Publications by authors named "Sami Musa"

27 Publications

  • Page 1 of 1

Is early exposure to cannabis associated with bipolar disorder? Results from a Finnish birth cohort study.

Addiction 2022 Mar 21. Epub 2022 Mar 21.

Faculty of Medicine, Department of Psychiatry, University of Turku, Turku, Finland.

Background And Aims: There are few longitudinal studies assessing the association of cannabis use and subsequent onset of bipolar disorder. We aimed to measure the association between early cannabis exposure and subsequent bipolar disorder.

Design, Setting And Participants: Observational study linking a sample from the northern Finland birth cohort 1986 (n = 6325) to nation-wide register data to examine the association of life-time cannabis exposure at age 15/16 years and subsequent bipolar disorder until age 33 (until the end of 2018); 6325 individuals (48.8% males) were included in the analysis.

Measurements: Cannabis exposure was measured via self-report. Bipolar disorder was measured via bipolar disorder-related diagnostic codes (ICD-10: F30.xx, F31.xx) collected from the Care Register for Health Care 2001-18, the Register of Primary Health Care Visits 2011-18, the medication reimbursement register of the Social Insurance Institution of Finland 2001-05 and the disability pensions of the Finnish Center for Pensions 2001-16. Potential confounders included demographic characteristics, parental psychiatric disorders, emotional and behavioral problems and other substance use.

Findings: Three hundred and fifty-two adolescents (5.6%) reported any cannabis use until the age of 15-16 years. Of the whole sample, 66 (1.0%) were diagnosed with bipolar disorder. Adolescent cannabis use was associated with bipolar disorder [hazard ratio (HR) = 3.46; 95% confidence interval (CI) = 1.81-6.61]. This association remained statistically significant after adjusting for sex, family structure and parental psychiatric disorders (HR = 3.00; 95% CI = 1.47-6.13) and after further adjusting for adolescent emotional and behavioral problems (HR = 2.34; 95% CI = 1.11-4.94). Further adjustments for frequent alcohol intoxications, daily smoking and lifetime illicit drug use attenuated the associations to statistically non-significant.

Conclusions: In Finland, the positive association between early cannabis exposure and subsequent development of bipolar disorder appears to be confounded by other substance use.
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http://dx.doi.org/10.1111/add.15881DOI Listing
March 2022

Neurobiology of Psychosis and Schizophrenia 2021: Nottingham Meeting.

Schizophr Bull 2022 03;48(2):289-291

Institute of Mental Health, University of Nottingham, Nottingham,UK.

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http://dx.doi.org/10.1093/schbul/sbab152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8886577PMC
March 2022

Psychoses in global context: do not forget the Muslim world.

Authors:
Musa Sami

Lancet Psychiatry 2021 11;8(11):947

Institute of Mental Health, University of Nottingham, Nottingham, UK. Electronic address:

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http://dx.doi.org/10.1016/S2215-0366(21)00255-8DOI Listing
November 2021

Eye movements in patients in early psychosis with and without a history of cannabis use.

NPJ Schizophr 2021 May 12;7(1):24. Epub 2021 May 12.

Institute of Psychiatry, Psychology and Neurosciences King's College London, London, UK.

It is unclear whether early psychosis in the context of cannabis use is different from psychosis without cannabis. We investigated this issue by examining whether abnormalities in oculomotor control differ between patients with psychosis with and without a history of cannabis use. We studied four groups: patients in the early phase of psychosis with a history of cannabis use (EPC; n = 28); patients in the early phase of psychosis without (EPNC; n = 25); controls with a history of cannabis use (HCC; n = 16); and controls without (HCNC; n = 22). We studied smooth pursuit eye movements using a stimulus with sinusoidal waveform at three target frequencies (0.2, 0.4 and 0.6 Hz). Participants also performed 40 antisaccade trials. There were no differences between the EPC and EPNC groups in diagnosis, symptom severity or level of functioning. We found evidence for a cannabis effect (χ = 23.14, p < 0.001), patient effect (χ = 4.84, p = 0.028) and patient × cannabis effect (χ = 4.20, p = 0.04) for smooth pursuit velocity gain. There was a large difference between EPC and EPNC (g = 0.76-0.86) with impairment in the non cannabis using group. We found no significant effect for antisaccade error whereas patients had fewer valid trials compared to controls. These data indicate that impairment of smooth pursuit in psychosis is more severe in patients without a history of cannabis use. This is consistent with the notion that the severity of neurobiological alterations in psychosis is lower in patients whose illness developed in the context of cannabis use.
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http://dx.doi.org/10.1038/s41537-021-00155-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115050PMC
May 2021

Are researchers getting the terms used to denote different types of recreational cannabis right?-a user perspective.

J Cannabis Res 2021 Apr 29;3(1):12. Epub 2021 Apr 29.

Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK.

Background: While current cannabis research has advanced our understanding into the effects of its individual components, there is a pressing need to identify simple terminology that is understood in the same way by researchers and users of cannabis. Current categorisation in research focuses on the two main cannabinoids: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD); and two different species of cannabis: indica and sativa. Recreational cannabis has also been categorised by researchers as 'skunk' or 'hash'. Focusing on individuals who use cannabis frequently, this study aimed to identify views on current terms used to denote different types of cannabis and to identify terms validated by participants. These views were extracted from responses of the Cannabis Experiences Questionnaire (CEQ), a widely used instrument in the literature.

Methods: We qualitatively analysed 236 free-text responses from Question 23 of the CEQ survey (using Iterative Categorisation) relating to categorization and consumption methods. Data was used from a previous study (Sami et al., Psychol Med 49:103-12, 2019), which recruited a convenience sample of 1231 participants aged 18 years and above who had previously used cannabis.

Results: Regarding type of cannabis used, specific strain names (n = 130), concentrates (n = 37), indica/sativa (n = 22) and THC/CBD terms (n = 22) were mentioned. Other terms used were hybrids (n = 10), origins of specific strains (n = 17), edibles (n = 8), and herbal cannabis (n = 7). Regarding problems with specific terms, participants were skeptical about terms such as skunk and super skunk (n = 78) preferring terms like THC/CBD, indica/sativa, specific marketed strains and references to preparation methods.

Conclusions: The results suggest a disparity between the common terms used by researchers in academia and those used by cannabis consumers. While there are advantages and limitations of using these terms to bridge views of researchers and individuals who use cannabis, this study underscores the importance of formally assessing chemical constituents rather than relying on self-report data and of incorporating cannabis user views on current terms used in research, potentially also incorporating descriptors of preparation and consumption methods.
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http://dx.doi.org/10.1186/s42238-021-00065-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086348PMC
April 2021

Cannabis use in patients with early psychosis is associated with alterations in putamen and thalamic shape.

Hum Brain Mapp 2020 10 20;41(15):4386-4396. Epub 2020 Jul 20.

Institute of Psychiatry, Psychology and Neurosciences King's College London, London, UK.

Around half of patients with early psychosis have a history of cannabis use. We aimed to determine if there are neurobiological differences in these the subgroups of persons with psychosis with and without a history of cannabis use. We expected to see regional deflations in hippocampus as a neurotoxic effect and regional inflations in striatal regions implicated in addictive processes. Volumetric, T1w MRIs were acquired from people with a diagnosis psychosis with (PwP + C = 28) or without (PwP - C = 26) a history of cannabis use; and Controls with (C + C = 16) or without (C - C = 22) cannabis use. We undertook vertex-based shape analysis of the brainstem, amygdala, hippocampus, globus pallidus, nucleus accumbens, caudate, putamen, thalamus using FSL FIRST. Clusters were defined through Threshold Free Cluster Enhancement and Family Wise Error was set at p < .05. We adjusted analyses for age, sex, tobacco and alcohol use. The putamen (bilaterally) and the right thalamus showed regional enlargement in PwP + C versus PwP - C. There were no areas of regional deflation. There were no significant differences between C + C and C - C. Cannabis use in participants with psychosis is associated with morphological alterations in subcortical structures. Putamen and thalamic enlargement may be related to compulsivity in patients with a history of cannabis use.
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http://dx.doi.org/10.1002/hbm.25131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502838PMC
October 2020

Early magnetic resonance imaging biomarkers of schizophrenia spectrum disorders: Toward a fetal imaging perspective.

Dev Psychopathol 2021 08;33(3):899-913

Institute of Mental Health, Jubilee Campus, University of Nottingham, Innovation Park, Nottingham, UK.

There is mounting evidence to implicate the intrauterine environment as the initial pathogenic stage for neuropsychiatric disease. Recent developments in magnetic resonance imaging technology are making a multimodal analysis of the fetal central nervous system a reality, allowing analysis of structural and functional parameters. Exposures to a range of pertinent risk factors whether preconception or in utero can now be indexed using imaging techniques within the fetus' physiological environment. This approach may determine the first "hit" required for diseases that do not become clinically manifest until adulthood, and which only have subtle clinical markers during childhood and adolescence. A robust characterization of a "multi-hit" hypothesis may necessitate a longitudinal birth cohort; within this investigative paradigm, the full range of genetic and environmental risk factors can be assessed for their impact on the early developing brain. This will lay the foundation for the identification of novel biomarkers and the ability to devise methods for early risk stratification and disease prevention. However, these early markers must be followed over time: first, to account for neural plasticity, and second, to assess the effects of postnatal exposures that continue to drive the individual toward disease. We explore these issues using the schizophrenia spectrum disorders as an illustrative paradigm. However, given the potential richness of fetal magnetic resonance imaging, and the likely overlap of biomarkers, these concepts may extend to a range of neuropsychiatric conditions.
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http://dx.doi.org/10.1017/S0954579420000218DOI Listing
August 2021

Association of extent of cannabis use and psychotic like intoxication experiences in a multi-national sample of first episode psychosis patients and controls.

Psychol Med 2020 Apr 28:1-9. Epub 2020 Apr 28.

Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, SE5 8AF, UK.

Background: First episode psychosis (FEP) patients who use cannabis experience more frequent psychotic and euphoric intoxication experiences compared to controls. It is not clear whether this is consequent to patients being more vulnerable to the effects of cannabis use or to their heavier pattern of use. We aimed to determine whether extent of use predicted psychotic-like and euphoric intoxication experiences in patients and controls and whether this differs between groups.

Methods: We analysed data on patients who had ever used cannabis (n = 655) and controls who had ever used cannabis (n = 654) across 15 sites from six countries in the EU-GEI study (2010-2015). We used multiple regression to model predictors of cannabis-induced experiences and to determine if there was an interaction between caseness and extent of use.

Results: Caseness, frequency of cannabis use and money spent on cannabis predicted psychotic-like and euphoric experiences (p ⩽ 0.001). For psychotic-like experiences (PEs) there was a significant interaction for caseness × frequency of use (p < 0.001) and caseness × money spent on cannabis (p = 0.001) such that FEP patients had increased experiences at increased levels of use compared to controls. There was no significant interaction for euphoric experiences (p > 0.5).

Conclusions: FEP patients are particularly sensitive to increased psychotic-like, but not euphoric experiences, at higher levels of cannabis use compared to controls. This suggests a specific psychotomimetic response in FEP patients related to heavy cannabis use. Clinicians should enquire regarding cannabis related PEs and advise that lower levels of cannabis use are associated with less frequent PEs.
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http://dx.doi.org/10.1017/S0033291720000847DOI Listing
April 2020

Association of cannabis with glutamatergic levels in patients with early psychosis: Evidence for altered volume striatal glutamate relationships in patients with a history of cannabis use in early psychosis.

Transl Psychiatry 2020 04 21;10(1):111. Epub 2020 Apr 21.

Institute of Psychiatry, Psychology and Neurosciences, King's College London, London, UK.

The associative striatum, an established substrate in psychosis, receives widespread glutamatergic projections. We sought to see if glutamatergic indices are altered between early psychosis patients with and without a history of cannabis use and characterise the relationship to grey matter. 92 participants were scanned: Early Psychosis with a history of cannabis use (EPC = 29); Early Psychosis with minimal cannabis use (EPMC = 25); Controls with a history of cannabis use (HCC = 16) and Controls with minimal use (HCMC = 22). Whole brain T1 weighted MR images and localised proton MR spectra were acquired from head of caudate, anterior cingulate and hippocampus. We examined relationships in regions with known high cannabinoid 1 receptor (CB1R) expression (grey matter, cortex, hippocampus, amygdala) and low expression (white matter, ventricles, brainstem) to caudate Glutamine+Glutamate (Glx). Patients were well matched in symptoms, function and medication. There was no significant group difference in Glx in any region. In EPC grey matter volume explained 31.9% of the variance of caudate Glx (p = 0.003) and amygdala volume explained 36.9% (p = 0.001) of caudate Glx. There was no significant relationship in EPMC. The EPC vs EPMC interaction was significant (p = 0.042). There was no such relationship in control regions. These results are the first to demonstrate association of grey matter volume and striatal glutamate in the EPC group. This may suggest a history of cannabis use leads to a conformational change in distal CB1 rich grey matter regions to influence striatal glutamatergic levels or that such connectivity predisposes to heavy cannabis use.
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http://dx.doi.org/10.1038/s41398-020-0790-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7174331PMC
April 2020

The 2019 Schizophrenia International Research Society Conference, 10-14 April, Orlando, Florida: A summary of topics and trends.

Psychiatry Res 2020 02 9;284:112672. Epub 2019 Nov 9.

Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

The Schizophrenia International Research Society (SIRS) recently held its first North American congress, which took place in Orlando, Florida from 10-14 April 2019. The overall theme of this year's congress was United in Progress - with the aim of cultivating a collaborative effort towards advancing the field of schizophrenia research. Student travel awardees provided reports of the oral sessions and concurrent symposia that took place during the congress. A collection of these reports is summarized and presented below and highlights the main themes and topics that emerged during the congress. In summary, the congress covered a broad range of topics relevant to the field of psychiatry today.
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http://dx.doi.org/10.1016/j.psychres.2019.112672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232873PMC
February 2020

Premorbid Adjustment and IQ in Patients With First-Episode Psychosis: A Multisite Case-Control Study of Their Relationship With Cannabis Use.

Schizophr Bull 2020 04;46(3):517-529

Department of Addiction, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Psychotic patients with a lifetime history of cannabis use generally show better cognitive functioning than other psychotic patients. Some authors suggest that cannabis-using patients may have been less cognitively impaired and less socially withdrawn in their premorbid life. Using a dataset comprising 948 patients with first-episode psychosis (FEP) and 1313 population controls across 6 countries, we examined the extent to which IQ and both early academic (Academic Factor [AF]) and social adjustment (Social Factor [SF]) are related to the lifetime frequency of cannabis use in both patients and controls. We expected a higher IQ and a better premorbid social adjustment in psychotic patients who had ever used cannabis compared to patients without any history of use. We did not expect such differences in controls. In both patients and controls, IQ was 3 points higher among occasional-users than in never-users (mean difference [Mdiff] = 2.9, 95% CI = [1.2, 4.7]). Both cases and control daily-users had lower AF compared to occasional (Mdiff = -0.3, 95% CI = [-0.5; -0.2]) and never-users (Mdiff = -0.4, 95% CI = [-0.6; -0.2]). Finally, patient occasional (Mdiff = 0.3, 95% CI = [0.1; 0.5]) and daily-users (Mdiff = 0.4, 95% CI = [0.2; 0.6]) had better SF than their never-using counterparts. This difference was not present in controls (Fgroup*frequency(2, 2205) = 4.995, P = .007). Our findings suggest that the better premorbid social functioning of FEP with a history of cannabis use may have contributed to their likelihood to begin using cannabis, exposing them to its reported risk-increasing effects for Psychotic Disorders.
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http://dx.doi.org/10.1093/schbul/sbz077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147569PMC
April 2020

Are cannabis-using and non-using patients different groups? Towards understanding the neurobiology of cannabis use in psychotic disorders.

J Psychopharmacol 2018 08 29;32(8):825-849. Epub 2018 Mar 29.

1 Institute of Psychiatry, Psychology & Neuroscience, King's College London, UK.

A substantial body of credible evidence has accumulated that suggest that cannabis use is an important potentially preventable risk factor for the development of psychotic illness and its worse prognosis following the onset of psychosis. Here we summarize the relevant evidence to argue that the time has come to investigate the neurobiological effects of cannabis in patients with psychotic disorders. In the first section we summarize evidence from longitudinal studies that controlled for a range of potential confounders of the association of cannabis use with increased risk of developing psychotic disorders, increased risk of hospitalization, frequent and longer hospital stays, and failure of treatment with medications for psychosis in those with established illness. Although some evidence has emerged that cannabis-using and non-using patients with psychotic disorders may have distinct patterns of neurocognitive and neurodevelopmental impairments, the biological underpinnings of the effects of cannabis remain to be fully elucidated. In the second and third sections we undertake a systematic review of 70 studies, including over 3000 patients with psychotic disorders or at increased risk of psychotic disorder, in order to delineate potential neurobiological and neurochemical mechanisms that may underlie the effects of cannabis in psychotic disorders and suggest avenues for future research.
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http://dx.doi.org/10.1177/0269881118760662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058406PMC
August 2018

Psychotic-like experiences with cannabis use predict cannabis cessation and desire to quit: a cannabis discontinuation hypothesis.

Psychol Med 2019 01 23;49(1):103-112. Epub 2018 Mar 23.

Institute of Psychiatry,Psychology & Neuroscience,King's College London,UK.

Background: Evidence suggests that cannabis-induced psychotic-like experiences may be a marker of psychosis proneness. The effect of such experiences on cannabis use has not systematically been examined.

Methods: We undertook a mixed-methods online survey of 1231 cannabis users (including 926 continued users) using the Cannabis Experiences Questionnaire. We examined the effect of psychotic-like and pleasurable experiences on cessation of cannabis and intention to quit. Socio-demographic variables, cannabis use parameters and substance misuse history were included as covariates. Free-text data explored subjective reasons for changes in use.

Results: Cessation of cannabis use was associated with greater psychotic-like experiences [p < 0.001, Exp(B) 1.262, 95% confidence interval (CI) 1.179-1.351], whilst continued cannabis users were more likely to report pleasurable experiences [p < 0.001, Exp(B) 0.717, 95% CI 0.662-0.776]. Intention to quit cannabis in continued users was associated with greater psychotic-like experiences [p < 0.003, Exp(B) 1.131, 95% CI 1.044-1.225], whilst intention to not quit was significantly associated with increased pleasurable experiences [p < 0.015, Exp(B) 0.892, 95% CI 0.814-0.978]. Whereas former users clearly ascribed cessation to negative experiences, continued users who expressed intention to quit less readily ascribed the intention to negative experiences.

Conclusions: Elucidation of psychotic-like experiences may form the basis of a therapeutic intervention for those who wish to quit. Cessation in those with cannabis-induced psychotomimetic experiences may offset the risk for the development of a psychotic disorder, in this higher risk group.
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http://dx.doi.org/10.1017/S0033291718000569DOI Listing
January 2019

How to approach psychotic symptoms in a non-specialist setting.

BMJ 2017 11 8;359:j4752. Epub 2017 Nov 8.

Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK

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http://dx.doi.org/10.1136/bmj.j4752DOI Listing
November 2017

Early psychosis for the non-specialist doctor.

BMJ 2017 11 8;357:j4578. Epub 2017 Nov 8.

Institute of Psychiatry, Psychology and Neuroscience, King's College London, London SE5 8AF, UK.

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http://dx.doi.org/10.1136/bmj.j4578DOI Listing
November 2017

Continued versus discontinued cannabis use in patients with psychosis: a systematic review and meta-analysis.

Lancet Psychiatry 2016 Mar 15;3(3):215-25. Epub 2016 Jan 15.

Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Electronic address:

Background: Although the link between cannabis use and development of psychosis is well established, less is known about the effect of continued versus discontinued cannabis use after the onset of psychosis. We aimed to summarise available evidence focusing on the relationship between continued and discontinued cannabis use after onset of psychosis and its relapse.

Methods: In this systematic review and meta-analysis, we searched MEDLINE for articles published in any language from the database inception date up until April 21, 2015 that included a sample of patients with a pre-existing psychotic disorder with a follow-up duration of at least 6 months. We used a combination of search terms for describing cannabis, the outcome of interest (relapse of psychosis), and the study population. We excluded studies if continued cannabis use or discontinued cannabis use could not be established. We compared relapse outcomes between those who continued (CC) or discontinued (DC) cannabis use or were non-users (NC). We used summary data (individual patient data were not sought out) to estimate Cohen's d, which was entered into random effects models (REM) to compare CC with NC, CC with DC, and DC with NC. Meta-regression and sensitivity analyses were used to address the issue of heterogeneity.

Findings: Of 1903 citations identified, 24 studies (16 565 participants) met the inclusion criteria. Independent of the stage of illness, continued cannabis users had a greater increase in relapse of psychosis than did both non-users (dCC-NC=0·36, 95% CI 0·22-0·50, p<0·0001) and discontinued users (dCC-DC=0·28, 0·12-0·44, p=0·0005), as well as longer hospital admissions than non-users (dCC-NC=0·36, 0·13 to 0·58, p=0·02). By contrast, cannabis discontinuation was not associated with relapse (dDC-NC=0·02, -0·12 to 0·15; p=0·82). Meta-regression suggested greater effects of continued cannabis use than discontinued use on relapse (dCC-NC=0·36 vs dDC-NC=0·02, p=0·04), positive symptoms (dCC-NC=0·15 vs dDC-NC=-0·30, p=0·05) and level of functioning (dCC-NC=0·04 vs dDC-NC=-0·49, p=0·008) but not on negative symptoms (dCC-NC=-0·09 vs dDC-NC=-0·31, p=0·41).

Interpretation: Continued cannabis use after onset of psychosis predicts adverse outcome, including higher relapse rates, longer hospital admissions, and more severe positive symptoms than for individuals who discontinue cannabis use and those who are non-users. These findings point to reductions in cannabis use as a crucial interventional target to improve outcome in patients with psychosis.

Funding: UK National Institute of Health Research.
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http://dx.doi.org/10.1016/S2215-0366(15)00363-6DOI Listing
March 2016

Convection associated with exclusion zone formation in colloidal suspensions.

Soft Matter 2016 Jan;12(4):1127-32

Department of Mechanical Engineering, Materials Technology, Eindhoven University of Technology, Eindhoven, The Netherlands. and Bernal Institute, University of Limerick, Limerick, Ireland.

The long-range repulsion of colloids from various interfaces has been observed in a wide range of studies from different research disciplines. This so-called exclusion zone (EZ) formation occurs near surfaces such as hydrogels, polymers, or biological tissues. It was recently shown that the underlying physical mechanism leading to this long-range repulsion is a combination of ion-exchange at the interface, diffusion of ions, and diffusiophoresis of colloids in the resulting ion concentration gradients. In this paper, we show that the same ion concentration gradients that lead to exclusion zone formation also imply that diffusioosmosis near the walls of the sample cell must occur. This should lead to convective flow patterns that are directly associated with exclusion zone formation. We use multi-particle tracking to study the dynamics of particles during exclusion zone formation in detail, confirming that indeed two pronounced vortex-like convection rolls occur near the cell walls. These dramatic flow patterns persist for more than 4 hours, with the typical velocity decreasing as a function of time. We find that the flow velocity depends strongly on the surface properties of the sample cell walls, consistent with diffusioosmosis being the main physical mechanism that governs these convective flows.
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http://dx.doi.org/10.1039/c5sm01502bDOI Listing
January 2016

Late onset mania as an organic syndrome: A review of case reports in the literature.

J Affect Disord 2015 Dec 8;188:226-31. Epub 2015 Sep 8.

Surrey & Borders NHS Partnership Trust, Brain Science Research Unit, ACU, Holloway Hill, Lyne, Chertsey Surrey KT16 0AE, UK. Electronic address:

Aims: Although First Episode Mania presenting over the age of 50 is reported in several cases, there has been little systematic compilation of these case reports. We report a review of case reports on these subjects.

Methods: We undertook a literature search on MEDLINE, PsychInfo and EMBASE to identify case reports of first episode of mania or hypomania presenting over the age of 50.

Results: 35 cases were identified. 29/35 (82%) had a suspected underlying organic cause. Organic causes included vascular causes, iatrogenic drug use, electrolyte imbalance, dementia and thyroid disease. Vascular risk factors were present in 17/35 cases (48%). In 10/35 (28%) of cases organic treatment contributed to successful remission of the manic episode.

Limitations: As evidently not all cases have been reported the main limitation is that of publication bias for this paper. Any such hypothesis generated from studying these cases would require replication in prospective longitudinal trials of this cohort of patients.

Conclusions: This review of case reports appears to add to evidence of late onset mania having an organic basis. Whether this is a separate organic syndrome remains to be established. Our provisional findings suggest that such patients should have a thorough medical and psychiatric screening in identifying an underlying cause.
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http://dx.doi.org/10.1016/j.jad.2015.08.027DOI Listing
December 2015

Psychosis, psychedelic substance misuse and head injury: A case report and 23 year follow-up.

Brain Inj 2015 7;29(11):1383-6. Epub 2015 Aug 7.

b Surrey & Borders Partnership NHS Foundation Trust , Epsom , Surrey , UK , and.

Background: This study describes the case of a 57 year old gentleman with a previous severe brain injury who developed a severe psychotic disorder 19 years after the injury. This appears to have been precipitated by heavy psychedelic substance use, including cannabis, salvia divinorum, ketamine, LSD, cocaine and DMT amongst others. The psychosis remained in the absence of drug intoxication and was associated with prominent apathy, lack of concern and abulia.

Case Study: This study discusses the heavy psychedelic substance misuse possibly potentiating a transition to psychosis in this individual. Little work has been undertaken in this area as substance misuse has traditionally been an exclusion criteria for investigating psychosis in this patient group.

Conclusions: It is suggested that psychedelic substance misuse should be investigated as a risk factor for psychotic illness in patients with brain injury, as this case clearly suggests.
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http://dx.doi.org/10.3109/02699052.2015.1046491DOI Listing
July 2016

Does cannabis affect dopaminergic signaling in the human brain? A systematic review of evidence to date.

Eur Neuropsychopharmacol 2015 Aug 30;25(8):1201-24. Epub 2015 Mar 30.

Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King׳s College London, De Crespigny Park, London SE5 8AF, UK. Electronic address:

A significant body of epidemiological evidence has linked psychotic symptoms with both acute and chronic use of cannabis. Precisely how these effects of THC are mediated at the neurochemical level is unclear. While abnormalities in multiple pathways may lead to schizophrenia, an abnormality in dopamine neurotransmission is considered to be the final common abnormality. One would thus expect cannabis use to be associated with dopamine signaling alterations. This is the first systematic review of all studies, both observational as well as experimental, examining the acute as well as chronic effect of cannabis or its main psychoactive ingredient, THC, on the dopamine system in man. We aimed to review all studies conducted in man, with any reported neurochemical outcomes related to the dopamine system after cannabis, cannabinoid or endocannabinoid administration or use. We identified 25 studies reporting outcomes on over 568 participants, of which 244 participants belonged to the cannabis/cannabinoid exposure group. In man, there is as yet little direct evidence to suggest that cannabis use affects acute striatal dopamine release or affects chronic dopamine receptor status in healthy human volunteers. However some work has suggested that acute cannabis exposure increases dopamine release in striatal and pre-frontal areas in those genetically predisposed for, or at clinical high risk of psychosis. Furthermore, recent studies are suggesting that chronic cannabis use blunts dopamine synthesis and dopamine release capacity. Further well-designed studies are required to definitively delineate the effects of cannabis use on the dopaminergic system in man.
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http://dx.doi.org/10.1016/j.euroneuro.2015.03.011DOI Listing
August 2015

Electroconvulsive therapy: a life course approach for recurrent depressive disorder.

BMJ Case Rep 2015 May 24;2015. Epub 2015 May 24.

Kent and Medway NHS and Social Care Partnership Trust, Ramsgate, UK.

We describe the case of an 89-year-old woman (deceased) with a 60-year history of recurrent depressive disorder treated with electroconvulsive therapy (ECT). It is estimated that she received up to 400 ECTs over her life course as her symptoms would not respond to oral medication. Despite extensive exposure to ECT, there was only minimal cognitive impairment and an excellent safety record, even in later life, as she became increasingly frail from multiple comorbidities. Over the years, there has been a drive to reduce the frequency of ECT administration. However, this case illustrates how in some patients ECT may be vital for acute episodes of severe depression as well as for maintenance therapy. This case report adds to observational evidence that maintenance ECT may be an underused treatment for recurrent depression and also recommends that greater emphasis be given to incorporating carers' views when planning individualised treatment approaches.
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http://dx.doi.org/10.1136/bcr-2015-209763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458620PMC
May 2015

The effectiveness of dopamine agonists for treatment of neuropsychiatric symptoms post brain injury and stroke.

Acta Neuropsychiatr 2015 Dec 8;27(6):317-26. Epub 2015 Apr 8.

2Consultant Neuropsychiatrist,St Andrew's Healthcare,Northampton,UK.

Objective: Traumatic brain injury and stroke are among the leading causes of neurological disability worldwide. Although dopaminergic agents have long been associated with improvement of neuropsychiatric outcomes, to date much of the evidence to date has been in case reports and case series or open label trials.

Methods: We undertook a systematic review of double-blinded randomised controlled trials (RCT) to determine the effect of dopaminergic agents on pre-defined outcomes of (a) apathy; (b) psychomotor retardation; (c) behavioural management and (d) cognitive function. Databases searched were: Medline, EMBASE, and PsychInfo for human studies. The Cochrane Clinical Trials Database and the TRIP Medical database were also searched. All identified studies, were further hand-searched.

Results: We identified six studies providing data on 227 participants, 150 of whom received dopaminergic therapy. Trials were compromised by cross-over design, inadequate wash out period, small numbers and heterogeneous outcome measures. However one good quality RCT demonstrates the efficacy of amantadine in behavioural management. One further RCT shows methylphenidate-levodopa is efficacious for mood post-stroke. One study shows rotigotine to improve hemi-inattention caused by prefrontal damage.

Conclusion: Our systematic review demonstrates an evolving evidence base to suggest some benefits in agitation and aggression, mood and attentional deficits. However, there are key limitations of the studies undertaken to date involving small numbers of participants, heterogeneous outcome measures, and variable study designs. There is a need for on-going large prospective double-blind RCTs in these medications using standardised criteria and outcomes to fully understand their effectiveness in this patient group.
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http://dx.doi.org/10.1017/neu.2015.17DOI Listing
December 2015

The natural course of anxiety disorders in the elderly: a systematic review of longitudinal trials.

Int Psychogeriatr 2015 Jul 5;27(7):1061-9. Epub 2014 Sep 5.

Brain Science Research Unit,ACU,Holloway Hill,Chertsey,Surrey KT16 0AE,UK.

Background: The anxiety disorders are a prevalent mental health problem in older age with a considerable impact on quality of life. Until recently there have been few longitudinal studies on anxiety in this age group, consequently most of the evidence to date has been cross-sectional in nature.

Methods: We undertook a literature search of Medline, PsycINFO, the Cochrane trials database and the TRIP medical database to identify longitudinal studies which would help elucidate natural history and prognosis of anxiety disorders in the elderly.

Results: We identified 12 papers of 10 longitudinal studies in our Review. This represented 34,691 older age participants with 5,199 with anxiety disorders including anxious depression and 3,532 individuals with depression without anxiety. Relapse rates of anxiety disorders are high over 6 year follow-up with considerable migration to mixed anxiety-depression and pure depressive mood episodes. Mixed anxiety-depression appears to be a poorer prognostic state than pure anxiety or pure depression with higher relapse rates across studies. In community settings treatment rates are low with 7-44% of the anxious elderly treated on antidepressant medications.

Conclusions: To our knowledge this is the first Systematic Review of longitudinal trials of anxiety disorders in older people. Major longitudinal studies of the anxious elderly are establishing the high risk of relapse and persistence alongside the progression to depression and anxiety depression states. There remains considerable under-treatment in community studies. Specialist assessment and treatment and major public health awareness of the challenges of anxiety disorders in the elderly are required.
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http://dx.doi.org/10.1017/S1041610214001847DOI Listing
July 2015

Severe agitation in depression precipitated by dasatinib.

BMJ Case Rep 2014 Aug 12;2014. Epub 2014 Aug 12.

Epsom Community Mental Health Recovery Service, Surrey & Borders NHS Partnership Foundation Trust, Surrey, UK.

We describe a case of a man with chronic myeloid leukaemia who achieved remission through dasatinib therapy after being unable to tolerate several tyrosine kinase inhibitor (TKI) regimens due to severe physical side effects. However, this coincided with the onset of distressing agitation, insomnia and motor restlessness leading him to take a large zopiclone overdose. Start of appropriate therapy with a clonazepam, venlafaxine and mirtazapine combination led to a rapid improvement in symptomatology. We discuss the differential diagnosis and review the literature of neuropsychiatric complications of TKIs. This case serves as an illustrative reminder that in cases of complicated agitation referral to specialist mental health teams for rational psychopharmacological management is advised.
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http://dx.doi.org/10.1136/bcr-2014-204166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139561PMC
August 2014

Diogenes syndrome causing life-threatening complications of Paget's disease.

Br J Hosp Med (Lond) 2014 Aug;75(8):470-1

CT3 Psychiatry, West Park Hospital, Surrey and Borders NHS Partnership Foundation Trust, Epsom, Surrey KT19 8PB.

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http://dx.doi.org/10.12968/hmed.2014.75.8.470DOI Listing
August 2014

Long-range repulsion of colloids driven by ion exchange and diffusiophoresis.

Proc Natl Acad Sci U S A 2014 May 18;111(18):6554-9. Epub 2014 Apr 18.

Department of Mechanical Engineering and Institute for Complex Molecular Systems , Eindhoven University of Technology, 5612 AZ, Eindhoven, The Netherlands.

Interactions between surfaces and particles in aqueous suspension are usually limited to distances smaller than 1 μm. However, in a range of studies from different disciplines, repulsion of particles has been observed over distances of up to hundreds of micrometers, in the absence of any additional external fields. Although a range of hypotheses have been suggested to account for such behavior, the physical mechanisms responsible for the phenomenon still remain unclear. To identify and isolate these mechanisms, we perform detailed experiments on a well-defined experimental system, using a setup that minimizes the effects of gravity and convection. Our experiments clearly indicate that the observed long-range repulsion is driven by a combination of ion exchange, ion diffusion, and diffusiophoresis. We develop a simple model that accounts for our data; this description is expected to be directly applicable to a wide range of systems exhibiting similar long-range forces.
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http://dx.doi.org/10.1073/pnas.1322857111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020040PMC
May 2014

Experimental study of bent multimode optical waveguides.

Appl Opt 2004 Oct;43(30):5705-7

Faculty of Applied Sciences, Optics Research Group, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, The Netherlands.

Bend losses of bent multimode waveguides have been experimentally studied. The results experimentally verify a simple analytical expression based on ray optics that can be used to determine bend losses in bent multimode waveguides. We have also shown that bend-induced losses in such multimode optical waveguides are wavelength independent.
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http://dx.doi.org/10.1364/ao.43.005705DOI Listing
October 2004
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