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1.
J Psychiatr Res ; 123: 119-127, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32065947

RESUMO

BACKGROUND: The molecular mechanisms underlying schizophrenia remain largely unclear, and we recently identified multiple proteins significantly altered in the postmortem prefrontal cortex (PFC) of schizophrenia patients amongst which aldehyde dehydrogenase 4 family member A1 (ALDH4A1) was especially elevated. In this study, we aimed to investigate the expression of ALDH4A1 in the PFC and superior temporal gyrus (STG) and to elucidate functional correlations between schizophrenia risk alleles and molecular expression profiles in the postmortem brains of patients with schizophrenia. METHODS: The levels of ALDH4A1 protein expression in the PFC and STG in postmortem brains from 24 patients with schizophrenia, 8 patients with bipolar disorder, and 32 controls were assessed using enzyme-linked immunosorbent assay. Moreover, we explored the associations between ALDH4A1 expression and genetic variants in enzymes associated with proline metabolism, including ALDH4A1 (schizophrenia [n = 22], bipolar disorder [n = 6], controls [n = 11]). RESULTS: ALDH4A1 levels were significantly elevated in both the PFC and STG in patients with schizophrenia and tended to elevate in patients with bipolar disorder. Furthermore, ALDH4A1 expression levels in the PFC were significantly associated with the following three single-nucleotide polymorphisms: rs10882639, rs33823, rs153508. We also found partial coexpression of ALDH4A1 in mitochondria in a subset of putative astrocytes of postmortem brain. LIMITATIONS: Our study population was relatively small, particularly for a genetic study. CONCLUSION: These findings indicate that altered expression of ALDH4A1 may reflect the potential molecular mechanisms underlying the pathogenesis of schizophrenia and bipolar disorder, and may aid in the development of novel drug therapies.

2.
J Atheroscler Thromb ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32009075

RESUMO

AIM: The Fukushima Daiichi Nuclear Power Plant accident dramatically changed the lifestyle of residents who lived near the plant. We evaluated the association of metabolic syndrome (MetS) with specific lifestyle- and disaster-related factors in residents following the accident. METHODS: This cross-sectional study included 20,920 residents who underwent both the Comprehensive Health Check and the Mental Health and Lifestyle Survey from June 2011 to March 2012. Associations between MetS and lifestyle- and disaster-related factors, including psychological distress (post-traumatic stress disorder [PTSD]), were estimated using logistic regression analysis, adjusted for demographic and lifestyle factors, in 2019. RESULTS: MetS was present in 30.4% of men and 11.5% of women. There were significant differences in smoking, drinking status, and PTSD prevalence between subjects with and without MetS. Multivariable logistic regression analysis showed that age, quitting smoking, light to moderate drinking, and low physical activity were significantly associated with MetS. Moreover, PTSD was also significantly associated with MetS in women. CONCLUSIONS: Lifestyle- and disaster-related factors, including PTSD, were associated with MetS among subjects who lived near the Fukushima Daiichi Nuclear Power Plant accident.

3.
J Am Heart Assoc ; 9(3): e014564, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31973606

RESUMO

Background The prevalence of depression and/or anxiety disorders is reported to be higher in patients with heart failure (HF) than in the general population, and patients with HF also have coexisting cognitive problems. Recently, the development of near-infrared spectroscopy (NIRS) has enabled noninvasive measurements of regional cerebral blood volume and brain activity, in terms of cerebral oxyhemoglobin in the cerebral cortex, with a high time resolution. The aim of the current study was to determine the associations between frontal brain activity and depressive symptoms, anxiety status, and cognitive function in patients with HF. Methods and Results We measured and compared frontal brain activity determined by NIRS during a verbal fluency task in patients with HF (n=35) and control subjects (n=28). The Center for Epidemiologic Studies Depression Scale for assessment of depressive symptoms, State-Trait Anxiety Inventory for assessment of anxiety status, Mini-Mental State Examination for assessment of cognitive function, and NIRS were simultaneously conducted. NIRS showed that frontal brain activity was significantly lower in the HF group than in the control subjects (28.5 versus 88.0 mM·mm; P<0.001). Next, we examined the associations between frontal brain activity and the findings of Center for Epidemiologic Studies Depression Scale, State-Trait Anxiety Inventory, Mini-Mental State Examination, and verbal fluency task. There were significant correlations between frontal brain activity and State-Trait Anxiety Inventory (R=-0.228, P=0.046), Mini-Mental State Examination (R=0.414, P=0.017), and verbal fluency task (R=0.338, P=0.007), but not with Center for Epidemiologic Studies Depression Scale (R=-0.160, P=0.233). Conclusions Frontal brain activity assessed by NIRS is reduced and is associated with high anxiety status and low cognitive function in patients with HF.

4.
Biol Psychol ; 151: 107848, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31981583

RESUMO

Both stream segregation and temporal integration are considered important for auditory scene analysis in the brain. Several previous studies have indicated that stream segregation may precede temporal integration when both processes are required. In the present study, we utilized mismatch negativity (MMN)-which reflects automatic change detection-to systematically estimate the threshold of the frequency difference at which stream segregation occurs prior to temporal integration when these functions occur together during a state of inattention. Electroencephalography (EEG) data were recorded from 22 healthy Japanese men presented with six blocks of alternating high pure tones (high tones) and low pure tones (low tones). Only high tones were omitted with 5 % probability in all blocks. Our results indicated that stream segregation should cancel temporal integration of close sounds, as indicated by omission-MMN elicitation, when the frequency difference is 1000 Hz or larger.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31994282

RESUMO

AIM: Mismatch negativity (MMN) deficit is one of the most robust and replicable findings in schizophrenia, and primarily reflects deficient functioning of the N-methyl-D-aspartate (NMDA) receptor system. Although the dopamine receptor is known not to modulate MMN over the short term, it is unclear whether the dopamine system affects MMN in the long term. METHODS: We explored correlations between MMN and levels of plasma dopamine and serotonin metabolites in 18 patients with schizophrenia psychiatrically evaluated with the Positive and Negative Syndrome Scale (PANSS). RESULTS: A significant negative correlation exists between MMN amplitude and plasma levels of dopamine metabolites. Plasma serotonin metabolite levels were not correlated with MMN. The PANSS total score and Negative score also showed negative correlations with MMN amplitude. CONCLUSION: The usual strong therapeutic blockade of dopamine receptors applied in cases of schizophrenia may reduce MMN over the long term.

6.
Nutrients ; 12(1)2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31906499

RESUMO

: Cardiometabolic risks were increasing in Fukushima residents after the Great East Japan Earthquake. We examined the association between dietary patterns and cardiometabolic risks in those aged ≥16 years. Dietary patterns were derived by principal component analysis for participants who underwent at least one diet assessment using a short-form food frequency questionnaire during 2011-2013 and a health checkup in 2014 and 2015 (n = 15,409 and 14,999, respectively). In 2014, the adjusted prevalence ratio (PR) and 95% confidence interval (CI) in the highest versus lowest quartile of accumulative mean scores were 0.97 (0.96-0.99) for overweight/obesity, 0.96 (0.95-0.97) for total cholesterol (TC) ≥220 mg/dL, 0.96 (0.95-0.98) for low-density lipoprotein cholesterol (LDL-C) ≥140 mg/dL, and 0.97 (0.96-0.99) for triglycerides ≥150 mg/dL for a vegetable diet and 1.03 (1.01-1.04) for TC ≥220 mg/dL and 1.02 (1.01-1.04) for LDL-C ≥140 mg/dL for a juice/milk diet. In 2015, we found consistently significant associations for the vegetable and juice/milk diets, and the PR and 95% CI were 0.99 (0.98-1.00) for HDL-C <40 mg/dL for a meat diet. The continuous promotion of the vegetable pattern diet is necessary to reduce cardiometabolic risks, particularly dyslipidemia, in Japan.

7.
Eur J Neurosci ; 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31894634

RESUMO

The human brain can automatically detect sound changes. Previous studies have reported that rare sounds presented within a sequence of repetitive sounds elicit the mismatch negativity (MMN) in the absence of attention in the latency range of 100-250 ms. On the other hand, a previous study discovered that occasional changes in sound location enhance the middle latency response (MLR) elicited in the latency range of 10-50 ms. Several studies have reported an increase in the amplitude of the MLR within the frame of oddball paradigms such as frequency and location changes. However, few studies have been conducted on paradigms employing a duration change. The purpose of the present study was to examine whether the peak amplitudes of the MLR components are enhanced by a change in duration. Twenty healthy Japanese men (age: 23.9 ± 2.9 years) participated in the present study. We used an oddball paradigm that contained standard stimuli with a duration of 10 ms and deviant stimuli with a duration of 5 ms. The peak amplitudes of the MLR for the deviant stimuli were then compared with those for the standard stimuli. No changes were observed in the peak amplitude of the MLR resulting from a duration change, whereas a definite MMN was elicited. The amplitude of the MLR was increased within the frame of oddball paradigms such as frequency and location changes. By contrast, the amplitude of the MLR was not changed within the duration change oddball paradigm that elicited the MMN.

8.
Medicine (Baltimore) ; 99(1): e18486, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895781

RESUMO

We have been examining the Comprehensive Health Check of the Fukushima Health Management Survey of residents of 13 municipalities who were forced by the government to evacuate due to the 2011 Great East Japan Earthquake (GEJE). Our findings showed that evacuation is a risk factor for polycythemia and suggested that experiencing an unprecedented disaster and exposure to chronic stress due to evacuation might be a cause of polycythemia.We analyzed the relationship between the prevalence of polycythemia and the following factors observed in the Mental Health and Lifestyle Survey in an observational study with a cross-sectional design: traumatic symptoms, depression status, socioeconomic factors such as residential environment, and working situation after the GEJE. Target population of the survey included men and women who were at least 15 years of age and who lived in the evacuation zones specified by the government. Participants analyzed consisted of 29,474 persons (12,379 men and 16,888 women) who had participated in both the 2011 Comprehensive Health Check and Mental Health and Lifestyle Survey from June 2011 through March 2012.The prevalence of polycythemia was not associated with mental states associated with traumatic symptoms (Post-Traumatic Stress Disorder Checklist Scale ≥ 44) and depression status (Kessler 6-item Scale ≥ 13). Furthermore, multivariate analysis showed that there was a tendency for males to develop polycythemia, with characteristics such as being aged 65 years and older, highly educated, obese (body mass index ≥ 25), hypertensive, diabetic, having liver dysfunction, and a smoker being significantly related to the prevalence of polycythemia.Our findings conclusively demonstrated that polycythemia was not significantly related to psychological factors, but was significantly related to the onset of lifestyle-related disease after the GEJE.


Assuntos
Acidente Nuclear de Fukushima , Policitemia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Causalidade , Comorbidade , Terremotos , Feminino , Humanos , Japão/epidemiologia , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Policitemia/etiologia , Policitemia/psicologia , Prevalência , Tsunamis , Adulto Jovem
9.
J Affect Disord ; 260: 432-439, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31539677

RESUMO

BACKGROUND: The present study examined the data from the Fukushima Health Management Survey conducted after the Great East Japan Earthquake to identify disaster-related factors affecting the mental health status of adolescents following the disaster and obtained basic data necessary in providing mental healthcare. METHODS: The study included 2808 adolescents aged 15-19 years (male: 1327; female: 1481) who completed the 2011 edition of the registered questionnaire. The Kessler Psychological Distress Scale scores, age, sex, health status, sleep satisfaction level, Great East Japan Earthquake experience, experience of losing a loved one, change in employment status, change in residence, and awareness of the impact of radiation on health were examined. RESULTS: Psychological distress was significantly correlated with sex, health status, sleep satisfaction of, experience of losing a loved one, change in employment status, extreme anxiety regarding the acute health impact of radiation, and extreme anxiety regarding the impact of radiation on health in adolescents and the next generation. LIMITATIONS: The present study is limited because of its cross-sectional design, due to which, the causal relationship between each factor and psychological distress could not be clarified. CONCLUSIONS: The results of the present study suggest that appropriate mental healthcare should be administered immediately following an earthquake to adolescents who have lost a loved one and experienced anxiety regarding the health impact of radiation following a nuclear accident.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31788981

RESUMO

AIMS: The brain function that detects deviations in the acoustic environment can be evaluated with mismatch negativity (MMN). MMN to sound duration deviance has recently drawn attention as a biomarker for schizophrenia. Nonhuman animals, including rats, also exhibit MMN-like potentials. Therefore, MMN research in nonhuman animals can help to clarify the neural mechanisms underlying MMN production. However, results from preclinical MMN studies on duration deviance have been conflicting. We investigated the effect of sound frequency on MMN-like potentials to duration deviance in rats. METHODS: Event-related potentials were recorded from an electrode placed on the primary auditory cortex of free-moving rats using an oddball paradigm consisting of 50-ms duration tones (standards) and 150-ms duration tones (deviants) at a 500-ms stimulus onset asynchrony. The sound frequency was set to three conditions: 3, 12, and 50 kHz. RESULTS: MMN-like potentials that depended on the short-term stimulus history of background regularity were only observed in the 12-kHz tone frequency condition. CONCLUSIONS: MMN-like potentials to duration deviance are subject to tone frequency of the oddball paradigm in rats, suggesting that rats have distinct sound duration recognition ability.

11.
EMBO Mol Med ; 11(12): e10695, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31657521

RESUMO

Mice with the C3H background show greater behavioral propensity for schizophrenia, including lower prepulse inhibition (PPI), than C57BL/6 (B6) mice. To characterize as-yet-unknown pathophysiologies of schizophrenia, we undertook proteomics analysis of the brain in these strains, and detected elevated levels of Mpst, a hydrogen sulfide (H2 S)/polysulfide-producing enzyme, and greater sulfide deposition in C3H than B6 mice. Mpst-deficient mice exhibited improved PPI with reduced storage sulfide levels, while Mpst-transgenic (Tg) mice showed deteriorated PPI, suggesting that "sulfide stress" may be linked to PPI impairment. Analysis of human samples demonstrated that the H2 S/polysulfides production system is upregulated in schizophrenia. Mechanistically, the Mpst-Tg brain revealed dampened energy metabolism, while maternal immune activation model mice showed upregulation of genes for H2 S/polysulfides production along with typical antioxidative genes, partly via epigenetic modifications. These results suggest that inflammatory/oxidative insults in early brain development result in upregulated H2 S/polysulfides production as an antioxidative response, which in turn cause deficits in bioenergetic processes. Collectively, this study presents a novel aspect of the neurodevelopmental theory for schizophrenia, unraveling a role of excess H2 S/polysulfides production.

12.
Sci Rep ; 9(1): 14877, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619735

RESUMO

Dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32) integrates dopaminergic signaling into that of several other neurotransmitters. Calcineurin (CaN), located downstream of dopaminergic pathways, inactivates DARPP-32 by dephosphorylation. Despite several studies have examined their expression levels of gene and protein in postmortem patients' brains, they rendered inconsistent results. In this study, protein expression levels of DARPP-32 and CaN were measured by enzyme-linked immunosorbent assay (ELISA) in the prefrontal cortex (PFC), and nucleus accumbens (NAc) of 49 postmortem samples from subjects with schizophrenia, bipolar disorder, and normal controls. We also examined the association between this expression and genetic variants of 8 dopaminergic system-associated molecules for 55 SNPs in the same postmortem samples. In the PFC of patients with schizophrenia, levels of DARPP-32 were significantly decreased, while those of CaN tended to increase. In the NAc, both of DARPP-32 and CaN showed no significant alternations in patients with schizophrenia or bipolar disorder. Further analysis of the correlation of DARPP-32 and CaN expressions, we found that positive correlations in controls and schizophrenia in PFC, and schizophrenia in NAc. In PFC, the expression ratio of DARPP-32/CaN were significantly lower in schizophrenia than controls. We also found that several of the aforementioned SNPs may predict protein expression, one of which was confirmed in a second independent sample set. This differential expression of DARPP-32 and CaN may reflect potential molecular mechanisms underlying the pathogenesis of schizophrenia and bipolar disorder, or differences between these two major psychiatric diseases.

13.
Fukushima J Med Sci ; 65(2): 68-69, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474663

RESUMO

This is based on a survey of two-year-old but not three-year-old cohorts. Therefore, we cannot state anything about the incidence of autism spectrum disorder (ASD) in over three-years-old children. We submit corrections in the following errata, because the original sentences might mislead the readers without evidence from three-year-old children. Also, we would like to exclude the phrase of "low-dose radiation" from the sections of Key word, Abstract, and Conclusion, because this study did not cover its influence.Author Shuntaro ItagakiAugust 05, 2019.

14.
Tohoku J Exp Med ; 248(4): 239-252, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31406089

RESUMO

Many studies have consistently reported the bidirectional relationship between problem drinking and psychological distress following a disaster, but the risk factors of problem drinking following a disaster remain unclear. In this study, we therefore aimed to explore the risk factors associated with the incidence of problem drinking among evacuees after the Great East Japan Earthquake of March 11, 2011. We used the data for evacuees of the Fukushima Daiichi nuclear power plant accident, obtained from the Mental Health and Lifestyle Survey. A total of 12,490 individuals from 13 municipalities, which included the evacuation order areas after the accident, completed surveys between 2012 and 2013. The CAGE (Cutting down, Annoyed by criticism, Guilty feeling, and Eye-opener) questionnaire was used to screen the participants for alcohol dependence, and a score ≥ 2 indicated problem drinking. Logistic regression models were applied to investigate the possible predictors of problem drinking. The results showed that insufficient sleep and heavy drinking (≥ 4 drinks per day) were significant risk factors for the incidence of problem drinking in both men and women. Additional risk factors included family financial issues due to the disaster and trauma symptoms among men and a diagnosed history of mental illness among women. Other remaining variables were not significantly associated with problem drinking. The present study is the first to identify the risk factors for problem drinking following a compound disaster. Our findings could be used to develop a primary intervention program to improve evacuees' health and lives following a disaster.


Assuntos
Alcoolismo/epidemiologia , Terremotos , Acidente Nuclear de Fukushima , Inquéritos Epidemiológicos , Adulto , Idoso , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Fatores de Risco , Inquéritos e Questionários
15.
Int Med Case Rep J ; 12: 185-188, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31297000

RESUMO

Objectives: Although clozapine is considered the only effective pharmacological option for patients with treatment-resistant schizophrenia (TRS), around 30-40% of patients show clozapine resistance. Modified electroconvulsive therapy augmentation is reportedly clinically effective for clozapine-resistant schizophrenia, but few case reports have described the efficacy of combining clozapine and continuous/maintenance ECT for patients with TRS. Methods: We present the case of a young patient with TRS who was treated using combination therapy with clozapine and maintenance ECT (m-ECT). Results: The patient achieved drastic improvement under combination therapy with clozapine and m-ECT. Total Positive and Negative Syndrome Scale (PANSS) score fell markedly by 36 (from 108 to 72) using the combination of clozapine and m-ECT. Behaviors not reflected directly by PANSS score also improved. For example, the problem of being unable to take oral drugs stably because of delusions of poisoning was resolved. Furthermore, the patient maintained improvement under m-ECT, and long-term homestays became possible. Conclusion: Combination therapy with clozapine and m-ECT proved greatly effective in this case. Further clinical trials of this combination therapy for TRS are needed to confirm the effectiveness. Further studies are also expected to examine effective periods for this therapy.

16.
EBioMedicine ; 45: 432-446, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31255657

RESUMO

BACKGROUND: Betaine is known to act against various biological stresses and its levels were reported to be decreased in schizophrenia patients. We aimed to test the role of betaine in schizophrenia pathophysiology, and to evaluate its potential as a novel psychotherapeutic. METHODS: Using Chdh (a gene for betaine synthesis)-deficient mice and betaine-supplemented inbred mice, we assessed the role of betaine in psychiatric pathophysiology, and its potential as a novel psychotherapeutic, by leveraging metabolomics, behavioral-, transcriptomics and DNA methylation analyses. FINDINGS: The Chdh-deficient mice revealed remnants of psychiatric behaviors along with schizophrenia-related molecular perturbations in the brain. Betaine supplementation elicited genetic background-dependent improvement in cognitive performance, and suppressed methamphetamine (MAP)-induced behavioral sensitization. Furthermore, betaine rectified the altered antioxidative and proinflammatory responses induced by MAP and in vitro phencyclidine (PCP) treatments. Betaine also showed a prophylactic effect on behavioral abnormality induced by PCP. Notably, betaine levels were decreased in the postmortem brains from schizophrenia, and a coexisting elevated carbonyl stress, a form of oxidative stress, demarcated a subset of schizophrenia with "betaine deficit-oxidative stress pathology". We revealed the decrease of betaine levels in glyoxylase 1 (GLO1)-deficient hiPSCs, which shows elevated carbonyl stress, and the efficacy of betaine in alleviating it, thus supporting a causal link between betaine and oxidative stress conditions. Furthermore, a CHDH variant, rs35518479, was identified as a cis-expression quantitative trait locus (QTL) for CHDH expression in postmortem brains from schizophrenia, allowing genotype-based stratification of schizophrenia patients for betaine efficacy. INTERPRETATION: The present study revealed the role of betaine in psychiatric pathophysiology and underscores the potential benefit of betaine in a subset of schizophrenia. FUND: This study was supported by the Strategic Research Program for Brain Sciences from AMED (Japan Agency for Medical Research and Development) under Grant Numbers JP18dm0107083 and JP19dm0107083 (TY), JP18dm0107129 (MM), JP18dm0107086 (YK), JP18dm0107107 (HY), JP18dm0107104 (AK) and JP19dm0107119 (KH), by the Grant-in-Aid for Scientific Research on Innovative Areas from the MEXT under Grant Numbers JP18H05435 (TY), JP18H05433 (AH.-T), JP18H05428 (AH.-T and TY), and JP16H06277 (HY), and by JSPS KAKENHI under Grant Number JP17H01574 (TY). In addition, this study was supported by the Collaborative Research Project of Brain Research Institute, Niigata University under Grant Numbers 2018-2809 (YK) and RIKEN Epigenetics Presidential Fund (100214-201801063606-340120) (TY).


Assuntos
Betaína/farmacologia , Colina Desidrogenase/genética , Psicotrópicos/farmacologia , Esquizofrenia/tratamento farmacológico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Metilação de DNA/efeitos dos fármacos , Suplementos Nutricionais , Modelos Animais de Doenças , Genótipo , Humanos , Japão , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Metanfetamina/farmacologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Locos de Características Quantitativas , Esquizofrenia/genética , Esquizofrenia/fisiopatologia
17.
Hum Psychopharmacol ; 34(3): e2696, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31044463

RESUMO

OBJECTIVE: This randomized controlled study evaluated the efficacy of low-dose (LD) and high-dose (HD) aripiprazole augmentation in major depressive disorder. Additionally, we examined the relationship between clinical response and changes in plasma homovanillic acid (pHVA) levels during aripiprazole augmentation. METHODS: Thirty-one patients with inadequate response to antidepressants were randomized to receive adjunctive treatment with LD (3 mg/day, n = 17) or HD (up to 12 mg/day, n = 14) aripiprazole for 6 weeks. We evaluated the Montgomery-Åsberg Depression Rating Scale (MADRS) and measured pHVA at baseline, Week 2, and end point. RESULTS: Both LD and HD aripiprazole significantly decreased MADRS score after 6 weeks, and the response rate was higher in HD aripiprazole group at end point. HD aripiprazole significantly decreased MADRS score at Week 2 compared with LD aripiprazole (p = .015). There was a significant difference in changes in pHVA between responders and nonresponders, showing pHVA decreased significantly in responders at Week 2 (p = .044). CONCLUSIONS: Increasing aripiprazole from the early period appeared useful for immediate response, although caution is needed when increasing the dose >6 mg/day. pHVA may be a possible indicator of the response to aripiprazole augmentation. Caution is needed in interpreting these findings because of the small sample size.

18.
Sci Rep ; 9(1): 7503, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31097747

RESUMO

Perinatal exposure to epidermal growth factor (EGF) induces various cognitive and behavioral abnormalities after maturation in non-human animals, and is used for animal models of schizophrenia. Patients with schizophrenia often display a reduction of mismatch negativity (MMN), which is a stimulus-change specific event-related brain potential. Do the EGF model animals also exhibit the MMN reduction as schizophrenic patients do? This study addressed this question to verify the pathophysiological validity of this model. Neonatal rats received repeated administration of EGF or saline and were grown until adulthood. Employing the odd-ball paradigm of distinct tone pitches, tone-evoked electroencephalogram (EEG) components were recorded from electrodes on the auditory and frontal cortices of awake rats, referencing an electrode on the frontal sinus. The amplitude of the MMN-like potential was significantly reduced in EGF-treated rats compared with saline-injected control rats. The wavelet analysis of the EEG during a near period of tone stimulation revealed that synchronization of EEG activity, especially with beta and gamma bands, was reduced in EGF-treated rats. Results suggest that animals exposed to EGF during a perinatal period serve as a promising neurodevelopmental model of schizophrenia.

19.
Front Psychiatry ; 10: 283, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31130880

RESUMO

This study examined parental recognition of bullying victimization and associated factors among evacuated children after the 2011 Fukushima Daiichi Nuclear Power Plant accident, using a 3-year follow-up data (wave 1: January 2012; wave 2: January 2013; wave 3: February 2014). The sample included the caregivers of 2,616 children in the first-sixth grades of elementary school, who lived in one of the 13 municipalities that were the target areas of the Mental Health and Lifestyle Survey, conducted as part of the Fukushima Mental Health Management Survey. Across 3 years, around 80% of caregivers responded "not true," 15% responded "somewhat true," and 5% responded "certainly true" in response to a question about bullying victimization of their children. Being male was significantly associated with the parental recognition of bullying victimization at wave 1 and wave 3. At wave 1, experiencing the nuclear plant explosion was significantly associated with parental recognition of bullying victimization. Moreover, age at wave 3 was negatively associated with parental recognition of bullying victimization. Our findings will be helpful for establishing community- and school-based mental health care for children, parents, and teachers.

20.
Psychiatry Clin Neurosci ; 73(9): 566-573, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31102310

RESUMO

AIM: Tissue pH and RNA integrity are crucial quality-control indicators of human post-mortem brain tissues in the identification of the pathogeneses of neuropsychiatric disorders, but pH has not been measured as often due to limitations in the amount of tissue available. This study was designed to develop and validate a protocol for tissue pH evaluation using a minimal amount of human post-mortem tissues. METHODS: A procedure that included a proper ratio of brain tissue weight to water for homogenization and the duration of homogenization was designed based on preliminary experiments using mouse brain tissues. The minimal (10 mg) and typical (100 mg) amounts of post-mortem brain tissue from 52 subjects were homogenized in 5 volumes (50 µL/10 mg tissue) and 10 volumes (1000 µL/100 mg tissue) of nuclease-free water and subjected to pH measurements using an InLab Ultra micro pH electrode. RESULTS: The pH values based on the new protocol using a minimal amount of tissue significantly correlated with measurements of the standard protocol (r2 = 0.86). The correlation coefficients of the pH values between gray and white matter of the same brain region, and the values between different brain regions were 0.73 and 0.54, respectively. CONCLUSION: The proposed protocol used one-tenth of the tissue amount of current standard protocol and enabled us to evaluate the exact quality of post-mortem brain tissue subjected to subsequent analyses. The application of this protocol may improve the detection of biological phenomena of interest in post-mortem brain studies by diminishing confounding factors.

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