Glutamine + glutamate level predicts the magnitude of microstructural organization in the gray matter in the healthy elderly.

BACKGROUND: Diffusion tensor imaging (DTI), which is a technique for measuring the degree and direction of movement of water molecules in tissue, has been widely used to noninvasively assess white matter (WM) or gray matter (GM) microstructures in vivo. Mean diffusivity (MD), which is the average diffusion across all directions, has been considered as a marker of WM tract degeneration or extracellular space enlargement in GM. Recent lines of evidence suggest that cortical MD can better identify early-stage Alzheimer's disease than structural morphometric parameters in magnetic resonance imaging. However, knowledge of the relationships between cortical MD and other biological factors in the same cortical region, e.g. metabolites, is still limited. METHODS: Thirty-three healthy elderly individuals [aged 50-77 years (mean, 63.8±7.4 years); 11 males and 22 females] were enrolled. We estimated the associations between cortical MD and neurotransmitter levels. Specifically, we measured levels of γ-aminobutyric acid (GABA) and glutamate + glutamine (Glx), which are inhibitory and excitatory neurotransmitters, respectively, in medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) using MEGA-PRESS magnetic resonance spectroscopy, and we measured regional cortical MD using DTI. RESULTS: Cortical MD was significantly negatively associated with Glx levels in both mPFC and PCC. No significant association was observed between cortical MD and GABA levels in either GM region. CONCLUSION: Our findings suggest that degeneration of microstructural organization in GM, as determined on the basis of cortical MD measured by DTI, is accompanied by the decline of Glx metabolism within the same GM region.

A case series on the safety of immunotherapy with reduced blood testing frequency in lung cancer patients.

BACKGROUND: The necessity of regular blood tests with the administration of immune checkpoint inhibitors has not been investigated. This study examined the safety of omitting a blood test every 2 weeks for patients with lung cancer who were injected an immune checkpoint inhibitor. METHODS: We conducted a retrospective review of the medical records of 201 patients diagnosed with lung cancer and administered with nivolumab or durvalumab between December 1, 2015, and February 30, 2020, in a single hospital. We extracted 16 patients who had treatments without blood testing every 2 weeks. RESULTS: Adverse events that resulted in discontinued treatment included two cases of interstitial pneumonia, one case of creatinine increase, and one infection. All four cases were detected by chest X-ray or their symptoms. CONCLUSIONS: Our results indicate that immune checkpoint inhibitor administration without a blood test every 2 weeks did not subject patients to more adverse side effects.

γ-Aminobutyric acid type A receptor binding affinity in the right inferior frontal gyrus at resting state predicts the performance of healthy elderly people in the visual sustained attention test.

ABSTRACTBackground:Although recent studies have suggested that the γ-aminobutyric acid type A (GABAA) receptor binding affinity can be a more sensitive marker of age-related neuronal loss than regional gray matter (GM) volume, knowledge about the relationship between decreased GABAA receptor binding affinity and cognitive decline during normal aging is still limited. METHODS: Thirty-seven healthy elderly individuals (aged 50-77 years (mean, 64.5 ± 7.3 years); 15 males and 22 females) were enrolled in this study. We investigated the association of the performance of the healthy elderly in the attentional function test with regional GM volume, regional cerebral bold flow (rCBF), and GABAA receptor binding affinity in the resting state by structural magnetic resonance imaging (MRI), arterial spin labeling (ASL), and 123I-iomazenil (IMZ) SPECT, with the analysis focusing on the bilateral inferior frontal gyri. RESULTS: The score of the rapid visual information processing (RVP) test, which is used to assess visual sustained attention, showed a positive correlation with GABAA receptor binding affinity in the right inferior frontal gyrus. No significant correlation was found between RVP test score and regional GM volume or rCBF. CONCLUSION: The findings of 123I-IMZ SPECT, but not those of structural MRI or ASL, suggest that a decreased GABAA receptor binding affinity can be a sensitive marker of cognitive impairment.

The inhibition/excitation ratio related to task-induced oscillatory modulations during a working memory task: A multtimodal-imaging study using MEG and MRS.

Detailed studies on the association between neural oscillations and the neurotransmitters gamma-aminobutyric acid (GABA) and glutamate have been performed in vitro. In addition, recent functional magnetic resonance imaging studies have characterized these neurotransmitters in task-induced deactivation processes during a working memory (WM) task. However, few studies have investigated the relationship between these neurotransmitters and task-induced oscillatory changes in the human brain. Here, using combined magnetoencephalography (MEG) and magnetic resonance spectroscopy (MRS), we investigated the modulation of GABA and glutamate + glutamine (Glx) concentrations related to task-induced oscillations in neural activity during a WM task. We first acquired resting-state MRS and MEG data from 20 healthy male volunteers using the n-back task. Time-frequency analysis was employed to determine the power induced during the encoding and retention phases in perigenual anterior cingulate cortex (pg-ACC), mid-ACC, and occipital cortex (OC). Statistical analysis showed that increased WM load was associated with task-induced oscillatory modulations (TIOMs) of the theta-gamma band relative to the zero-back condition (TIOM0B) in each volume of interest during the encoding phase of the n-back task. The task-induced oscillatory modulations in the two-back condition relative to the zero-back condition (TIOM2B-0B) were negatively correlated with the percent rate change of the correct hit rate for 2B-0B, but positively correlated with GABA/Glx. The positive correlation between TIOM2B-0B and GABA/Glx during the WM task indicates the importance of the inhibition/excitation ratio. In particular, a low inhibition/excitation ratio is essential for the efficient inhibition of irrelevant neural activity, thus producing precise task performance.

Relationship of γ-aminobutyric acid and glutamate+glutamine concentrations in the perigenual anterior cingulate cortex with performance of Cambridge Gambling Task.

The anterior cingulate cortex (ACC), consisting of the perigenual ACC (pgACC) and mid-ACC (i.e., affective and cognitive areas, respectively), plays a significant role in the performance of gambling tasks, which are used to measure decision-making behavior under conditions of risk. Although recent neuroimaging studies have suggested that the γ-aminobutyric acid (GABA) concentration in the pgACC is associated with decision-making behavior, knowledge regarding the relationship of GABA concentrations in subdivisions of the ACC with gambling task performance is still limited. The aim of our magnetic resonance spectroscopy study is to investigate in 20 healthy males the relationship of concentrations of GABA and glutamate+glutamine (Glx) in the pgACC, mid-ACC, and occipital cortex (OC) with multiple indexes of decision-making behavior under conditions of risk, using the Cambridge Gambling Task (CGT). The GABA/creatine (Cr) ratio in the pgACC negatively correlated with delay aversion score, which corresponds to the impulsivity index. The Glx/Cr ratio in the pgACC negatively correlated with risk adjustment score, which is reported to reflect the ability to change the amount of the bet depending on the probability of winning or losing. The scores of CGT did not significantly correlate with the GABA/Cr or Glx/Cr ratio in the mid-ACC or OC. Results of this study suggest that in the pgACC, but not in the mid-ACC or OC, GABA and Glx concentrations play a distinct role in regulating impulsiveness and risk probability during decision-making behavior under conditions of risk, respectively.

Intralobar pulmonary sequestration presenting as multiple nodular pulmonary lesions and focal emphysema.

The features of intralobar pulmonary sequestration vary on computed tomography (CT). Many cases demonstrate a mass or cystic lesion within a lower lobe. We report herein a case of a 55-year-old, female patient presenting with right back pain. Contrast enhanced (CE) CT revealed multiple, nodular, pulmonary lesions suggesting recurrent infections with surrounding focal emphysema. Three-dimensional (3D) reconstruction demonstrated a sequestrated lung segment with a systemic, arterial blood supply. Based on these findings, intralobar pulmonary sequestration was diagnosed. Intralobar pulmonary sequestration can present as multiple, nodular, pulmonary lesions with focal emphysema rather than as a mass or cyst. CE-CT with 3D reconstruction is useful for diagnosing this condition. Patients with recurrent pulmonary infections have a high index of suspicion of intralobar pulmonary sequestration.

Real-world Prognostic Data on Unresectable Stage III Non-small-cell Lung Cancer Treated with Concurrent Chemoradiation Therapy by Histological Type.

Objective The current standard treatment for locally advanced, unresectable stage III non-small-cell lung cancer (NSCLC) is concurrent chemoradiation therapy (CCRT) and durvalumab administration. Although reports have indicated that the prognosis of squamous cell carcinoma is poorer than that of adenocarcinoma, real-world data are currently inadequate. Methods The present study analyzed patients with stage III NSCLC who received CCRT at the study center between April 2018 and February 2022. These patients were retrospectively classified into adenocarcinoma and squamous cell carcinoma groups for an analysis of the progression-free survival (PFS), overall survival (OS), and patient background factors, including the age, performance status, smoking history, and pre-CCRT laboratory data. Results A total of 109 patients were included for the analysis; 25 were excluded, and 44 and 40 patients were classified into the adenocarcinoma and squamous cell carcinoma groups, respectively. The median PFS was significantly longer in the adenocarcinoma group than in the squamous cell carcinoma group [27.9 (95% confidence interval {CI}: 15.2-not achieved) vs. 9.63 (95% CI: 5.88-13.9) months; p<0.01]. Similarly, the median OS was significantly longer in the adenocarcinoma group than in the squamous cell carcinoma group [not achieved (95% CI: 48.1-not achieved) vs. 23.8 (95% CI; 14.6-not achieved) months; p<0.01]. In the multivariate Cox proportional hazard analysis, the histological type was the only prognostic factor for the PFS (p<0.05) and OS (p<0.05). Conclusion The median PFS and OS were poorer in patients with squamous cell carcinoma than in those with stage III NSCLC treated with CCRT and durvalumab. The histological type was an independent factor affecting the PFS and OS.

Associations among parenting experiences during childhood and adolescence, hypothalamus-pituitary-adrenal axis hypoactivity, and hippocampal gray matter volume reduction in young adults.

Recent human studies have indicated that adverse parenting experiences during childhood and adolescence are associated with adulthood hypothalamus-pituitary-adrenal (HPA) axis hypoactivity. Chronic HPA axis hypoactivity inhibits hippocampal gray matter (GM) development, as shown by animal studies. However, associations among adverse parenting experiences during childhood and adolescence, HPA axis activity, and brain development, particularly hippocampal development, are insufficiently investigated in humans. In this voxel-based structural magnetic resonance imaging study, using a cross-sectional design, we examined the associations among the scores of parental bonding instrument (PBI; a self-report scale to rate the attitudes of parents during the first 16 years), cortisol response determined by the dexamethasone/corticotropin-releasing hormone test, and regional or total hippocampal GM volume in forty healthy young adults with the following features: aged between 18 and 35 years, no cortisol hypersecretion in response to the dexamethasone test, no history of traumatic events, or no past or current conditions of significant medical illness or neuropsychiatric disorders. As a result, parental overprotection scores significantly negatively correlated with cortisol response. Additionally, a significant positive association was found between cortisol response and total or regional hippocampal GM volume. No significant association was observed between PBI scores and total or regional hippocampal GM volume. In conclusion, statistical associations were found between parental overprotection during childhood and adolescence and adulthood HPA axis hypoactivity, and between HPA axis hypoactivity and hippocampal GM volume reduction in healthy young adults, but no significant relationship was observed between any PBI scores and adulthood hippocampal GM volume.

Micropolygyria in an infant born to a patient with severe anorexia nervosa: a case report.

We report the case of an anorexia nervosa (AN) patient with extremely low body weight who became pregnant following ovulation induction and subsequently delivered an infant with micropolygyria. To the best of our knowledge, no previous report has described live birth for a patient with such low body weight. The patient underwent hMG-hCG therapy for ovulation induction. Despite becoming pregnant, weight loss continued with extreme anemia occurring during the pregnancy. However, blood transfusion therapy was used for successful treatment. Despite the therapeutic and protective measures instituted, the child was born with micropolygyria. Pregnancy in an AN patient with extremely low body weight needs therapeutic intervention during early pregnancy with aggressive precautionary measures, particularly against anemia. On the basis of our experience, we consider that ovulation induction therapy should not be administered without sufficient caution for an AN patient with low body weight.

Effects of antidepressants and mood stabilizers on serum levels of adiponectin.

The effect of antidepressants and mood stabilizers on serum levels of adiponectin was investigated. Fluvoxamine (30 and 50 mg/kg/day) or lithium (40 and 60 mg/kg/day) was dissolved in distilled water and administered orally to rats every day for 4 weeks. Fluvoxamine (50 mg/kg/day) alone significantly elevated the serum level of adiponectin, but no significant difference was found between other drug-treated groups and the control group. This difference of these drugs' effectiveness on serum adiponectin might contribute to their differences of action mechanisms and therapeutic effects.

Association between the baseline tumor size and outcomes of patients with non-small cell lung cancer treated with first-line immune checkpoint inhibitor monotherapy or in combination with chemotherapy.

Background: The baseline tumor size (BTS) is a prognostic factor for patients with non-small cell lung cancer (NSCLC) who received immune checkpoint inhibitor monotherapy (ICI-mono). However, this relationship is not yet known in patients treated with ICI in combination with chemotherapy (ICI-chemo). Methods: This single-center retrospective study evaluated 159 patients with advanced NSCLC who received first-line ICI-mono or ICI-chemo from January 2016 to April 2021. Their BTS values were estimated using the maximum BTS (max BTS) (maximum target lesions' longest diameter) and total BTS (sum of target lesions' longest diameters) in a radiological assessment according to the Response Evaluation Criteria for Solid Tumors. Results: Based on a multivariable analysis, the large max BTS group had worse progression-free survival (PFS) in patients treated with ICI-mono (P=0.009), but it was not associated with worse PFS in patients treated with ICI-chemo (P=0.132). The group treated with ICI-mono had worse PFS compared to the group treated with ICI-chemo in patients with max BTS ≥50 mm (P=0.004), and the group treated with ICI-mono was not associated with worse PFS compared to the group treated with ICI-chemo in patients with max BTS <50 mm (P=0.107). Conclusions: While a large max BTS was identified as a prognostic factor for worse PFS in patients treated with ICI-mono, it was not identified as such in patients treated with ICI-chemo. The max BTS may have different predicting efficacy for patients with NSCLC treated with ICI-mono and ICI-chemo.

Keratinocyte growth factor induces vascular endothelial growth factor-A expression in colorectal cancer cells.

Keratinocyte growth factor (KGF), which is also called fibroblast growth factor (FGF)-7, belongs to the FGF family. KGF is not commonly produced by human cancer cells, but the KGF receptor (KGFR) is expressed in most cancer cells and particularly highly expressed in well-differentiated types of cancer. Recently, it has been reported that vascular endothelial growth factor (VEGF)-A expression is induced by KGF in pancreatic cancer cells. VEGF-A is produced by some cancer cells and plays important roles in the angiogenesis and metastasis of cancer cells including those in the colorectum. In this study, we examined whether recombinant human KGF (rhKGF) induces major angiogenic growth factors including VEGF-A, FGF-2 and hepatocyte growth factor (HGF) in human colorectal cancer cells (HCT-15), which express a high level of KGFR, but a low or negligible level of KGF. rhKGF significantly increased the VEGF-A expression level in a serum-free medium of HCT-15 cells, but FGF-2 and HGF expression levels were too low to detect. Furthermore, the expression levels of the angiogenic growth factors were evaluated in KGF-transfected HCT-15 cells, which were induced to stably overexpress KGF by KGF gene transfection and mock-transfected cells (Mock). KGF and VEGF-A expression levels in the cells and the protein concentrations in serum-free medium were significantly higher in KGF-transfected HCT-15 cells than in Mock cells. In contrast, the FGF-2 and HGF mRNA expression levels were not significantly different between KGF-transfected HCT-15 cells and Mock cells and the protein concentrations in serum-free medium of the cells were below the detection level. These findings suggest that administration of rhKGF and over-expression of endogenous KGF genes in colorectal cancer cells increase VEGF-A production and may relate to angiogenesis in cancer.

Application of a multifractal analysis to study brain white matter abnormalities of schizophrenia on T2-weighted magnetic resonance imaging.

Multifractal analysis provides a precise quantitative description of the structural complexity of white matter (WM) on magnetic resonance imaging (MRI). To test this new technique as an aid to elucidating the pathology of schizophrenia, we examined a multifractal dimension (i.e. Deltaalpha) of WM in schizophrenia patients and their relations to clinical variables. We examined 16 patients with schizophrenia and 16 controls matched for age, sex and handedness. Delta alpha value of WM in the prefrontal and frontoparietal lobes and the corpus callosum (genu and splenium) on T2-weighted MRI was calculated. Delta alpha was not significantly different between groups in either region of interest. However, group-by-side interaction for Deltaalpha was found in the frontoparietal WM; post-hoc analysis revealed normal left dominant asymmetry in Deltaalpha for frontoparietal WM in control subjects, which was absent in schizophrenia patients. Furthermore, the patients with schizophrenia had a lower asymmetry coefficient ([R-L]/[R+L]) for Deltaalpha in frontoparietal WM. Relations to clinical symptoms from the Positive and Negative Syndrome Scale, Deltaalpha in corpus callosum, and the asymmetry coefficient in prefrontal WM were correlated with negative and general psychopathology symptom scores. Our results support the left-sided dysfunction hypothesis of schizophrenia and its relation to schizophrenic symptoms. Multifractal analysis reveals abnormal patterns of WM structures in schizophrenia that could be implicated in the disorder's etiology.

Associations between trait anxiety, insulin resistance, and atherosclerosis in the elderly: a pilot cross-sectional study.

Anxiety has been shown to be associated with cardiovascular disease. Atherosclerosis is responsible for the vast majority of cardiovascular events. Recent evidence is accumulating to show that insulin resistance (IR) plays a central role in determining the clinical manifestations of established atherosclerotic lesions. The current preliminary study aimed to investigate the associations between trait anxiety, IR, and atherosclerotic progression in healthy elderly subjects with normal fasting glucose and without metabolic syndrome. Thirty-five healthy elderly subjects (19 males and 16 females, mean age 64.5+/-4.7 years) were enrolled in this study. Trait anxiety was measured using a questionnaire corresponding to the trait anxiety scale taken from the State and Trait Anxiety Inventory. The homeostasis model assessment (HOMA-R) and plasma leptin-to-adiponectin ratio (L/A ratio), which are convenient IR indexes calculated from fasting blood sampling, were examined. As measurements of atherosclerotic progression, we performed two ultrasound methods, namely brachial artery flow-mediated dilation (FMD), an endothelial function assessment quantitatively reflecting the endothelium-dependent vasodilation responses following hyperemia, and measurement of carotid intima-media thickness (IMT). The severity of trait anxiety was positively associated with HOMA-R and L/A ratio, and negatively associated with the percent change of brachial artery FMD (%FMD). HOMA-R and L/A ratio were positively associated with carotid IMT, and L/A ratio was negatively associated with %FMD. These data showed the associations between trait anxiety, IR indexes and endothelial dysfunction or atherosclerotic progression. This pilot study, with a cross-sectional design, supports the promising role of IR for clarifying the pathophysiological mechanism by which anxiety contributes to an increasing risk of atherosclerosis.

Adiponectin multimer distribution, not absolute amount of plasma, correlates with depression severity in healthy elderly subjects.

Adiponectin is an adipocyte-specific secretory protein that circulates in serum as three oligomeric complexes known as the high, medium and low molecular weight form (HMW, MMW and LMW). HMW adiponectin has been suggested to be a better predictor of metabolic variables, and it was recently reported that the ratio of HMW to total adiponectin or to LMW, not the absolute amount of plasma adiponectin, might be crucial in determining insulin sensitivity. Insulin resistance (IR) is considered to be a primary component of vascular risk factors. Although the association of depression with atherosclerotic vascular diseases has been well documented, the contribution of IR to the evolution and progression of depression-associated vascular morbidity and mortality remains unknown. The current preliminary study showed that the ratio of HMW to total adiponectin or to LMW, not the absolute amount of plasma adiponectin, was negatively associated with depression severity in healthy elderly subjects without metabolic syndrome. This pilot study supports a promising role of adiponectin multimer distribution for clarifying the pathophysiological mechanism by which depression is associated with increased risk for IR, leading to cardiovascular disease, metabolic syndrome or type 2 diabetes.

Interactions among higher trait anxiety, sympathetic activity, and endothelial function in the elderly.

Negative psychological characteristics have been recognized as independent risk factors of cardiovascular disease (CVD). The purpose of this study was to evaluate the influence of depression and anxiety on cardiac autonomic function and endothelial function in healthy elderly subjects. Forty-six healthy elderly volunteers (mean age 60.8 years) were enrolled in this study. Cardiac autonomic function was assessed by spectral analysis of heart rate variability (HRV) with the head-up tilt test. Brachial artery endothelium-dependent flow-mediated dilation (FMD) was measured using high-resolution ultrasound. A significant positive correlation was observed between the State and Trait Anxiety Inventory (STAI)-trait score as a parameter of anxiety and HRV sympathetic modulation in the supine position (baseline), and a significant negative correlation between this score and the head-up-induced HRV sympathetic response from the baseline. The STAI-trait score also showed a significant negative correlation with the percent change of FMD (%FMD). Analysis using structural equation modeling showed that higher trait anxiety reduced %FMD via abnormalities of sympathetic activity. On the other hand, psychometric parameters of depression were not associated with any HRV component or %FMD. These results suggest that there are specific interactions among higher trait anxiety, abnormalities of sympathetic activity, and endothelial dysfunction. This finding may be useful in clarifying the pathophysiological mechanism by which anxiety is associated with increased risks for atherosclerosis and CVD.

Association between Scale-Free Brain Dynamics and Behavioral Performance: Functional MRI Study in Resting State and Face Processing Task.

The scale-free dynamics of human brain activity, characterized by an elaborate temporal structure with scale-free properties, can be quantified using the power-law exponent (PLE) as an index. Power laws are well documented in nature in general, particularly in the brain. Some previous fMRI studies have demonstrated a lower PLE during cognitive-task-evoked activity than during resting state activity. However, PLE modulation during cognitive-task-evoked activity and its relationship with an associated behavior remain unclear. In this functional fMRI study in the resting state and face processing + control task, we investigated PLE during both the resting state and task-evoked activities, as well as its relationship with behavior measured using mean reaction time (mRT) during the task. We found that (1) face discrimination-induced BOLD signal changes in the medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), amygdala, and fusiform face area; (2) PLE significantly decreased during task-evoked activity specifically in mPFC compared with resting state activity; (3) most importantly, in mPFC, mRT significantly negatively correlated with both resting state PLE and the resting-task PLE difference. These results may lead to a better understanding of the associations between task performance parameters (e.g., mRT) and the scale-free dynamics of spontaneous and task-evoked brain activities.

Plasma levels of adiponectin and tumor necrosis factor-alpha in patients with remitted major depression receiving long-term maintenance antidepressant therapy.

Adiponectin, an adipose tissue-specific plasma protein, is involved in insulin sensitization and has anti-atherosclerotic properties, whereas tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory protein, plays important roles in inflammatory endothelial injury and atherosclerotic changes. It has been reported that adiponectin and TNF-alpha inhibit each other's expression and production in adipocytes. Several in vitro studies indicated that antidepressant medications decreased the production of pro-inflammatory cytokines including TNF-alpha, but the effect of antidepressants on the expression of adiponectin is still unknown. We examined the plasma levels of TNF-alpha and adiponectin in patients with remitted depression receiving maintenance antidepressant therapy for longer than half a year, and compared the levels with those in healthy controls. The plasma levels of TNF-alpha and adiponectin in the remitted depression group were significantly lower and higher than those in the control group, respectively. This preliminary cross-sectional study suggests the possibility that maintenance antidepressant therapy may have anti-inflammatory effects and prevent the development of atherosclerosis.

Blood Transcriptomic Markers in Patients with Late-Onset Major Depressive Disorder.

We investigated transcriptomic markers of late-onset major depressive disorder (LOD; onset age of first depressive episode ≥ 50 years) from the genes expressed in blood cells and identified state-dependent transcriptomic markers in these patients. We assessed the genes expressed in blood cells by microarray and found that the expression levels of 3,066 probes were state-dependently changed in the blood cells of patients with LOD. To select potential candidates from those probes, we assessed the genes expressed in the blood of an animal model of depression, ovariectomized female mice exposed to chronic ultra-mild stress, by microarray and cross-matched the differentially expressed genes between the patients and the model mice. We identified 14 differentially expressed genes that were similarly changed in both patients and the model mice. By assessing statistical significance using real-time quantitative PCR (RT-qPCR), the following 4 genes were selected as candidates: cell death-inducing DFFA-like effector c (CIDEC), ribonuclease 1 (RNASE1), solute carrier family 36 member-1 (SLC36A1), and serine/threonine/tyrosine interacting-like 1 (STYXL1). The discriminating ability of these 4 candidate genes was evaluated in an independent cohort that was validated. Among them, CIDEC showed the greatest discriminant validity (sensitivity 91.3% and specificity 87.5%). Thus, these 4 biomarkers should be helpful for properly diagnosing LOD.

Gazefinder as a clinical supplementary tool for discriminating between autism spectrum disorder and typical development in male adolescents and adults.

BACKGROUND: Gaze abnormality is a diagnostic criterion for autism spectrum disorder (ASD). However, few easy-to-use clinical tools exist to evaluate the unique eye-gaze patterns of ASD. Recently, we developed Gazefinder, an all-in-one eye-tracking system for early detection of ASD in toddlers. Because abnormal gaze patterns have been documented in various ASD age groups, we predicted that Gazefinder might also detect gaze abnormality in adolescents and adults. In this study, we tested whether Gazefinder could identify unique gaze patterns in adolescents and adults with ASD. METHODS: We measured the percentage of eye fixation time allocated to particular objects depicted in movies (i.e., eyes and mouth in human face movies, upright and inverted biological motion in movies that presented these stimuli simultaneously, and people and geometry in movies that presented these stimuli simultaneously) by male adolescents and adults with ASD (N = 26) and age-matched males with typical development (TD; N = 35). We compared these percentages between the two groups (ASD and TD) and with scores on the social responsiveness scale (SRS). Further, we conducted discriminant analyses to determine if fixation times allocated to particular objects could be used to discriminate between individuals with and without ASD. RESULTS: Compared with the TD group, the ASD group showed significantly less fixation time at locations of salient social information (i.e., eyes in the movie of human faces without lip movement and people in the movie of people and geometry), while there were no significant groupwise differences in the responses to movies of human faces with lip movement or biological motion. In a within-group correlation analysis, a few of the fixation-time items correlated with SRS, although most of them did not. No items significantly correlated with SRS in both ASD and TD groups. The percentage fixation times to eyes and people, which exhibited large effect sizes for the group difference, could differentiate ASD and TD with a sensitivity of 81.0% and a specificity of 80.0%. CONCLUSIONS: These findings suggest that Gazefinder is potentially a valuable and easy-to-use tool for objectively measuring unique gaze patterns and discriminating between ASD and TD in male adolescents and adults.