Potential Molecular and Cellular Mechanism of Psychotropic Drugs

Seo, Mi Hae; Scarr, Elizabeth; Lai, Chi-Yu; Dean, Brian

doi:10.9758/cpn.2014.12.2.94

Cited by 16 publications

(5 citation statements)

References 131 publications

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“…29 ) As a result of this receptor binding there were secondary changes in the intracellular signal transduction pathways and activity of nerve growth factors, effects that were similar to classical mood stabilizers like lithium. 30 )…”

Section: Main Subjectsmentioning

confidence: 99%

Pharmacotherapy of Bipolar Disorder with Quetiapine: A Recent Literature Review and an Update

Muneer

2015

Clin Psychopharmacol Neurosci

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Bipolar disorder is a chronic, recurrent condition with the usual onset during adolescence or early adulthood. In the Diagnostic and Statistical Manual of Mental Disorders 5th edition, it is conceptualized as a spectrum disorder usually associated with such comorbidities as anxiety disorders and substance use disorders. It is a relatively prevalent condition often complicated by mixed episodes, rapid cycling, subsyndromal symptoms, and treatment refractoriness. In spite of carrying substantial morbidity and mortality, effective treatments are few and far between and conventional mood stabilizers are often unsuccessful in controlling the various manifestations of the disorder. In this scenario, second generation antipsychotics are emerging as treatments with valid efficacy in all phases of bipolar disorder. Quetiapine is a versatile atypical antipsychotic which was first approved for the treatment of schizophrenia, but latter on the basis of controlled studies earned United States Food and Drug Administration's approval for acute as well as maintenance treatment of this difficult to treat condition. In this review, recently published studies in the last 10 years were examined to update the knowledge about the efficacy and safety of quetiapine in the treatment of bipolar disorder. The medication's clinical pharmacology was first considered followed by a literature review summarizing its uses in bipolar disorder. The conclusion was that quetiapine was efficacious in manic, mixed and depressive episodes and as a maintenance agent with a good tolerability profile.

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Section: Main Subjectsmentioning

confidence: 99%

Pharmacotherapy of Bipolar Disorder with Quetiapine: A Recent Literature Review and an Update

Muneer

2015

Clin Psychopharmacol Neurosci

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“…Psychiatric medications have shown inconsistent responses to the cAMP cascade. Previous study demonstrated that haloperidol increased cAMP levels, chronic usage of clozapine has been found to decrease cAMP levels [ 59 ]. The forward MR analysis identified PDE1A as a risk factors for ASD, while suggesting potential protective effects of PDE2A in SCZ and TS.…”

Section: Discussionmentioning

confidence: 99%

Phosphodiesterase and psychiatric disorders: a two-sample Mendelian randomization study

Jiang,

Yan,

Zhang

et al. 2023

J Transl Med

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Background Phosphodiesterases (PDEs) have been associated with psychiatric disorders in observational studies; however, the causality of associations remains unestablished. Methods Specifically, cyclic nucleotide PDEs were collected from genome-wide association studies (GWASs), including PDEs obtained by hydrolyzing both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) (PDE1A, PDE2A, and PDE3A), specific to cGMP (PDE5A, PDE6D, and PDE9A) and cAMP (PDE4D and PDE7A). We performed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the relationship between PDEs and nine psychiatric disorders. The inverse-variance-weighted (IVW) method, MR-Egger, and weighted median were used to estimate causal effects. The Cochran’s Q test, MR-Egger intercept test, MR Steiger test, leave-one-out analyses, funnel plot, and MR pleiotropy residual sum and outlier (MR-PRESSO) were used for sensitivity analyses. Results The PDEs specific to cAMP were associated with higher-odds psychiatric disorders. For example, PDE4D and schizophrenia (SCZ) (odds ratios (OR) = 1.0531, PIVW = 0.0414), as well as major depressive disorder (MDD) (OR = 1.0329, PIVW = 0.0011). Similarly, PDE7A was associated with higher odds of attention-deficit/hyperactivity disorder (ADHD) (OR = 1.0861, PIVW = 0.0038). Exploring specific PDE subtypes and increase intracellular cAMP levels can inform the development of targeted interventions. We also observed PDEs (which hydrolyzes both cAMP and cGMP) was associated with psychiatric disorders [OR of PDE1A was 1.0836 for autism spectrum disorder; OR of PDE2A was 0.8968 for Tourette syndrome (TS) and 0.9449 for SCZ; and OR of PDE3A was 0.9796 for MDD; P < 0.05]. Furthermore, psychiatric disorders also had some causal effects on PDEs [obsessive–compulsive disorder on increased PDE6D and decreased PDE2A and PDE4D; anorexia nervosa on decreased PDE9A]. The results of MR were found to be robust using multiple sensitivity analysis. Conclusions In this study, potential causal relationships between plasma PDE proteins and psychiatric disorders were established. Exploring other PDE subtypes not included in this study could provide a more comprehensive understanding of the role of PDEs in psychiatric disorders. The development of specific medications targeting PDE subtypes may be a promising therapeutic approach for treating psychiatric disorders.

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“…Another study demonstrated that during 3- and 6-month follow-up, clinical attention deficit symptoms were negatively correlated with the relative expression of miR-4655-3p and miR-7641 [ 23 ]. Some available data have suggested that therapy with psychotropic drugs (specifically, antipsychotics, antidepressants, and mood stabilizers) appears to have complex and region-dependent effects on epigenetic mechanisms [ 24 ]. MPH has been shown to upregulate the expression of Homer 1a and to ameliorate ADHD-like behaviors [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs serve as prediction and treatment-response biomarkers of attention-deficit/hyperactivity disorder and promote the differentiation of neuronal cells by repressing the apoptosis pathway

et al. 2022

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Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder. This study aimed to examine whether miRNA expression abundance in total white blood cells (WBCs) facilitated the identification of ADHD and reflected its response to treatment. Furthermore, whether miRNA markers facilitated the growth of the human cortical neuronal (HCN-2) cells was also investigated. Total WBC samples were collected from 145 patients and 83 controls, followed by RNA extraction and qPCR assays. Subsequently, WBC samples were also collected at the endpoint from ADHD patients who had undergone 12 months of methylphenidate treatment. The determined ΔCt values of 12 miRNAs were applied to develop an ADHD prediction model and to estimate the correlation with treatment response. The prediction model applying the ΔCt values of 12 examined miRNAs (using machine learning algorithm) demonstrated good validity in discriminating ADHD patients from controls (sensitivity: 96%; specificity: 94.2%). Among the 92 ADHD patients completing the 12-month follow-up, miR-140-3p, miR-27a-3p, miR-486-5p, and miR-151-5p showed differential trends of ΔCt values between treatment responders and non-responders. In addition, the in vitro cell model revealed that miR-140-3p and miR-126-5p promoted the differentiation of HCN-2 cells by enhancing the length of neurons and the number of junctions. Microarray and flow cytometry assays confirmed that this promotion was achieved by repressing apoptosis and/or necrosis. The findings of this study suggest that the expression levels of miRNAs have the potential to serve as both diagnostic and therapeutic biomarkers for ADHD. The possible biological mechanisms of these biomarker miRNAs in ADHD pathophysiology were also clarified.

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Potential Molecular and Cellular Mechanism of Psychotropic Drugs

Cited by 16 publications

References 131 publications

Pharmacotherapy of Bipolar Disorder with Quetiapine: A Recent Literature Review and an Update

Pharmacotherapy of Bipolar Disorder with Quetiapine: A Recent Literature Review and an Update

Phosphodiesterase and psychiatric disorders: a two-sample Mendelian randomization study

MicroRNAs serve as prediction and treatment-response biomarkers of attention-deficit/hyperactivity disorder and promote the differentiation of neuronal cells by repressing the apoptosis pathway

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