Variability of 128 schizophrenia-associated gene variants across distinct ethnic populations.

Schizophrenia is a common polygenetic disease affecting 0.5-1% of individuals across distinct ethnic populations. PGC-II, the largest genome-wide association study investigating genetic risk factors for schizophrenia, previously identified 128 independent schizophrenia-associated genetic variants (GVs). The current study examined the genetic variability of GVs across ethnic populations. To assess the genetic variability across populations, the 'variability indices' (VIs) of the 128 schizophrenia-associated GVs were calculated. We used 2504 genomes from the 1000 Genomes Project taken from 26 worldwide healthy samples comprising five major ethnicities: East Asian (EAS: n=504), European (EUR: n=503), African (AFR: n=661), American (AMR: n=347) and South Asian (SAS: n=489). The GV with the lowest variability was rs36068923 (VI=1.07). The minor allele frequencies (MAFs) were 0.189, 0.192, 0.256, 0.183 and 0.194 for EAS, EUR, AFR, AMR and SAS, respectively. The GV with the highest variability was rs7432375 (VI=9.46). The MAFs were 0.791, 0.435, 0.041, 0.594 and 0.508 for EAS, EUR, AFR, AMR and SAS, respectively. When we focused on the EAS and EUR population, the allele frequencies of 86 GVs significantly differed between the EAS and EUR (P<3.91 × 10-4). The GV with the highest variability was rs4330281 (P=1.55 × 10-138). The MAFs were 0.023 and 0.519 for the EAS and EUR, respectively. The GV with the lowest variability was rs2332700 (P=9.80 × 10-1). The MAFs were similar between these populations (that is, 0.246 and 0.247 for the EAS and EUR, respectively). Interestingly, the mean allele frequencies of the GVs did not significantly differ between these populations (P>0.05). Although genetic heterogeneities were observed in the schizophrenia-associated GVs across ethnic groups, the combination of these GVs might increase the risk of schizophrenia.

Structural alterations of the superior temporal gyrus in schizophrenia: Detailed subregional differences.

BACKGROUND: Reduced gray matter volumes in the superior temporal gyrus (STG) have been reported in patients with schizophrenia. Such volumetric abnormalities might denote alterations in cortical thickness, surface area, local gyrification or all of these factors. The STG can be anatomically divided into five subregions using automatic parcellation in FreeSurfer: lateral aspect of the STG, anterior transverse temporal gyrus of Heschl gyrus (HG), planum polare (PP) of the STG, planum temporale (PT) of the STG and transverse temporal sulcus. METHODS: We acquired magnetic resonance imaging (MRI) 3T scans from 40 age- and sex-matched patients with schizophrenia and 40 healthy subjects, and the scans were automatically processed using FreeSurfer. General linear models were used to assess group differences in regional volumes and detailed thickness, surface area and local gyrification. RESULTS: As expected, patients with schizophrenia had significantly smaller bilateral STG volumes than healthy subjects. Of the five subregions in the STG, patients with schizophrenia showed significantly and marginally reduced volumes in the lateral aspect of the STG and PT of the STG bilaterally compared with healthy subjects. The volumetric alteration in bilateral lateral STG was derived from both the cortical thickness and surface area but not local gyrification. There was no significant laterality of the alteration in the lateral STG between patients and controls and no correlation among the structures and clinical characteristics. CONCLUSIONS: These findings suggest that of five anatomical subregions in the STG, the lateral STG is one of the most meaningful regions for brain pathophysiology in schizophrenia.

Abnormal asymmetries in subcortical brain volume in schizophrenia.

Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.

DEGS2 polymorphism associated with cognition in schizophrenia is associated with gene expression in brain.

A genome-wide association study of cognitive deficits in patients with schizophrenia in Japan found association with a missense genetic variant (rs7157599, Asn8Ser) in the delta(4)-desaturase, sphingolipid 2 (DEGS2) gene. A replication analysis using Caucasian samples showed a directionally consistent trend for cognitive association of a proxy single-nucleotide polymorphism (SNP), rs3783332. Although the DEGS2 gene is expressed in human brain, it is unknown how DEGS2 expression varies during human life and whether it is affected by psychiatric disorders and genetic variants. To address these questions, we examined DEGS2 messenger RNA using next-generation sequencing in postmortem dorsolateral prefrontal cortical tissue from a total of 418 Caucasian samples including patients with schizophrenia, bipolar disorder and major depressive disorder. DEGS2 is expressed at very low levels prenatally and increases gradually from birth to adolescence and consistently expressed across adulthood. Rs3783332 genotype was significantly associated with the expression across all subjects (F3,348=10.79, P=1.12 × 10(-)(3)), particularly in control subjects (F1,87=13.14, P=4.86 × 10(-4)). Similar results were found with rs715799 genotype. The carriers of the risk-associated minor allele at both loci showed significantly lower expression compared with subjects homozygous for the non-risk major allele and this was a consistent finding across all diagnostic groups. DEGS2 expression showed no association with diagnostic status after correcting for multiple testing (P>0.05). Our findings demonstrate that a SNP showing genome-wide association study significant association with cognition in schizophrenia is also associated with regulation of DEGS2 expression, implicating a molecular mechanism for the clinical association.

The Piccolo Intronic Single Nucleotide Polymorphism rs13438494 Regulates Dopamine and Serotonin Uptake and Shows Associations with Dependence-Like Behavior in Genomic Association Study.

Piccolo (PCLO) inhibits methamphetamine-induced neuropharmacological effects via modulation of dopamine (DA) uptake and regulation of the transport of synaptic vesicles in neuronal cells. Clinical studies have recently suggested that the single nucleotide polymorphism (SNP) rs13438494 in the intron 24 of the PCLO gene is associated with psychiatric disorder, in the meta-analysis of GWAS. Therefore, in this study, we attempted to evaluate the possible role of the PCLO SNP in the mechanisms of uptake of monoamines. To characterize rs13438494 in the PCLO gene, we constructed plasmids carrying either the C or A allele of the SNP and transiently transfected them into SH-SY5Y cells to analyze genetic effects on the splicing of PCLO mRNA. The C and A allele constructs produced different composition of the transcripts, indicating that the intronic SNP does affect the splicing pattern. We also transfected DA and serotonin (5-hydroxytryptamine; 5- HT) transporters into cells and analyzed their uptakes to elucidate the association to psychiatric disorders. In the cells transfected with the C allele, both the DA and 5-HT uptake were enhanced compared to the A allele. We also conducted a clinical study, in order to clarify the genetic associations. PCLO rs13438494 exhibits a relationship with the symptoms of drug dependence or related parameters, such as the age of first exposure to methamphetamine, eating disorders, tobacco dependence and fentanyl requirement. Our findings suggest that rs13438494 is associated with drug abuse and contributes to the pathogenesis of psychiatric disorders via modulation of neurotransmitter turnover.

Imaging genetics and psychiatric disorders.

Imaging genetics is an integrated research method that uses neuroimaging and genetics to assess the impact of genetic variation on brain function and structure. Imaging genetics is both a tool for the discovery of risk genes for psychiatric disorders and a strategy for characterizing the neural systems affected by risk gene variants to elucidate quantitative and mechanistic aspects of brain function implicated in psychiatric disease. Early studies of imaging genetics included association analyses between brain morphology and single nucleotide polymorphisms whose function is well known, such as catechol-Omethyltransferase (COMT) and brain-derived neurotrophic factor (BDNF). GWAS of psychiatric disorders have identified genes with unknown functions, such as ZNF804A, and imaging genetics has been used to investigate clues of the biological function of these genes. The difficulty in replicating the findings of studies with small sample sizes has motivated the creation of largescale collaborative consortiums, such as ENIGMA, CHARGE and IMAGEN, to collect thousands of images. In a genome-wide association study, the ENIGMA consortium successfully identified common variants in the genome associated with hippocampal volume at 12q24, and the CHARGE consortium replicated this finding. The new era of imaging genetics has just begun, and the next challenge we face is the discovery of small effect size signals from large data sets obtained from genetics and neuroimaging. New methods and technologies for data reduction with appropriate statistical thresholds, such as polygenic analysis and parallel independent component analysis (ICA), are warranted. Future advances in imaging genetics will aid in the discovery of genes and provide mechanistic insight into psychiatric disorders.

Common variants at 1p36 are associated with superior frontal gyrus volume.

The superior frontal gyrus (SFG), an area of the brain frequently found to have reduced gray matter in patients with schizophrenia, is involved in self-awareness and emotion, which are impaired in schizophrenia. However, no genome-wide association studies of SFG volume have investigated in patients with schizophrenia. To identify single-nucleotide polymorphisms (SNPs) associated with SFG volumes, we demonstrated a genome-wide association study (GWAS) of gray matter volumes in the right or left SFG of 158 patients with schizophrenia and 378 healthy subjects. We attempted to bioinformatically ascertain the potential effects of the top hit polymorphism on the expression levels of genes at the genome-wide region. We found associations between five variants on 1p36.12 and the right SFG volume at a widely used benchmark for genome-wide significance (P<5.0 × 10(-8)). The strongest association was observed at rs4654899, an intronic SNP in the eukaryotic translation initiation factor 4 gamma, 3 (EIF4G3) gene on 1p36.12 (P=7.5 × 10(-9)). No SNP with genome-wide significance was found in the volume of the left SFG (P>5.0 × 10(-8)); however, the rs4654899 polymorphism was identified as the locus with the second strongest association with the volume of the left SFG (P=1.5 × 10(-6)). In silico analyses revealed a proxy SNP of rs4654899 had effect on gene expression of two genes, HP1BP3 lying 3' to EIF4G3 (P=7.8 × 10(-6)) and CAPN14 at 2p (P=6.3 × 10(-6)), which are expressed in moderate-to-high levels throughout the adult human SFG. These results contribute to understand genetic architecture of a brain structure possibly linked to the pathophysiology of schizophrenia.

The relationship between psychosocial problems including depression and behavioural trends among middle-aged menopausal women in a cohort study.

OBJECTIVE: We investigated the association of psychosocial problems, menopausal symptoms such as hot flushes, and trends of smoking and use of cosmetics in our previous study. In this follow-up study, we researched psychiatric disorders and psychosocial problems in menopausal women. METHODS: We designed a cohort study with 577 Japanese women aged 30-64 years. Subjects were selected randomly from among women who visited the department of gender-specific medicine at Tokyo Women's Medical University East Medical Center between June 2010 and September 2011. We analysed trends such as smoking, using cosmetics, and menopausal symptoms and their association with the first lifetime episode of severe depression and anxiety using structured clinical interviews for the DSM-IV (structured clinical interview for DSM-IV, outpatient version [SCID]), the Center for Epidemiological Studies Depression Scale (CES-D) and the State-Trait Anxiety Inventory (STAI). RESULTS: Significant associations were observed between hot flushes, smoking and the frequency of using cosmetics. Furthermore, the trends in cosmetic use and smoking affected not only psychosocial problems, but also physical problems. Younger women suffered from psychosocial problems more than twice the rate of post-menopausal women. Those who reported their first severe depression episode were also affected by severe anxiety disorders and physical problems. CONCLUSION: By self-checking the frequency of using cosmetics is up to date knowledge of psychosocial mood problems and improving women's quality of life.

The psychosocial influence to habit using make-up of women aged 40 to 59 years menopausal Japanese women.

We conducted a survey to elucidate the psychosocial influence of menopausal symptoms on the habit of using make-up. This study included 420 Japanese women (age, 40-59 years) who were examined for the first time in a specialized women's outpatient clinic of our institution from June 2010 to September 2011. Using the Menopause-Specific Quality of Life questionnaire (MENQOL), we analysed the scores in relation to menopausal symptoms and whether and how frequently the subject used make-up (including foundation, lip rouge and eyebrow brushing). JMP version 9.0 software was used to statistically analyse the data. Significant results were observed for psychosocial symptoms (P = 0.0002) but not for vasomotor symptoms. Psychosocial symptoms tended to be more severe in women with climacteric <5 years previously. Furthermore, the frequency of make-up use was positively correlated with menopausal symptoms (P = 0.0251). There were strong relationships between psychological symptoms and make-up use in menopausal women. Psychological condition and the frequency of make-up use were inversely correlated, especially in women with climacteric <5 years previously.

Comparison of the symptoms of menopause and symptoms of thyroid disease in Japanese women aged 35-59 years.

OBJECTIVE: In this study, we surveyed thyroid function abnormalities and menopausal symptoms in young as well as in menopausal women. METHODS: We conducted a random survey among outpatients at our facility from September 2008 to June 2011. The study included 853 women aged 35-59 years. We assessed the subjects according to the Simplified Menopause Index, menstrual status, thyroid hormone measurements (thyroid stimulating hormone, free thyroxine, free triiodothyronine), the presence of Hashimoto's disease antibodies (anti-thyroid peroxidase antibody or anti-thyroglobulin antibody), the presence of Grave's disease (anti-TSH receptor antibody), markers of thyroid tumor (high thyroglobulin), and thyroid ultrasonography studies. The data were analyzed by means of the statistical program JMP version 8.0. RESULTS: 'Facial flushing', 'sweating', and 'thyroid tumor' were all positively related with age and menstrual status. 'Breathlessness and palpitations' were positively related to Grave's disease. Moreover, 'sweating', 'irritability', and 'stiff shoulders, low back pain, and joint pain' were related to thyroid tumors. 'Insomnia' decreased with age. Patients with Hashimoto's disease were very rare because they were usually treated at other hospitals that specialize in thyroid disease. CONCLUSION: The symptoms of thyroid function abnormalities were shown to be very similar to menopausal symptoms and were found to occur in younger women before the onset of menopause. This study shows the need to differentiate menopausal symptoms from those of thyroid diseases.

A study of menopausal symptoms in relation to habits of smoking and make-up using in Japanese women aged 35-59.

We conducted a survey to elucidate the influence with menopause symptoms and the impact of not only smoking but also using make-up among for Japanese women, included ages above and below the menopausal generation. The subjects of this study were 335 Japanese women from 35 to 59 years of age who were examined for the first time in the specialized women's outpatient clinic of our institution from July 2010 to June 2011 for 1 year period. We used the items of the Menopause-Specific Quality of Life Questionnaire. Similarly, we analysed the scores in relation to menopausal symptoms and whether the subject smoked, whether the subject used make-up depend on women (including foundation, lip rouge, brush one's eyebrows), how frequently she used make-up. The JMP version 9.0 software program was used to statistically analyse the score data. Significant associations were observed in psychosocial (P = 0.0196), tended to be more severe in women before menopause and after climacteric. Furthermore, the frequency of using make-up were negative relations with menopause symptoms (P = 0.0251) after climacteric. Smoking had made worse for physical symptoms (P < 0.001). Menopause symptoms are already experienced by younger women, especially, psychological symptoms. Also, physical conditions were influenced by smoking. Using make-up frequently was often seen after climacteric because of appearance changes by oestrogen dynamic decline.

Differences in the pharmacokinetics of Cyp3a substrates in TSOD and streptozotocin-induced diabetic mice.

The pharmacokinetics of drugs can change in diabetes mellitus and even among diabetics. They may differ between type I diabetes (T1DM) and type 2 diabetes (T2DM). As triazolam was administered orally to Tsumura, Suzuki, obese, diabetes (TSOD) mice and streptozotocin (STZ) mice, clearance per body (CL/F) in TSOD mice did not differ compared with Tsumura, Suzuki, non-obesity (TSNO) mice. In STZ mice, CL/F was greater than in control mice. Small intestinal cytochrome P450 (Cyp) 3a expression in TSOD mice was significantly lower than in TSNO mice. No significant difference existed in small intestinal Cyp3a expression between STZ mice and control mice. In insulin-treated mice, small intestinal Cyp3a expression was significantly lower than in control mice. These results suggested that the differences in changes in small intestinal Cyp3a expression between T1DM and T2DM may be due to differences in plasma insulin concentrations. This may be a factor in the difference in the drug pharmacokinetics between T2DM and T1DM patients.

Four-point correlation function of a passive scalar field in rapidly fluctuating turbulence: Numerical analysis of an exact closure equation.

A numerical analysis is made on the four-point correlation function in a similarity range of a model of two-dimensional passive scalar field ψ advected by a turbulent velocity field with infinitely small correlation time. The model yields an exact closure equation for the four-point correlation Ψ{4} of ψ, which may be casted into the form of an eigenvalue problem in the similarity range. The analysis of the eigenvalue problem gives not only the scale dependence of Ψ{4} , but also the dependence on the configuration of the four points. The numerical analysis gives S4(R)∝R{ζ{4}} in the similarity range in which S2(R)∝R{ζ{2}} , where S_{N} is the structure function defined by S{N}(R)≡⟨[ψ(x+R)-ψ(x)]{N} and ζ{4}≠2ζ{2} . The estimate of ζ_{4} by the numerical analysis of the eigenvalue problem is in good agreement with numerical simulations so far reported. The agreement supports the idea of universality of the exponent ζ{4} in the sense that ζ_{4} is insensitive to conditions of ψ outside the similarity range. The numerical analysis also shows that the correlation C(R,r)≡[ψ(x+R)-ψ(x)]{2}[ψ(x+r)-ψ(x)]{2}> is stronger than that given by the joint-normal approximation, and scales like C(R,r)∝(r/R){χ} for r/R<<1 with R and r in the similarity range, where χ is a constant depending on the angle between R and r .

TATA box-binding protein gene is associated with risk for schizophrenia, age at onset and prefrontal function.

Schizophrenia is a common polygenic disease in distinct populations, while spinocerebellar ataxia type 17 (SCA17) is a rare autosomal dominant neurodegenerative disorder. Both diseases involve psychotic symptoms. SCA17 is caused by an expanded polyglutamine tract in the TATA box-binding protein (TBP) gene. In the present study, we investigated the association between schizophrenia and CAG repeat length in common TBP alleles with fewer than 42 CAG repeats in a Japanese population (326 patients with schizophrenia and 116 healthy controls). We found that higher frequency of alleles with greater than 35 CAG repeats in patients with schizophrenia compared with that in controls (p = 0.042). We also examined the correlation between CAG repeats length and age at onset of schizophrenia. We observed a negative correlation between the number of CAG repeats in the chromosome with longer CAG repeats out of two chromosomes and age at onset of schizophrenia (p = 0.020). We further provided evidence that TBP genotypes with greater than 35 CAG repeats, which were enriched in patients with schizophrenia, were significantly associated with hypoactivation of the prefrontal cortex measured by near-infrared spectroscopy during the tower of Hanoi, a task of executive function (right PFC; p = 0.015, left PFC; p = 0.010). These findings suggest possible associations of the genetic variations of the TBP gene with risk for schizophrenia, age at onset and prefrontal function.

Increased digitalis-like immunoreactive substances in neonatal plasma measured using fluorescence polarization immunoassay.

OBJECTIVE: To better define the reported increased digitalis-like immunoreactive substances (DLIS) in neonatal plasma, we studied the relation among plasma DLIS level, blank intensity (BLK-I) value at FPIA measurement and plasma total bilirubin level. METHODS: The DLIS levels were measured in 10 neonates with or without jaundice and 10 infants in good health, using fluorescence polarization immunoassay (FPIA) and microparticle enzyme immunoassay (MEIA). BLK-I value and plasma total bilirubin level were also measured simultaneously. RESULTS: In neonates with jaundice, DLIS using FPIA, BLK-I and total bilirubin level were 0.58 +/-0.13 ng/mL, 2598 +/- 408, and 17.98 +/- 1.13 mg/dL, respectively, before phototherapy, and 0.33 +/-0.06 ng/mL, 1886 +/- 237, and 15.16 +/- 2.07 mg/dL after phototherapy. Corresponding values in neonates without jaundice were (DLIS: 0.34 +/-0.04 ng/mL; BLK-I: 1,764 +/- 278; total bilirubin: 10.37 +/- 4.54 mg/dL); in healthy infants (0.12 +/-0.06 ng/mL, 400.7 +/- 4.6 and 0.42 +/- 0.13 mg/dL, respectively) and in healthy volunteers (0.10 +/-0.07 ng/mL, 403.1 +/- 8.4, and 0.58 +/- 0.30 mg/dL, respectively). Using MEIA, DLIS was not detected in 10 neonates, 10 infants and 20 healthy volunteers. CONCLUSIONS: A fluorescent compound related to bilirubin increased the BLK-I value in the measurement of neonatal plasma using FPIA. The fluorescence was not the result of endogenous digitalis-like factors.

Features of bacterial cellulose synthesis in a mutant generated by disruption of the diguanylate cyclase 1 gene of Acetobacter xylinum BPR 2001.

The diguanylate cyclase 1 (DGC1) (dgc1) gene in Acetobacter xylinum BPR 2001--a bacterial cellulose (BC) producer--was cloned and sequenced, and a DGC1 gene-disrupted mutant, strain DD, was constructed. The production and structural characteristics of the BC formed by DD were compared with those of the parental strain BPR 2001. BC production by DD was almost the same as that by BPR 2001 in static cultivation and in shake flask cultivation. However, in a jar fermentor DD produced about 36% more BC than the parental strain. DD produced suspended particle materials that cannot aggregate owing to their random structural characteristics in static cultivation; more uniformly dispersed BC pellicles and smaller BC pellets are produced on average in a jar fermentor, as reflected by the higher BC production by DD than by the parental strain in a jar fermentor. Micrographs of BC produced by DD revealed that the width of cellulose ribbons assemblies decreased as a result of differences in the ultrastructure and mechanism of formation of BC between the two strains. These results reveal that disruption of the dgc1 gene, which catalyzes synthesis of c-di-GMP (an effector of BC synthase), is not fatal for BC synthesis, although it affects BC structure.

Purification, characterization, and relation to bikunin of rat urinary trypsin inhibitors.

Two forms of urinary trypsin inhibitor (UTI-1 and UTI-2) were purified from pooled urine of normal male rats to apparent homogeneity by salting out, affinity chromatography, gel filtration, and reverse-phase HPLC. UTIs-1 and 2 were shown to be thermostable glycoproteins with the respective molecular weights of 22,000 and 18,000 estimated by SDS-PAGE. These inhibitors combined with bovine trypsin in a 1:1 molar ratio: the Kd values were 2.5 x 10(-10) and 2.3 x 10(-10) M, respectively. Amino acid composition and sequence analysis indicated that UTI-1 corresponded to rat bikunin of which the amino acid sequence was deduced from a rat liver cDNA clone encoding alpha1-microglobulin [Lindqvist et al. (1992), Biochim. Biophys. Acta 1130, 63-67] except that the protein sequence seemed to lack C-terminal serine, and UTI-2 corresponded to UTI-1 lacking N-terminal 21 amino acid residues.

Substructuring pseudo-dynamic simulations on real inelastic responses of steel braced frame monitored during moderate earthquake

This paper presents a series of substructuring pseudo-dynamic tests on steel brace members in order to simulate the real inelastic responses of the steel braced frame monitored during moderate earthquakes. A pair of brace members at the first story were chosen as sub-structure specimens for loading tests. As for other fictitious portions, linear-elastic behavior was assumed, and the whole system was solved as a shear-type 3-DOF planar system. Monitored responses and the tests results are also compared with completely numerical response analysis using a mathematical model for brace members.(AU)

Effects of test H-reflex size on reciprocal inhibition in forearm muscles.

We studied effects of test H-reflex size on reciprocal Ia inhibition in forearm muscles. In both healthy control subjects and hemiplegic patients, the amount of Ia inhibition decreased as the test H-reflex size increased. It is possible that forearm reciprocal Ia inhibition in hemiplegics reported previously might be underestimated due to larger test H-reflexes used in the hemiplegics than in the controls.