Nicola Kalk

South London and Maudsley NHS Foundation Trust · Department of Psychiatry

Despite associations between alcohol use and suicidal acts, little research measures prognoses of alcohol‐using patients treated by Crisis Resolution Teams (CRTs), an intensive community‐based intervention. We estimated the association of alcohol use amongst patients accepted following suicidal acts or ideation in four London‐based Crisis Resolutio...

Background : The coronavirus pandemic resulted in many changes which had the potential to impact mortality related to opioid agonist therapy (OAT; methadone, buprenorphine), including changes in the prescribing and dispensing of OAT and patterns of drug availability and use. We aimed to assess the impact of the first lockdown (initiated March 23rd...

Aim The global prevalence of novel benzodiazepines (BZDs) has increased significantly in recent years with the predominant BZDs constantly changing to evade bans pertaining to specific chemical structures. As of 2020 the European Union Early Warning System (EWS) was monitoring 30 novel BZDs, 16 of which have been reported since 2016. Evidence of no...

The gabapentinoids were reclassified as Schedule II medications and Class C drugs in the UK in 2019 due to their misuse potential. In this study we examined deaths following gabapentinoid use in England reported to the National Programme on Substance Abuse Deaths. 3,051 deaths were reported (gabapentin: 913 cases; pregabalin: 2,322 cases [both dete...

Background Opioid-related deaths are increasing globally. Respiratory complications of opioid use and underlying respiratory disease in people with Opioid Use Disorder (OUD) are potential contributory factors. Individual variation in susceptibility to overdose is, however, incompletely understood. This study investigated the prevalence of respirato...

Setting Based at a busy city hospital, the alcohol care team is a drug and alcohol specialist service, taking referrals for a wide range of patients with substance use disorders (SUD). Objectives Patients with SUD are at high risk of vitamin D deficiency; this relates to frequent fractures and proximal myopathy. The coronavirus pandemic brought vi...

This extensively revised new edition provides a practical guide to understanding, assessing and managing physical, psychological and social complications related to drug and alcohol use. It presents a clear review of the aetiology, epidemiology, prevention and treatment of the problematic use of and dependence on alcohol, illicit and prescribed dru...

Introduction In the UK, opioid-related deaths are at record numbers after continually increasing year-on-year (ONS, 2019). This increase is believed to be driven by an ageing cohort of people with Opioid Use Disorder (OUD) and a high prevalence of comorbidities including chronic obstructive pulmonary disease (COPD). Our previous findings suggest th...

Background Alcohol use is a multidimensional risk factor for suicidal behaviour. However, suicide prevention strategies often take ‘one-size-fits-all’ approaches to alcohol use, reflecting an evidence base built on unidimensional measures. Latent Class Analysis can use a range of measures to differentiate distinct patterns of alcohol using behaviou...

Aims Clinical substance misuse presentations are commonly managed by Psychiatry Core Trainees (CTs) out of hours. However, specialist teaching is not included in the Maudsley Training Program (MTP) induction. We aimed to investigate whether this was of clinical concern and, if so identify interventions to address it. Background The association of...

Background and Aims Anti‐seizure medications (ASMs) have been used historically as treatment options in alcohol withdrawal syndrome (AWS). In the past 10 years, there have been no large‐scale meta‐analyses comparing ASMs with placebo or the current AWS treatment standard, benzodiazepines. We aimed to evaluate the efficacy and tolerability of ASMs i...

Background: In a large UK study we investigated the relationship between smartphone addiction and sleep quality in a young adult population. Methods: We undertook a large UK cross-sectional observational study of 1,043 participants aged 18 to 30 between January 21st and February 30th 2019. Participants completed the Smartphone Addiction Scale Short...

Introduction This study investigates whether there is a relationship between alcohol and cocaine use in deaths where suicide by self‐injury is the suspected cause of death. Methods Adults referred by coroners to the Imperial College London Toxicology Unit for toxicological analysis between 2012 and 2016 were reviewed for inclusion criteria. Those...

Aim: To identify drug-related death trends associated with synthetic cannabinoid receptor agonists (SCRAs) reported to the National Programme on Substance Abuse Deaths (NPSAD) from England. Design: Case reports from NPSAD (England) where a SCRA was detected in post-mortem tissue(s) and/or implicated in the death were extracted, analyzed, and compa...

Introduction Despite the association of alcohol use with recurrent suicidal acts, individuals attempting suicide after drinking alcohol face barriers accessing crisis care following emergency assessment, demonstrated by higher odds of inpatient admission for those whose suicide attempt did not feature alcohol. This disparity may be due to suicidali...

An amendment to this paper has been published and can be accessed via the original article.

Background: Substance use and psychiatric illness, particularly psychotic disorders, contribute to violence in emergency healthcare settings. However, there is limited research regarding the relationship between specific substances, psychotic symptoms and violent behaviour in such settings. We investigated the interaction between recent cannabinoi...

Introduction Take-home naloxone (THN) is a clinically effective and cost-effective means of reducing opioid overdose fatality. Nonetheless, naloxone administration that successfully saves a person’s life can still produce undesirable and harmful effects. Aim: To better understand factors associated with two widely reported adverse outcomes followin...

Introduction and objectives Cannabis use has been associated with psychosis and with poor outcome in patients with mental illness. Synthetic cannabinoids (SCs) have been suggested to pose an even greater risk to mental health, but the effect on clinical outcome has not been directly measured. In this study, we aimed to investigate the demographics...

Background and aims: Globally, more than 100,000 people die annually from opioid overdose. Opportunities to study physiological events in at-risk individuals are limited. This study examined variation of opioid dose and impact on respiratory depression in a chronic injecting heroin user at separate time points during his long-term diamorphine main...

After publication of our article [1] we were notified that one of the author names was misspelled.

Background: Over the past decade, smartphone use has become widespread amongst today's children and young people (CYP) which parallels increases in poor mental health in this group. Simultaneously, media concern abounds about the existence of 'smartphone addiction' or problematic smartphone use. There has been much recent research concerning the p...

Synthetic cannabinoid receptor agonists (SCRAs) are suggested to have increased potential to induce psychosis compared to natural cannabis (NC). In this review we synthesise current knowledge about the association of SCRA use with psychotic symptoms. Following a literature search we identified 2 toxicology reports, 4 case-control studies, 3 cross-s...

Commentary to: What defines a clinically meaningful outcome in the treatment of substance use disorders: reductions in direct consequences of drug use or improvement in overall functioning?

The history of opiate treatment in the United Kingdom (UK) since the early 1980s is a rich source of learning about the benefits and pitfalls of drug treatment policy. We present five possible lessons to be learnt about how factors outside the clinic, including government, charities and researchers can influence treatment and outcomes. First, do no...

Addictions are highly prevalent in bipolar disorder and greatly affect clinical outcomes. In this editorial, we review the evidence that addictions are a key challenge in bipolar disorder, examine putative neurobiological mechanisms, and reflect on the limited clinical trial evidence base with suggestions for treatment strategies and further develo...

Reliable diagnosis of mood disorders continues to pose a challenge. This is surprising because they have been recognised clinically since classical times. Mood disorders are also common: major depressive disorder affects nearly 300 million people worldwide and bipolar affective disorder nearly 60 million and they are a major cause of disability. No...

Objective: To assess microglial activation in lesions and in normal appearing white matter of multiple sclerosis (MS) patients using positron emission tomography (PET). Methods: 34 MS patients (7 with secondary progressive MS (SPMS), 27 with relapsing remitting MS (RRMS)) and 30 healthy volunteers, genetically stratified for translocator protein (T...

Repeated withdrawal from alcohol is clinically associated with progressive cognitive impairment. Microglial activation occurring during pre-clinical models of alcohol withdrawal is associated with learning deficits. We investigated whether there was microglial activation in recently detoxified alcohol-dependent patients (ADP), using [¹¹C]PBR28 posi...

Aims To investigate the underlying neurobiology between alcohol use, misuse and dependence and cognitive impairment, particularly Alzheimer's disease (AD). Methods Review of the literature using searches of Medline, Pubmed, EMBASE, PsycInfo, and meeting abstracts and presentations. Results The role of alcohol as a risk factor and contributor for...

An evolving problem that is difficult to detect and treat The Psychoactive Substances Act 2016, which came into force in May, signals a new approach to drug controls in the UK. For the first time, the basis for illegality is pharmacological action rather than chemical structure. The act made it illegal to produce or supply “spice” or synthetic can...

Methods: Five subjects with HAM and 2 HTLV-1 asymptomatic carriers were studied. All underwent clinical neurologic assessment including cognitive function and objective measures of gait, quantification of HTLV-1 proviral load in peripheral blood mononuclear cells, and human leukocyte antigen-antigen D related expression on circulating CD8+ lymphoc...

Supplementary material

Objective: To explore the effects of microglial activation on brain function and structure, and its relationship with peripheral inflammatory markers, in treated, HIV-positive individuals, using in vivo [(11)C]PBR28 PET (to measure the 18 kDa translocator protein [TSPO]). Methods: Cognitively healthy HIV-positive individuals on suppressive antir...

The importance of the GABA-benzodiazepine receptor complex and its subtypes are increasingly recognised in addiction. Using the α1/α5 benzodiazepine receptor PET radioligand [(11)C]Ro15 4513, we previously showed reduced binding in the nucleus accumbens and hippocampus in abstinent alcohol dependence. We proposed that reduced [(11)C]Ro15 4513 bindi...

Objective: The purpose of this study was to determine whether microglial activity, measured using translocator-protein positron emission tomography (PET) imaging, is increased in unmedicated persons presenting with subclinical symptoms indicating that they are at ultra high risk of psychosis and to determine whether microglial activity is elevated...

Drug and alcohol dependence are global problems with substantial societal costs. There are few treatments for relapse prevention and therefore a pressing need for further study of brain mechanisms underpinning relapse circuitry. The Imperial College Cambridge Manchester (ICCAM) platform study is an experimental medicine approach to this problem: us...

Background: Peripheral inflammatory markers are elevated in patients with schizophrenia, and data from PET studies assessing elevations of microglial activity suggest that inflammation is also evident centrally. However it is unclear whether neuroinflammatory processes become active before the onset of the disorder or after it has developed.To dete...

Though GABA is the major inhibitory neurotransmitter in the brain, involved in a wide variety of brain functions and many neuropsychiatric disorders, its intracellular and metabolic presence provides uncertainty in the interpretation of the GABA signal measured by 1H-MRS. Previous studies demonstrating the sensitivity of this technique to pharmacol...

Objective: HAM is a chronic debilitating neuro-inflammatory disease, with predilection for the thoracic cord. Cases of generalized encephalitisare also reported. We examined and compared the clinical markers of disease severity and brains of patients with HAM and HTLV-1 infection without myelopathy using [11C]PBR28, T1-weighted and diffusion-weight...

The inhibitory γ-aminobutyric acid (GABA) neurotransmitter system is associated with the regulation of normal cognitive functions and dysregulation has been reported in a number of neuropsychiatric disorders including anxiety disorders, schizophrenia and addictions. Investigating the role of GABA in both health and disease has been constrained by d...

Positron emission tomography (PET) targeting the 18 kDa translocator protein (TSPO) is used to quantify neuroinflammation. Translocator protein is expressed throughout the brain, and therefore a classical reference region approach cannot be used to estimate binding potential (BPND). Here, we used blockade of the TSPO radioligand [11C]PBR28 with the...

Positron emission tomography (PET) targeting the 18 kDa translocator protein (TSPO) is used to quantify neuroinflammation. Translocator protein is expressed throughout the brain, and therefore a classical reference region approach cannot be used to estimate binding potential (BPND). Here, we used blockade of the TSPO radioligand [(11)C]PBR28 with t...

Background: Anxiety has been linked to initiation, maintenance and relapse of alcohol dependence. Neurobiological models of anxiety have proposed important roles for amygdala-insula and amygdala-medial prefrontal cortex interactions in the generation and regulation of anxiety states, respectively. Objectives: This study tested the hypotheses tha...

Background. Peripheral cytokines are related to cognitive impairment in delirium and dementia. During alcohol detoxification, elevation of pro- and anti-inflammatory cytokines is reported. However, the relationship between peripheral cytokines and cognitive function in alcohol dependence has not been examined. We characterised the serum cytokine pr...

Acamprosate is effective pharmacotherapy for relapse prevention in alcohol dependence. Although this has been known for almost two decades and has been confirmed in several meta-analyses, evidence regarding its mechanism of action has accrued more slowly. In 1995, John Littleton proposed that acamprosate prevents relapse in alcohol dependence by de...

This positron emission tomography (PET) study aimed to further define selectivity of [(11)C]Ro15-4513 binding to the GABARα5 relative to the GABARα1 benzodiazepine receptor subtype. The impact of zolpidem, a GABARα1-selective agonist, on [(11)C]Ro15-4513, which shows selectivity for GABARα5, and the nonselective benzodiazepine ligand [(11)C]flumaze...

Generalized Anxiety Disorder (GAD) may involve hypo-responsiveness of noradrenaline a2 receptors. To test this hypothesis, we used (99m)Tc-hexa-methyl-propylene-amine-oxime (HMPAO) Single Photon Emission Computed Tomography to measure regional cerebral perfusion in patients with untreated GAD, venlafaxine-treated patients and healthy controls durin...

Cue-exposure therapy (CET) has been advocated as a potentially effective treatment of addictive behaviours. Strategies that enhance learning may improve the outcome of CET. D-cycloserine (DCS), a partial N-methyl-D-aspartate receptor agonist, has been shown to facilitate extinction of learned fear in rats and augment exposure-based treatment in som...

The quality of communication with our patients is of paramount importance and it is crucial to promoting successful therapeutic engagement. We recently completed a study, similar to that by Bhandari,[1][1] exploring the readability of assessment letters being produced by an adult community mental

Serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressants have evidence of efficacy in the treatment of generalized anxiety disorder (GAD); however, it is not clear whether there is an advantage over selective serotonin reuptake inhibitor (SSRI) medicines and there is limited evidence for noradrenergic dysfunction in GAD. We tested whet...

The nature of the noradrenergic dysregulation in clinical anxiety disorders remains unclear. In panic disorder, the predominant view has been that central noradrenergic neuronal networks and/or the sympathetic nervous system was normal in patients at rest, but hyper-reactive to specific stimuli, for example carbon dioxide. These ideas have been ext...

Our knowledge about the neuropharmacology of addiction is increasing and is leading to more informed development of pharmacotherapy. Although the dopaminergic mesolimbic system plays a central role in ‘liking’, reward and motivation, medications directly targeting it have not proved a very fruitful approach to treating addictions. A review of the l...

Aims and Methods The internet is an important source of mental health information. Given variable literacy levels in the general public, patient information websites need to be easily readable to prevent misunderstanding and consequent misinformation about mental health problems being propagated. the aim was to ascertain the readability of websites...

Although depressive mood is an important psychological determinate of chronic pain, the neural circuitry that mediates its influence on the pain experience is largely unknown. We used functional magnetic resonance imaging (FMRI) to investigate the neurophysiological interactions between depressive symptoms and disease-relevant pain in rheumatoid ar...