < .05). Low TST was associated with poor bonding (r = -.82; p = .02), especially attitudes of “rejection and anger”. Severity of depression (BDI) was correlated with parenting stress (r =.50; p =.005). Mothers with high parenting stress tended to have more difficulties in bonding (r =.65; p =.016). Neither sleep parameters nor parenting stress and bonding were correlated with the infant's age.

In PPD poor sleep should be recognized and treated early, because it is associated to parenting stress and disturbed bonding, which might have a detrimental impact on mother-infant relationship.

Evaluate the effects of once-daily extended release quetiapine fumarate (quetiapine XR) monotherapy in patients with major depressive disorder (MDD) according to disease severity.

Pooled data (quetiapine XR 50, 150 and 300mg/day doses combined) from four 6- or 8-week placebo-controlled quetiapine XR monotherapy studies (D1448C00001, D1448C00002, D1448C00003, D1448C00004) were analysed. Key inclusion criterion for all 4 studies: HAM-D total score ≥22. Primary endpoint: change from randomisation in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. A post-hoc analysis assessed change from randomisation in MADRS total score and MADRS response (≥ 50% reduction in MADRS total score) at endpoint (Week 6 or Week 8) in 6 severity cohorts (defined by a MADRS total score at randomisation ≥24, ≥26, ≥28, ≥30, ≥32 or ≥34).

1752 patients (comprising the l’ all patients’ group) were evaluated (MADRS score ≥24 at randomisation, n=1601; ≥26, n=1467; ≥28, n=1269; ≥30, n=1038; ≥32, n=745; ≥34, n=500). Quetiapine XR significantly reduced mean MADRS total score at endpoint in lrsquo;all patients’ (p< 0.001 vs placebo) and in all 6 severity cohorts (≥24, ≥26, ≥28, ≥30 and ≥32, p< 0.001 vs placebo; ≥34, p< 0.01 vs placebo). MADRS response rates were significantly higher in the quetiapine XR group vs placebo in the ‘all patients’ group (p< 0.001 vs placebo) and in all 6 severity cohorts (≥24, ≥26, ≥28, ≥30 and ≥32, p< 0.001 vs placebo; ≥34, p=0.001 vs placebo).

Quetiapine XR monotherapy significantly improved depressive symptoms in patients with MDD irrespective of disease severity, including the most severe levels of depression.

AstraZeneca funded

To evaluate once-daily extended release quetiapine fumarate (quetiapine XR) as monotherapy (50, 150 and 300mg/day) (acute and maintenance treatment) or adjunct treatment (150 and 300mg/day) in patients with MDD.

Eight (7 acute, 1 maintenance) placebo-controlled studies were analysed. Primary endpoints: change from randomisation in Montgomery-Åsberg Depression Rating Scale (MADRS) scores (acute); time from randomisation to depressed event (maintenance). Statistical analyses: ANCOVA for difference between quetiapine XR and placebo in LSM change in MADRS total score from randomisation to study end (LOCF; acute); hazard ratio (HR) for time to recurrence of a depressed event (maintenance).

Figure 1 shows treatment differences (95% CIs) for primary efficacy variable for the seven acute studies. Four monotherapy studies (D1448C00001, D1448C00002, D1448C00003, D1448C00014) were significant in favour of quetiapine XR; Study D1448C00004 (monotherapy) was not. Studies D1448C00006 and D1448C00007 were significant in favour of adjunct quetiapine XR. Time from randomisation to depressed event (Study D1448C00005) significantly increased with quetiapine XR; HR (95% CI): 0.34(0.25, 0.46); p< 0.001; number of depressed events: 55, quetiapine XR; 132, placebo. Safety findings were consistent with the known tolerability profile of quetiapine.

Quetiapine XR consistently demonstrated antidepressant efficacy, with 6/7 acute studies positive in favour of quetiapine XR (monotherapy or adjunct). Quetiapine XR maintenance therapy significantly reduced risk of a depressed event, demonstrating relapse prevention. AstraZeneca funded

Impaired sleep quality and dyssomnia disorders in particular have repeatedly been linked to affective symptoms. However reports about systematic assessments in larger study samples are generally lacking. Furthermore the associative relationships of fatigue and sleepiness complaints to sleep quality and affective symptoms are poorly described.

During a one-year period we recruited 570 patients (mean age 28(0.26), 287 males) attending the sleep laboratory of a general University Hospital. Psychometrics were performed using the Pittsburgh Sleep Quality Index (PSQI), the Hospital Anxiety and Depression Scale (HAD), the Fatigue Severity Scale (FSS) and the Epworth Sleepiness Scale (ESS). All patients underwent two consecutive nights of full polysomnographic recording (PSG).

Both fatigue (FSS) and sleepiness (ESS) were related to affective symptoms (HAD, p< 0.001 and p=0.012 respectively). Fatigue and affective symptom intensity but not sleepiness, were correlated to sleep quality (p< 0.001). The HAD was related to REM-Sleep Latency (HAD, p=0.017). Slow Wave Sleep duration of the second night was negatively correlated to affective symptoms (p=0.21). Body mass index (BMI) was correlated to fatigue (p< 0.001), sleepiness (p=0.18) and to sleep quality (p=0.006) but not to affective symptoms.

These results confirm the tight relations between sleep quality, daytime fatigue or sleepiness and affective symptoms. Residual fatigue is a common and invalidating complaint in mental disorders as major depression. Achievement of clinical remission can be compromised because of residual treatment resistant symptoms. PSG might be useful in certain conditions to rule out co-morbid sleep disorders and to orientate treatment attitudes.

Clinical studies demonstrate that quetiapine is efficacious in schizophrenia, bipolar mania, bipolar depression, major depressive disorder, and generalized anxiety disorder. The pharmacological basis for this broad range of clinical effects is not completely understood. The current experiments evaluated pharmacological assays investigating the receptor-binding characteristics of quetiapine and norquetiapine (the major human metabolite) and compared these with other atypical antipsychotics and standard antidepressants.

In vitro receptor-binding assays utilized cloned human targets including norepinephrine transporter (NET), dopamine D2 receptor, and serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors stably expressed in CHO or HEK cell lines. In vitro functional studies included uptake-inhibition assays for NET and GTPgammaS assays for D2/D3 antagonist and 5-HT1A agonist activity.

Norquetiapine demonstrated high affinity at 5-HT2A receptors (5 nM) and moderate/high affinity at NET (29 nM) and 5-HT2C receptors (76 nM), while quetiapine had moderate affinity at 5-HT2A receptors (29 nM), weak affinity at 5-HT2C receptors (2800 nM), and lacked appreciable affinity at NET. Both quetiapine and norquetiapine showed moderate affinity at D2 receptors (56 nM and 59 nM, respectively) with moderate/low-potency antagonist activity. Both quetiapine and norquetiapine exhibited low affinity at 5-HT1A receptors (1800 nM and 570 nM, respectively) with low-potency agonist activity.

These experiments confirm that quetiapine-norquetiapine have multiple pharmacological effects at targets associated with psychotropic drug action. This combination of effects by quetiapine-norquetiapine at dopaminergic, serotonergic, and noradrenergic targets may explain the antipsychotic, antidepressant, and anxiolytic properties of quetiapine.

Supported by funding from AstraZeneca Pharmaceuticals LP.

Asenapine is indicated in adults for acute treatment of schizophrenia and bipolar I disorder. We describe the efficacy and tolerability of adjunctive asenapine in bipolar patients showing incomplete response to lithium or valproate monotherapy.

In a 12-week core study, patients were randomized to flexible-dose asenapine (5 or 10 mg BID) or placebo as an adjunct to continued mood stabilizer therapy. Patients completing the core study without protocol violations could enter a 40-week extension. Changes from core study baseline on the Young Mania Rating Scale (YMRS) and Montgomery-Asberg Depression Rating Scale (MADRS) total scores were assessed at week 3 of the core study and at week 52 in the extension. Efficacy in the core study was assessed using ANCOVA with LOCF to impute missing data. The extension was not powered for statistical comparisons; descriptive statistics were employed.

The intent-to-treat population comprised 318 patients (asenapine, 155; placebo, 163) in the core study and 71 (38; 33) in the extension. Mean±SD changes at week 3 with asenapine and placebo, respectively, were -9.7±10.1 versus -7.7±9.6 (P=0.0257) on YMRS and -2.8±7.2 versus -2.2±6.8 (P=0.3684) on MADRS. Mean±SD changes at week 52 with asenapine and placebo were -17.2±13.7 versus -19.7±11.8 on YMRS and -3.3±9.8 versus -3.9±7.7 on MADRS. The incidence of treatment-emergent AEs with asenapine and placebo was 73% and 69% in the core study, 78% and 69% in the extension.

Asenapine was effective as an adjunct to mood stabilizer in bipolar I disorder and was well tolerated.

Bipolar Disorder treatment includes not only the remission of Major Depressive or Manic/Hypomanic Episodes, but also the prevention of recurrences. Purpose of this trial is to evaluate the effectiveness of Mood Stabilizers and Atypical Antipsychotics in preventing recurrences.

67 patients with a diagnosis of Bipolar Disorder type 1 and 2 were followed retrospectively for a period of 48 months. Clinical and demographic information were collected by clinical charts and interviews with patients. A survival analysis was performed considering death events change of treatment, a Major Depressive or Hypomanic/Manic Episode or a hospitalization.

Patients treated with Lithium survived longer than patients treated with Valproate (Log Rank: χ2=3.86, p=0.05) which resulted to be superior in terms of recurrence prevention compared to Atypical Antipsychotics in monotherapy (Olanzapine, Quetiapine or Risperidone) (Log Rank: χ2=4.54, p=0.03). Lithium association with an Atypical Antipsychotic resulted more efficacious in terms of recurrence prevention compared to Lithium (Log Rank: χ2=7.01, p=0.008) or Atypical Antipsychotics in monotherapy (Log Rank: χ2=8.61, p=0.003).

These preliminary data would indicate that Lithium association with an Atypical Antipsychotic would be more effective in preventing Major Depressive or Hypomanic/Manic recurrences in bipolar patients.

An undiagnosed bipolarity may be one of the reasons connected with treatment resistance in major depressive disorder. In recent years, the tools have been introduced helping to assess the bipolarity such as the Hypomania Checklist (HCL-32) and the Mood Disorder Questionnaire (MDQ). The objective of the study was to compare scores of bipolarity measured with these scales between patients with treatment-resistant and treatment non-resistant depression within the framework of all-Poland multi-center study TRES-DEP.

One-thousand and fifty-one patients recruited from 150 outpatient psychiatric clinics in Poland and fulfilling DSM-IV criteria for single or recurrent major depressive episode were studied. Five-hundred and sixty-nine patients were identified as having treatment-resistant depression on account of non-obtaining remission in recent depressive episode after minimum of two courses of adequate treatment with antidepressant drugs. They were compared with 482 patients with non-treatment-resistant depression. All patients were assessed using the structured demographic and clinical data interview, as well as the Polish version of HCL-32 and MDQ

Patients with treatment-resistant depression scored significantly higher compared with non-resistant depression both on HCL-32 and MDQ (11.9+8.3 vs 8.5±7.7 and 4.3±3.5 vs 2.7±2.9, respectively). Independent risk factors of treatment resistance were scoring of14 or higher on HCL-32, and 6 or higher on MDQ.

Higher scoring by patients with treatment-resistant depression on both HCL-32 and MDQ may suggest a possible association between bipolarity and worse response to antidepressant drugs in patients with major depressive disorder.

In patients with major depression (MD), mean BDNF serum concentration increases during antidepressant treatment. This increase has been associated with symptom amelioration. In a previous analysis of the time course of BDNF serum concentration, we could show a high association between early and final changes of BDNF levels during antidepressant treatment. The aim of this study was to analyse the predictive value of early BDNF changes for BDNF changes after 4 to 6 weeks of antidepressant treatment in individual patients with MD.

Forty-six patients with MD according to DSM-IV were included in this study. All patients were treated as clinically indicated. Depression severity was assessed by HAMD-17 by trained raters from baseline to week 6 in weekly intervals. Serum at each visit (baseline, V1-V6) was obtained from whole blood after centrifugation with 1.000 × g for 10 minutes. Aliquots were frozen at -80°C until analysis. BDNF serum concentration was determined with ELISA (R&D Systems). We determined sensitivity and specificity of early changes (from baseline to weeks 1 and 2) of BDNF serum concentration to BDNF changes in the later course (from baseline to weeks 4 to 6) of treatment.

BDNF increase from BL to week 2 predicted BDNF increase from baseline to week 5 with high sensitivity (81%) and specificity (73%). Further analyses revealed comparable results (data not shown).

These results suggest that early BDNF increase is predictive for final BDNF increase in individual patients with MD during antidepressant treatment.