Comparison study of venlafaxine and paroxetine for the treatment of depression in elderly Chinese inpatients.
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Aged↗
Biomedical subjects
Shih-Jen Tsai
Publications and source records attributed to Shih-Jen Tsai.
Dopamine receptor downregulation: an alternative strategy for schizophrenia treatment.
Schizophrenia is a common and devastating illness. The cause of schizophrenia is still unknown and the simplest formulation of the "Dopamine hypothesis" posits that schizophrenia results from dopaminergic hyperactivity. Under the hypothesis of dopaminergic hyperactivity in schizophrenia, antipsychotics blocking the dopamine D2 receptor (DRD2) and other approaches to reduce dopamine (DA) transmission have been used to treat schizophrenia. I propose that dopamine receptor (DR) downregulation could be an alternative strategy to compromise dopaminergic overactivity implicated in the pathogenesis of schizophrenia. Agonist-induced receptor downregulation includes receptor proteolysis, modulation of receptor gene transcription and affecting of RNA stability. These processes cause a decrease of existing receptors and reduction of receptor synthesis. This hypothesis could explain the antipsychotic mechanisms of DA agonists or partial agonists, like aripiprazole. It is suggested that the development of agents that increase DR downregulation could be an alternative strategy for schizophrenia treatment.
Animals↗
Is mania caused by overactivity of central brain-derived neurotrophic factor?
Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, can modulate synaptic plasticity and neurotransmitter release across multiple neurotransmitter systems, as well as the intracellular signal-transduction pathway. Recent studies had demonstrated that BDNF may play a role in the antidepressant mechanism and the pathogenesis of major depression. These findings implicated that BDNF may involve in mood regulation. In addition, (1). studies found positive association between BDNF genetic polymorphism and bipolar affective disorders; (2). agents which potentially induce manic states also increase BDNF, and (3). increase in mossy fibers were noted for bipolar affective disorder brain and BDNF is related to the induction of aberrant mossy fiber sprouting. From these finding, it is proposed that BDNF overactivity may be implicated in the manic state. The notion of BDNF overactivity in mania suggests that factors associated with increased BDNF activity may proffer the etiological fundamentals for bipolar affective disorder. Further, exploration of this hypothesis can provide a new direction in the treatment of the bipolar affective disorder.
Animals↗
Down-regulation of the Trk-B signal pathway: the possible pathogenesis of major depression.
Major depressive disorder (MDD) is a common mental disease with unknown etiology. Recent studies have suggested that decreased brain-derived neurotrophic factor (BDNF) may be implicated in the pathogenesis of MDD. Instead of a decrease in central BDNF, however, studies utilizing genetic depression animal models have found elevated levels of the factor. In the brain, BDNF exerts its influence chiefly by signaling through tyrosine receptor kinase B (Trk-B). In this report, it is suggested that Trk-B pathway down-regulation may be the major pathogenesis for MDD, while stress, which may reduce central BDNF, acts as a precipitation factor to further dampen central BDNF activity and contribute to the development of depression. Further, several possible mechanisms of Trk-B pathway down-regulation, and the implications for this down-regulation in MDD are discussed.
Brain↗
Association study of onset age, attempted suicide, aggressive behavior, and schizophrenia with a serotonin 1B receptor (A-161T) genetic polymorphism.
Located on the presynaptic and postsynaptic terminals of serotonergic neurons, serotonin 1B receptors (5-HT1B) are involved in the modulation of serotonergic activity. The implications of 5-HT1B study of animal models of schizophrenia and antipsychotic activity involving defective sensory processes suggest that this receptor may be involved in the pathogenesis of schizophrenic disorders. In a population-based association study, we tested the hypothesis that the allelic variant, A-161T, of the 5-HT1B gene confers susceptibility to schizophrenic disorders and is associated with age of onset, aggressive behavior and attempted suicide. We genotyped the A-161T polymorphism in 110 patients with schizophrenic disorders and in 215 normal controls. No association was demonstrated between 5-HT1B genotype or allele frequencies and schizophrenic disorders, except for a trend for later age at disease onset in A/A homozygote schizophrenics in comparison with A/T heterozygote patients (p = 0.071). No significant difference in genotype distribution was determined comparing patients with and without aggressive behavior, and those with and without a history of suicide attempt. These findings suggest that the investigated 5-HT1B genetic polymorphism does not play a major role in the pathogenesis of schizophrenic disorders.
Adult↗
Association analysis of brain-derived neurotrophic factor Val66Met polymorphisms with Alzheimer's disease and age of onset.
Because of a decrease in central brain-derived neurotrophic factor (BDNF) levels in Alzheimer's disease (AD) and the important role of BDNF in neuronal survival, BDNF may represent a candidate gene conferring susceptibility to AD. Recently, a functional BDNF Val66Met polymorphism has been associated with AD in an Italian population. In the present study, we investigated a possible role of this BDNF polymorphism in the susceptibility of AD or AD onset in a Chinese population. Comparing AD patients and controls, the distribution of the BDNF genotypes and alleles did not differ significantly. The onset age was not significantly different comparing the three BDNF genotype groups. Our negative findings suggest that it is unlikely that the BDNF Val66Met polymorphism plays a major role in the pathogenesis of AD in the Chinese population and do not support previous findings that homozygosity for the 66Val allele confers an increased risk for AD. Further studies with genetic variations in BDNF relating either to AD-associated depression or to the AD treatment response are suggested.
Age of Onset↗
Association study of a brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and personality trait and intelligence in healthy young females.
Brain-derived neurotrophic factor (BDNF), a member of the nerve-growth-factor family, plays an important role in neuronal survival and development, and it can modulate serotonergic activity. Further, BDNF has been implicated in the expression of personality traits and in cognitive function. We tested the associations between functional BDNF Val66Met genetic variants, and personality trait and intelligence in a cohort of 114 healthy young Chinese females. Subjects with the Val/Val genotype had a significantly higher mean performance IQ than Val/Met carriers, especially for the Object Assembly subtest. No significant association was demonstrated for the BDNF polymorphism and any of the Tridimensional Personality Questionnaire personality-factor scores, including harm avoidance. These results suggest that genetic variants of the BDNF gene may play a role in specific cognitive functions, but not in overall intelligence. In contrast to a recent report, however, this polymorphism does not appear to be associated with the neuroticism-related personality trait.
Adult↗
Association study of a brain-derived neurotrophic factor (Val66Met) genetic polymorphism and panic disorder.
Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, plays an important role in the development, maintenance and function of several neuronal systems. Recent studies have demonstrated that antidepressants, commonly used for panic disorder treatment, can increase central BDNF. In addition, animals with BDNF deficits have higher levels of anxiety when exposed to stressors in comparison to normal controls. The present study tested the hypothesis that the BDNF gene Val66Met polymorphism is associated with panic disorder. In this study, therefore, the incidence of this polymorphism was compared in 103 panic disorder patients and 180 normal controls. The genotype and allele frequencies for the BDNF gene Val66Met polymorphism did not differ comparing the two groups. Furthermore, no association was demonstrated between this BDNF polymorphism and either mitral valve prolapse or agoraphobia in panic disorder patients. These findings suggest that the investigated BDNF polymorphism does not play a major role in the pathogenesis of panic disorder in this Chinese population. Further studies exploring the relationship between genetic variations of BDNF and the cerebral atrophy associated with, and antidepressant treatment response in, panic disorder may be appropriate.
Adult↗
Association study of a functional catechol-O-methyltransferase genetic polymorphism with age of onset, cognitive function, symptomatology and prognosis in chronic schizophrenia.
The gene coding for catechol-O-methyltransferase (COMT), which is involved in the metabolism of catecholamines, has long been implicated as a candidate gene for schizophrenia. This study aimed to assess the relationship between a functional polymorphism (Val158Met) of the COMT gene and age of onset (AOO), symptomatology, global cognitive function and prognosis in patients with schizophrenia. The study enrolled 154 patients with schizophrenia from chronic wards. Results failed to show a significant association between the Val158Met polymorphism and the Brief Psychiatric Rating Scale scores, Mini-Mental State Examination scores, and Social and Occupational Functioning Assessment Scale scores, but COMT Val158Met heterozygotes had a later AOO than homozygous patients. However, by further expanding the number of patients to 228 patients, the differences in AOO among the three COMT genotypic groups was not significant. The COMT Val158Met polymorphism did not appear to significantly affect susceptibility, symptomatology, global cognitive function and prognosis in Chinese patients with schizophrenia, but the possible association with AOO merits further investigation.
Adolescent↗
Association study of adrenergic beta3 receptor (Trp64Arg) and G-protein beta3 subunit gene (C825T) polymorphisms and weight change during clozapine treatment.
Weight gain, a common adverse effect of clozapine, may impair health and affect patient compliance during treatment with this agent. The aim of this study was to investigate the relationship between genetic variants of the adrenergic beta3 receptor (ADRB3) and the G-protein beta3 subunit (GNB3) and clozapine-induced body weight change (BWC). Eighty-seven treatment-resistant schizophrenic patients were weighed before and after 4 months of clozapine treatment, with the subjects gaining an average of 2.6 kg in body weight. No statistically significant relationship was demonstrated for the investigated ADRB3 Trp64Arg and the GNB3 C825T polymorphisms in terms of BWC post-treatment, suggesting these two polymorphisms do not play a significant role in clozapine-induced BWC. Further exploration of other genetic variants implicated in clozapine-induced BWC is important, however, in order to predict and reduce clozapine-associated weight gain.
Adolescent↗
Association study of catechol-O-methyltransferase gene and dopamine D4 receptor gene polymorphisms and personality traits in healthy young chinese females.
Human personality traits, which are substantially heritable, may be modulated by monoamine neurotransmitters. It has been demonstrated that the catechol-O-methyltransferase (COMT) Val158Met genetic polymorphism, a functional polymorphism that may affect monoamine metabolism, is possibly associated with specific personality traits. In addition, a polymorphism in the dopamine D4 receptor (DRD4) gene exon 3 has been associated in some, but not all, studies with the novelty seeking personality trait, as evaluated by the Tridimensional Personality Questionnaire (TPQ). In this study, associations between these two polymorphisms and TPQ personality traits were investigated in a sample population of 120 healthy young Chinese females. The results of this analysis reveal that the COMT Val158Met polymorphism was significantly associated with novelty seeking (p = 0.017) and reward dependence scores (p = 0.015) in our sample. However, no significant differences were demonstrated comparing TPQ-specific scores for subjects bearing different DRD4 genotypes. The present study suggests that the functional COMT Val158Met genetic polymorphism contributes to individual differences in the personality traits novelty seeking and reward dependence. Similar to the results of a recent meta-analytic review, however, no association was demonstrated between this DRD4 polymorphism and novelty seeking in our young Chinese female sample population.
Adult↗
Association study of serotonin 1B receptor (A-161T) genetic polymorphism and suicidal behaviors and response to fluoxetine in major depressive disorder.
Serotonin 1B receptors (5-HT1B) are autoreceptors involved in the local inhibitory control of serotonin release, and have been suggested to play a role in the pathogenesis of major depressive disorder (MDD) and the antidepressant effects of the selective serotonin reuptake inhibitors in patients. We genotyped the 5-HT1B A-161T polymorphism in 160 patients with MDD and 160 normal controls. We then tested the hypothesis that the allelic variant, A-161T, of the 5-HT1B gene confers susceptibility to MDD or is associated with suicide attempt. We also examined the association of this polymorphism with therapeutic response in 116 of the MDD patients who received fluoxetine treatment for 4 weeks. No significant difference was found in the A-161T genetic polymorphism between MDD patients and controls. The genotype distribution between patients with and without suicide attempt, or between fluoxetine treatment responders and nonresponders were also similar. Our findings suggest that 5-HT1B A-161T genetic polymorphism does not play a major role in the susceptibility to MDD, nor is it related to suicidal attempt or the therapeutic response to fluoxetine in MDD.
Adult↗
Possible association between serotonin transporter promoter region polymorphism and extremely violent crime in Chinese males.
The neurotransmitter, serotonin, has been implicated in aggressive behavior. The serotonin transporter (5-HTT), which reuptakes serotonin into the nerve terminal, plays a critical role in the regulation of serotonergic function. Previous western reports have demonstrated that the low-activity short (S) allele of the 5-HTT gene-linked polymorphic-region (5-HTTLPR) polymorphism is associated with aggressive behavior and associated personality traits. In the present study, we investigated this 5-HTTLPR genetic polymorphism in a group of Chinese males who had been convicted for extremely violent crime (n = 135) and a normal control group (n = 111). The proportion of S-allele carriers was significantly higher in the criminal group than in the controls (p = 0.006). A significant association was not demonstrated for the relationship between the 5-HTTLPR polymorphism and antisocial personality disorder, substance abuse or alcohol abuse in the criminal group. Our findings demonstrate that carriage of the low-activity S allele is associated with extremely violent criminal behavior in Chinese males, and suggests that the 5-HTT may be implicated in the mechanisms underlying violent behaviors.
Adult↗
Association analysis for MAOA gene polymorphism with long-latency auditory evoked potentials in healthy females.
The components of auditory evoked potentials (AEPs) have been demonstrated to be heritable and to be influenced by different neurotransmitter activities such as serotonin or dopamine. Monoamine oxidase A (MAOA) is a mitochondrial enzyme involved in the degradation of dopamine, serotonin and norepinephrine. We examined the potential association of the functional 30-bp repeat MAOA gene-linked polymorphism region (MAOA-LPR) in 234 normal young Chinese females. The results demonstrated that there is no association for MAOA-LPR polymorphism and AEP components. Our negative findings suggested that this genetic polymorphism does not play a major role in the modulation of AEPs in normal young females, but we could not exclude that other polymorphisms of the MAOA gene affect AEP components. Further exploration of the other polymorphisms of the MAOA gene and multiple interactions of the polymorphisms in various neurotransmitter systems may be needed in future studies.
Adult↗
Association analysis for the C-1019G promoter variant of the 5-HT1A receptor gene with auditory evoked potentials in major depression.
Involvement of the serotonergic system in N1 and P2 components of auditory evoked potentials (AEPs) has been implicated. Moreover, studies have indicated the presence of heritability in the genesis of AEP components. The serotonin 1A (5-HT1A) receptor gene is a strong candidate for N1 and P2 components of the AEPs because 5-HT1A receptor regulates the firing of serotonergic neurons. The present study tested the hypothesis that the 5-HT1A promoter genetic polymorphism (C-1019G) is associated with N1 and P2 components of AEPs in unmedicated major depression patients. The sample consisted of 221 Chinese patients (mean age: 44.3 years; male/female: 93/128) diagnosed with major depression. AEPs and 5-HT1A genotyping were done for each patient. Patients with the C/C genotype had a significantly shorter P2 latency when compared with C/G or G/G genotype patients (p = 0.049), and the difference in P2 latency was significant among the 5-HT1A genotype groups in male patients (p = 0.031) but not in female patients (p = 0.398). These findings suggest that this 5-HT1A polymorphism may affect AEP P2 latency in a gender-dependent manner. Further studies with other genetic polymorphisms in the serotonergic system may help to clarify the relation between serotonergic function and AEP components.
Adolescent↗
Fluoxetine-induced memory impairment in four family members.
OBJECTIVE: Fluoxetine, a selective serotonin reuptake inhibitor antidepressant agent, has been implicated in learning and memory. Here, we report four cases from the same family of fluoxetine-related memory-impairment. RESULTS: Memory-impairment resulted after fluoxetine treatment and disappeared after changing to another selective serotonin reuptake inhibitor. CONCLUSIONS: There may be a relationship between fluoxetine-related memory impairment and genetic factors, and this side-effect appears to be specific to fluoxetine treatment. Possible mechanisms underlying this effect may be the drug's influence on the central serotonergic system or brain-derived neurotrophic factor.
Adult↗
A case of parenteral zolpidem dependence with opioid-like withdrawal symptoms.
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Adult↗
Brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms in Parkinson's disease and age of onset.
Given the implications with respect to neuronal survival and the decreased level of the protein in the striatal region in Parkinson's disease (PD), brain-derived neurotrophic factor (BDNF) may be a candidate gene conferring susceptibility to PD. In a recent study of a Japanese population, a functional BDNF Val66Met polymorphism was associated with PD, however, an analogous investigation of a western population did not replicate this finding. In the present study of a Chinese sample, we have investigated the associations between the BDNF polymorphism and susceptibility to PD and PD onset age. The distribution of the BDNF genotypes and alleles did not differ significantly comparing PD patients and controls. Further, the onset age was not significantly different comparing the three BDNF genotype groups. Thus, our negative findings suggest that it is unlikely that the BDNF Val66Met polymorphism plays a major role in the pathogenesis of PD in the Chinese population. Other BDNF genetic variants, and the association of these variants with PD symptomatology or treatment response, may merit further investigation.
Age of Onset↗