Efficacy of Quetiapine in Patients With Bipolar I and II Depression: A Multicenter, Prospective, Open-Label, Observational Study.

Efficacy of quetiapine in patients with bipolar I and II depression: a multicenter, prospective, open-label, observational study.

Neuropsychiatr Dis Treat. 2013; 9: 197-204
Jeong JH, Bahk WM, Woo YS, Seo HJ, Hong SC, Jon DI, Min KJ, Yoon BH

To evaluate and compare the therapeutic efficacy of quetiapine in bipolar I and II depression patients in the clinical setting.This was an 8-week, multicenter, open-label, observational study for bipolar depression. The dosage of quetiapine was flexible, and concomitant medications were permitted on clinician’s judgments. A total of 1097 patients were enrolled, and 764 bipolar depression patients who exhibited good therapeutic compliance (>75% compliance rate) were analyzed.Clinical Global Impression – Bipolar scale and Montgomery-Asberg Depression Rating Scale scores were significantly improved at weeks four and eight compared with the baseline scores. At the end of the 8-week study, the response rate was 58.9%, and the remission rate was 42.1%. However, there were no significant differences in the response and remission rates between bipolar I and II disorder (BD-I and BD-II) patients (response rate 60.1% versus 56.3%; remission rate 44.5% versus 37.0%). Montgomery-Asberg Depression Rating Scale score at baseline (? = 0.612, P < 0.001), duration of current episode (? = -0.152, P = 0.001), and presence of remission on previous episode (? = 0.111, P = 0.012) were significantly associated with improvements in depressive symptoms. Fatigue (16.0%), somnolence (14.9%), and manic/hypomanic switching (0.6% at week four, 0.3% at week eight) were observed throughout the study period.The results of this study suggest that quetiapine improves depressive symptoms in BD-I and BD-II patients with a minimal incidence of manic switching. The therapeutic efficacy of quetiapine increased with time. Quetiapine could be an effective and safe modality for the treatment of BD-I and BD-II. HubMed – depression

Translational profiling of hypocretin neurons identifies candidate molecules for sleep regulation.

Genes Dev. 2013 Feb 21;
Dalal J, Roh JH, Maloney SE, Akuffo A, Shah S, Yuan H, Wamsley B, Jones WB, Strong CD, Gray PA, Holtzman DM, Heintz N, Dougherty JD

Hypocretin (orexin; Hcrt)-containing neurons of the hypothalamus are essential for the normal regulation of sleep and wake behaviors and have been implicated in feeding, anxiety, depression, and reward. The absence of these neurons causes narcolepsy in humans and model organisms. However, little is known about the molecular phenotype of these cells; previous attempts at comprehensive profiling had only limited sensitivity or were inaccurate. We generated a Hcrt translating ribosome affinity purification (bacTRAP) line for comprehensive translational profiling of all ribosome-bound transcripts in these neurons in vivo. From this profile, we identified >6000 transcripts detectably expressed above background and 188 transcripts that are highly enriched in these neurons, including all known markers of the cells. Blinded analysis of in situ hybridization databases suggests that ?60% of these are expressed in a Hcrt marker-like pattern. Fifteen of these were confirmed with double labeling and microscopy, including the transcription factor Lhx9. Ablation of this gene results in a >30% loss specifically of Hcrt neurons, without a general disruption of hypothalamic development. Polysomnography and activity monitoring revealed a profound hypersomnolence in these mice. These data provide an in-depth and accurate profile of Hcrt neuron gene expression and suggest that Lhx9 may be important for specification or survival of a subset of these cells. HubMed – depression

Jumping from the surface of water by the long-legged fly Hydrophorus (Diptera, Dolichopodidae).

J Exp Biol. 2013 Feb 21;
Burrows M

The fly, Hydrophorus that is 4 mm long and has a mass of 4.7 mg moves around upon and jumps from water without its tarsi penetrating the surface. All 6 tarsi have a surface area of 1.3 mm(-2) in contact with the water but did not dimple its surface when standing. Jumping was propelled by depression of the trochantera and extension of the tibiae of both hind and middle legs which are 40% longer than the front legs and 170% longer than the body. As these four legs progressively propelled the insect to take-off, they each created dimples on the water surface that expanded in depth and area. No dimples were associated with the front legs, which were not moved in a consistent sequence. The wings opened while the legs were moving and then flapped at a frequency of 148 Hz. The body was accelerated in a mean time of 21 ms to a mean take-off velocity of 0.7 m s(-1). The best jumps reached velocities of 1.6 m s(-1), required an energy output of 7 µJ and a power output of 0.6 mW, with the fly experiencing a force of 140 g. The required power output indicates that direct muscle contractions could propel the jump without the need for elaborate mechanisms for energy storage. Take-off trajectories were steep with a mean of 87 degrees to the horizontal. Take-off velocity fell if a propulsive tarsus penetrated the surface of the water. If more tarsi became submerged, take-off was not successful. A second strategy for take-off was powered only by the wings and was associated with slower (1 degree ms(-1) compared with 10 degrees ms(-1) when jumping) and less extensive movements of the propulsive joints of the middle and hind legs. No dimples were then created on the surface of the water. When jumping was combined with wing flapping, the acceleration time to take-off was reduced by 84 % and the take-off velocity was increased by 168 %. Jumping can potentially therefore enhance survival when threatened by a potential predator. HubMed – depression

Adjunctive agomelatine therapy in the treatment of acute bipolar II depression: a preliminary open label study.

Neuropsychiatr Dis Treat. 2013; 9: 243-51
Fornaro M, McCarthy MJ, De Berardis D, De Pasquale C, Tabaton M, Martino M, Colicchio S, Cattaneo CI, D’Angelo E, Fornaro P

The circadian rhythm hypothesis of bipolar disorder (BD) suggests a role for melatonin in regulating mood, thus extending the interest toward the melatonergic antidepressant agomelatine as well as type I (acute) or II cases of bipolar depression.Twenty-eight depressed BD-II patients received open label agomelatine (25 mg/bedtime) for 6 consecutive weeks as an adjunct to treatment with lithium or valproate, followed by an optional treatment extension of 30 weeks. Measures included the Hamilton depression scale, Pittsburgh Sleep Quality Index, the Clinical Global Impression Scale-Bipolar Version, Young Mania Rating Scale, and body mass index.Intent to treat analysis results demonstrated that 18 of the 28 subjects (64%) showed medication response after 6 weeks (primary study endpoint), while 24 of the 28 subjects (86%) responded by 36 weeks. When examining primary mood stabilizer treatment, 12 of the 17 (70.6%) valproate and six of the 11 (54.5%) lithium patients responded by the first endpoint. At 36 weeks, 14 valproate treated (82.4%) and 10 lithium treated (90.9%) subjects responded. At 36 weeks, there was a slight yet statistically significant (P = 0.001) reduction in body mass index and Pittsburgh Sleep Quality Index scores compared to respective baseline values, regardless of mood stabilizer/outcome. Treatment related drop-out cases included four patients (14.28%) at week 6 two valproate-treated subjects with pseudo-vertigo and drug-induced hypomania, respectively, and two lithium-treated subjects with insomnia and mania, respectively. Week 36 drop outs were two hypomanic cases, one per group.Agomelatine 25 mg/day was an effective and well-tolerated adjunct to valproate/lithium for acute depression in BD-II, suggesting the need for confirmation by future double blind, controlled clinical trials. HubMed – depression