Parallel detection of multiple zoonotic parasites using a real-time fluorogenic loop-mediated isothermal amplification-based quadruple-sample microfluidic chip.

Zoonotic parasites pose significant health risks globally. In the present study, we combined a microfluidic chip with loop-mediated isothermal amplification (on-chip LAMP) to detect five zoonotic parasites: Toxoplasma gondii, Cryptosporidium parvum, Cryptosporidium hominis, Clonorchis sinensis, and Taenia solium. This method enabled the simultaneous parallel analysis of five genetic markers from a maximum of four samples per chip. The on-chip LAMP assay was conducted in a highly automated format via the addition (by pipetting) of each sample in a single operation. The reaction was performed in volumes as low as 5 µL at a temperature of 65°C for 60 min, achieving limits of detection ranging from 10-2 to 10-3 pg./µL of recombinant plasmid DNA. All the time-to-positive values were less than 40 min, and almost all the coefficients of variation were less than 10%, even when using limit of detection concentrations for multiple pathogens, indicating robust reproducibility among replicates. The clinical sensitivity and specificity for detecting 135 field samples were 98.08 and 97.59%, respectively, compared with traditional biological methods, indicating good applicability in the detection of field samples. This on-chip LAMP assay allows for low reagent consumption, ease of operation, and multiple analyses of samples and genetic targets, and is applicable for on-site detection and the routine monitoring of multiple zoonotic parasites.

Prevalence, Demographic, and Clinical Correlates of Comorbid Depressive Symptoms in Chinese Psychiatric Patients With Alcohol Dependence.

BACKGROUND: Depressive symptoms are common among psychiatric patients with alcohol dependence (AD). However, the prevalence and clinical correlates of comorbid depressive symptoms are less well studied in Chinese Han patients. METHODS: In this hospital-based survey, we recruited 378 psychiatric patients diagnosed with AD according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV). All patients completed the Beck Depression Inventory (BDI) to evaluate depressive symptoms and the Alcohol Use Disorders Identification Test (AUDIT) to assess the severity of drinking. RESULTS: Compared to patients without depressive symptoms, 48.9% (185/378) of the patients with comorbid depressive symptoms were younger, had a more unstable marital status, had a higher AUDIT total score, and had a higher adverse consequences subscore (all P < 0.05). Further logistic regression analysis showed that unstable marital status (Odds ratios [OR] = 2.20, 95% confidence interval [CI] 1.21-3.99) and AUDIT total score (OR=1.07, 95% CI 1.03-1.11) were significantly associated with depressive symptoms. CONCLUSIONS: Our findings indicate high comorbidity between AD and depressive symptoms in Chinese psychiatric patients. Moreover, some variables are correlates of comorbid depressive symptoms. Particular attention should be paid to the early detection and intervention for this comorbid condition and its risk factors.

Memory Retrieval-Extinction Combined With Virtual Reality Reducing Drug Craving for Methamphetamine: Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Relapse, often precipitated by drug-associated cues that evoke craving, is a key problem in the treatment of methamphetamine use disorder (MUD). Drug-associated memories play a major role in the maintenance of relapse. Extinction training is a common method for decreasing drug craving by suppressing drug-associated memories. However, the effects are often not permanent, which is evident in form of spontaneous recovery or renewal of cue-elicited responses. Based on memory reconsolidation theory, the retrieval-extinction (R-E) paradigm may be more effective in decreasing spontaneous recovery or renewal responses than extinction. After the original memory reactivated to a labile state, extinction will be introduced within the reconsolidation window, thereby updating drug-associated memories. However, there are still some controversial results, which suggest that the reactivation of drug-associated memories and the 10 min-6 h of limited time window are two main elements in the R-E protocol. Virtual reality (VR) is supposed to promote memory reactivation by providing vivid drug-related stimuli when compared with movies. OBJECTIVE: The aim of this study is to examine the effectiveness of R-E training combined with VR on reducing spontaneous recovery or renewal of cue-elicited responses, in comparison to extinction, R-E training provided outside the time window of 6 h and R-E training retrieved using videos, in methamphetamine abusers. METHODS: The study is a parallel matched controlled study including 95 participants with MUD. Participants will be randomly assigned to either a R-10 min-E group (methamphetamine-related cues retrieval in VR followed by extinction after 10 min) or a NR-10 min-E group (neutral cues retrieval in VR followed by extinction after 10 min) or a R-6 h-E group (methamphetamine-related cues retrieval in VR followed by extinction after 6 h) or a RV-10 min-E group (methamphetamine-related cues retrieval in videos followed by extinction after 10 min). Cue-evoked craving and reactivity will be assessed at pre-test and at 1 day, 1 week, 1 month, and 6-month post-tests. DISCUSSION: To our knowledge, this study will probably be the first study to examine the efficacy of R-E training combined with VR to reduce cue-evoked responses in people with MUD. This innovative non-pharmacological intervention targeting drug-associated memories may provide significant clinical implications for reducing relapse, providing the study confirms its efficacy. CLINICAL TRIAL REGISTRATION: The trial is registered with Chinese Clinical Trial Registry at 17 October 2018, number: ChiCTR1800018899, URL: http://www.chictr.org.cn/showproj.aspx?proj=30854.

Smartphone Use and Sleep Quality in Chinese College Students: A Preliminary Study.

BACKGROUND: Chinese college students are at high risk of sleep problems, and smartphone use is common among this population. However, the relationship between smartphone use characteristics and sleep problems in Chinese college students has been inadequately studied. In this preliminary study, we examined the association of poor sleep quality with smartphone use in a sample of Chinese college students from a health vocational college in Changsha, China. METHODS: A total of 439 college students completed a self-report questionnaire containing the Pittsburgh Sleep Quality Index (PSQI) and questions regarding demographic information, psychosocial factors, physical health, smartphone use characteristics, and mobile phone addiction (MPA). RESULTS: The results showed that the prevalence of poor sleep quality (PSQI > 7) in Chinese college students was 9.8%. In multiple logistic regression analysis, poor sleep quality was significantly associated with male gender (OR: 2.80, P: 0.022), not having good physical health (OR: 2.61, P: 0.020), headache (OR: 2.47, P: 0.014), more severe depressive symptoms (OR: 2.17, P: 0.049), > four years of smartphone use (OR: 3.38, P: 0.001), > five hours of daily smartphone use (OR: 2.19, P: 0.049), and more severe inability to control MPA craving (OR: 2.04, P: 0.040). CONCLUSION: Our findings suggest that excessive smartphone use and MPA are associated with poor sleep quality in a sample of Chinese college students from a health vocational college. Because of the limited sample representativeness and cross-sectional design of this study, large-scale prospective representative studies are warranted to confirm these associations.

Neurofunctional Differences Related to Methamphetamine and Sexual Cues in Men With Shorter and Longer Term Abstinence Methamphetamine Dependence.

BACKGROUND: Stimulant use and sexual behaviors have been linked in behavioral and epidemiological studies. Although methamphetamine-related neurofunctional differences have been investigated, few studies have examined neural responses to drug and sexual cues with respect to shorter or longer term methamphetamine abstinence in individuals with methamphetamine dependence. METHODS: Forty-nine men with shorter term methamphetamine abstinence, 50 men with longer term methamphetamine abstinence, and 47 non-drug-using healthy comparison men completed a functional magnetic resonance imaging cue-reactivity task consisting of methamphetamine, sexual, and neutral visual cues. RESULTS: Region-of-interest analyses revealed greater methamphetamine cue-related activation in shorter term methamphetamine abstinence and longer term methamphetamine abstinence individuals relative to healthy comparison men in the ventromedial prefrontal cortex. A significant interaction of group and condition in the anterior insula was found. Relative to healthy comparison participants, both shorter term methamphetamine abstinence and longer term methamphetamine abstinence groups displayed greater sexual cue-related anterior insula activation relative to methamphetamine cues and neutral cues, but there were no differences between shorter term methamphetamine abstinence and longer term methamphetamine abstinence groups in anterior insula responses. Subsequent whole-brain analyses indicated a group-by-condition interaction with longer term methamphetamine abstinence participants showing greater sexual-related activation in the left superior frontal cortex relative to healthy comparison men. Shorter term methamphetamine abstinence participants showed greater superior frontal cortex activation to sexual relative to neutral cues, and longer term methamphetamine abstinence participants showed greater superior frontal cortex activation to sexual relative to neutral and methamphetamine cues. CONCLUSIONS: The findings suggest that abstinence from methamphetamine may alter how individuals respond to drug and sexual cues and thus may influence drug use and sexual behaviors. Given the use of methamphetamine for sexual purposes and responses to natural vs drug rewards for addiction recovery, the findings may have particular clinical relevance.

Prevalence and correlates of suicide attempt among Chinese individuals receiving methadone maintenance treatment for heroin dependence.

To date, there have been very limited studies regarding the clinical epidemiology of attempted suicide in Chinese individuals with heroin-dependence. The objective of this study was to examine the prevalence and correlates of suicide attempt in Chinese individuals receiving methadone maintenance treatment for heroin dependence. Demographic, clinical, and psychosocial data of 603 methadone-maintained patients with heroin dependence were collected with a standardized self-administered questionnaire. The presence of suicide attempt and antisocial personality disorder was assessed by using a single question and the Mini-International Neuropsychiatric Interview 5.0. The one-month and lifetime prevalence rates of suicide attempt were 9.5% and 34.2%, respectively. In multivariable logistic regression, lifetime suicide attempt was significantly associated with female gender (OR = 2.81), being 20-39 years old (OR = 2.73), an education level of primary school or lower (OR = 2.07), poor economic status (OR = 3.06), injecting heroin before methadone maintenance treatment (OR = 2.92), depressive symptoms (OR = 3.46), anxiety symptoms (OR = 1.88), and antisocial personality disorder (OR = 2.85). Suicide attempt is very prevalent among Chinese individuals receiving methadone maintenance treatment for heroin dependence. Services for patients with heroin dependence in methadone maintenance treatment clinics in China should include psychosocial supports, periodic screening for suicide attempt and other suicidal behaviors and, when needed, psychiatric treatment and crisis intervention.

Craving Responses to Methamphetamine and Sexual Visual Cues in Individuals With Methamphetamine Use Disorder After Long-Term Drug Rehabilitation.

Studies utilizing functional magnetic resonance imaging (fMRI) cue-reactivity paradigms have demonstrated that short-term abstinent or current methamphetamine (MA) users have increased brain activity in the ventral striatum, caudate nucleus and medial frontal cortex, when exposed to MA-related visual cues. However, patterns of brain activity following cue-reactivity in subjects with long-term MA abstinence, especially long-term compulsory drug rehabilitation, have not been well studied. To enrich knowledge in this field, functional brain imaging was conducted during a cue-reactivity paradigm task in 28 individuals with MA use disorder following long-term compulsory drug rehabilitation, and 27 healthy control subjects. The results showed that, when compared with controls, individuals with MA use disorder displayed elevated activity in the bilateral medial prefrontal cortex (mPFC) and right lateral posterior cingulate cortex in response to MA-related images. Additionally, the anterior cingulate region of mPFC activation during the MA-related cue-reactivity paradigm was positively correlated with craving alterations and previous frequency of drug use. No significant differences in brain activity in response to pornographic images were found between the two groups. Compared to MA cues, individuals with MA use disorder had increased activation in the occipital lobe when exposed to pornographic cues. In conclusion, the present study indicates that, even after long-term drug rehabilitation, individuals with MA use disorder have unique brain activity when exposed to MA-related cues. Additionally, our results illustrate that the libido brain response might be restored, and that sexual demand might be more robust than drug demand, in individuals with MA use disorder following long-term drug rehabilitation.

The effect of Fe2O3 crystal phases on CO2 hydrogenation.

The effect of Fe2O3 crystal phases on their performance in CO2 hydrogenation was studied. α-Fe2O3 crystal was prepared by precipitation method from Fe(NO3)3·9H2O and (NH4)2CO3, and γ-Fe2O3 was prepared by grinding Fe(NO3)3·9H2O and L(+)-Tartaric acid in agate mortar completely. The crystal phases of Fe2O3 influence the distribution of promoter Zn, K and Cu on catalysts. The dispersity of K on γ-Fe2O3 surface is higher than α-Fe2O3. On the contrary, Cu and Zn are more dispersive on α-Fe2O3 surface than γ-Fe2O3. The catalyst in γ-Fe2O3 phase is easily reduced relative to the catalyst in α-Fe2O3 phase. The former presents higher CO2 conversion and C2+ hydrocarbon selectivity than the latter in CO2 hydrogenation.

Prevalence, correlates and treatment status of alcohol use disorders in psychiatric patients in China.

OBJECTIVE: To determine the prevalence, associated factors and treatment status of alcohol use disorders (AUDs) in psychiatric patients in China. METHODS: We asked 24,379 consecutive patients aged ≥18years who presented at the psychiatric departments in eight hospitals in 2013 whether they had consumed alcoholic beverages in the previous month. Of the 2964 (12.2%) patients who answered yes and were then screened with the Alcohol Use Disorders Identification Test (AUDIT), 1304 (5.3%) screened positive (AUDIT≥7) and, based on DSM-IV criteria, were diagnosed with AUDs by psychiatrists. The treatments prescribed for them were also recorded. Logistic regression was used to identify AUDs associated factors. RESULTS: The prevalence of AUDs was 2.4% (95% CI: 2.2-2.6%). None of the patients diagnosed with AUDs had got medical treatment for preventing relapse. The risk factors for AUDs were middle-aged or elderly (OR=1.86, 95% CI: 1.23-2.80), and consuming beverages with high degree of alcohol content (OR=2.92, 95% CI: 2.11-4.06). CONCLUSIONS: The prevalence of AUDs in psychiatric patients in China was not high, but the rate of treatment was dramatically low, indicating the serious neglect of AUDs. Our study suggests an urgent need to improve the situation of unmet need for treatment of psychiatric patients with AUDs.

Decreased Thalamocortical Connectivity in Chronic Ketamine Users.

Disintegration in thalamocortical integration suggests its role in the mechanistic 'switch' from recreational to dysregulated drug seeking/addiction. In this study, we aimed to address whether thalamic nuclear groups show altered functional connectivity within the cerebral cortex in chronic ketamine users. One hundred and thirty subjects (41 ketamine users and 89 control subjects) underwent rsfMRI (resting-state functional Magnetic Resonance Imaging). Based on partial correlation functional connectivity analysis we partitioned the thalamus into six nuclear groups that correspond well with human histology. Then, in the area of each nuclear group, the functional connectivity differences between the chronic ketamine user group and normal control group were investigated. We found that the ketamine user group showed significantly less connectivity between the thalamic nuclear groups and the cortical regions-of-interest, including the prefrontal cortex, the motor cortex /supplementary motor area, and the posterior parietal cortex. However, no increased thalamic connectivity was observed for these regions as compared with controls. This study provides the first evidence of abnormal thalamocortical connectivity of resting state brain activity in chronic ketamine users. Further understanding of pathophysiological mechanisms of the thalamus in addiction (ketamine addiction) may facilitate the evaluation of much-needed novel pharmacological agents for improved therapy of this complex disease.

Docosahexaenoic acid intake ameliorates ketamine-induced impairment of spatial cognition and learning ability in ICR mice.

Several studies have reported the ketamine-induced cognitive impairment. Docosahexaenoic acid (DHA) supplementation improves cognitive function in human infants and protects against learning impairment in patients with Alzheimer's disease (AD). In this study, we investigated the effect of DHA on ketamine-induced impairment of spatial cognition and learning ability in Institute of Cancer Research (ICR) mice. Morris water maze (MWM) was used to assess spatial learning and memory. Gamma-aminobutyric acid (GABA) levels in the hippocampus and prefrontal cortex were measured using high-performance liquid chromatography (HPLC). The results showed that intraperitoneal injection of ketamine (30mg/kg, twice per day) for 4 weeks led to the decline of spatial cognitive ability in mice, and 420mg/(kgd) DHA supplementation for 6 weeks improved ketamine-induced spatial cognitive impairment to a certain extent. The up-regulation of GABA levels in the hippocampus and prefrontal cortex was related to the improvement in spatial learning. Our results suggested that DHA supplementation would be a promising intervention to improve ketamine-induced spatial memory and cognitive dysfunction, and this effect of DHA might be correlated with the up-regulation of GABA levels.

[Clinical characteristics and cognitive function of unipolar and bipolar depression].

OBJECTIVE: To determine the clinical characteristics and cognitive dysfunction of bipolar depression and unipolar depression. METHODS: Fifty patients with unipolar depression, 48 bipolar depression, and 50 normal controls were assessed with Hamilton Depression Scale, Hamilton Anxiety Scale, Life Events Scale, and The Wisconsin Card Sorting Test. General demographic data, clinical data, and the scores of recognitive function in the 3 groups were compared. RESULTS: The patients with bipolar depression occured at young age and had obvious family history compared with those with unipolar depression. The patients with bipolar or unipolar disorders had lower scores in most neuropsychological tests than those in the control group (P<0.05). The patients with bipolar depression in understanding memory and Wisconsin card sorting test were worse than those with unipolar depression (P<0.05). CONCLUSION: There is cognitive dysfunction in patients with bipolar or unipolar disorder. Understanding memory and executive function damage may be cognitive features in bipolar disorder.

Altered spontaneous activity in young chronic cigarette smokers revealed by regional homogeneity.

BACKGROUND: Few studies have been previously published about the resting state brain activity in young chronic smokers, although many previous fMRI studies have shown that the task-related activity pattern is altered in chronic smokers. METHODS: In the present study, forty-five healthy smokers (age: 27.9 ± 5.6 year) and forty-four healthy non-smoking control subjects (age: 26.3 ± 5.8 year) have been imaged with functional magnetic resonance imaging (fMRI) and analyzed with the regional homogeneity (ReHo) approach. RESULTS: Compared with healthy controls, decreased ReHo was found in smokers in the right inferior frontal cortex and increased ReHo was found in the left superior parietal lobe (P < 0.01, 35 Voxels,Alphasim corrected). CONCLUSIONS: Our data suggested that, during resting state, neural function is less synchronized in the right inferior frontal cortex and more synchronized in the left superior parietal lobe in chronic smokers compared to non-smokers. The decreased synchronization in the right inferior frontal cortex may reflect lacking of control over reward-related behavior, and the increased synchronization may reflect smoking urges.

Alterations in regional homogeneity of resting-state brain activity in ketamine addicts.

Ketamine is a non-competitive anatognist of the N-methyl-D-aspartate (NMDA) receptor commonly used as an anesthetic and analgesic. In sub-anesthetic doses, it can induce temporary psychotic symptoms and has served as a pharmacological model for schizophrenia. While its acute effects on brain and behavior have been studied, the effects of long-term exposure to ketamine on brain activity have been largely unexplored. In this study, we aimed to examine such effects on spontaneous brain dynamics measure using resting-state functional magnetic resonance imaging (fMRI). Forty-one patients with ketamine dependence and forty-four healthy control subjects were imaged with BOLD fMRI using a 3.0-Tesla Siemens scanner at the Magnetic Resonance Center of Hunan Provincial People's Hospital, analyzed with the regional homogeneity (ReHo) method. Compared with healthy controls, decreased ReHo was found in ketamine users in the right anterior cingulate cortex and increased ReHo was found in left precentral frontal gyrus (p<0.05, cluster-level corrected). We also observed negative correlations between increased ReHo in precentral frontal gyrus and estimated total lifetime ketamine consumption and ketamine craving levels. To our knowledge, this is the first study the long-term effects of ketamine exposure on brain functional activity. Our findings indicate that ketamine dependence is associated with alterations in the functional connectivity of medial and lateral prefrontal cortices.

Protective effects of the antioxidant sulforaphane on behavioral changes and neurotoxicity in mice after the administration of methamphetamine.

RATIONALE: Methamphetamine (METH) is a powerfully addictive stimulant associated with serious health conditions. Accumulating evidence suggests a role of oxidative stress in METH-induced behavioral abnormalities. Sulforaphane (SFN), found in cruciferous vegetables, is a potent antioxidant. It is of interest to determine whether SFN can attenuate behavioral and neuropathological changes associated with METH exposure. OBJECTIVES: This study was undertaken to examine the effects of SFN on behavioral changes and dopaminergic neurotoxicity in mice exposed to METH. METHODS: The effects of SFN on acute hyperlocomotion and the development of behavioral sensitization induced by the administration of METH were examined. Levels of dopamine (DA) and its major metabolite 3,4-dihydroxyphenyl acetic acid (DOPAC) in the striatum were measured. In addition, DA transporter (DAT) immunoreactivity was also performed. RESULTS: Pretreatment with SFN at 1, 3, and 10 mg/kg elicited a dose-dependent attenuation of acute hyperlocomotion in mice, after a single administration of METH (3 mg/kg). The development of behavioral sensitization after repeated administrations of METH (3 mg/kg/day, once daily for 5 days) was significantly reduced by pretreatment with SFN (10 mg/kg). In addition, the lowering of DA levels and DOPAC as well as DAT immunoreactivity in the striatum, usually seen after repeated administration of METH, was significantly attenuated by both pretreatment and the subsequent administration of SFN. Furthermore, SFN significantly reduced microglial activation in the striatum after repeated exposure to METH. CONCLUSION: It is therefore likely that SFN can be a useful drug for the treatment of signs associated with METH abuse in humans.

Bilateral fronto-parietal integrity in young chronic cigarette smokers: a diffusion tensor imaging study.

BACKGROUND: Cigarette smoking continues to be the leading cause of preventable morbidity and mortality in China and other countries. Previous studies have demonstrated gray matter loss in chronic smokers. However, only a few studies assessed the changes of white matter integrity in this group. Based on those previous reports of alterations in white matter integrity in smokers, the aim of this study was to examine the alteration of white matter integrity in a large, well-matched sample of chronic smokers and non-smokers. METHODOLOGY/PRINCIPAL FINDINGS: Using in vivo diffusion tensor imaging (DTI) to measure the differences of whole-brain white matter integrity between 44 chronic smoking subjects (mean age, 28.0±5.6 years) and 44 healthy age- and sex-matched comparison non-smoking volunteers (mean age, 26.3±5.8 years). DTI was performed on a 3-Tesla Siemens scanner (Allegra; Siemens Medical System). The data revealed that smokers had higher fractional anisotropy (FA) than healthy non-smokers in almost symmetrically bilateral fronto-parietal tracts consisting of a major white matter pathway, the superior longitudinal fasciculus (SLF). CONCLUSION/SIGNIFICANCE: We found the almost symmetrically bilateral fronto-parietal whiter matter changes in a relatively large sample of chronic smokers. These findings support the hypothesis that chronic cigarette smoking involves alterations of bilateral fronto-parietal connectivity.

[Follow-up study on refractory schizophrenia with brain stereotaxis therapy].

OBJECTIVE: To determine the long-term effect and security of refractory schizophrenia with brain stereotaxis multi-target therapy technique. METHODS: A total of 87 patients with refractory schizophrenia were treated with brain stereotaxis multi-target therapy and were followed up over 2 years. The scores of Clinical Global Impression, Brief Psychiatric Rating Scale, Positive and Negative Symptom Scale, Wechsler Adult Intelligence Scale, Wechsler Memory Scale, Actives of Daily Living, and Social Disability Screening Schedule were compared before and after the operation. RESULTS: Of the 87 patients, 40 obviously improved, 24 improved, 12 improved little, 7 did not change. None grew worse, 1 died, and 3 shed. There was a significant difference in the scales before and after the operation (P<0.01). No severe complications and sequelae occurred. CONCLUSION: Stereotaxic multi-target therapy is effective and safe for refractory schizophrenia. After the operation, drug therapy should be maintained and recovery of social function is helpful.

Pharmacological characterization of [³H]CHIBA-3007 binding to glycine transporter 1 in the rat brain.

Glycine transporter-1 (GlyT-1) in glial cells regulates extracellular levels of glycine, which acts as an obligatory co-agonist at the N-methyl-D-aspartate (NMDA) receptors in the brain. In the present study, we developed a novel radioligand, [³H]3-chloro-N-((S)-((R)-1-methylpiperidin-2-yl)(thiophen- 3-yl)methyl)-4- (trifluoromethyl)picolinamide ([³H]CHIBA-3007), for studying GlyT-1 in the brain. The presence of a single saturable high-affinity binding component for [³H]CHIBA-3007 binding to the rat brain membranes was detected. Scatchard analysis revealed an apparent equilibrium dissociation constant (K(d)) of 1.61±0.16 nM and a maximal number of binding sites (B(max)) of 692.8±22.8 fmol/mg protein (mean ± SEM, n = 3). The specific binding of [³H]CHIBA-3007 was inhibited by a number of GlyT-1 inhibitors, such as CHIBA-3007, desmethyl-CHIBA-3007, CHIBA-3008, SSR504734, NFPS/ALX5407, LY2365109 and Org24598, consistent with the pharmacological profiles of GlyT-1 inhibitors. Interestingly, the potency of eight GlyT-1 inhibitors (CHIBA-3007, desmethyl-CHIBA-3007, NFPS/ALX5407, LY2365109, Org24598, SSR504734, sarcosine, and glycine) for blocking in vitro specific binding of [³H]CHIBA-3007 was significantly correlated with the potency of these inhibitors for inhibiting [¹4C]glycine uptake in the rat brain membranes. In contrast, the GlyT-2 inhibitor ALX1393 exhibited very weak for [³H]CHIBA-3007 binding. Furthermore, the regional distribution of [³H]CHIBA-3007 binding in the rat brain was similar to the previously reported distribution of GlyT-1. The present findings suggest that [³H]CHIBA-3007 would be a useful new radioligand for studying GlyT-1 in the brain.

Reduced dorsal prefrontal gray matter after chronic ketamine use.

BACKGROUND: Use of ketamine as a recreational drug is spreading rapidly among young people all over the world. Epidemiological studies have linked chronic ketamine use with a number of problems, including cognitive impairments, bladder dysfunction, and ketamine-related death. However, little is known about the long-term effects of ketamine use on brain structure and function. METHODS: We used voxel based morphometry in conjunction with statistical parametric mapping on the structural magnetic resonance images of ketamine-dependent (n = 41) and drug-naive control individuals (n = 44) to assess differences in gray matter volume between the two groups. RESULTS: We observed significant decreases in gray matter volume in bilateral frontal cortex (left superior frontal gyrus and right middle frontal gyrus) of ketamine users in comparison with control subjects (p < .05 corrected for multiple comparisons at cluster-level). Duration of ketamine use was negatively correlated with gray matter volume in bilateral frontal cortex, whereas the estimated total lifetime ketamine consumption was negatively correlated with gray matter volume in left superior frontal gyrus. CONCLUSIONS: We have demonstrated a reduction in frontal gray matter volume in patients after chronic ketamine use. The link between frontal gray matter attenuation and the duration of ketamine use and cumulative doses of ketamine perhaps suggests a dose-dependent effect of long-term use of the drug. Our results have important connotations for the clinical picture that is likely to emerge with the growing recreational use of ketamine and is also relevant to the status of the drug as a model for schizophrenia.