Could repetitive transcranial magnetic stimulation be effective in autism?
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Autistic Disorder↗
Biomedical subjects
Shih-Jen Tsai
Publications and source records attributed to Shih-Jen Tsai.
Is autism caused by early hyperactivity of brain-derived neurotrophic factor?
Autism, a childhood-onset neurodevelopmental disorder, is characterized by disturbances in socialization and language skills, as well as in perception. Several studies indicate the importance of both genetic and environmental factors in the development of idiopathic autism, but the underlying pathogenesis of this disorder is still unknown. Brain-derived neurotrophic factor (BDNF) is important for normal neuronal development. Early BDNF hyperactivity may play an etiological role in autism early in life. This hypothesis is supported by the finding that serum and brain tissue BDNF levels are increased in autism compared with normal controls. Furthermore, BDNF hyperactivity may be associated with early brain outgrowth, increased prevalence of seizures in autism, and similar behaviors observed in autism and fragile X syndrome. Further studies of serum BDNF levels and genetic studies of the BDNF signaling pathway may help to clarify the role of BDNF in the pathogenesis of autism. Attempts to prove the BDNF hyperactivity hypothesis may lead investigators in a new direction for the study of the pathogenesis of autism and the development of an effective intervention of this disorder.
Alleles↗
Asthma, major depression and brain-derived neurotrophic factor.
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Animals↗
Possible involvement of brain-derived neurotrophic factor in the antinociceptive effect of antidepressants in neuropathic pain.
Neuropathic pain, a chronic pain state caused by injury to the nervous system, usually responds poorly to standard pain treatment. Antidepressants have been used to treat neuropathic pain, and animal and clinical studies have showed beneficial effects. However, the mechanisms underlying antidepressant antinociceptive effect in neuropathic pain are still unknown. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, can modulate synaptic plasticity and neurotransmitter release across multiple neurotransmitter systems. Recent animal and human studies have demonstrated that antidepressants can increase central as well as plasma BDNF levels. In addition: (1) BDNF is produced by a subset of primary sensory neurons that are located in the dorsal root ganglion; (2) BDNF levels change in animal models of neuropathic pain; (3) BDNF can indirectly depress sensory neuron transmission in the dorsal horn. From these findings, it is proposed that BDNF may play an important role in the antidepressant antinociceptive effect in neuropathic pain. The notion of BDNF mediating the therapeutic mechanisms of antidepressant in neuropathic pain may help to select the specific type and the optimal dose of antidepressants for the treatment of neuropathic pain. Exploration of this hypothesis could provide a new direction in the treatment of neuropathic pain, as well as other pain disorders.
Analgesics↗
The novel atypical antipsychotic aripiprazole as treatment for and prophylaxis against progressive multifocal leukoencephalopathy.
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Antipsychotic Agents↗
Possible involvement of the BDNF-dependent pathway in treatment-emergent suicidality or decreased response to antidepressants.
Antidepressants are the main biological treatment for major depression. However, a substantial proportion of depressed patients do not improve clinically despite appropriate treatment and, in rare cases, antidepressants can induce or increase suicidal tendencies. These phenomena are more commonly found in young patients. The causes underlying treatment-emergent suicidality or poor response to antidepressants are still unknown. Animal and postmortem studies have demonstrated that antidepressants increase central brain-derived neurotrophic factor (BDNF) levels and activate the BDNF-tyrosine kinase receptor B (TrkB) pathway, which plays an important role in their therapeutic mechanism. In this report, several possible mechanisms relating to the BDNF-dependent pathway are proposed to account for treatment-emergent suicidality and poor response to antidepressants. These include: (1) antidepressant-induced reduction in central BDNF expression acutely; (2) antidepressant dose-dependent effect on central BDNF levels; (3) age-related effect of antidepressants on BDNF expression; (4) overexpression of truncated TrkB or underexpression of full-length TrkB; (5) TrkB pathway dysfunction and (6) antidepressant-induced mania due to increased central BDNF levels. Further exploration of these hypotheses would help to design specific treatment strategies for depressed patients who have experienced unfavourable responses to antidepressant treatment.
Adaptation, Physiological↗
Association study of a monoamine oxidase a gene promoter polymorphism with major depressive disorder and antidepressant response.
Monoamine oxidase A (MAOA), a mitochondrial enzyme involved in the degradation of biogenic amines, may be implicated in the pathogenesis of major depressive disorder (MDD) and be related to the therapeutic effects of antidepressants. To elucidate a genetic predisposition of MDD, we studied a variable-number-tandem-repeat (VNTR) polymorphism in the promoter region of the MAOA gene in a Chinese population of 230 MDD patients and 217 controls. We also examined the association of this polymorphism and antidepressant therapeutic response in the MDD patients who underwent a 4-week fluoxetine treatment. Our results showed a significantly increased frequency of 4-repeat (4R) allele in MDD patients, especially in the female population. Furthermore, MDD female patients who were 3R homozygotes had a significantly better response to 4-week fluoxetine treatment when compared to 4R carriers (p=0.024), but there was a nonsignificant difference found in male patients (p=0.081). Since the 4R allele transcribed 2-10 times more efficiently than those with 3R allele, our findings suggest that the MAOA-uVNTR may be involved in the pathogenesis of MDD and the antidepressant therapeutic mechanisms in Chinese population, and that there may be a gender effect in this association.
Adolescent↗
The efficacy and safety of quetiapine for treatment of geriatric psychosis.
Quetiapine, an atypical antipsychotic, is effective for psychosis in younger patients, with limited adverse effects reported. This open-label naturalistic study was conducted to assess the 4-week efficacy and safety of quetiapine for treatment of geriatric psychosis. Clinical efficacy was evaluated using the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Improvement (CGI-I) instruments before and after 4 weeks of quetiapine treatment. The sample population consisted of 100 geropsychiatric inpatients with psychosis, with the therapeutic evaluation completed by 91. Eighty-one of these 91 patients (89.0%) experienced mild-to-substantial improvement, as determined from the CGI-I. Further, a mean reduction in BPRS score of 39.5% (from baseline) was also determined. The mean daily dose of quetiapine for the fourth week was 276.1 177.2mg/day (range 50-800). Higher quetiapine dosages were administered for patients with functional psychoses compared to an analogous group with organic mental disorders. The most common adverse effects were somnolence (30.0%), lower-limb weakness (28.0%) and dizziness (27.0%). Body weight and fasting triglyceride were significantly elevated after quetiapine treatment (2.2% and 8.9% from baseline, respectively). Based on the results of this study, it appears that quetiapine is an efficacious and safe treatment for geriatric inpatients with psychosis, however, there is a wide dosing range and optimal dosage is diagnosis-dependent.
Aged↗
Loudness dependence of the auditory evoked potential and response to antidepressants in Chinese patients with major depression.
OBJECTIVE: To investigate the loudness dependence of the auditory evoked potential (LDAEP) in predicting response to treatment for major depression. METHODS: One hundred patients of Chinese ethnicity with major depression were divided into 2 groups, having strong or weak pretreatment LDAEP; the cutoff was the median of the LDAEP slope (for amplitude as a function of intensity). There were no between-group differences before treatment in terms of score on the Hamilton Depression Rating Scale (HDRS), age or sex distribution. The LDAEP for 4 intensity levels (60, 70, 80 and 90 dB) was recorded before treatment. Each patient then received fluoxetine 20 mg per day for 4 weeks. The response to treatment was evaluated by means of the HDRS. RESULTS: At week 4, the HDRS score had declined by 44.3; for the group with strong LDAEP and by 34.4% for the group with weak LDAEP (t for mean difference = 2.584, p = 0.011). CONCLUSION: Strong pretreatment LDAEP predicted a favourable response to treatment with a selective serotonin reuptake inhibitor in patients with major depression.
Acoustic Stimulation↗
Association study of A2a adenosine receptor genetic polymorphism in panic disorder.
The adenosine A2a receptor (A2aAR) is thought to be implicated in the pathogenesis of panic disorder because caffeine, a potent antagonist for A2aAR, can precipitate panic attacks, and because disruption of the A2aAR gene increased anxiety-behaviors in mice. Recent studies demonstrated that the A2aAR 1976T > C genetic variant confers susceptibility to panic disorder though not by all studies. The present study tested the hypothesis that the A2aAR 1976T > C genetic variant confers susceptibility to panic disorder using a Chinese population of 104 panic disorder patients and 192 normal controls. We also tested whether the A2aAR 1976T > C polymorphism relates to the age of onset or subtype of panic disorders. Neither the distribution of the A2aAR 1976T > C genotypes (P = 0.296) or alleles (P = 0.864), nor the age of onset (P = 0.719) were significantly different among genotype groups. Furthermore, no association was demonstrated between this A2aAR polymorphism and either mitral-valve prolapse or agoraphobia in panic-disorder patients. These findings suggested that it is unlikely that the A2aAR 1976T > C polymorphism plays a major role in panic disorder pathogenesis in the Chinese population. The positive association between this polymorphism and panic disorder found in western population but not in Asian population suggests that this association could be ethnicity-dependent. The 1976C > T polymorphism may be in linkage disequilibrium with a functional variant that affects panic disorder, and the extent of this linkage disequilibrium is not similar for all ethnic populations.
Adult↗
Effect of age and global function score on schizophrenic p300 characteristics.
The relationship between function level and P300 has long been ignored and awaits clarification. Further, previous Western studies have discussed the trait/state markers of schizophrenic P300; this has not been assessed for an analogous Chinese population. P300 was recorded and compared in 153 schizophrenic patients and 101 normal controls. Reduced and delayed P300 was demonstrated for the schizophrenic group. Regression analysis was performed to determine the factors contributing to P300 amplitude and latency variation. Global Assessment of Functioning score and age had a significant influence on P300 latency prolongation. Amplitude decrement was not affected by age, duration of illness, education, psychotic status, antipsychotic dosage, or function level. Our results were grossly concordant with analogous Western reports and provided evidence that function level is an important variable contributing to P300 latency change in Chinese schizophrenics. Besides, the effect of gender on P300 amplitude was noted in normal population.
Adult↗
Association analysis for the muscarinic M1 receptor genetic polymorphisms and Alzheimer's disease.
In the ongoing search to reveal the pathophysiology of Alzheimer's disease (AD), the cholinergic system is important due to its role in cognitive function and its significance with respect to the results of postmortem pathology and animal model studies. For this investigation, we tested the hypothesis that the allelic variant (C267A) of the cholinergic receptor muscarinic 1 (CHRM1) confers susceptibility to AD or is related to its age of onset, in a sample population of 232 AD patients and 169 normal controls. The distribution of the CHRM1 genotypes (p = 0.919) and alleles (p = 0.327) did not differ significantly comparing AD patients and controls, even after stratification according to apolipoprotein E genotype. The onset age was not significantly different comparing the CHRM1 genotype groups. Our negative findings suggest that it is unlikely that the CHRM1 C267A polymorphism plays a substantial role in conferring susceptibility to AD. We propose that other genetic variations of CHRM1, relating either to AD or to the therapeutic response for AD, may need further investigation.
Aged↗
X-box binding protein 1 (XBP1) C--116G polymorphisms in bipolar disorders and age of onset.
X-box binding protein 1 (XBP1), a critical gene in the endoplasmic reticulum stress response, is located on chromosome 22q12, which has been linked with bipolar disorders in several studies. Recently, associations have been reported between a polymorphism (-116C --> G) in the promoter region of XBP1, and bipolar disorders in both case-control study and family-based association study, however, this finding is not yet confirmed by other research using independent sample populations. To replicate this finding and determine the association between onset age of bipolar disorders and the XBP1 C--116G polymorphism, we investigated the prevalence of this polymorphism in a Chinese population (153 bipolar disorder patients and 174 controls). We were unable, however, to demonstrate a significant association between the C--116G polymorphism and bipolar disorders (P = 0.674 for genotype and P = 0.436 for allele frequency) or age at onset (P = 0.563). Further, no association was demonstrated between this polymorphism and family history in bipolar disorder patients. These negative findings suggest that the XBP1 C--116G polymorphism does not play a major role in the pathogenesis of bipolar disorders in Chinese populations.
Adult↗
Association study of PICK1 rs3952 polymorphism and schizophrenia.
Protein interacting with C-kinase-1 (PICKl) plays an important role in the targeting and clustering of neuronal receptors and amine transporters. The PICK1 gene may play a role in conferring susceptibility to schizophrenia as it has been mapped to chromosome 22q13.1, a region thought to contain a gene for schizophrenia. We tested the hypothesis that an allelic variant of the PICK1 gene was associated with a diagnosis of schizophrenia. The PICK1 rs3952 polymorphism was genotyped in 225 schizophrenia and 260 controls. Results demonstrated that the PICK1 rs3952 genotype and allele distribution was significantly different between the two groups. The positive association suggests that the PICK1 gene may play a role in the pathogenesis of schizophrenia.
Adult↗
Case-control and family-based association studies between the neuregulin 1 (Arg38Gln) polymorphism and schizophrenia.
Genetic variations in the neuregulin 1 (NRG1), a critical gene in neuronal development, have been reported to be associated with schizophrenia in several reports. Association has been reported between a non-synonymous NRG1 polymorphism (Arg38Gln) and schizophrenia in a Chinese family-based association study; however, this finding is not yet confirmed by other research findings analyzed using independent sample. To replicate this finding and assess the association between age at onset of schizophrenia and the NRG1 Arg38Gln polymorphism, we investigated the prevalence of this polymorphism in a Chinese population (228 schizophrenic disorder patients and 269 controls). We were unable, however, to demonstrate a significant association between the NRG1 Arg38Gln polymorphism and schizophrenia (P = 0.869 for genotype and P = 0.597 for allelic frequencies) or age at onset (P = 0.940). Our family-based association study (15 schizophrenic bios and 221 schizophrenic trios) demonstrated 38Gln was transmitted in excess by the parent to the affected offspring (P = 0.052). However, this result contrasts with a previous finding in Chinese that 38Arg was transmitted in excess by the parent to the affected offspring. On the basis of the contrast between the findings of other study and our family-based study and the negative findings of our case-control association study, we conclude that NRG1 Arg38Gln polymorphism is not likely to play a major role in the pathogenesis of schizophrenia in Chinese populations.
Adult↗
Expression of c-Fos-like immunoreactivity in the brain of mice with learned helplessness.
The learned helplessness (LH) developed after repeat inescapable stress is a well validated animal model of human major depression and is not species specific. c-Fos, the protein product of the protooncogene c-fos, is expressed in neurons under a variety of stressors and could reflect the regional neuronal activation. Using the LH paradigm in mice, we examined c-Fos expression in several brain regions related to stress response or major depression. The LH mice showed significantly lower c-Fos-like immunoreactivity (FLI) in the hippocampus dentate gyrus and the lateral septal nucleus, and higher FLI in the hypothalamic paraventricular nucleus compared with the naive mice. Our finding in the mice LH model supported previous studies in rats showing that the lateral septal nucleus and the hypothalamic paraventricular nucleus are important in LH behaviors. We further demonstrated that hippocampus dentate gyrus, a region important for learning and major depression, may also be involved in the LH behaviors. These related brain regions could provide a basis for further exploration of the molecular mechanisms underlying LH behaviors.
Animals↗
Association study of the human partially duplicated alpha7 nicotinic acetylcholine receptor genetic variant with bipolar disorder.
The human alpha7 nicotinic acetylcholine receptor subunit (CHRNA7) gene cluster maps to the chromosome 15q13-q14 and is implicated as a candidate gene for bipolar disorder (BPD) by genetic linkage study. A -2 bp deletion polymorphism has been found in the duplicated CHRNA7 (CHRNA7-like) gene, which is located 1 Mb apart from CHRNA7. We tested the hypothesis that the allelic variant, 2 bp deletion (-2 bp), confers susceptibility to BPD or is related to the psychotic features of BPD. We genotyped the -2 bp polymorphism in 77 patients with BPD and 135 normal controls. The distribution of -2 bp genotypes showed a moderately significant difference between the BPD patients and controls (P=0.044). Three BPD patients carried more than two alleles of the -2 bp deletion genotype, while this genotype was not found in the control group. The -2 bp polymorphism was not associated with age of onset or psychotic features in BPD patients. The results of this study suggest that the -2 bp polymorphism or a nearby polymorphism may play a role in the pathogenesis of BPD. Determination of the functional impact of the -2 bp variant in the nervous system and, in particular, the effect of harboring more than two alleles of the -2 bp deletion needs further exploration.
Adult↗
Personality traits in young female apolipoprotein E (apoE) epsilon4 and non-epsilon4 carriers.
Apolipoprotein E (apoE) is the major brain apolipoprotein, and is related to the functional integrity of the central nervous system. It has been reported that the apoE genetic polymorphism is associated with several components of childhood and adolescent temperament. To study the effect of the presence of the apoE epsilon4 allele on adult personality factors, tridimensional personality questionnaire (TPQ) scores were compared for epsilon4 and non-epsilon4 carriers in a sample population consisting of 135 young females. No significant differences were demonstrated comparing the scores for the two groups. Our findings suggest that the investigated apoE polymorphism does not play a major role in personality trait factors, as assessed by TPQ.
Adult↗