A review of genetic alterations in the serotonin pathway and their correlation with psychotic diseases and response to atypical antipsychotics

Baou, Maria; Boumba, Vassiliki A.; Petrikis, Petros; Rallis, Georgios; Vougiouklakis, Theodore; Mavreas, Venetsanos

doi:10.1016/j.schres.2015.11.003

Cited by 32 publications

(29 citation statements)

References 217 publications

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“…Meanwhile, 5-HT4 and 5-HT6 were barely expressed in TCam-2 cells (Figure 6A). It has been known that activation of 5-HTs resulted in activation of transcriptional factor, cAMP response element-binding protein (CREB), in brain or several organs [21]. Many reports show that CREB binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the downstream genes [22].…”

Section: Resultsmentioning

confidence: 99%

Androgen suppresses testicular cancer cell growth in vitro and in vivo

Nakagawa

Ueda

et al. 2016

Oncotarget

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Silencing of androgen receptor (AR)-meditated androgen signaling is thought to be associated with the development of testicular germ cell tumors (TGCTs). However, the role of the androgen/AR signal in TGCT development has not been investigated. In this study, we show that the androgen/AR signal suppressed the cell growth of seminomas (SEs), a type of TGCT, in vitro and in vivo. Growth of SE cells was suppressed by DHT treatment and reduction of androgen levels by surgical castration promoted cancer cell growth in an in vivo xenograft model. Tryptophan hydroxylase 1 (TPH1), the rate limit enzyme in serotonin synthesis, was one of the genes which expression was reduced in DHT-treated SE cells. TPH1 was highly expressed in SE cancer tissues compared with adjacent normal tissues. Activation of androgen/AR signaling in SE cells reduced the expression of TPH1 in SE cells, followed by the reduction of serotonin secretion in cell culture supernatant. These results suggested that silencing of androgen/AR signaling may cause initiation and progression of SE through increase in TPH1 gene expression level.

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Section: Resultsmentioning

confidence: 99%

Androgen suppresses testicular cancer cell growth in vitro and in vivo

Nakagawa

Ueda

et al. 2016

Oncotarget

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“…In fact, treatment response has been reported to be associated with a number of factors, including genetic background. 39 Further investigations such as genetic studies to identify more detailed predictors for good treatment response in BPSD are warranted. Thus, the results of this study should be interpreted with caution in the clinical settings.…”

Section: Discussionmentioning

confidence: 99%

Lack of Early Improvement with Antipsychotics is a Marker for Subsequent Nonresponse in Behavioral and Psychological Symptoms of Dementia: Analysis of CATIE-AD Data

Yoshida

Roberts

Suzuki

et al. 2017

The American Journal of Geriatric Psychiatry

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Objective Prediction of response/non-response to antipsychotics is especially important in patients with behavioral and psychological symptoms of dementia (BPSD) in whom antipsychotic exposure increases risks of death. We aimed to examine whether presence/absence of early improvement of BPSD with antipsychotics is associated with subsequent response/non-response. Design Post-hoc analysis of the Clinical Antipsychotic Trials in Intervention Effectiveness with Alzheimer’s Disease (CATIE-AD) study (2001–2004) (trial registration: NCT00015548). Setting 45 sites in the United States. Participants 245 subjects (olanzapine, n=90; quetiapine, n=81; risperidone, n=74) with a DSM-IV diagnosis of dementia of the Alzheimer’s type who presented with a score of 1 or more in the Brief Psychiatric Rating Scale (BPRS) at baseline (Phase 1 of CATIE-AD). Intervention Subjects were randomly assigned to treatment with olanzapine, quetiapine, risperidone, or placebo in a double-blind manner. Measurements We examined associations between response at week 8, and demographic and clinical characteristics, including BPRS total score reduction at week 2, using logistic regression analyses. Prediction performance of binary classification (presence/absence) of improvement/no improvement at week 2 for response at week 8 was examined. Results BPRS total score reduction at week 2 (mean percentage score reduction, 12.6%) was significantly associated with response at week 8 (odds ratio, 1.18; 95% CI, 1.11–1.26). The 5% score reduction cut-off at week 2 showed the highest accuracy (0.71) with sensitivity, specificity, PPV, and NPV of 0.76, 0.65, 0.69, and 0.72, respectively. Conclusion Lack of even a very small early improvement with antipsychotic treatment may be a marker of subsequent non-response in BPSD.

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“…As previously mentioned, five of these six genes (AR, BDNF, COMT, DBH, NOS1) identified to be dysregulated in this study in AD and aggression have been implicated in the development, onset and/or propagation of schizophrenia. Interestingly both “ dopaminergic and serotoninergic hypotheses for schizophrenia ”, involving an elevated genetically-based capacity for striatal increased L-phenylalanine- and/or L-tyrosine-derived DA biosynthesis, altered DA release and defects in the tryptophan-derived serotonin (5-HT) and the serotonin receptor, transporter and synaptic vesicle trafficking systems have been implicated in several of the longest held pathoetiologic- and pathogenic-hypotheses for schizophrenia (Zhang et al, 2014; Baou et al, 2016; Cocchi et al, 2016; Egbujo et al, 2016; Garay et al, 2016; Howes et al, 2017). The overlapping participation of dopaminergic and serotoninergic pathways, especially with DA-metabolizing COMT pathways and serotonin (5-HT) reuptake inhibitors (SSRIs; Zoloft, Paxil, Prozac and other antidepressants) and blockage of serotonin transporter activities are remarkable.…”

Section: Discussionmentioning

confidence: 99%

Genetics of Aggression in Alzheimer’s Disease (AD)

Lukiw

Rogaev

2017

Front. Aging Neurosci.

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Alzheimer’s disease (AD) is a terminal, age-related neurological syndrome exhibiting progressive cognitive and memory decline, however AD patients in addition exhibit ancillary neuropsychiatric symptoms (NPSs) and these include aggression. In this communication we provide recent evidence for the mis-regulation of a small family of genes expressed in the human hippocampus that appear to be significantly involved in expression patterns common to both AD and aggression. DNA array- and mRNA transcriptome-based gene expression analysis and candidate gene association and/or genome-wide association studies (CGAS, GWAS) of aggressive attributes in humans have revealed a surprisingly small subset of six brain genes that are also strongly associated with altered gene expression patterns in AD. These genes encoded on five different chromosomes (chr) include the androgen receptor (AR; chrXq12), brain-derived neurotrophic factor (BDNF; chr11p14.1), catechol-O-methyl transferase (COMT; chr22q11.21), neuronal specific nitric oxide synthase (NOS1; chr12q24.22), dopamine beta-hydroxylase (DBH chr9q34.2) and tryptophan hydroxylase (TPH1, chr11p15.1 and TPH2, chr12q21.1). Interestingly, (i) the expression of three of these six genes (COMT, DBH, NOS1) are highly variable; (ii) three of these six genes (COMT, DBH, TPH1) are involved in DA or serotonin metabolism, biosynthesis and/or neurotransmission; and (iii) five of these six genes (AR, BDNF, COMT, DBH, NOS1) have been implicated in the development, onset and/or propagation of schizophrenia. The magnitude of the expression of genes implicated in aggressive behavior appears to be more pronounced in the later stages of AD when compared to MCI. These recent genetic data further indicate that the extent of cognitive impairment may have some bearing on the degree of aggression which accompanies the AD phenotype.

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A review of genetic alterations in the serotonin pathway and their correlation with psychotic diseases and response to atypical antipsychotics

Cited by 32 publications

References 217 publications

Androgen suppresses testicular cancer cell growth in vitro and in vivo

Androgen suppresses testicular cancer cell growth in vitro and in vivo

Lack of Early Improvement with Antipsychotics is a Marker for Subsequent Nonresponse in Behavioral and Psychological Symptoms of Dementia: Analysis of CATIE-AD Data

Genetics of Aggression in Alzheimer’s Disease (AD)

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