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1.
Opt Lett ; 49(11): 3090-3093, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824335

ABSTRACT

Tunable ultrashort pulses in the ultraviolet spectral region are in great demand for a wide range of applications, including spectroscopy and pump-probe experiments. While laser sources capable of producing such pulses exist, they are typically very complex. Notably, resonant dispersive-wave (RDW) emission has emerged as a simple technique for generating such pulses. However, the required pulse energy used to drive the RDW emission, so far, is mostly at the microjoule level, requiring complicated and expensive pump sources. Here, we present our work on lowering the pump energy threshold for generating tuneable deep ultraviolet pulses to the level of tens of nanojoules. We fabricated a record small-core antiresonant fiber with a hollow-core diameter of just 6 µm. When filled with argon, the small mode area enables higher-order soliton propagation and deep ultraviolet (220 to 270 nm) RDW emission from 36 fs pump pulses at 515 nm with the lowest pump energy reported to date (tens of nanojoules). This approach will allow the use of low-cost and compact laser oscillators to drive nonlinear optics in gas-filled fibers for the first time to our knowledge.

2.
Opt Express ; 32(6): 8520-8526, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38571109

ABSTRACT

We report an anti-resonant hollow core fibre with ultraviolet transmission down to 190 nm, covering the entire UV-A, UV-B and much of the UV-C band. Guidance from 190 - 400 nm is achieved apart for a narrow high loss resonance band at 245 - 265 nm. The minimum attenuation is 0.13 dB/m at 235 nm and 0.16 dB/m at 325 nm. With an inscribed core diameter of ∼12 µm, the fibre's bend loss at 325 nm was 0.22 dB per turn for a bend radius of 3 cm at 325 nm.

4.
Opt Express ; 32(1): 922-931, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38175113

ABSTRACT

We present a method with potential for fabricating freeform air-silica optical fibre preforms which is free from the stacking constraints associated with conventional stack-and-draw. The method, termed Axi-Stack, is enabled by the precision machining of short cross-sectional preform discs by ultrafast laser assisted etching; a laser-based microfabrication technique which facilitates near arbitrary shaping of the preform structure. Several preform discs are stacked axially and fused together via ultrafast laser welding to construct the preform, which can be drawn to fibre using conventional methods. To illustrate the Axi-Stack process, we detail the fabrication of a 30 cm long solid-core photonic crystal fibre preform with a square lattice of cladding holes and characterise fibre drawn from it.

5.
J Psychoactive Drugs ; : 1-7, 2023 Nov 27.
Article in English | MEDLINE | ID: mdl-38009828

ABSTRACT

Hallucinogen Persisting Perception Disorder (HPPD) is considered rare in hallucinogen users although there are conflicting reports about its incidence and prevalence. HPPD may be more common in those with trait neuroticism. In this study, we invited hallucinogen and other drug users to complete an online questionnaire about their use of hallucinogens, their experience of HPPD symptoms, and their trait neuroticism and mental health symptoms. We received 802 responses with 415 of these containing adequate data for further analysis. 39.7% of responders reported symptoms corresponding to Type I HPPD, and 4.3% reported symptoms corresponding to Type II HPPD. We found no significant difference between neuroticism scores for participants with or without HPPD. Individuals with Type II HPPD were more likely to report mental health symptoms including anxiety, obsessional thoughts, paranoia, hypochondria and panic attacks (p < .05). We also found that individuals with Type II HPPD were more likely to report the use of 25I-NBOMe, dextromethorphan, nitrous oxide and benzodiazepines (p < .05). 47.3% of participants had never tested their drugs, making the attribution of HPPD severity to specific drugs difficult. Further work into the development of HPPD is required, particularly with the rise of hallucinogens as potential treatments for depression and other mental illnesses.

6.
Front Psychiatry ; 14: 1232433, 2023.
Article in English | MEDLINE | ID: mdl-37614653

ABSTRACT

Background: Continuous assessment of affective behaviors could improve the diagnosis, assessment and monitoring of chronic mental health and neurological conditions such as depression. However, there are no technologies well suited to this, limiting potential clinical applications. Aim: To test if we could replicate previous evidence of hypo reactivity to emotional salient material using an entirely new sensing technique called optomyography which is well suited to remote monitoring. Methods: Thirty-eight depressed and 37 controls (≥18, ≤40 years) who met a research diagnosis of depression and an age-matched non-depressed control group. Changes in facial muscle activity over the brow (corrugator supercilli) and cheek (zygomaticus major) were measured whilst volunteers watched videos varying in emotional salience. Results: Across all participants, videos rated as subjectively positive were associated with activation of muscles in the cheek relative to videos rated as neutral or negative. Videos rated as subjectively negative were associated with brow activation relative to videos judged as neutral or positive. Self-reported arousal was associated with a step increase in facial muscle activation across the brow and cheek. Group differences were significantly reduced activation in facial muscles during videos considered subjectively negative or rated as high arousal in depressed volunteers compared with controls. Conclusion: We demonstrate for the first time that it is possible to detect facial expression hypo-reactivity in adults with depression in response to emotional content using glasses-based optomyography sensing. It is hoped these results may encourage the use of optomyography-based sensing to track facial expressions in the real-world, outside of a specialized testing environment.

7.
JAMA Psychiatry ; 80(8): 842-847, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37314797

ABSTRACT

Importance: The microbiota-gut-brain axis is a promising target for novel treatments for mood disorders, such as probiotics. However, few clinical trials have been conducted, and further safety and efficacy data are needed to support this treatment approach. Objective: To provide acceptability and tolerability data and estimates of intervention effect size for probiotics as adjunctive treatment for patients with major depressive disorder (MDD). Design, Setting, and Participants: In this single-center, double-blind, placebo-controlled pilot randomized clinical trial, adults aged 18 to 55 years with MDD taking antidepressant medication but having an incomplete response were studied. A random sample was recruited from primary and secondary care services and general advertising in London, United Kingdom. Data were collected between September 2019 and May 2022 and analyzed between July and September 2022. Intervention: Multistrain probiotic (8 billion colony-forming units per day) or placebo daily for 8 weeks added to ongoing antidepressant medication. Main Outcomes and Measures: The pilot outcomes of the trial were retention, acceptability, tolerability, and estimates of putative treatment effect on clinical symptoms (depression: Hamilton Depression Rating Scale [HAMD-17] and Inventory of Depressive Symptomatology [IDS] scores; anxiety: Hamilton Anxiety Rating Scale [HAMA] and General Anxiety Disorder [GAD-7] scores) to be used as indicators for a definitive trial. Results: Of 50 included participants, 49 received the intervention and were included in intent-to-treat analyses; of these, 39 (80%) were female, and the mean (SD) age was 31.7 (9.8) years. A total of 24 were randomized to probiotic and 25 to placebo. Attrition was 8% (1 in the probiotic group and 3 in the placebo group), adherence was 97.2%, and there were no serious adverse reactions. For the probiotic group, mean (SD) HAMD-17 scores at weeks 4 and 8 were 11.00 (5.13) and 8.83 (4.28), respectively; IDS, 30.17 (11.98) and 25.04 (11.68); HAMA, 11.71 (5.86) and 8.17 (4.68); and GAD-7, 7.78 (4.12) and 7.63 (4.77). For the placebo group, mean (SD) HAMD-17 scores at weeks 4 and 8 were 14.04 (3.70) and 11.09 (3.22), respectively; IDS, 33.82 (9.26) and 29.64 (9.31); HAMA, 14.70 (5.47) and 10.95 (4.48); and GAD-7, 10.91 (5.32) and 9.48 (5.18). Standardized effect sizes (SES) from linear mixed models demonstrated that the probiotic group attained greater improvements in depressive symptoms according to HAMD-17 scores (week 4: SES, 0.70; 95% CI, 0.01-0.98) and IDS Self Report scores (week 8: SES, 0.64; 95% CI, 0.03-0.87) as well as greater improvements in anxiety symptoms according to HAMA scores (week 4: SES, 0.67; 95% CI, 0-0.95; week 8: SES, 0.79; 95% CI, 0.06-1.05), but not GAD-7 scores (week 4: SES, 0.57; 95% CI, -0.01 to 0.82; week 8: SES, 0.32; 95% CI, -0.19 to 0.65), compared with the placebo group. Conclusions and Relevance: The acceptability, tolerability, and estimated effect sizes on key clinical outcomes are promising and encourage further investigation of probiotics as add-on treatment for people with MDD in a definitive efficacy trial. Trial Registration: ClinicalTrials.gov Identifier: NCT03893162.


Subject(s)
Depressive Disorder, Major , Adult , Humans , Female , Male , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/chemically induced , Depression , Antidepressive Agents/therapeutic use , Anxiety Disorders/drug therapy , Double-Blind Method , Treatment Outcome
8.
Curr Psychol ; : 1-8, 2023 May 04.
Article in English | MEDLINE | ID: mdl-37359672

ABSTRACT

Binaural beats (BB) are an auditory phenomenon produced from a combination of two sine waves with slightly different frequencies presented to each ear. Previous research has implicated the role of BBs through brainwave entrainment in potentially giving rise to benefits ranging from enhanced memory and attention to reduced anxiety and stress. Here, we investigated the effect of gamma (40-Hz) BBs on attention using the attention network test (ANT), a previously unused task that assesses three subtypes of attention: Alerting, Orienting, and Executive Control. Fifty-eight healthy adults performed the ANT remotely under the exposure of 340-Hz BBs and a 380-Hz control tone. All completed a rating scale for levels of anxiety before and after each exposure. Performance on the ANT task (reaction time and error rates) between BB and control groups was evaluated using Wilcoxon signed-rank tests. We found no significant differences in Reaction Time (RT), Error Rate (ER), or the efficacy of the Attention Networks (AN) between the experimental and control conditions (p > 0.05). We found no effect of BB on self-rated measures of anxiety. Our findings do not provide evidence for improvement in attention with gamma BB. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-023-04681-3.

9.
Transl Psychiatry ; 13(1): 184, 2023 05 31.
Article in English | MEDLINE | ID: mdl-37253720

ABSTRACT

The neuromodulator dopamine and excitatory neurotransmitter glutamate have both been implicated in the pathogenesis of psychosis, and dopamine antagonists remain the predominant treatment for psychotic disorders. To date no study has measured the effect of antipsychotics on both of these indices together, in the same population of people with psychosis. Striatal dopamine synthesis capacity (Kicer) and anterior cingulate glutamate were measured using 18F-DOPA positron emission tomography and proton magnetic resonance spectroscopy respectively, before and after at least 5 weeks' naturalistic antipsychotic treatment in people with first episode psychosis (n = 18) and matched healthy controls (n = 20). The relationship between both measures at baseline and follow-up, and the change in this relationship was analyzed using a mixed linear model. Neither anterior cingulate glutamate concentrations (p = 0.75) nor striatal Kicer (p = 0.79) showed significant change following antipsychotic treatment. The change in relationship between whole striatal Kicer and anterior cingulate glutamate, however, was statistically significant (p = 0.017). This was reflected in a significant difference in relationship between both measures for patients and controls at baseline (t = 2.1, p = 0.04), that was not present at follow-up (t = 0.06, p = 0.96). Although we did not find any effect of antipsychotic treatment on absolute measures of dopamine synthesis capacity and anterior cingulate glutamate, the relationship between anterior cingluate glutamate and striatal dopamine synthesis capacity did change, suggesting that antipsychotic treatment affects the relationship between glutamate and dopamine.


Subject(s)
Antipsychotic Agents , Psychotic Disorders , Humans , Dopamine , Antipsychotic Agents/therapeutic use , Antipsychotic Agents/pharmacology , Glutamic Acid , Gyrus Cinguli/diagnostic imaging , Psychotic Disorders/diagnostic imaging , Psychotic Disorders/drug therapy , Corpus Striatum , Positron-Emission Tomography/methods
10.
IEEE Trans Biomed Eng ; 70(8): 2374-2383, 2023 08.
Article in English | MEDLINE | ID: mdl-37022914

ABSTRACT

Fiber-based Raman spectroscopy in the context of in vivo biomedical application suffers from the presence of background fluorescence from the surrounding tissue that might mask the crucial but inherently weak Raman signatures. One method that has shown potential for suppressing the background to reveal the Raman spectra is shifted excitation Raman spectroscopy (SER). SER collects multiple emission spectra by shifting the excitation by small amounts and uses these spectra to computationally suppress the fluorescence background based on the principle that Raman spectrum shifts with excitation while fluorescence spectrum does not. We introduce a method that utilizes the spectral characteristics of the Raman and fluorescence spectra to estimate them more effectively, and compare this approach against existing methods on real world datasets.


Subject(s)
Spectrum Analysis, Raman , Spectrum Analysis, Raman/methods
11.
Front Immunol ; 14: 1100161, 2023.
Article in English | MEDLINE | ID: mdl-36845117

ABSTRACT

Introduction: Pulmonary-resident memory T cells (TRM) and B cells (BRM) orchestrate protective immunity to reinfection with respiratory pathogens. Developing methods for the in situ detection of these populations would benefit both research and clinical settings. Methods: To address this need, we developed a novel in situ immunolabelling approach combined with clinic-ready fibre-based optical endomicroscopy (OEM) to detect canonical markers of lymphocyte tissue residency in situ in human lungs undergoing ex vivo lung ventilation (EVLV). Results: Initially, cells from human lung digests (confirmed to contain TRM/BRM populations using flow cytometry) were stained with CD69 and CD103/CD20 fluorescent antibodies and imaged in vitro using KronoScan, demonstrating it's ability to detect antibody labelled cells. We next instilled these pre-labelled cells into human lungs undergoing EVLV and confirmed they could still be visualised using both fluorescence intensity and lifetime imaging against background lung architecture. Finally, we instilled fluorescent CD69 and CD103/CD20 antibodies directly into the lung and were able to detect TRM/BRM following in situ labelling within seconds of direct intra-alveolar delivery of microdoses of fluorescently labelled antibodies. Discussion: In situ, no wash, immunolabelling with intra-alveolar OEM imaging is a novel methodology with the potential to expand the experimental utility of EVLV and pre-clinical models.


Subject(s)
Immunologic Memory , Lung , Humans , Lung/diagnostic imaging , CD8-Positive T-Lymphocytes , Lymphocytes
12.
Schizophr Bull ; 49(3): 569-580, 2023 05 03.
Article in English | MEDLINE | ID: mdl-36573631

ABSTRACT

BACKGROUND AND HYPOTHESIS: Converging lines of evidence suggest that dysfunction of cortical GABAergic inhibitory interneurons is a core feature of psychosis. This dysfunction is thought to underlie neuroimaging abnormalities commonly found in patients with psychosis, particularly in the hippocampus. These include increases in resting cerebral blood flow (CBF) and glutamatergic metabolite levels, and decreases in ligand binding to GABAA α5 receptors and to the synaptic density marker synaptic vesicle glycoprotein 2A (SV2A). However, direct links between inhibitory interneuron dysfunction and these neuroimaging readouts are yet to be established. Conditional deletion of a schizophrenia susceptibility gene, the tyrosine kinase receptor Erbb4, from cortical and hippocampal inhibitory interneurons leads to synaptic defects, and behavioral and cognitive phenotypes relevant to psychosis in mice. STUDY DESIGN: Here, we investigated how this inhibitory interneuron disruption affects hippocampal in vivo neuroimaging readouts. Adult Erbb4 conditional mutant mice (Lhx6-Cre;Erbb4F/F, n = 12) and their wild-type littermates (Erbb4F/F, n = 12) were scanned in a 9.4T magnetic resonance scanner to quantify CBF and glutamatergic metabolite levels (glutamine, glutamate, GABA). Subsequently, we assessed GABAA receptors and SV2A density using quantitative autoradiography. RESULTS: Erbb4 mutant mice showed significantly elevated ventral hippccampus CBF and glutamine levels, and decreased SV2A density across hippocampus sub-regions compared to wild-type littermates. No significant GABAA receptor density differences were identified. CONCLUSIONS: These findings demonstrate that specific disruption of cortical inhibitory interneurons in mice recapitulate some of the key neuroimaging findings in patients with psychosis, and link inhibitory interneuron deficits to non-invasive measures of brain function and neurochemistry that can be used across species.


Subject(s)
Glutamine , Psychotic Disorders , Mice , Animals , Glutamine/metabolism , Parvalbumins/metabolism , Receptor, ErbB-4/genetics , Receptor, ErbB-4/metabolism , Psychotic Disorders/diagnostic imaging , Psychotic Disorders/metabolism , Interneurons/metabolism , Phenotype , Neuroimaging , Hippocampus/diagnostic imaging , Hippocampus/metabolism
13.
Front Psychiatry ; 13: 929306, 2022.
Article in English | MEDLINE | ID: mdl-36203844

ABSTRACT

Zinc transporter 3 (ZnT3) has been implicated in the aetiopathology of schizophrenia. In this pilot study, we tested the hypothesis that the presence of a minor allele of two variants in the gene encoding ZnT3 (SLC30A3) affects brain glutamate and cognitive activity in patients with schizophrenia and bipolar affective disorder. Fifteen patients with schizophrenia (SCZ), 15 with bipolar affective disorder type 2 (BD), and 14 healthy volunteers (HV) were genotyped for two SLC30A3 single nucleotide polymorphisms (rs11126936 and rs11126929). They also underwent structural and functional MRI (n-back) imaging as well as static (PRESS) and functional magnetic resonance spectroscopy (n-back) on a 3 Tesla MRI system. SCZ with at least one copy of the minor allele showed reductions in dorsal anterior cingulate cortex glutamate during the n-back task, whereas SCZ without the minor allele showed an increase in glutamate. BD with the minor allele had reduced glutamate in the anterior cingulate cortex (p < 0.05). There was no effect of SLC30A3 genotype on BOLD activation during n-back or on cortical brain volume. This study supports the further investigation of SLC30A3 and its role in glutamatergic neurotransmission and in the neuropathology of mental illness.

14.
Opt Express ; 30(21): 37303-37313, 2022 Oct 10.
Article in English | MEDLINE | ID: mdl-36258321

ABSTRACT

The two-stage stack and draw technique is an established method for fabricating microstructured fibers, including hollow-core fibers. A stack of glass elements of around a meter in length and centimeters in outer diameter forms the first stage preform, which is drawn into millimeter scale canes. The second stage preform is one of the canes, which is drawn, under active pressure, into microscopic fiber. Separately controlled pressure lines are connected to different holes or sets of holes in the cane to control the microstructure of the fiber being drawn, often relying on glues or other sealants to isolate the differently-pressured regions. We show that the selective fusion and collapse of the elements of the stack, before it is drawn to cane or fiber, allows the stack to be drawn directly under differential pressure without introducing a sealant. Three applications illustrate the advantages of this approach. First, we draw antiresonant hollow-core fiber directly from the stack without making a cane, allowing a significantly longer length of fiber to be drawn. Second, we fabricate canes under pressure, such that they are structurally more similar to the final fiber. Finally, we use the method to fabricate new types of microstructured resonators with a non-circular cross-section.

15.
Neurosci Biobehav Rev ; 140: 104800, 2022 09.
Article in English | MEDLINE | ID: mdl-35914624

ABSTRACT

Opioid receptors are widely distributed throughout the brain and play an essential role in modulating aspects of human mood, reward, and well-being. Accumulating evidence indicates the endogenous opioid system is dysregulated in depression and that pharmacological modulators of mu, delta, and kappa opioid receptors hold potential for the treatment of depression. Here we review animal and clinical data, highlighting evidence to support: dysregulation of the opioid system in depression, evidence for opioidergic modulation of behavioural processes and brain regions associated with depression, and evidence for opioidergic modulation in antidepressant responses. We evaluate clinical trials that have examined the safety and efficacy of opioidergic agents in depression and consider how the opioid system may be involved in the effects of other treatments, including ketamine, that are currently understood to exert antidepressant effects through non-opioidergic actions. Finally, we explore key neurochemical and molecular mechanisms underlying the potential therapeutic effects of opioid system engagement, that together provides a rationale for further investigation into this relevant target in the treatment of depression.


Subject(s)
Analgesics, Opioid , Depression , Animals , Antidepressive Agents , Humans , Receptors, Opioid , Receptors, Opioid, kappa , Receptors, Opioid, mu
16.
Psychosom Med ; 84(3): 313-324, 2022 04 01.
Article in English | MEDLINE | ID: mdl-35067654

ABSTRACT

OBJECTIVE: The increased prevalence and incidence of affective disorders among patients with gastrointestinal disease have been well established. However, few studies have investigated the inverse relationship. We aimed to identify all pieces of evidence of the prevalence and incidence of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) in people with depression and bipolar disorder. METHODS: We conducted a systematic review of studies reporting the association between affective disorders (exposure) and IBS or IBD (outcome) in adults. Evidence was evaluated for quality using Joanna Briggs Institute Critical Appraisal tools. Where suitable data were available, meta-analyses were performed. RESULTS: We identified 18 studies that met the selection criteria, of which 11 provided data on IBS, 5 on IBD, and 2 on both. Overall, people with depression were significantly more likely to have comorbid IBS (risk ratio = 2.42, 95% confidence interval = 1.98-2.96) and to develop new-onset IBS (risk ratio = 1.90, 95% confidence interval = 1.41-2.56) compared with people without depression. They were also more likely to have and develop IBD, and among patients with IBD, significantly increased rates of depression were observed as early as 5 years before diagnosis. Bipolar disorder was not consistently associated with risk of either condition. CONCLUSIONS: People with depression are at an increased risk of both having and developing lower gastrointestinal disorders. These findings have important implications for how we understand, manage, and prevent this comorbidity in clinical practice. Further studies are needed to improve our understanding of the relationship between bipolar disorder and bowel disease as well as the role of psychotropic medication, particularly selective serotonin reuptake inhibitors.


Subject(s)
Bipolar Disorder , Inflammatory Bowel Diseases , Irritable Bowel Syndrome , Adult , Bipolar Disorder/epidemiology , Depression/epidemiology , Humans , Incidence , Inflammatory Bowel Diseases/epidemiology , Irritable Bowel Syndrome/complications , Irritable Bowel Syndrome/epidemiology , Prevalence
17.
Neuropsychopharmacology ; 47(3): 687-695, 2022 02.
Article in English | MEDLINE | ID: mdl-34743200

ABSTRACT

Hippocampal hyperactivity driven by GABAergic interneuron deficits and NMDA receptor hypofunction is associated with the hyperdopaminergic state often observed in schizophrenia. Furthermore, previous research in the methylazoxymethanol acetate (MAM) rat model has demonstrated that repeated peripubertal diazepam administration can prevent the emergence of adult hippocampal hyperactivity, dopamine-system hyperactivity, and associated psychosis-relevant behaviors. Here, we sought to characterize hippocampal GABAA and NMDA receptors in MAM-treated rats and to elucidate the receptor mechanisms underlying the promising effects of peripubertal diazepam exposure. Quantitative receptor autoradiography was used to measure receptor density in the dorsal hippocampus CA1, ventral hippocampus CA1, and ventral subiculum. Specifically, [3H]-Ro15-4513 was used to quantify the density of α5GABAA receptors (α5GABAAR), [3H]-flumazenil to quantify α1-3;5GABAAR, and [3H]-MK801 to quantify NMDA receptors. MAM rats exhibited anxiety and schizophrenia-relevant behaviors as measured by elevated plus maze and amphetamine-induced hyperlocomotion (AIH), although diazepam only partially rescued these behaviors. α5GABAAR density was reduced in MAM-treated rats in all hippocampal sub-regions, and negatively correlated with AIH. Ventral hippocampus CA1 α5GABAAR density was positively correlated with anxiety-like behavior. Dorsal hippocampus CA1 NMDA receptor density was increased in MAM-treated rats, and positively correlated with AIH. [3H]-flumazenil revealed no significant effects. Finally, we found no significant effect of diazepam treatment on receptor densities, potentially related to the only partial rescue of schizophrenia-relevant phenotypes. Overall, our findings provide first evidence of α5GABAAR and NMDA receptor abnormalities in the MAM model, suggesting that more selective pharmacological agents may become a novel therapeutic mechanism in schizophrenia.


Subject(s)
Methylazoxymethanol Acetate , Schizophrenia , Animals , Disease Models, Animal , Hippocampus , Methylazoxymethanol Acetate/pharmacology , Rats , Receptors, N-Methyl-D-Aspartate , gamma-Aminobutyric Acid
18.
Psychopharmacology (Berl) ; 239(11): 3421-3429, 2022 Nov.
Article in English | MEDLINE | ID: mdl-34228135

ABSTRACT

RATIONALE: Ketamine may model aspects of schizophrenia arising through NMDA receptor activity deficits. Although acute ketamine can induce effects resembling both positive and negative psychotic symptoms, chronic use may be a closer model of idiopathic psychosis. OBJECTIVES: We tested the hypotheses that ketamine users had lower brain volumes, as measured using MRI, and greater sub-threshold psychotic symptoms relative to a poly-drug user control group. METHODS: Ketamine users (n = 17) and poly-drug using controls (n = 19) were included in the study. All underwent volumetric MRI imaging and measurement of sub-threshold psychotic symptoms using the Comprehensive Assessment of At-Risk Mental State (CAARMS). Freesurfer was used to analyse differences in regional brain volume, cortical surface area and thickness between ketamine users and controls. The relationship between CAARMS ratings and brain volume was also investigated in ketamine users. RESULTS: Ketamine users were found to have significantly lower grey matter volumes of the nucleus accumbens, caudate nucleus, cerebellum and total cortex (FDR p < 0.05; Cohen's d = 0.36-0.75). Within the cortex, ketamine users had significantly lower grey matter volumes within the frontal, temporal and parietal cortices (Cohen's d 0.7-1.31; FDR p < 0.05). They also had significantly higher sub-threshold psychotic symptoms (p < 0.05). Frequency of ketamine use showed an inverse correlation with cerebellar volume (p < 0.001), but there was no relationship between regional brain volumes and sub-threshold psychotic symptoms. CONCLUSIONS: Chronic ketamine use may cause lower grey matter volumes as well as inducing sub-threshold psychotic symptoms, although these likely arise through distinct mechanisms.


Subject(s)
Ketamine , Psychotic Disorders , Schizophrenia , Humans , Schizophrenia/diagnostic imaging , Ketamine/adverse effects , Receptors, N-Methyl-D-Aspartate , Psychotic Disorders/diagnostic imaging , Magnetic Resonance Imaging , Gray Matter/diagnostic imaging , Brain/diagnostic imaging
19.
Sensors (Basel) ; 21(24)2021 Dec 17.
Article in English | MEDLINE | ID: mdl-34960527

ABSTRACT

We developed a novel miniature micro-lensed fibre probe for Raman spectroscopy. The fibre probe consists of a single negative-curvature fibre (NCF) and a spliced, cleaved, micro-lensed fibre cap. Using a single NCF, we minimized the Raman background generated from the silica and maintained the diameter of the probe at less than 0.5 mm. In addition, the cap provided fibre closure by blocking the sample from entering the hollow parts of the fibre, enabling the use of the probe in in vivo applications. Moreover, the micro-lensed cap offered an improved collection efficiency (1.5-times increase) compared to a cleaved end-cap. The sensing capabilities of the micro-lensed probe were demonstrated by measuring different concentrations of glucose in aqueous solutions.


Subject(s)
Lenses , Spectrum Analysis, Raman , Equipment Design , Silicon Dioxide
20.
JAMA Psychiatry ; 78(12): 1343-1354, 2021 12 01.
Article in English | MEDLINE | ID: mdl-34524405

ABSTRACT

Importance: Evidence of gut microbiota perturbations has accumulated for multiple psychiatric disorders, with microbiota signatures proposed as potential biomarkers. However, no attempts have been made to evaluate the specificity of these across the range of psychiatric conditions. Objective: To conduct an umbrella and updated meta-analysis of gut microbiota alterations in general adult psychiatric populations and perform a within- and between-diagnostic comparison. Data Sources: Cochrane Library, PubMed, PsycINFO, and Embase were searched up to February 2, 2021, for systematic reviews, meta-analyses, and original evidence. Study Selection: A total of 59 case-control studies evaluating diversity or abundance of gut microbes in adult populations with major depressive disorder, bipolar disorder, psychosis and schizophrenia, anorexia nervosa, anxiety, obsessive compulsive disorder, posttraumatic stress disorder, or attention-deficit/hyperactivity disorder were included. Data Extraction and Synthesis: Between-group comparisons of relative abundance of gut microbes and beta diversity indices were extracted and summarized qualitatively. Random-effects meta-analyses on standardized mean difference (SMD) were performed for alpha diversity indices. Main Outcomes and Measures: Alpha and beta diversity and relative abundance of gut microbes. Results: A total of 34 studies provided data and were included in alpha diversity meta-analyses (n = 1519 patients, n = 1429 control participants). Significant decrease in microbial richness in patients compared with control participants were found (observed species SMD = -0.26; 95% CI, -0.47 to -0.06; Chao1 SMD = -0.5; 95% CI, -0.79 to -0.21); however, this was consistently decreased only in bipolar disorder when individual diagnoses were examined. There was a small decrease in phylogenetic diversity (SMD = -0.24; 95% CI, -0.47 to -0.001) and no significant differences in Shannon and Simpson indices. Differences in beta diversity were consistently observed only for major depressive disorder and psychosis and schizophrenia. Regarding relative abundance, little evidence of disorder specificity was found. Instead, a transdiagnostic pattern of microbiota signatures was found. Depleted levels of Faecalibacterium and Coprococcus and enriched levels of Eggerthella were consistently shared between major depressive disorder, bipolar disorder, psychosis and schizophrenia, and anxiety, suggesting these disorders are characterized by a reduction of anti-inflammatory butyrate-producing bacteria, while pro-inflammatory genera are enriched. The confounding associations of region and medication were also evaluated. Conclusions and Relevance: This systematic review and meta-analysis found that gut microbiota perturbations were associated with a transdiagnostic pattern with a depletion of certain anti-inflammatory butyrate-producing bacteria and an enrichment of pro-inflammatory bacteria in patients with depression, bipolar disorder, schizophrenia, and anxiety.


Subject(s)
Dysbiosis/microbiology , Gastrointestinal Microbiome , Mental Disorders/microbiology , Humans
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