Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder.

We conducted a genome-wide association study (GWAS) and a follow-up study of bipolar disorder (BD), a common neuropsychiatric disorder. In the GWAS, we investigated 499,494 autosomal and 12,484 X-chromosomal SNPs in 682 patients with BD and in 1300 controls. In the first follow-up step, we tested the most significant 48 SNPs in 1729 patients with BD and in 2313 controls.

The Hypomania Checklist-32 and the Mood Disorder Questionnaire as screening tools--going beyond samples of purely mood-disordered patients.

Background: Bipolar disorders are often not recognized. Several screening tools have been developed, e.g.

Lithium's emerging role in the treatment of refractory major depressive episodes: augmentation of antidepressants.

Background: The late onset of therapeutic response and a relatively large proportion of nonresponders to antidepressants remain major concerns in clinical practice. Therefore, there is a critical need for effective medication strategies that augment treatment with antidepressants.

Methods: To review the available evidence on the use of lithium as an augmentation strategy to treat depressive episodes.

Relationship among latitude, climate, season and self-reported mood in bipolar disorder.

Objective: Many researchers have analyzed seasonal variation in hospital admissions for bipolar disorder with inconsistent results. We investigated if a seasonal pattern was present in daily self-reported daily mood ratings from patients living in five climate zones in the northern and southern hemispheres. We also investigated the influence of latitude and seasonal climate variables on mood.

Frequency of subsyndromal symptoms and employment status in patients with bipolar disorder.

Objective: This study investigated the frequency of episodes and subsyndromal symptoms based on employment status in patients with bipolar disorder.

Methods: Patients with bipolar disorder (n = 281) provided daily self-reported mood ratings for 5 months, returning 46,292 days of data. Data were analyzed using three employment status groups: disabled (n = 75), full-time employee or full-time student (n = 135), and other (n = 71).

Efficacy of quetiapine monotherapy in rapid-cycling bipolar disorder in comparison with sodium valproate.

Background: Rapid-cycling bipolar disorder is often characterized by a lack of response to psychopharmacological treatment, and a standard therapy has not been developed yet. The aim of this study was to examine the long-term efficacy and safety of a monotherapy with quetiapine or sodium valproate (VPA) in patients with rapid-cycling bipolar disorder.

Methods: This open-label, randomized, parallel group monotherapy pilot study was conducted at 3 German centers.

Genetic variants in FKBP5 affecting response to antidepressant drug treatment.

Introduction: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is a pathogenic mechanism of depression, and genetic polymorphisms in HPA axis genes have been described to influence response to antidepressant drugs. In particular, two polymorphisms in FKBP5, a co-chaperone of the glucocorticoid receptor, were strongly associated with response to therapy. We aimed to analyze whether these findings could be reproduced in a different sample of otherwise comparable inpatients with major depression.

Self-reporting software for bipolar disorder: validation of ChronoRecord by patients with mania.

With the widespread recognition of the value of active patient participation in their care, ChronoRecord software was developed to automate daily self-reporting by patients with bipolar disorder. A prior study demonstrated concurrent validity between self-ratings on ChronoRecord and clinician ratings on the Hamilton Depression Rating Scale (HAMD), but validity with the Young Mania Rating Scale (YMRS) could not be shown due to a lack of data when the outpatients were manic (Bauer et al., Bipolar Disorders 6, 67-74, 2004).

Self-reported data from patients with bipolar disorder: frequency of brief depression.

Objective: Patients with bipolar disorder often report depressive symptoms that do not meet the DSM-IV criteria for an episode. Using daily self-reported mood ratings, we studied how changing the length requirement to that typical of recurrent brief depression (2-4 days) would impact the number of depressed episodes.

Method: 203 patients (135 bipolar I and 68 bipolar II by DSM-IV criteria) recorded mood daily using ChronoRecord software on a home computer (30,348 total days; mean 150 days).

Bone mineral density during maintenance treatment with supraphysiological doses of levothyroxine in affective disorders: a longitudinal study.

Background: This prospective study was designed to determine whether patients with prophylaxis-resistant affective disorders, receiving adjunctive maintenance therapy with supraphysiological doses of levothyroxine (L-T4), show evidence of accelerated bone loss compared to the reference population database.

Methods: In 21 patients, bone mineral density (BMD) of the spine (lumbar vertebrae L1-L4) and femur (femoral neck, trochanter, and Ward's triangle) was measured by dual energy X-ray absorptiometry (DXA). BMD measurement was performed first after patients had been on thyroid-stimulating hormone (TSH)-suppressive therapy with L-T4 (mean dose=411 mcg/d) for an average of 16.

Trimipramine pharmacokinetics after intravenous and oral administration in carriers of CYP2D6 genotypes predicting poor, extensive and ultrahigh activity.

Objective: The tricyclic antidepressant trimipramine is one of the drugs with the most pronounced differences in pharmacokinetics caused by the CYP2D6 genetic polymorphism. However, the effect of CYP2D6 genotype on steady state kinetics and on bioavailability has not been studied so far. In addition, we were interested in trimipramine pharmacokinetics in genetically defined ultra rapid metabolizers.

Bupropion and 4-OH-bupropion pharmacokinetics in relation to genetic polymorphisms in CYP2B6.

Bupropion is applied in depression and smoking cessation. Genetic polymorphisms in cytochrome P450 2B6 (CYP2B6) may cause variability in bupropion pharmacokinetics since hydroxylation is known to be mediated by CYP2B6. Bupropion may be a probe drug for CYP2B6 activity in humans.

Lithium augmentation therapy in refractory depression: clinical evidence and neurobiological mechanisms.

Objective: This systematic review examines the evidence and discusses the clinical relevance of lithium augmentation as a treatment strategy for refractory major depressive episodes. It also examines hypotheses on the mode of action of lithium augmentation, with a focus on serotonin (5-HT) and neuroendocrine systems, and proposes recommendations for future research.

Method: We searched the Medline computer database and the Cochrane Library for relevant original studies published in English from January 1966 to February 2003.