A preliminary composite of blood-based biomarkers to distinguish major depressive disorder and bipolar disorder in adolescents and adults.

BACKGROUND: Since diagnosis of mood disorder heavily depends on signs and symptoms, emerging researches have been studying biomarkers with the attempt to improve diagnostic accuracy, but none of the findings have been broadly accepted. The purpose of the present study was to construct a preliminary diagnostic model to distinguish major depressive disorder (MDD) and bipolar disorder (BD) using potential commonly tested blood biomarkers. METHODS: Information of 721 inpatients with an ICD-10 diagnosis of MDD or BD were collected from the electronic medical record system. Variables in the nomogram were selected by best subset selection method after a prior univariable screening, and then constructed using logistic regression with inclusion of the psychotropic medication use. The discrimination, calibration and internal validation of the nomogram were evaluated by the receiver operating characteristic curve (ROC), the calibration curve, cross validation and subset validation method. RESULTS: The nomogram consisted of five variables, including age, eosinophil count, plasma concentrations of prolactin, total cholesterol, and low-density lipoprotein cholesterol. The model could discriminate between MDD and BD with an area under the ROC curve (AUC) of 0.858, with a sensitivity of 0.716 and a specificity of 0.890. CONCLUSION: The comprehensive nomogram constructed by the present study can be convenient to distinguish MDD and BD since the incorporating variables were common indicators in clinical practice. It could help avoid misdiagnoses and improve prognosis of the patients.

Fully continuous spiral phase plate for ultraintense optical vortices.

Ultraintense optical vortices carrying orbital angular momentum have attracted much attention in strong-field laser physics due to their spiral phase and hollow intensity. This Letter introduces a fully continuous spiral phase plate (FC-SPP) that enables the generation of an ultraintense Laguerre-Gaussian beam. An optimization design method based on the spatial filter technique and chirp-z transform is proposed to match the polishing processing and the tightly focusing performance. To enable its use in high-power laser systems, a large-aperture (200 × 200 mm2) FC-SPP has been fabricated on a fused silica substrate through magnetorheological finishing without the use of mask techniques. The far-field phase pattern and intensity distribution based on vector diffraction calculation were compared with those of ideal spiral phase plate and fabricated FC-SPP, which confirmed the high quality of the output vortex beams and their feasibility for producing high-intensity vortices.

Evaluation of changes in the cognitive function of adult cynomolgus monkeys under stress induced by audio-visual stimulation by applying modified finger maze test.

Stress in life is ubiquitous and unavoidable. Prolonged exposure to severe stress can lead to physical intolerance and impair cognitive function. Non-human primates are considered to be the best animal model for studying cognitive function, especially memory and attention. The finger maze test, with the advantages of short training time and lower cost, is recommended to evaluate learning and memory in non-human primates. In this study, we modified the finger maze test method to evaluate the cognitive function of single-housed cynomolgus monkeys. The flexibility and attention of cynomolgus monkeys were assessed by performing the complex task test and the stranger intrusion interference test, respectively, which increased the difficulty of obtaining rewards, and the ability of long-term memory was also evaluated by the memory test. Furthermore, the changes in cognitive function of the cynomolgus monkeys were tested by using the finger maze test after audio-visual stimulation, and the changes in the cortisol levels during stimulation were also analyzed. We found that, after completing the learning test, there was no significant decrease in their success rate when monkeys processed multitasks at the same time. In the stranger intrusion interference test, all subjects were distracted, but the accuracy did not decrease. The monkeys completed the memory tests in the 1st and 2nd months after the learning tests, with a high success rate. However, the success rate decreased significantly at the end of the 4th month. During audio-visual stimulation, the plasma cortisol level significantly increased in the first 2 months and was maintained at a high level thereafter. One month after audio-visual stimulation, the accuracy of the memory test was significantly reduced, and the total time of distraction was significantly prolonged. In conclusion, chronic audio-visual stimulation can increase blood cortisol levels and impair cognitive function. The modified finger maze test can evaluate many aspects of cognitive function and assess the changes in the cognitive function of adult cynomolgus monkeys under stress.

BDNF Alleviates Microglial Inhibition and Stereotypic Behaviors in a Mouse Model of Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is a severe mental illness characterized by obsessions and compulsions. However, its underlying mechanisms remain to be elucidated. Recent studies have suggested that neuroimmune dysregulation is involved in the pathogenesis of OCD. To investigate the role of microglia in this disorder, we established a pharmacological mouse model by using the serotonin (5-HT) 1A/1B receptor agonist RU24969 to mimic monoamine dysregulation in OCD, and we examined the morphological and functional alterations of microglia in this model. We found that RU24969 treatment led to compulsive circling behavior in mice. Strikingly, we found that the density and mobility of microglia in the prelimbic cortex were much lower in RU24969-treated mice than in control mice. Moreover, the expression of cytokines and chemokines, including BDNF, IL-1ß, IL-6, TNFα, CD80, CD86, MHC-I, and MHC-II, also decreased in RU24969-treated mice. Importantly, we found that injection of BDNF or induction of BDNF expression by trehalose completely reversed microglial dysfunction and reduced stereotypic behavior. These results indicate that microglial dysfunction is closely related to stereotypic behaviors in our mouse model of OCD and that BDNF could be an effective treatment for stereotypic behaviors.

Correlations Between Working Memory Impairment and Neurometabolites of the Prefrontal Cortex in Drug-Naive Obsessive-Compulsive Disorder.

PURPOSE: This study aimed to investigate the mechanism of working memory (WM) impairment in drug-naive obsessive-compulsive disorder (OCD) by using neuropsychological tests and proton magnetic resonance spectroscopy (1H-MRS). PATIENTS AND METHODS: A total of 55 patients with drug-naive OCD and 55 healthy controls (HCs) were recruited for this study. The working memory (WM) was evaluated using the digit span test (DST), visual space memory test (VSMT), and the 2-back task and stroop color word test (SCWT). The bilateral metabolite levels of the prefrontal cortex (PFC) were evaluated by 1H-MRS, then determined the ratios of N-acetyl aspartate (NAA), choline-containing compounds (Cho), and myo-inositol (MI) to creatine (Cr). The independent sample t-test was used to analyse the differences in WM performance and neurometabolite ratios. Multivariate linear regression analysis was performed to screen the influential factors of WM, with an introduction level of 0.05 and a rejection level of 0.10. RESULTS: 1) Patients with OCD performed significantly worse on DST (score), VSMT (score), 2-back task (accuracy rate), SCWT (execution time) when compared with HCs. 2) NAA/Cr and Cho/Cr in the left PFC (lPFC) and MI/Cr ratios in the bilateral PFC of OCD patients were significantly lower when compared to HCs. 3) For OCD patients, the NAA/Cr ratio in the lPFC was negatively correlated with the score of DST (forwards), the Cho/Cr ratio in the lPFC was positively correlated with the accuracy rate of 2-back task, and the MI/Cr ratio in the right PFC (rPFC) was positively correlated with the score of DST (forwards) and the accuracy rate of VSMT. We also found that the compulsive symptoms showed a positive correlation with MI/Cr ratio of the rPFC. CONCLUSION: Drug-naive OCD patients have demonstrated WM impairments, including phonological loop, visual-spatial sketchpad and central executive system, and the WM impairments might be associated with hypometabolism in the PFC, especially the lPFC.

Distinct behavioral traits and associated brain regions in mouse models for obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a mental disease with heterogeneous behavioral phenotypes, including repetitive behaviors, anxiety, and impairments in cognitive functions. The brain regions related to the behavioral heterogeneity, however, are unknown. METHODS: We systematically examined the behavioral phenotypes of three OCD mouse models induced by pharmacological reagents [RU24969, 8-hydroxy-DPAT hydrobromide (8-OH-DPAT), and 1-(3-chlorophenyl) piperazine hydrochloride-99% (MCPP)], and compared the activated brain regions in each model, respectively. RESULTS: We found that the mouse models presented distinct OCD-like behavioral traits. RU24969-treated mice exhibited repetitive circling, anxiety, and impairments in recognition memory. 8-OH-DPAT-treated mice exhibited excessive spray-induced grooming as well as impairments in recognition memory. MCPP-treated mice showed only excessive self-grooming. To determine the brain regions related to these distinct behavioral traits, we examined c-fos expression to indicate the neuronal activation in the brain. Our results showed that RU24969-treated mice exhibited increased c-fos expression in the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), prelimbic cortex (PrL), infralimbic cortex (IL), nucleus accumbens (NAc), hypothalamus, bed nucleus of the stria terminalis, lateral division, intermediate part (BSTLD), and interstitial nucleus of the posterior limb of the anterior commissure, lateral part (IPACL), whereas in 8-OH-DPAT-treated mice showed increased c-fos expression in the ACC, PrL, IL, OFC, NAc shell, and hypothalamus. By contrast, MCPP did not induce higher c-fos expression in the cortex than control groups. CONCLUSION: Our results indicate that different OCD mouse models exhibited distinct behavioral traits, which may be mediated by the activation of different brain regions.

Frequency division combined machining method to improve polishing efficiency of continuous phase plate by bonnet polishing.

Continuous phase plate (CPP), as a key diffractive optical element, is difficult to manufacture owing to its random and small features. In this paper, a novel frequency division combined machining (FDCM) method was proposed to improve polishing efficiency of CPP by optimizing the tool influence functions (TIFs) over targeted frequency bands. In addition, the convergence rate of power spectral density (CR-PSD) was proposed to evaluate the correct ability of TIF in different frequency bands, and to determine the division frequency for the combined processing. Through simulation verification, the combined processing with optimized TIFs by FDCM enabled high precision in less total time than that with single TIF processing. The experimental results verified that the method could imprint a 300 × 300 mm CPP with residual root-mean-square 24.7 nm after approximately 6-h bonnet polishing. Comparing the focal spots of designed and fabricated CPPs, the deviation of their energy concentration within 500 microns is only 0.22%. Hence, bonnet polishing using the FDCM is a new technical option for the production of large-aperture CPPs. Furthermore, the FDCM method shows a significant increase in efficiency, and it could be a generic method for CPP processing through other technologies, including magnetorheological and ion beam finishing.

Dysregulated plasma levels of miRNA-132 and miRNA-134 in patients with obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a severe, chronic, disabling neuropsychiatric disorder, the pathophysiology of which has yet to be fully understood. In this study, we aimed to detect the levels of miRNA-132 and miRNA-134 in the plasma of patients with OCD and to analyze the factors influencing OCD. METHODS: The levels of miRNA-132 and miRNA-134 in peripheral blood of 30 patients with OCD and 32 normal controls were detected by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Patients were assessed using clinical scales, including the Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD), and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). RESULTS: The plasma levels of miRNA-132 and miRNA 134 in the OCD group were significantly higher than those in the control group (P<0.05). There was no significant correlation between the plasma levels of miR-132 and miR-134 in the OCD group and general demographic (gender, age, and education level) and clinical characteristics (duration of disease, HAMA, HAMD, and Y-BOCS scores). CONCLUSIONS: Patients with OCD have abnormal plasma levels of miRNA-132 and miRNA-134, which may influence the number of dendrites in the cerebral cortex and formation of synapses. Therefore, miRNA-132 and miRNA-134 plasma levels should be considered as potential biomarkers for OCD detection.

Alterations of white matter fractional anisotropy in unmedicated obsessive-compulsive disorder.

BACKGROUND: Abnormalities in white matter (WM) have previously been reported in patients with obsessive-compulsive disorder (OCD). However, there was some inconsistency in the results obtained for altered regions of WM. The aim of this study was to investigate fractional anisotropy (FA) in the WM of the whole brain in patients with OCD by using diffusion tensor imaging (DTI). METHODS: In total, 28 unmedicated patients with OCD and 28 healthy volunteers underwent DTI scan. A voxel-based analysis was used to compare FA values in WM of the two groups at a voxel threshold of P<0.005 with an extent threshold of k>72 voxels (P<0.05; Alphasim correction). Subsequently, correlation analysis was conducted in order to find the correlation between the mean FA values in significantly altered brain regions and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores of the OCD patients. RESULTS: Compared with healthy volunteers, the OCD patients had lower FA value in the left lingual gyrus, right midbrain, and right precuneus. There were no regions with significantly higher FA values in OCD patients compared with healthy volunteers. The mean FA values in the above regions (left lingual, r=0.019, P=0.923; right midbrain, r=-0.208, P=0.289; and right precuneus, r=-0.273, P=0.161) had no significant correlation with the Y-BOCS scores of the OCD patients. CONCLUSION: The findings of this study suggest that alterations in WM of the left lingual gyrus, right midbrain, and right precuneus are associated with the pathophysiology mechanism of OCD, and these microstructural alterations do not correlate with symptom severity of OCD.

Neuroleptic malignant syndrome and subsequent clozapine-withdrawal effects in a patient with refractory schizophrenia.

Here, we report a female patient developing neuroleptic malignant syndrome following the use of a combination of clozapine and haloperidol. Subsequently, the patient presented withdrawal effects after an abrupt discontinuation of clozapine. Psychiatrists not aware of possible clozapine-withdrawal effects may misdiagnose as a part of the primary mental illness or as the initial symptoms worsening, if unrecognized.

[Magnetic resonance spectroscopy in lenticular nucleus of Bipolar II disorder and its relation with cognitive function].

OBJECTIVE: To explore the magnetic resonance spectroscopy characteristics of lenticular nucleus in Bipolar II disorder and its relation with cognitive function. METHODS: Thirty Bipolar II disorder patients in hospital from 2012 September to 2013 April and twenty healthy controls were evaluated with Multi-Voxel 1H-MRS scans on lenticular nucleus to assess the NAA, Cho, Cr and MI. All subjects were assessed for attention using the Stroop Test and executive function by Wisconsin card sorting test. RESULTS: NAA, Cho, Cr in right lenticular nucleus and Cr in left lenticular nucleus were lower than healthy controls (P < 0.05). The patients showed significant cognitive impairment in all aspects of Stroop Test and Wisconsin card sorting test (P < 0.05). NAA in right lenticular nucleus was positively correlated with correct number of Stroop-CW. CONCLUSIONS: Neural dysfunction in right lenticular nucleus of Bipolar II disorder may influence attention function. Cellular energy metabolism rate was reduced in bilateral lenticular nucleus.

Neurocognitive dysfunction and regional cerebral blood flow in medically naïve patients with obsessive-compulsive disorder.

Previous research characterizes obsessive compulsive disorder (OCD) as a complex neurobehavioral disorder that may have multiple etiologies ( den Braber et al., 2008 ). This study analyzed neurocognitive function and change in regional cerebral blood flow (rCBF) to characterize OCD. Neurocognitive function and rCBF were examined in medically naïve patients with OCD and contrasted with controls. Results of this study indicated that the neurocognitive functions impaired in OCD are memory, attention, and executive function, which are primarily associated with the frontal and occipital lobes. Dysfunction in the basal ganglia and occipital lobes were associated with OCD and may be an etiological factor in the disorder.

Evaluation of headache and regional cerebral flood flow in patients with migraine.

PURPOSE OF THE REPORT: The aim of this study is to observe the abnormalities of regional cerebral blood flow (rCBF) in migraine patients and to evaluate its relation to the severity of the headache in patients with migraine. PATIENTS AND METHODS: The rCBF imaging was done on 19 patients with migraine and 15 normal controls using single-photon emission computed tomography (SPECT). The abnormal character of cerebral perfusion function was analyzed with Statistical Parametric Mapping (SPM) software, and the headache grade of patients was evaluated with the headache severity measuring scale. RESULTS: The results of SPM analysis demonstrated a decreased rCBF on both sides of the frontal and temporal lobes, left parietal lobe, and right occipital lobe (P < 0.001), and increased rCBF focus on the left prefrontal lobe and right temporal lobe (P < 0.001). The headache scores in migraineurs were correlated to the rCBF on the bilateral temporal lobes and right frontal lobe (P < 0.001). CONCLUSIONS: The migraineurs had lower rCBF at the frontal and temporal lobes, and the lower rCBF was correlated to the degree of headache.

Pharmacotherapy response and regional cerebral blood flow characteristics in patients with obsessive-compulsive disorder.

OBJECTIVE: To analyze the correlation between the pharmacotherapy response and the characteristics of the pre-treatment regional cerebral blood flow (rCBF) in patients with obsessive-compulsive disorder (OCD). METHODS: Single-photon emission-computed tomography (SPECT) was used to determine the pre-treatment rCBF in 30 OCD patients and 30 normal controls. Based on their clinical remission response, the subjects were divided into two groups: selective serotonin reuptake inhibitors (SSRIs) and SSRIs plus quetiapine. The subjects with clinical remission response were identified after treatment for a period of 24 weeks, and the rCBF imaging data were processed using statistical parametric mapping (SPM) software with two-sample Z-tests. RESULTS: Nineteen OCD patients who achieved clinical remission were included in the study. Increased rCBF in forebrain regions, including the frontal lobe, cingulate gyrus, hypothalamus, and basal ganglia, was found in 11 responders to SSRIs compared to normal control patients. The eight SSRI plus quetiapine responders exhibited a decrease in rCBF within posterior brain regions, including the parietal lobe, cerebellar vermis, and occipital lobe, and an increase in rCBF in the frontal lobe, thalamus, basal ganglia, and cerebellum tonsil compared to normal control patients. CONCLUSIONS: The characteristics of increased rCBF in forebrain regions and decreased rCBF in posterior brain regions before treatment of OCD patients was a potentially predictor of treatment response to guide treatment options.

Prolactin serum levels in first-episode neuroleptic-naive patients with pituitary microadenoma and comorbid psychosis.

This study was designed to explore the relationship between pituitary microadenoma and psychosis and to evaluate the role that prolactin plays in pituitary microadenoma and comorbid psychosis. In this study, the prolactin serum levels were compared between 74 first-episode drug-naive patients with a pituitary microadenoma with psychosis (PMP), and 58 patients with a pituitary microadenoma with no psychosis (PMNP). Patients with PMP had significantly higher prolactin serum levels; male patients with PMP had a mean [S.D.] prolactin level of 705.4 uIU/ml [226.1] vs. 433.1 uIU/ml [58.4] for male patients with PMNP, while female patients with PMP had a mean prolactin level of 1890.1 uIU/ml [1138.7] vs. 978.6 uIU/ml [657.9] for female patients with PMNP. The size of microadenoma in the patients with PMP was larger than those in the patients with PMNP, regardless of sex. Our data suggested that a higher prolactin serum level is a characteristic of first-episode neuroleptic-naive patients with PMP.

Valproate (VPA)-associated hyperammonemic encephalopathy independent of elevated serum VPA levels: 21 cases in China from May 2000 to May 2012.

Valproate (VPA) is a medication that is widely used in the treatment of neurological and psychiatric disorders, such as epilepsy and bipolar disorder. Valproate-induced hyperammonemic encephalopathy (VHE) is a rare central nervous system adverse effect of this medication that is characterized by impaired consciousness, which can range from drowsiness to coma; increased seizure frequency; acute cognitive symptoms; and gastrointestinal symptoms. In this manuscript, we report a single case and also review previous cases of VHE (n=20) in Chinese patients to identify risk factors for VHE. Increasing clinicians' awareness of VHE during concomitant VPA therapy is of utmost importance. Serum ammonia level is a useful and important diagnostic test. The discontinuation of VPA is currently the mainstay of treatment for VHE.

Hallucinations and comorbid renal tubular acidosis caused by topiramate in a patient with psychiatric history.

Few studies have shown that topiramate may induce psychiatric symptoms and metabolic disorders, respectively. Here, we reported a 13-year-old female who presented with topiramate-induced hallucinations and comorbid renal tubular acidosis. She had a history of psychiatric illness and had been taking the medication for 3 months without prior side effects. After the discontinuation of topiramate, she was treated with supplementary potassium and sodium bicarbonate. Subsequently, her psychiatric symptoms and biochemical findings improved. Recognition of drug-induced psychotic symptoms and renal tubular acidosis is important during concomitant topiramate therapy in psychiatric clinic.

[Change characteristics of regional cerebral blood flow and curative efficacy in patients with obsessive-compulsive disorder].

OBJECTIVE: To explore the change characteristics of regional cerebral blood flow (rCBF) and its correlation with curative efficacy in patients with obsessive-compulsive disorder (OCD). METHODS: The images of rCBF and computed tomography (CT) were acquired from 30 OCD and 30 normal controls by single photon emission computed tomography (SPECT) and CT. The tomographic data of rCBF were normalized, smoothed and statistically processed with the statistical parametric mapping (SPM) software with two-sample Z-test. And the OCD grade was evaluated with the Y-BOCS at pre- and post-medication. RESULTS: The abnormal results of CT were not found. The SPM Z-test showed that the sections of higher rCBF in the OCD patients were predominantly located in basal ganglia and occipital lobe compared with the normal controls (P < 0.001). The scores of Y-BOCS in 30 patients were markedly lower at post-medication than those at pre-medication (24 ± 7 vs 11 ± 6, P < 0.001). At post-medication, the scores of Y-BOCS with higher rCBF in basal ganglia and occipital lobe were higher than those in basal ganglia or occipital lobe (P < 0.05). CONCLUSION: The OCD patients have higher rCBF in basal ganglia and occipital lobe. The curative efficacy of OCD with higher rCBF in basal ganglia and occipital lobe is worse than that in basal ganglia or occipital lobe.

Serum uric acid levels and the clinical characteristics of depression.

OBJECTIVE: This study was designed to investigate the correlation between serum uric acid (UA) levels and the clinical characteristics of depression. DESIGN AND METHODS: The serum UA levels were measured in 124 patients with depression, 660 patients with different types of other mental disorders (OMD) and 42 healthy subjects. Clinical characteristics of depression and OMD were also investigated. RESULTS: Depressive patients (271.97 ± 77.50 µmol/L) had significantly lower UA levels than those with delirium, dementia, amnesia and other cognitive disorders (339.95 ± 141.74 µmol/L, P=0.004), substances related disorders (359.61 ± 125.02 µmol/L, P=0.022), schizophrenia (341.03 ± 106.84 µmol/L, P=0.000), schizoaffective disorder (336.78 ± 155.49 µmol/L, P=0.024), bipolar disorder (323.04 ± 108.70 µmol/L, P=0.008) and the healthy control group (315.76 ± 87.50 µmol/L, P=0.012). We also found that the UA levels of depressive patients normalised after a five week treatment with antidepressants. CONCLUSION: Our data suggested that a lowered UA level is another characteristic of depression.