The bridge between classical and ‘synthetic’/chemical psychoses: towards a clinical, psychopathological and therapeutic perspective

© 2019 Orsolini, Chiappini, Papanti, De Berardis, Corkery and Schifano. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.The critical spread and dissemination of novel psychoactive substances (NPS), particularly among the most vulnerable youngsters, may pose a further concern about the psychotic trajectories related to the intake of new synthetic drugs. The psychopathological pattern of the “new psychoses” appears to be extremely different from the classical presentation. Therefore, clinicians need more data on these new synthetic psychoses and recommendations on how to manage them. The present mini-review aims at deepening both the clinical, psychopathological features of synthetic/chemical NPS-induced psychoses and their therapeutic strategies, according to the different NPS classes implicated, by underlining the main differences with the “classical” psychoses. A comprehensive review was conducted using the PubMed/Medline database by combining the search strategy of free-text terms and exploding a range of MESH headings relating to the topics of novel psychoactive substances and synthetic/chemical psychoses as follows: {(Novel Psychoactive Substances[Title/Abstract]) AND Psychosis[Title/Abstract])} and for each NPS categories as well, focusing on synthetic cannabinoids and cathinones, without time and/or language restrictions. Finally, an overview of the main clinical and psychopathological features between classical versus NPS-induced chemical/synthetic psychoses is provided for clinicians working with dual disorders and addiction psychiatry. Further insight is given here on therapeutic strategies and practical guidelines for managing patients affected with synthetic/chemical NPS-induced psychoses.Peer reviewedFinal Published versio

Memory impairment and alterations in prefrontal cortex gamma band activity following methamphetamine sensitization

RATIONALE: Repeated methamphetamine (MA) use leads to increases in the incentive motivational properties of the drug as well as cognitive impairments. These behavioral alterations persist for some time following abstinence, and neuroadaptations in the structure and function of the prefrontal cortex (PFC) are particularly important for their expression. However, there is a weak understanding of the changes in neural firing and oscillatory activity in the PFC evoked by repeated drug use, thus complicating the development of novel treatment strategies for addiction. OBJECTIVES: The purpose of the current study was to assess changes in cognitive and brain function following MA sensitization. METHODS: Sensitization was induced in rats, then temporal and recognition memory were assessed after 1 or 30 days of abstinence. Electrophysiological recordings from the medial PFC were also acquired from rats whereupon simultaneous measures of oscillatory and spiking activity were examined. RESULTS: Impaired temporal memory was observed after 1 and 30 days of abstinence. However, recognition memory was only impaired after 1 day of abstinence. An injection of MA profoundly decreased neuronal firing rate and the anesthesia-induced slow oscillation (SO) in both sensitized (SENS) and control (CTRL) rats. Strong correlations were observed between the SO and gamma band power, which was altered in SENS animals. A decrease in the number of neurons phase-locked to the gamma oscillation was also observed in SENS animals. CONCLUSIONS: The changes observed in PFC function may play an integral role in the expression of the altered behavioral phenotype evoked by MA sensitization

The neurobiology of methamphetamine induced psychosis

Chronic methamphetamine abuse commonly leads to psychosis, with positive and cognitive symptoms that are similar to those of schizophrenia. Methamphetamine induced psychosis (MAP) can persist and diagnoses of MAP often change to a diagnosis of schizophrenia over time. Studies in schizophrenia have found much evidence of cortical GABAergic dysfunction. Methamphetamine psychosis is a well studied model for schizophrenia, however there is little research on the effects of methamphetamine on cortical GABAergic function in the model, and the neurobiology of MAP is unknown. This paper reviews the effects of methamphetamine on dopaminergic pathways, with focus on its ability to increase glutamate release in the cortex. Excess cortical glutamate would likely damage GABAergic interneurons, and evidence of this disturbance as a result of methamphetamine treatment will be discussed. We propose that cortical GABAergic interneurons are particularly vulnerable to glutamate overflow as a result of subcellular location of NMDA receptors on interneurons in the cortex. Damage to cortical GABAergic function would lead to dysregulation of cortical signals, resulting in psychosis, and further support methamphetamine induced psychosis as a model for schizophrenia

Theory of mind: assessment development and investigation of cocaine dependents

BACKGROUND: Substance use-related disorders are characterized by social problems, thought to be the result of social cognition impairments. In particular, the ability to interpret the thoughts of other people - Theory of Mind (ToM) - seems to be impaired. In view of this, this study aimed to investigate ToM functioning in a cocaine dependent (COD) sample. METHOD: This dissertation comprised four studies. The first is a systematic review of ToM in substance users. The second and the third deal with the development of instruments for the ToM assessment. The second is the translation and adaption of the Reading the Mind in the Eyes Test (RMET) into the Brazilian Portuguese, and the third describes the validation of the Hinting task and the ToM Stories task. The fourth work represents the main study of this dissertation – the investigation of the ToM of COD women. 30 COD women and 30 healthy controls (HC) matched for sex, age, education, individual income and IQ took part in this study. All participants were assessed with the RMET, the Hinting Task and the ToM stories. Cognitive and clinical factors were also assessed in order to control for possible differences. RESULTS: The systematic review revealed that ToM deficits were present in substance use-related disorders. Besides that, the review indicated that these impairments were related to daily life and clinical features of substance use-related disorders. In addition, this dissertation advanced with regard the technological development, since it guaranteed a translated and adapted Brazilian version of the RMET. By the same token, in the third study the Hinting Task and the ToM Stories were shown to have convergent, predictive, concurrent, discriminative and diagnostic validity. Finally, in the fourth study, COD women were found to have impaired ToM in comparison with HC. Additionally, correlations indicated ToM was negatively associated with dependence chronicity. CONCLUSION: Results were consistent with the published literature, suggesting that COD like other drug dependence disorders, is associated with ToM deficits. In view of the results that suggested an association between ToM and social and clinical outcomes, we have proposed a framework in which there is a bidirectional, facilitative relationship between drug use and ToM impairments. The implications of the results for future research and potential interventions based on targeting the psychosocial problems found to be impaired in substance use disorders are discussed.INTRODUÇÃO: Transtornos relacionados ao uso de substâncias são caracterizados por problemas sociais. Acredita-se que a origem de tais comprometimentos se deva a déficits em funções da cognição social. Em particular, a Teoria da Mente (ToM) – capacidade de inferir e interpretar os pensamentos de outras pessoas – parece estar prejudicada em dependentes químicos. Portanto, o objetivo deste trabalho foi investigar a ToM em uma amostra de mulheres dependentes de cocaína.MÉTODO: Esta dissertação é composta por quarto artigos. O primeiro é uma revisão sistemática sobre a ToM em usuários de drogas. O segundo e terceiro foram dedicados ao desenvolvimento de instrumentos para a avaliação da ToM. O segundo é a tradução e a adaptação ao português brasileiro do Reading the Mind in the Eyes Test (RMET), e o terceiro é a validação do Hinting Task e do ToM Stories. O quarto trabalho representa o principal objetivo da dissertação – investigar a ToM de mulheres dependentes de cocaína. Participaram 30 mulheres com diagnóstico de dependência de cocaína e 30 mulheres saudáveis, sendo os grupos pareados por sexo, idade, anos de estudo, renda e QI. Todas participantes responderam ao RMET, ao Hinting Task e ao ToM Stories. As participantes também foram avaliadas quanto à sintomatologia psiquiátrica e ao desempenho neuropsicológico. RESULTADOS: A revisão sistemática revelou que o uso de álcool e drogas é relacionado a prejuízos na ToM, e que a ToM é associada com aspectos do dia-a-dia e do curso da dependência. No segundo estudo avançou-se no desenvolvimento tecnológico garantindo uma adequada versão traduzida e adaptada do RMET para o português brasileiro. Além disso, no terceiro artigo revelou-se as propriedades psicométricas do Hinting Task e do ToM Stories. Ambas tarefas demonstraram possuir validades convergente, preditiva, concorrente, discriminativa e diagnóstica. Por fim, o quarto estudo revelou que mulheres dependentes de cocaína obtiveram um desempenho significativamente inferior ao do grupo de mulheres saudáveis nas tarefas de ToM. A performance de ToM foi encontrada negativamente correlacionada com o nível de severidade da dependência de cocaína. CONCLUSÕES: Os resultados indicam que mulheres dependentes de cocaína possuem desempenho inferior ao de mulheres saudáveis em tarefas de ToM. Tais achados são consistentes com os da literatura e corroboram com o fato da ToM estar relacionada com manifestações sintomáticas da doença. Com base nos resultados, um modelo ilustrativo da participação bidirecional da ToM no curso da dependência química foi proposto. O modelo sugere que por um lado, prejuízos na habilidade de inferir e interpretar os pensamentos de terceiros vulnerabilizam pessoas ao uso de substância, e, em contrapartida, o uso de substâncias causa eventos tóxicos ao cérebro que acabam alterando circuitos neurobiológicos importantes para a integridade da ToM. As implicações dos resultados e conclusões desta dissertação reforçam o potencial que intervenções que visem a promoção de habilidades psicossociais possuem no tratamento de transtornos aditivos

Methamphetamine-induced deficits in social interaction are not observed following abstinence from single or repeated exposures

The purpose of the current study was to assess social interaction (SI) following acute and repeated methamphetamine (MA) administration. Rats were injected with 5.0 mg/kg of MA and SI was tested 30 minutes or 24 hours later. In another group of animals, MA sensitization was induced using 5.0 mg/kg of MA, and SI was assessed after one day or thirty days of abstinence. SI was reduced in rats injected with MA 30 minutes, but not 24 hours, prior to testing, compared with saline controls. Impaired SI was observed in combination with active avoidance of the conspecific animal. Repeated injections of MA progressively reduced locomotor activity and increased stereotypy, indicating that animals were sensitized. However, no differences in SI were observed 24 hours or 30 days following the induction of sensitization. The absence of detectable differences in SI following MA sensitization may be attributable to the relatively short regimen used to induce sensitization. However, the current series of experiments provides evidence that an acute injection of MA decreases SI and simultaneously increases avoidance behavior, which supports a link between psychostimulant use and impaired social functioning. These data suggest that the acute injection model may provide a useful model to explore the neural basis of impaired social functioning and antisocial behavior

Using a drug-word Stroop task to differentiate recreational from dependent drug use.

Distinguishing dependent from recreational drug use can be a surprisingly difficult task, and the current means for identifying substance abuse can be inadequate or even misleading. In subjective self-reports, those who are most at risk may down play their consumption, not admitting to the full extent of their habit, and measures purely of quantity of use rarely capture the true nature of an individual's relationship to the drug, such as a psychological dependence on the substance. This trend is particularly true for heavy stimulant use, which is absent of the physical withdrawal symptoms that can help identify opiate or alcohol dependence. As such, a simple objective measure to help identify substance abuse, particularly in individuals who might not otherwise raise suspicion, would be a valuable tool in both clinical and experimental settings. We propose that the drug-word Stroop task, an objective assessment of attentional bias and distraction to salient drug-related stimuli, would be a valuable tool in helping to make these categorizations. This measure has been shown to correlate with drug craving, as well as to successfully distinguish dependent from recreational stimulant users and to help to predict outcomes in treatment-seeking individuals. Here, we survey prior literature on the drug-word Stroop task and provide a perspective on using the assessment as a potential diagnostic for drug use severity.Original research presented in this review was funded by a Medical Research Council (MRC) grant (G0701497), and conducted within the Behavioural and Clinical Neuroscience Institute (BCNI), which is jointly funded by an award from the MRC and Wellcome Trust (G00001354). DGS is supported by a studentship from the Cambridge Overseas Trust. KDE is supported by the MRC.This is the author accepted manuscript. The final version is available from Cambridge University Press via https://doi.org/10.1017/S109285291400013

Decreased modulation by the risk level on the brain activation during decision making in adolescents with internet gaming disorder

Greater impulse and risk-taking and reduced decision-making ability were reported as the main behavioral impairments in individuals with internet gaming disorder (IGD), which has become a serious mental health issue worldwide. However, it is not clear to date how the risk level modulates brain activity during the decision-making process in IGD individuals. In this study, 23 adolescents with IGD and 24 healthy controls (HCs) without IGD were recruited, and the balloon analog risk task (BART) was used in a functional magnetic resonance imaging experiment to evaluate the modulation of the risk level (the probability of balloon explosion) on brain activity during risky decision making in IGD adolescents. Reduced modulation of the risk level on the activation of the right dorsolateral prefrontal cortex (DLPFC) during the active BART was found in IGD group compared to the HCs. In the IGD group, there was a significant negative correlation between the risk-related DLPFC activation during the active BART and the Barratt impulsivity scale (BIS-11) scores, which were significantly higher in IGD group compared with the HCs. Our study demonstrated that, as a critical decision-making-related brain region, the right DLPFC is less sensitive to risk in IGD adolescents compared with the HCs, which may contribute to the higher impulsivity level in IGD adolescents

Methamphetamine Use among HIV-Positive Men Who Have Sex with Men (MSM)

The highly addictive drug methamphetamine has been associated with impairments in social and neurological functioning. With assistance from previous studies on methamphetamine use and HIV, the theory that the risk of HIV is increased with the use of methamphetamine will be supported. The purpose of this paper is to educate and illustrate the dangerous effects of methamphetamine use among individuals with HIV. The paper will conclude with an examination of possible HIV treatment and prevention options to better assist individuals who use methamphetamine