A dual program for CRP-mediated regulation in bacterial alarmone (p)ppGpp.

Gene expression and proper downstream cellular functions upon facing environmental shifts depend on the combined and cooperative regulation of genetic networks. Here, we identified cAMP receptor protein (CRP) as a master regulator of (p)ppGpp (guanosine tetra- and penta-phosphate) homeostasis. Via CRP-mediated direct transcriptional regulation of the (p)ppGpp synthetase/hydrolase RelA and SpoT, cAMP-CRP stimulates pervasive accumulation of (p)ppGpp under glucose-limiting conditions. Notably, CRP exerts a nonclassical property as a translational regulator through YfiQ-dependent acetylation of ribosome protein S1 at K247, which further enhances the translation of RelA, SpoT, and CRP itself. From a synthetic biology perspective, this self-activating feedback loop for (p)ppGpp synthesis highlights the function of CRP-mediated dual enhancement (CMDE) in controlling bacterial gene expression, which enables stable activation of genetic circuits. CMDE applied in synthetic circuits leads to a stable increase in p-coumaric acid, cinnamic acid, and pinosylvin production. Our findings showed that CRP-mediated dual circuits for (p)ppGpp regulation enable robust activation that could address bioproduction and other biotechnological needs.IMPORTANCETranscriptional-translational coordination is fundamental for rapid and efficient gene expression in most bacteria. Here, we uncovered the roles of cAMP-CRP in this process. We found that CRP distinctly increases RelA and SpoT transcription and translation, and that acetylation of S1 at K247 accelerates the self-activation of the leading CRP under glucose-limiting conditions. We further found that elevated (p)ppGpp significantly impedes the formation of the cAMP-CRP complex, an active form responsible for transcriptional activation. A model was created in which cAMP-CRP and (p)ppGpp cooperate to dynamically modulate the efficiency of transcriptional-translational coordination responses to stress. More broadly, productive activation in synthetic circuits was achieved through the application of CRP-mediated dual enhancement (CMDE), promising to inspire new approaches for the development of cell-based biotechnologies.

Life's essential 8 and risk of subclinical atherosclerosis progression: a prospective cohort study.

BACKGROUND: Previous studies have demonstrated the benefits of ideal cardiovascular health (CVH) in reducing cardiovascular risk. However, its role in subclinical atherosclerosis (SA) progression remains unclear. We aim to examine the association of CVH, estimated by the American Heart Association's new Life's Essential 8 (LE8), with the progression of SA. METHODS: This prospective cohort study was conducted among 972 asymptomatic Chinese participants and followed up for 5.7 years. The LE8 score (range, 0-100) consisted of blood pressure, lipids, glucose, body mass index, smoking status, diet health, physical activity and sleep health was evaluated in 1998 and 2008-2009. Progression of SA was determined by carotid plaque and coronary artery calcification (CAC) in 2008-2009 and 2013-2014. Log-binomial regression model was used to estimate the association of LE8 score with SA progression. RESULTS: Each 10 points increment in LE8 score was associated with 15.2% (RR: 0.848, 95% CI: 0.797-0.902), 17.7% (RR: 0.823, 95% CI: 0.766-0.884) and 12.0% (RR: 0.880, 95% CI: 0.845-0.916) lower risks of carotid plaque, CAC and overall SA progression, respectively. Compared with participants with non-ideal CVH at both visits, the participants with ideal CVH at both visits had 39.1% (RR: 0.609, 95% CI: 0.494-0.752), 41.0% (RR: 0.590, 95% CI: 0.456-0.764) and 29.7% (RR: 0.703, 95% CI: 0.598-0.825) lower risks of carotid plaque, CAC and overall SA progression, respectively. CONCLUSIONS: Higher LE8 scores were associated with lower risks of SA progression. Besides, long-term maintenance of optimal CVH was more beneficial to prevent SA progression.

A network of acetyl phosphate-dependent modification modulates c-di-AMP homeostasis in Actinobacteria.

Cyclic purine nucleotides are important signal transduction molecules across all domains of life. 3',5'-cyclic di-adenosine monophosphate (c-di-AMP) has roles in both prokaryotes and eukaryotes, while the signals that adjust intracellular c-di-AMP and the molecular machinery enabling a network-wide homeostatic response remain largely unknown. Here, we present evidence for an acetyl phosphate (AcP)-governed network responsible for c-di-AMP homeostasis through two distinct substrates, the diadenylate cyclase DNA integrity scanning protein (DisA) and its newly identified transcriptional repressor, DasR. Correspondingly, we found that AcP-induced acetylation exerts these regulatory actions by disrupting protein multimerization, thus impairing c-di-AMP synthesis via K66 acetylation of DisA. Conversely, the transcriptional inhibition of disA was relieved during DasR acetylation at K78. These findings establish a pivotal physiological role for AcP as a mediator to balance c-di-AMP homeostasis. Further studies revealed that acetylated DisA and DasR undergo conformational changes that play crucial roles in differentiation. Considering the broad distribution of AcP-induced acetylation in response to environmental stress, as well as the high conservation of the identified key sites, we propose that this unique regulation of c-di-AMP homeostasis may constitute a fundamental property of central circuits in Actinobacteria and thus the global control of cellular physiology.IMPORTANCESince the identification of c-di-AMP is required for bacterial growth and cellular physiology, a major challenge is the cell signals and stimuli that feed into the decision-making process of c-di-AMP concentration and how that information is integrated into the regulatory pathways. Using the bacterium Saccharopolyspora erythraea as a model, we established that AcP-dependent acetylation of the diadenylate cyclase DisA and its newly identified transcriptional repressor DasR is involved in coordinating environmental and intracellular signals, which are crucial for c-di-AMP homeostasis. Specifically, DisA acetylated at K66 directly inactivates its diadenylate cyclase activity, hence the production of c-di-AMP, whereas DasR acetylation at K78 leads to increased disA expression and c-di-AMP levels. Thus, AcP represents an essential molecular switch in c-di-AMP maintenance, responding to environmental changes and possibly hampering efficient development. Therefore, AcP-mediated posttranslational processes constitute a network beyond the usual and well-characterized synthetase/hydrolase governing c-di-AMP homeostasis.

Factors influencing the help-seeking behavior in patients with mild cognitive impairment: a qualitative study.

BACKGROUND: The early diagnosis and intervention of mild cognitive impairment (MCI) patients is expected to delay the progression of AD. Delayed treatment will lead to MCI patients missing the best intervention expectation. At present, the medical help-seeking behavior of this group is not optimistic. This study aimed to explore influencing factors of help-seeking behavior among patients with MCI in China based on the help-seeking behavior model. METHODS: Twenty-two patients with MCI were recruited to participate in semi-structured interviews via purposeful sampling with a qualitative, descriptive design. Data were analyzed by qualitative content analysis. RESULTS: The study revealed the main influencing factors of help-seeking behavior among MCI patients in China included perceived disease threat, symptom attribution, disease knowledge, use of cognitive compensation strategies, sense of foreseeable burden, social support, economic condition, and accessibility of medical service. CONCLUSIONS: The help-seeking behavior of patients with MCI is affected by multiple factors. There are some key factors in different stages of the help-seeking process. Healthcare providers can utilize these factors to design targeted interventions for promoting early help-seeking of patients with MCI.

A taxonomic study of Muscidifurax Girault & Sanders from China (Hymenoptera, Chalcidoidea, Pteromalidae).

Five species of Muscidifurax Girault & Sanders (Hymenoptera: Pteromalidae) are studied from mainland China, of which three new species, M.similadanacus Xiao & Zhou, sp. n., M.sinesensilla Xiao & Zhou, sp. n., M.neoraptorellus Xiao & Zhou, sp. n., and one newly recorded species, M.adanacus Doganlar, are reported. All species have been reared from pupae of Muscadomestica Linnaeus. A key to Chinese Muscidifurax and illustrations of external features of the species are provided.

Asparaginyl endopeptidase enhances pancreatic ductal adenocarcinoma cell invasion in an exosome-dependent manner and correlates with poor prognosis.

Pancreatic cancer is one of the most lethal types of cancer; owing to low early detection rates and high metastasis rates, it is associated with an extremely poor prognosis. Therefore, a better understanding of the molecular mechanisms that underlie its metastasis and the identification of potential prognostic biomarkers are urgently required. Although high expression levels of asparaginyl endopeptidase (AEP) have been detected in various types of solid tumor, the expression and functions of AEP in pancreatic carcinomas have yet to be determined. The present study aimed to examine the putative functions of AEP in pancreatic carcinoma. Immunohistochemical analysis revealed that AEP was highly expressed in pancreatic cancer tissues compared with adjacent normal tissues. Patients with high AEP expression exhibited a significantly shorter overall survival time. Results from multivariate Cox regression analysis revealed that AEP was an independent prognostic factor for overall survival. Gain- and loss-of-function experiments demonstrated that knockdown of AEP expression significantly reduced the invasive ability of pancreatic cancer cells, whereas overexpression of AEP increased the invasive ability. In addition, AEP was detected in exosomes that were derived from cultured pancreatic ductal adenocarcinoma cells (PDACs) and in the serum from patients with PDAC. The Matrigel-Transwell invasion assay revealed that exosomes enriched with AEP were able to enhance the invasive ability of PDAC cells, whereas exosomes lacking AEP decreased the invasive ability. Furthermore, results from the present study suggested that AEP may be crucial for activation of the phosphoinositide 3-kinase/RAC­α serine/threonine-protein kinase signaling pathway in PDAC cells. The present study data indicated that high AEP expression may be important for pancreatic carcinoma progression in an exosome-dependent manner, and that AEP may be an independent indicator of poor prognosis in patients with PDAC and may be a novel prognostic biomarker or therapeutic target in pancreatic carcinoma.

Basic Research and Clinical Application of Pterygoplatione Fossa Projection on Lateral Nasal Wall.

Infection, neoplasms, and tumor-like lesion in pterygoplatione fossa (PPF) are common in Chinese people. Owing to its deep anatomic location, surgery through this region is difficult. Maxillary sinus pathway is widely used, but the obvious disadvantage of destroying maxillary sinus even disfigurement cannot be avoided. This study provides a new method to locate PPF by choosing some landmarks situated at lateral wall of nasal cavity as reference points to obtain credible and detailed information for clinical management. The authors measured the location of anterior wall, posterior wall, and medial wall of PPF in the planes of middle nasal concha osseous extremity, inferior nasal concha osseous extremity, and middle nasal meatus. In addition, the authors measured the distance and the angle between the upper and lower bound of the PPF and the apertura sinus maxillaris. All PPF and landmarks of 196 patients were well demonstrated on computed tomographic angiography images. The new location method is stable and direct. As for the shape of PPF, the line connecting anterior wall in different planes is curve, convex backward, and concave frontward. Pterygoplatione fossa tapers gradually. The authors also found that with the traditional method, after entering the maxillary sinus, the needle should be inserted <26 mm when aimed at the upper bound and 30 mm in women and 31 mm in men when aimed at the lower bound.

Selective medial temporal volume reduction in the hippocampus of patients with idiopathic generalized tonic-clonic seizures.

BACKGROUND: Different subtypes of idiopathic generalized epilepsy may indicate different mechanisms and outcomes, suggesting that it is necessary to use a 'pure sample' of a single subtype. METHODS: A volumetric study, in conjunction with cognition assessments, was performed in a pure sample of patients with idiopathic generalized tonic-clonic seizures (IGE-GTCS; 15 males and 15 females) matched with normal control subjects (15 males and 17 females). The volumetric measurements were focused on the hippocampus and its surrounding structures, including the amygdala, the parahippocampal gyrus, the entorhinal cortex and the perirhinal cortex. The Wechsler Adult Intelligence Scale-Revised in China was administered to assess cognitive status. RESULTS: A volume reduction was found only in the hippocampus, with a more severe effect on the left side than the right side. The total number and frequency of seizures had significant negative correlations with multiple cognitive measures. Furthermore, the hippocampal volume reduction was significantly correlated with some aspects of cognitive impairment. CONCLUSION: These findings suggest that compared with the other medial temporal structures, the hippocampus may be more vulnerable to the neuropathology of IGE-GTCS. The observation that cognitive deterioration was correlated with an increased frequency and total number of seizures highlights the critical importance of preventing seizures from recurrence.

Development of an automatic approaching system for electrochemical nanofabrication using visual and force-displacement sensing.

In this paper, a fast automatic precision approaching system is developed for electrochemical nanofabrication using visual and force-displacement sensing. Before the substrate is fabricated, the template should approach the substrate accurately to establish the initial gap between the template and substrate. During the approaching process, the template is first quickly moved towards the substrate by the stepping motor until a specified gap is detected by the visual feedback. Then, the successive approach using the switch of macro-micro motion with a force-displacement sensing module is triggered to make the template contact with the substrate to nanometre accuracy. The contact force is measured by the force-displacement sensing module which employs the high-resolution capacitive displacement sensor and flexure compliant mechanism. The high sensitivity of this capacitive displacement sensor ensures high accuracy of the template-substrate contact. The experimental results show that the template can reach the substrate accurately and smoothly, which verifies the effectiveness of the proposed approaching system with the visual and the force-displacement sensing modules.

Longitudinal MRI study of the pituitary volume in chronic schizophrenia: a preliminary report.

This longitudinal MRI study investigated the pituitary volume in 17 patients with chronic schizophrenia and 17 matched controls. In contrast to previous findings of pituitary expansion during the first episode of schizophrenia, the chronic patients showed non-significant mild pituitary atrophy, suggesting that the pituitary volume changes differently at different illness stages.

A follow-up MRI study of the fusiform gyrus and middle and inferior temporal gyri in schizophrenia spectrum.

While longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive gray matter reduction of the superior temporal gyrus (STG) during the early phases of schizophrenia, it remains largely unknown whether other temporal lobe structures also exhibit similar progressive changes and whether these changes, if present, are specific to schizophrenia among the spectrum disorders. In this longitudinal MRI study, the gray matter volumes of the fusiform, middle temporal, and inferior temporal gyri were measured at baseline and follow-up scans (mean inter-scan interval=2.7 years) in 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. Both schizophrenia and schizotypal patients had a smaller fusiform gyrus than controls bilaterally at both time points, whereas no group difference was found in the middle and inferior temporal gyri. In the longitudinal comparison, the schizophrenia patients showed significant fusiform gyrus reduction (left, -2.6%/year; right, -2.3%/year) compared with schizotypal patients (left: -0.4%/year; right: -0.2%/year) and controls (left: 0.1%/year; right: 0.0%/year). However, the middle and inferior temporal gyri did not exhibit significant progressive gray matter change in all diagnostic groups. In the schizophrenia patients, a higher cumulative dose of antipsychotics during follow-up was significantly correlated with less severe gray matter reduction in the left fusiform gyrus. The annual gray matter loss of the fusiform gyrus did not correlate with that of the STG previously reported in the same subjects. Our findings suggest regional specificity of the progressive gray matter reduction in the temporal lobe structures, which might be specific to overt schizophrenia within the schizophrenia spectrum.

Longitudinal volume changes of the pituitary gland in patients with schizotypal disorder and first-episode schizophrenia.

An enlarged volume of the pituitary gland has been reported in the schizophrenia spectrum, possibly reflecting the hypothalamic-pituitary-adrenal (HPA) hyperactivity. However, it remains largely unknown whether the pituitary size longitudinally changes in the course of the spectrum disorders. In the present study, longitudinal magnetic resonance imaging (MRI) data were obtained from 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. The pituitary volume was measured at baseline and follow-up (mean, 2.7 years) scans and was compared across groups. The pituitary volume was larger in the schizophrenia patients than controls at baseline, and both patient groups had significantly larger pituitary volume than controls at follow-up. In a longitudinal comparison, both schizophrenia (3.6%/year) and schizotypal (2.7%/year) patients showed significant pituitary enlargement compared with controls (-1.8%/year). In the schizophrenia patients, greater pituitary enlargement over time was associated with less improvement of delusions and higher scores for thought disorders at the follow-up. These findings suggest that the pituitary gland exhibits ongoing volume changes during the early course of the schizophrenia spectrum as a possible marker of state-related impairments.

A follow-up MRI study of the superior temporal subregions in schizotypal disorder and first-episode schizophrenia.

While longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive gray matter reduction of the superior temporal gyrus (STG) during the early phases of schizophrenia, it remains unknown whether patients with schizotypal features exhibit similar STG changes. In this study, longitudinal MRI data were obtained from 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. The volumes of the STG and its subregions [planum polare (PP), Heschl gyrus (HG), planum temporale (PT), rostral STG, and caudal STG] were measured on baseline and follow-up (mean: 2.7 years) scans and were compared across groups. At the baseline, both the schizophrenia and schizotypal patients had smaller left PT and left caudal STG than the controls. In a longitudinal comparison, the schizophrenia patients showed significant gray matter reduction of the STG over time (left: -2.8%/year; right: -1.5%/year) compared with the schizotypal patients (left: -0.6%/year; right: -0.3%/year) and controls (left: 0.0%/year; right: -0.1%/year) without a prominent effect of subregion or type of antipsychotic (typical/atypical). In the schizophrenia patients, greater annual volume reductions of the left PP and right PT were correlated with less improvement of positive psychotic symptoms. A higher cumulative dose of antipsychotics during follow-up in schizophrenia was significantly correlated with less severe gray matter reductions in the left PT and bilateral caudal STG. Our findings suggest that the left posterior STG subregions are commonly reduced in diseases of the schizophrenia spectrum; whereas, schizophrenia patients exhibit further progressive STG changes associated with overt psychosis in the early years of the illness.

Insular cortex gray matter changes in individuals at ultra-high-risk of developing psychosis.

Morphologic abnormalities of the insular cortex have been described in psychotic disorders such as schizophrenia, but it remains unclear whether these changes predate the onset of psychosis or develop progressively over the course of illness. In this study, we used magnetic resonance imaging to investigate the gray matter volume of the long and short insular cortices in 97 neuroleptic-naïve individuals at ultra-high-risk (UHR) for developing psychosis [of whom 31 (32%) later developed psychosis (UHR-P) and 66 (68%) did not (UHR-NP)] and 55 age- and gender-matched healthy comparisons. We also conducted a longitudinal comparison of the insular cortex gray matter changes in 31 UHR individuals (20 UHR-NP and 11 UHR-P) and 20 controls for whom follow-up MRI data between 1 and 4 years later were available. In the cross-sectional comparison, the UHR-P subjects had a significantly smaller insular cortex compared with the UHR-NP subjects bilaterally and with the controls on the right hemisphere, especially for the short insular region. More severe negative symptoms in UHR-P subjects at baseline were associated with smaller volumes of the right long insular cortex. In the longitudinal comparison, the UHR-P subjects showed greater gray matter reduction of insular cortex bilaterally (-5.0%/year) compared with controls (-0.4%/year) or UHR-NP subjects (-0.6%/year). Our findings suggest that insular cortex gray matter abnormalities in psychotic disorders may reflect pre-existing vulnerability, but that there are also active progressive changes of the insular cortex during the transition period into psychosis. Whether these longitudinal changes are features of the disorder or related to treatment with antipsychotic medication remains to be determined.

The Disrupted-in-Schizophrenia-1 Ser704Cys polymorphism and brain morphology in schizophrenia.

The Disrupted-in-Schizophrenia-1 (DISC1) polymorphism is a strong candidate for a schizophrenia-susceptibility gene as it is widely expressed in cortical and limbic regions, but the effect of its genotype variation on brain morphology in schizophrenia is not well known. This study examined the association between the DISC1 Ser704Cys polymorphism and volumetric measurements for a broad range of fronto-parietal, temporal, and limbic-paralimbic regions using magnetic resonance imaging in a Japanese sample of 33 schizophrenia patients and 29 healthy comparison subjects. The Cys carriers had significantly larger volumes of the medial superior frontal gyrus and short insular cortex than the Ser homozygotes only for healthy comparison subjects. The Cys carriers tended to have a smaller supramarginal gyrus than the Ser homozygotes in schizophrenia patients, but not in healthy comparison subjects. The right medial superior frontal gyrus volume was significantly correlated with daily dosage of antipsychotic medication in Ser homozygote schizophrenia patients. These different genotype effects of the DISC1 Ser704Cys polymorphism on the brain morphology in schizophrenia patients and healthy comparison subjects suggest that variation in the DISC1 gene might be, at least partly, involved in the neurobiology of schizophrenia. Our findings also suggest that the DISC1 genotype variation might have some relevance to the medication effect on brain morphology in schizophrenia.

Increased pituitary volume in schizophrenia spectrum disorders.

While hypothalamic-pituitary-adrenal (HPA) axis hyperactivity has been implicated in psychotic disorders, previous magnetic resonance imaging (MRI) studies of the pituitary gland volume in schizophrenia have yielded controversial results. It is also unknown whether patients with schizophrenia spectrum such as schizotypal disorder exhibit pituitary volume changes. In this study, we investigated the pituitary volume using MRI in 47 schizotypal disorder patients (29 males, mean age=25.0 years), 72 schizophrenia patients (38 males, mean age=26.2 years), and 81 age and gender matched healthy controls (46 males, mean age=24.5 years). Both patient groups had a larger pituitary volume compared with controls, but no difference was found between the schizophrenia and schizotypal patients. The pituitary volume was larger in females than in males for all diagnostic groups. There was no association between the pituitary volume and type (typical versus atypical), daily dosage, or duration of antipsychotic medication in either patient group. These findings are consistent with a stress-diathesis model of schizophrenia and further suggest that the schizotypal patients share HPA axis hyperactivity with young established schizophrenia patients reflecting a common vulnerability to stress within the schizophrenia spectrum.

The relationship between prefrontal brain volume and characteristics of memory strategy in schizophrenia spectrum disorders.

The present study investigated the relationship between memory strategy use and prefrontal gray/white matter volumes of healthy control subjects, patients with schizophrenia or schizotypal disorder. Gray/white matter volumes were measured for the superior, middle, inferior, ventral medial and orbital prefrontal regions, using high-resolution magnetic resonance (MR) images that were acquired from 35 patients with schizophrenia, 25 patients with schizotypal disorder and 19 healthy subjects. Participants were also administered the Japanese Verbal Learning Test (JVLT). In control subjects, larger left inferior frontal and straight gyrus's gray matter volumes were associated with higher semantic clustering rates on the JVLT, and smaller left inferior frontal gray matter volumes were associated with higher serial clustering ratio. In schizophrenic patients, smaller left orbitofrontal gray matter volumes were associated with lower semantic clustering rates on the JVLT. In schizotypal patients, smaller left inferior frontal white matter volume was associated with smaller serial clustering rates and larger semantic clustering rate. These findings suggest that semantic organization in schizophrenic patients might depend on mobilization of a memory strategy that is mediated by orbitofrontal cortex functioning. Failure to use a semantic organization strategy might be related to reduced volume in the inferior frontal gyrus. The findings for schizotypal patients suggest a compensation mechanism to remember the words using a serial processing strategy is at work when the inferior frontal gyrus cannot mediate semantic processing.

Prevalence and length of the adhesio interthalamica in schizophrenia spectrum disorders.

We used magnetic resonance imaging to investigate the prevalence and length of the adhesio interthalamica (AI) in 72 schizophrenia patients, 47 schizotypal disorder patients, and 81 healthy controls. The AI was more often absent and shorter in both disorders than in controls, possibly reflecting common neurodevelopmental abnormalities in the schizophrenia spectrum.

The association of genotypic combination of the DRD3 and BDNF polymorphisms on the adhesio interthalamica and medial temporal lobe structures.

Abnormal neurodevelopment in midline structures such as the adhesio interthalamica (AI), as well as in the medial temporal lobe structures has been implicated in schizophrenia, while its genetic mechanism is unknown. This magnetic resonance imaging study investigated the effect of the genotypic combination of the dopamine D3 receptor (DRD3) Ser9Gly and brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms on the AI length and volumetric measures of the medial temporal lobe structures (amygdala, hippocampus, and parahippocampal gyrus) in 33 schizophrenia patients and 29 healthy controls. The subjects with a combination of the Ser/Ser genotype of DRD3 and Met-containing genotypes of BDNF (high-risk combination) had a shorter AI than those without it in the healthy controls, but not in the schizophrenia patients. The subjects carrying the high-risk combination had a smaller posterior hippocampus than those without it for both diagnostic groups. These genotypic combination effects on brain morphology were not explained by the independent effect of each polymorphism. These findings suggest the effect of gene-gene interaction between the DRD3 and BDNF variations on brain morphology in midline and medial temporal lobe structures, but do not support its specific role in the pathogenesis of schizophrenia.

Association between the brain-derived neurotrophic factor Val66Met polymorphism and brain morphology in a Japanese sample of schizophrenia and healthy comparisons.

Magnetic resonance imaging was used to investigate the relation between the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and volumetric measurements for the medial temporal lobe structures (amygdala, hippocampus, and parahippocampal gyrus) and prefrontal sub-regions (the superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, ventral medial prefrontal cortex, orbitofrontal cortex, and straight gyrus) in a Japanese sample of 33 schizophrenia patients and 29 healthy subjects. For the controls, the Met carriers had significantly smaller parahippocampal and left superior frontal gyri than the Val homozygotes. The schizophrenia patients carrying the Met allele had a significantly smaller right parahippocampal gyrus than those with the Val/Val genotype, but the genotype did not affect the prefrontal regions in schizophrenia patients. These findings might reflect different genotypic effects of BDNF on brain morphology in schizophrenia patients and healthy controls, implicating the possible role of the brain morphology as an endophenotype for future genetic studies in schizophrenia.