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Shih-Jen Tsai

Publications and source records attributed to Shih-Jen Tsai.

At least 37 records · Page 2Linked to original sources
PubMed2005

The Val66Met polymorphism of the brain-derived neurotrophic-factor gene is associated with geriatric depression.

Brain-derived neurotrophic-factor (BDNF), the most abundant of the neurotrophins in the brain, has been implicated in both major depression and cognitive function. This study examines the association between the BDNF-gene Val66Met polymorphism and depression susceptibility and severity, age-of-onset, cognitive function and suicidal attempt history in an elderly Chinese sample population. We genotyped the BDNF-gene Val66Met polymorphism in 110 elderly inpatients diagnosed with major depression and 171 age- and sex-similar control subjects. All patients were assessed with the Hamilton Rating Scale for Depression (HAM-D) for depression severity and the Mini-Mental Status Examination (MMSE) for cognitive function after admission. Suicide attempt history and age-of-onset of depression were evaluated by interview and medical record. The BDNF Val66Met genotype distribution was significantly different between depressed patients and control subjects (P=0.003) and there was a significant excess of Met allele in the depressed patients compared to the control group (P=0.001). The BDNF polymorphism did not affect age-of-onset, depression severity, cognitive function or suicidal attempt history. The results suggest that the BDNF Val66Met polymorphism is a relevant risk factor for geriatric depression.

Aged↗
PubMed2005

Deltamethrin, a pyrethroid insecticide, could be a potential antidepressant agent.

Antidepressants, including tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors and serotonin-noradrenalin reuptake inhibitors, are the main biological treatment for major depression. However, not all depressed patients improve clinically despite appropriate treatment. Thus, the exploration of novel antidepressants with novel mechanisms of action may help to develop more effective agents. Deltamethrin is a pyrethroid insecticide that is a widely used and has a low acute toxicity in mammals. Recent studies in vivo and in vitro have shown that the inducible effect of deltamethrin on brain-derived neurotrophic factor (BDNF) gene expression is very potent and tends to be sustained. With recent evidence that the activation of the BDNF-dependent pathway plays an important role in the mechanism of antidepressant therapeutic action, deltamethrin or derivatives thereof could have potential antidepressant therapeutic effects. Further evaluation of the therapeutic and toxic effects of this drug in animal models is needed before clinical trials can begin.

Animals↗
PubMed2005

The possible role of tissue-type plasminogen activator and the plasminogen system in the pathogenesis of major depression.

Major depressive disorder (MDD) is one of the most common psychiatric illnesses with an unknown etiology. Evidence from animal and human studies has suggested that brain-derived neurotrophic factor (BDNF) function may be implicated in the pathogenesis of MDD. Tissue-type plasminogen activator (tPA) is a highly specific serine proteinase that catalyses the generation of zymogen plasminogen from the proteinase plasmin. Recent studies have found that the proteolytic cleavage of proBDNF, a BDNF precursor, to BDNF by the plasmin represents a mechanism by which the direction of BDNF action is controlled. Furthermore, studies using mice deficient in tPA has demonstrated that tPA is important for the stress reaction, a common precipitating factor for MDD. A study of the serum levels of the plasminogen activator inhibitor-1 (PAI-1), the major inhibitor of tPA, found that women with MDD had a higher PAI-1 concentration than normal controls. From these findings, it is proposed that the tPA/plasminogen system may play a role in the pathogenesis of MDD. Attempts to confirm the tPA/plasminogen hypothesis may lead to new directions in the study of the pathogenesis of MDD and the development of a novel intervention of this disorder.

Major Depressive Disorder↗
PubMed2005

Interleukin-6 genetic polymorphism and Chinese major depression.

BACKGROUND: It has been reported that serum concentrations of interleukin-6 (IL-6), a pro-inflammatory cytokine, were significantly higher in major depressive disorder (MDD). OBJECTIVES: The aim of the present study was to examine whether the IL-6 genetic variant confers susceptibility to MDD. METHODS: We genotyped a functional polymorphism in the promoter region (position -634) of the IL-6 gene in a sample of 257 MDD patients and 105 normal controls. RESULTS: No significant differences were demonstrated for the genotype or allele frequency of the IL-6 polymorphism when comparing the MDD and control groups. CONCLUSIONS: Our findings suggested that the investigated IL-6 polymorphism does not affect MDD susceptibility. We propose that other genetic variations of IL-6, relating either to MDD or to the clinical manifestations of MDD, may need further investigation.

Adult↗
PubMed2005

Central N-acetyl aspartylglutamate deficit: a possible pathogenesis of schizophrenia.

The "glutamate hypothesis" of schizophrenia has emerged from the finding that phencyclidine (PCP) induces psychotic-like behaviors in rodents, possibly by blocking the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, thereby causing increased glutamate release. N-acetyl aspartylglutamate (NAAG), an endogenous peptide abundant in mammalian nervous systems, is localized in certain brain cells, including cortical and hippocampal pyramidal neurons. NAAG is synthesized from N-acetylaspartate (NAA) and glutamate, and NAA availability may limit the rate of NAAG synthesis. Although NAAG is known to have some neurotransmitter-like functions, NAA does not. NAAG is a highly selective agonist of the type 3 metabotropic glutamate receptor (mGluR3, a presynaptic autoreceptor) and can inhibit glutamate release. In addition, at low levels, NAAG is an NMDA receptor antagonist, and blocking of NMDA receptors may increase glutamate release. Taken together, low central NAAG levels may antagonize the effect of glutamate at NMDA receptors and decrease its agonistic effect on presynaptic mGluR3; both activities could increase glutamate release, similar to the increase demonstrated in the PCP model of schizophrenia. In this report, it is suggested that the central NAAG deficit, possibly through decreased synthesis or increased degradation of NAAG, may play a role in the pathogenesis of schizophrenia. Evidence is presented and discussed from magnetic resonance, postmortem, animal model, schizophrenia treatment, and genetic studies. The central NAAG deficit model of schizophrenia could explain the disease process, from the perspectives of both neurodevelopment and neurodegeneration, and may point to potential treatments for schizophrenia.

Animals↗
PubMed2005

Distribution of androgen receptor CAG repeat polymorphism in Chinese schizophrenia and its correlation with age at onset.

The action of androgens is mediated by the androgen receptors (ARs), which are located throughout the brain. The AR gene is implicated in the pathogenesis of schizophrenia because male siblings with schizophrenia share alleles at this gene at a rate higher than chance predicts, and differences in sex hormone function may explain the gender difference in schizophrenic manifestations. Since the shorter alleles of the AR CAG repeat polymorphism are associated with increased gene expression, we tested the hypothesis that the AR CAG repeat variant confers susceptibility to schizophrenia using a sample of 225 people with schizophrenia and 247 normal controls. Using the median AR repeat length in the normal group as the arbitrary cut-off point (<24 and >25 CAG repeats), the results show no association between the AR repeat length and schizophrenia in either sex. Furthermore. AR CAG repeat length did not affect the age of symptom onset in the schizophrenic population. Our findings suggest that it is unlikely that the AR CAG repeat polymorphism plays a major role in the pathogenesis of schizophrenia. Nevertheless, given that androgens affect cognitive function, violent behavior and mood, the effect of the AR CAG polymorphism on the clinical manifestations of schizophrenia may warrant further exploration.

Adult↗
PubMed2005

Brain-derived neurotrophic factor (Val66Met) genetic polymorphism is associated with substance abuse in males.

Data from animal studies and from genetic scans in humans suggest that brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, may be involved in the mechanisms underlying substance abuse. The present study tested the hypothesis that the BDNF-gene Val66Met polymorphism is associated with substance abuse. We studied this polymorphism in 103 methamphetamine- and 200 heroin-dependent cases and 122 normal controls. We also considered the association of this polymorphism with age of onset of substance abuse in the heroin-dependent cases. Significant differences in BDNF Val66Met genotype distribution were found between subjects dependent on methamphetamine (P = 0.046) or heroin (P = 0.045) and controls, suggesting that the lower 66Met carrier frequency is associated with substance abuse. Furthermore, in the heroin-dependent group, the Val/Val homozygotes had a later onset of substance abuse compared with the Met allele carriers. The results suggest that the BDNF Val66Met polymorphism or a nearby locus may be involved in the pathogenesis of substance abuse. Our findings support previous genetic scan results showing that BDNF may contribute to substance abuse vulnerability.

Amino Acid Substitution↗
PubMed2005

Association study of a functional MAOA-uVNTR gene polymorphism and personality traits in Chinese young females.

Monoamine oxidase A (MAOA), a mitochondrial outer membrane enzyme, degrades biogenic amines including norepinephrine, dopamine and serotonin, which have been implicated in the expression of personality traits. We tested the associations between functional MAOA-uVNTR genetic variants and personality traits in a cohort of 370 healthy young Chinese females. Subjects who were homozygous for the 4-repeat allele of the MAOA-uVNTR gene tended to have a higher total score on the Harm Avoidance (HA) dimension of the Tridimensional Personality Questionnaire (TPQ) (p = 0.056), and had a significantly higher score on subdimension 4 of HA (p = 0.020) compared with the 3-repeat carriers. No significant association was demonstrated for MAOA-uVNTR polymorphism and the other two dimensions (Novelty Seeking and Reward Dependence) of TPQ. These results suggest that genetic variants of the MAOA gene may play a role in HA, but not in Novelty Seeking or Reward Dependence.

Adult↗
PubMed2005

TrkB partial agonists: potential treatment strategy for epilepsy, mania, and autism.

Brain-derived neurotrophic factor (BDNF) is a member of a family of neurotrophins that, by activating a tyrosine kinase B receptor (TrkB), regulates a wide variety of processes in the nervous system, including neural development, function and survival. Evidence suggests that excess BDNF is involved in the pathogenesis of epilepsy, mania and autism. Thus, agents that can decrease BDNF-TrkB pathway signaling may be therapeutic for these diseases. However, blocking BDNF-TrkB pathways with TrkB antagonists may be harmful, as BDNF-TrkB deficiency has been related to major depression and Alzheimer's disease. A partial agonist is an agent that elicits a maximum response that is less than that of an agonist (e.g., the physiological ligand), so, in the presence of excess full agonist, a partial agonist would act as an antagonist. Interestingly, a dopaminergic partial agonist, aripiprazole, has been successfully developed for the treatment of psychotic disorders. Recently specific TrkB partial agonists have been synthesized by O'Leary and Hughes; it is proposed that these partial TrkB agonists may provide a novel strategy for the treatment of epilepsy, mania or autism, which may be associated with BDNF-TrkB hyperfunction.

Aripiprazole↗
PubMed2005

Repetitive transcranial magnetic stimulation: a possible novel therapeutic approach to eating disorders.

The two most common eating disorders, anorexia nervosa and bulimia nervosa, are characterized by aberrant eating patterns and disturbances in body image. Treatment involves combining individual, behavioural, group, and family therapies, possibly with medications. Studies have found that medication, chiefly antidepressants, could be of help in bulimia nervosa but the evidence is weaker for use in anorexia nervosa. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that briefly stimulates or depresses cortical areas within the brain. It has been used in the treatment of various psychiatric disorders, especially major depression, which is a condition that patients with eating disorders often experience as a significant comorbidity. Given that both disorders may share a common pathogenesis, this report proposes that rTMS may represent an alternative strategy for the treatment of eating disorders. Other evidence that supports this notion comes from animal studies that show that rTMS can change feeding behaviours and central neurotransmitters related to the regulation of eating behaviours. Further investigation into the dose, duration and type of rTMS stimulus is needed to verify the efficacy of this intervention in eating disorders.

Animals↗
PubMed2005

Association study of a functional MAOA-uVNTR gene polymorphism and cognitive function in healthy females.

Monoamine oxidase A (MAOA) is a mitochondrial enzyme involved in the degradation of dopamine, serotonin and norepinephrine and these neurotransmitters are hypothesized to be involved in the cognitive function of humans. This study of a cohort of 191 healthy young Chinese females attempts to utilize the intelligence quotient (IQ), Wisconsin Card Sorting Test (WCST) and P300 event-related potentials as cognitive assessments for testing the relationship between the polymorphism with a variable number of tandem repeats (VNTR) in the upstream regulatory region (MAOA-uVNTR) and cognition. The results demonstrate that subjects bearing the 4/4-repeat genotype have a significantly higher full IQ than subjects bearing the 3/3-repeat genotype. However, there is no significant association between this MAOA-uVNTR polymorphism and the WCST and P300. Our study shows that the MAOA-uVNTR genetic polymorphism plays a role in the IQ; however, this may be a chance finding as the result was negative after using the Bonferroni adjustment. Therefore, we suggest that our study should be replicated and that the testing method, sex, disease and ethnicity should also be considered in future studies.

Adult↗
PubMed2005

Serotonin dysfunction and suicide attempts in major depressives: an auditory event-related potential study.

BACKGROUND: Serotonergic dysfunction is believed to be involved in suicide attempts. The loudness-dependent auditory evoked potential (LDAEP) is one of the validated indicators of the activity of the central serotonin system in humans. OBJECTIVES: This study was designed to investigate possible differences in the LDAEP and P300 between those depressed patients who attempted suicide and those who did not. METHODS: The LDAEP and P300 levels were recorded for 66 depressive patients (among which 16 had attempted suicide). RESULTS: Those who had attempted suicide showed a sharper slope of the LDAEP and increased frontal P300 amplitude. A high correlation between the LDAEP and P300, and a gender difference were also noted. CONCLUSIONS: Our results are concordant with previous assumptions about serotonin dysfunction in depressives who attempt suicide.

Adult↗
PubMed2005

Effects of subchronic clozapine administration on serum glucose, cholesterol and triglyceride levels, and body weight in male BALB/c mice.

Atypical antipsychotics, like clozapine, have fewer extrapyramidal side effects compared with typical antipsychotics, however, such treatment is associated with several adverse metabolic effects such as weight gain, hyperglycemia and hyperlipidemia in patients with schizophrenia. In this study, we investigated the effects of 30-day clozapine treatment on weight change, and serum fasting glucose, cholesterol and triglyceride levels in male BALB/c mice. The results demonstrate that 10.0 mg/kg clozapine group gained significantly less weight but had higher cholesterol compared with controls and the 2.0 mg/kg clozapine group. Our findings indicate the possibility of using mice to study the mechanisms of body weight change and lipid dysregulations induced by clozapine.

Animals↗
PubMed2005

A study of the association of (Val66Met) polymorphism in the brain-derived neurotrophic factor gene with alcohol dependence and extreme violence in Chinese males.

From studies of genetic-knockout animals, brain-derived neurotrophic factor (BDNF), a member of the neurotrophin growth-factor family, has been implicated in both alcohol preference and aggressive behaviour. To test whether a BDNF genetic variant may be associated with alcohol-dependent and violent behaviours, we studied Val66Met polymorphism of the BDNF-gene in 110 cases of alcohol-dependence, in 134 extremely violent convicts, and in 149 individuals without psychosis or mood disorders. We also examined the association of this polymorphism with antisocial personality disorder comorbidity in the extremely violent convicts. The results showed that the genotype and allele frequencies for Val66Met polymorphism at the BDNF-gene site did not differ among the three groups. Furthermore, it was not demonstrated that this polymorphism is associated with antisocial personality disorder comorbidity in the extremely violent convicts. Based on these findings, it seems reasonable to suggest that this BDNF-gene Val66Met polymorphism is unlikely to play a major role in the genetic susceptibility to the traits of alcohol-dependence or violence proneness.

Adult↗
PubMed2005

Adenosine A2a receptor/dopamine D2 receptor hetero-oligomerization: a hypothesis that may explain behavioral sensitization to psychostimulants and schizophrenia.

The mechanisms underlying psychostimulant-induced behavioral sensitization and schizophrenia are yet to be fully elucidated. Evidence suggests that the dopamine D2 receptor (DRD2) as well as other neurotransmitter system receptors may be involved in the two conditions, and previous reports have hypothesized that oligomerization of dopamine receptors and analogs from other neurotransmitter systems may underlie the mechanism responsible. This paper describes findings which show co-localization of DRD2 and the adenosine A2a receptor (A2aAR) in the striatum, interaction between the two receptors and A2aAR/DRD2 hetero-oligomerization in the neuronal cell. The possibility that A2aAR/DRD2 hetero-oligomerization may be involved in the development of psychostimulant-induced behavioral sensitization or the pathogenesis of schizophrenia is explored. A2aAR/DRD2 hetero-oligomerization can enhance dopaminergic function, resulting in an increased behavioral response to psychostimulants or the development of psychotic symptoms. Receptor oligomerization can affect receptor degradation, which may affect the persistence of behavioral sensitization or psychotic symptoms. The proposed A2aAR/DRD2 hetero-oligomerization model may suggest new directions in the understanding and treatment of schizophrenia.

Animals↗