This is a sequential multiple assignment randomized trial for adults (ages > 18) with a bipolar disorder type 1 diagnosis currently experiencing a depressive episode. It is a randomized pragmatic trial that will compare four commonly prescribed treatments for bipolar depression, which includes three FDA-approved medications (Cariprazine, Quetiapine and Lurasidone) and one antipsychotic/antidepressant combination (Aripiprazole/Escitalopram).

Start Date01 Sep 2024

Sponsor / Collaborator

The General Hospital Corp.

[+1]

100 Clinical Results associated with SERT x 5-HT1A receptor x D3 receptor x D2 receptor x 5-HT2A receptor

100 Translational Medicine associated with SERT x 5-HT1A receptor x D3 receptor x D2 receptor x 5-HT2A receptor

0 Patents (Medical) associated with SERT x 5-HT1A receptor x D3 receptor x D2 receptor x 5-HT2A receptor

Literatures (Medical) associated with SERT x 5-HT1A receptor x D3 receptor x D2 receptor x 5-HT2A receptor

01 Jun 2009·Genes, Brain and BehaviorQ3 · PSYCHOLOGY

Investigation of 17 candidate genes for personality traits confirms effects of the HTR2A gene on novelty seeking

Q3 · PSYCHOLOGY

Article

Author: A. Ellgas ; A. Heck ; R. Lieb ; H. Pfister ; F. Holsboer ; S. Lucae ; B. Müller-Myhsok ; M. Ising ; B. Pütz ; M. Uhr ; D. Roeske

Genes involved in serotonergic and dopaminergic neurotransmission have been hypothesized to affect different aspects of personality, but findings from genetic association studies did not provide conclusive results so far. In previous studies, however, only one or a few polymorphisms within single genes were investigated neglecting the possibility that the genetic associations might be more complex comprising several genes or gene regions. To overcome this limitation, we performed an extended genetic association study analyzing 17 serotonergic (SLC6A4, HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR6, MAOA, TPH1, TPH2) and dopaminergic genes (SLC6A3, DRD2, DRD3, DRD4, COMT, MAOA, TH, DBH), which have been previously reported to be implicated with personality traits.One hundred and ninety‐five single nucleotide polymorphisms (SNPs) within these genes were genotyped with the Illumina BeadChip technology (HumanHap300, Human‐1) in a sample of 366 mentally healthy Caucasians. Additionally, we tried to replicate our results in an independent sample of further 335 Caucasians. Personality traits in both samples were assessed with the German version of Cloninger's Tridimensional Personality Questionnaire.From 30 SNPs showing associations at a nominal level of significance, two intronic SNPs, rs2770296 and rs927544, both located in the HTR2A gene, withstood correction for multiple testing. These SNPs were associated with the personality trait novelty seeking. The effect of rs927544 could be replicated for the novelty seeking subscale extravagance, and the same SNP was also associated with extravagance inthe combined samples.Our results show that HTR2A polymorphisms modulate facets of novelty seeking behaviour in healthy adults suggesting that serotonergic neurotransmission is involved in this phenotype.

01 Aug 2003·NeuropsychopharmacologyQ1 · MEDICINE

Aripiprazole, A Novel Atypical Antipsychotic Drug with a Unique and Robust Pharmacology

Q1 · MEDICINE

Article

Author: Richard Mailman ; Sean Renock ; David A. Shapiro ; David R. Sibley ; Bryan L. Roth ; Elaine Arrington ; Li Xin Liu ; Louis A. Chiodo

Atypical antipsychotic drugs have revolutionized the treatment of schizophrenia and related disorders. The current clinically approved atypical antipsychotic drugs are characterized by having relatively low affinities for D(2)-dopamine receptors and relatively high affinities for 5-HT(2A) serotonin receptors (5-HT, 5-hydroxytryptamine (serotonin)). Aripiprazole (OPC-14597) is a novel atypical antipsychotic drug that is reported to be a high-affinity D(2)-dopamine receptor partial agonist. We now provide a comprehensive pharmacological profile of aripiprazole at a large number of cloned G protein-coupled receptors, transporters, and ion channels. These data reveal a number of interesting and potentially important molecular targets for which aripiprazole has affinity. Aripiprazole has highest affinity for h5-HT(2B)-, hD(2L)-, and hD(3)-dopamine receptors, but also has significant affinity (5-30 nM) for several other 5-HT receptors (5-HT(1A), 5-HT(2A), 5-HT(7)), as well as alpha(1A)-adrenergic and hH(1)-histamine receptors. Aripiprazole has less affinity (30-200 nM) for other G protein-coupled receptors, including the 5-HT(1D), 5-HT(2C), alpha(1B)-, alpha(2A)-, alpha(2B)-, alpha(2C)-, beta(1)-, and beta(2)-adrenergic, and H(3)-histamine receptors. Functionally, aripiprazole is an inverse agonist at 5-HT(2B) receptors and displays partial agonist actions at 5-HT(2A), 5-HT(2C), D(3), and D(4) receptors. Interestingly, we also discovered that the functional actions of aripiprazole at cloned human D(2)-dopamine receptors are cell-type selective, and that a range of actions (eg agonism, partial agonism, antagonism) at cloned D(2)-dopamine receptors are possible depending upon the cell type and function examined. This mixture of functional actions at D(2)-dopamine receptors is consistent with the hypothesis proposed by Lawler et al (1999) that aripiprazole has "functionally selective" actions. Taken together, our results support the hypothesis that the unique actions of aripiprazole in humans are likely a combination of "functionally selective" activation of D(2) (and possibly D(3))-dopamine receptors, coupled with important interactions with selected other biogenic amine receptors--particularly 5-HT receptor subtypes (5-HT(1A), 5-HT(2A)).

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