Littérature scientifique sur le sujet « Schizophrenia, substance, cognition, COMT »

IntroductionEarlier studies have shown that candidate gene risk polymorphisms and psychoactive substance abuse influence the frequency and severity of psychosis.ObjectivesIn this study we examined whether the most studied schizophrenia risk polymorphisms and psychoactive substance abuse interact in their influence on symptom severity and neurocognition.MethodsWe analyzed the clinical data of 280 schizophrenia patients, including genotyping data of the candidate genes NRG1, DTNBP1, RGS4, G72/G30 and PIP5K2A. Patients were assessed clinically by the Positive and Negative Symptom Scale (PANSS) and information about substance abuse was based on self-report and reviewing patient charts. We tested for possible interactional effects using the General Linear Model (GLM) analysis.Results15,8% of patients reported episodic or regular substance abuse, the vast majority (92%) used cannabis or the combination of cannabis and another drug. Substance abuse was associated with higher scores of the PANSS hostility/excitement factor, independent of sex, age, or genetic results (F = 4,02;p = 0,04). We found significant interactional effects of the DTNBP1 gene risk polymorphisms and substance abuse on different PANSS factors: rs2619528 and positive substance abuse interaction were associated with higher scores on the PANSS negative factor (F = 4,6;p = 0,03), and the PANSS depression factor (F = 4,75;p = 0,03). Moreover the rs3213207 - substance abuse interaction was associated with higher scores on the PANSS cognitive factor (F = 7,55;p = 0,006). Carriers of the Val allele of the COMT Val158Met polymorphism demonstrated significantly higher scores on the PANSS depression factor (F = 5,53;p = 0,02).ConclusionsOur results underscore the importance of gene-environment interactions in the phenotypic heterogeneity of schizophrenia.

AbstractBackground:Previous work suggests that reaction time variability (RTV) in attentional tasks, as a measure of cognitive stability, is associated with degree of Val loading in COMT Val158Met genotype, and that this association may be relevant for the aetiology of schizophrenia. This study examined (i) to what degree RTV pertaining to tasks of varying cognitive complexity would be associated with increased risk for schizophrenia and (ii) to what degree this would be mediated by Val loading.Methods:COMT genotyping was investigated in a sample of 23 patients with schizophrenia, 33 first-degree relatives, and 21 controls. All participants performed the Flanker continuous performance test.Results:Schizophrenia liability was associated with number of correct trials of the Flanker test, but not with RTV, and this association was not mediated by COMT Val158Met genotype. Similarly, Met loading was associated with number of correct trials and with RTV, but this was not mediated by schizophrenia liability.Conclusions:Associations between COMT Val158Met genotype and RTV do not appear to reflect transmission of schizophrenia liability in families. Differential associations with Val and Met alleles across studies suggest indirect effects through gene–gene interactions or the influence of a functional polymorphism near COMT Val158Met.

AbstractP300 wave anomalies correlate with genetic risk for schizophrenia and constitute a plausible endophenotype for the disease. The COMT gene is thought to influence cognitive performance and to be a susceptibility gene for schizophrenia. Unlike two previous studies, we found no significant influence of the COMT gene on P300 amplitude or latency in 189 individuals examined. The well-supported role of the COMT gene both in dopamine catabolism as well as in prefrontal cognition makes a strong theoretical case for the influence of COMT Val158Met polymorphism on P300 endophenotypes. However, the available neurophysiologic evidence suggests that any such association, if present, must be very subtle.

AbstractCatechol-O-methyl transferase (COMT) enzyme has a role in the inactivation of catecholamine neurotransmitters. Functional polymorphism in the COMT gene has been reported to play an important role in schizophrenia, bipolar affective disorder, aggressive and antisocial behavior, suicide attempts and the pathogenesis of Parkinson’s disease. In this study, we aimed to investigate the effect of the Vall58Met polymorphism of the COMT gene on substance use, and treatment history in patients with synthetic cannabinoid (SC) intoxication. The COMT enzyme Val158Met polymorphisms from DNA of 49 patients who were evaluated in the Emergency Department after SC use and 50 healthy control groups aged 18-45 years, were identified by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analyses as reported in the literature. Information regarding recurrent intake or hospitalization due to substance use was obtained from hospital records. Wild-type (WT) genotypes in 14 (28.6%) patients, heterozygous genotypes in 25 (51.0%) and homozygous genotypes in 10 (20.4%) patients were detected. Wild-type genotypes The homozygous genotype was found to be significantly higher in patients hospitalized due to drug addiction and substance use (p 0.008). The Vall58 Met polymorphism of the COMT gene was not found to be significant in the first use after substance intake, while a significant relationship was found in terms of this polymorphism in patients with substance addiction diagnosis and treatment history.

Schizophrenia, a severe psychiatric condition, is characterized by disturbances of cognition, emotion, and social functioning. The disease affects almost 1% of world population. Recent studies evaluating the role of catechol-O-methyltransferase enzyme (COMT) polymorphisms in the pathogenesis of schizophrenia have resulted in ambiguous findings. The current study examined the association of schizophrenia with three COMT polymorphisms, namely, rs737865, rs4680, and rs165599 in a Greek population. There was no significant association between schizophrenia and any of the three SNPs examined. However, haplotype analysis showed that cases have higher frequency of the T-A-A haplotype, and participants with that haplotype were at increased risk for developing schizophrenia (OR = 1.52; CL : 1.12–2.08; ). Furthermore, patients with schizophrenia displayed an excess of TC/AA/AA and the TT/AA/GA genotypes. Similarly a protective effect of TT/GG/GG and TT/GA/GG was suggested by our results.

BackgroundAuditory P50 sensory gating deficits correlate with genetic risk for schizophrenia and constitute a plausible endophenotype for the disease. The well-supported role of catechol-O-methyltransferase (COMT), brain-derived neurotrophic factor (BDNF) and neuregulin 1 (NRG1) genes in neurodevelopment and cognition make a strong theoretical case for their influence on the P50 endophenotype.MethodThe possible role of NRG1, COMT Val158Met and BDNF Val66Met gene polymorphisms on the P50 endophenotype was examined in a large sample consisting of psychotic patients, their unaffected relatives and unrelated healthy controls using linear regression analyses.ResultsAlthough P50 deficits were present in patients and their unaffected relatives, there was no evidence for an association between NRG1, COMT Val158Met or BDNF Val66Met genotypes and the P50 endophenotype.ConclusionsThe evidence from our large study suggests that any such association between P50 indices and NRG1, COMT Val158Met or BDNF Val66Met genotypes, if present, must be very subtle.

BACKGROUND: le caratteristiche cognitive e genetiche sono sempre più centrali nello studio della Schizofrenia. La compromissione delle Funzioni Esecutive (FE), definite come un complesso di abilità cognitive superiori attribuibili alle regioni della corteccia prefrontale, e della Facial Emotion Recognition (FER) rappresentano elementi centrali nel disturbo schizofrenico. Ad oggi, però, il paradigma del (dis)funzionamento cognitivo nella Schizofrenia poggia su studi che hanno escluso i soggetti schizofrenici con storia di abuso di sostanze (SUD), che ha mostrato un impatto peggiorativo sulla cognitività nella popolazione con disturbo da uso di sostanze. La letteratura ha inoltre negli anni definito polimorfismi potenzialmente implicati sia nella Schizofrenia sia nei disturbi da uso di alcol e sostanze, come quello (rs4680) relativo al gene della catecol-O-metiltransferasi (COMT). Viste la prevalenza del fenomeno e l’associazione fra cognition, outcome funzionale e le polimorfismi genetici, lo studio di tali correlati nei pazienti schizofrenici con abuso di sostanze costituisce una questione imprescindibile per una più puntuale stratificazione diagnostica, prognostica e dei trattamenti. SCOPO DEL LAVORO: valutare l’impatto del polimorfismo del COMT e dell’abuso di alcol e sostanze sulle performance cognitive in una popolazione di soggetti con schizofrenia. MATERIALI E METODI: si tratta di uno studio descrittivo­osservazionale. Sono stati reclutati 62 soggetti (M=50; F=12) con diagnosi di Schizofrenia secondo il DSM-IV (valutata attraverso la Structured Clinical Interview for DSM­IV, SCID I). Il campione è stato suddiviso a seconda della presenza o meno dell’abuso di alcol e sostanze correlato (valutato con l’Alcohol e la Drug Use Scale -AUS e DUS­) in due gruppi, che sono stati poi confrontati per quanto riguarda le caratteristiche socio­demografiche e cliniche (Positive and Negative Syndrome Scale - PANSS­). È stata analizzata quindi l’associazione tra condizione di abuso, polimorfismo del COMT e risultati ottenuti all’Intra-Extra Dimensional Set Shift (IED), che valuta le FE e il test di Ekman, che valuta la FER, controllando per variabili socio­demografiche e cliniche. RISULTATI: I due gruppi SKZ+SUD (n=28) e SKZ-SUD (n=34) presentano una differenza statisticamente significativa per età con media (SD) pari a 47.21 (9.41) negli abusatori e 36.04 (10.09) nei non abusatori (p<0.001). All’IED gli abusatori tendono a compiere meno errori (IED Total errors adjusted 47.32 (47.77) vs 70.59 (70.84); p=0.26), un minor numero di prove (IED Total trials adjusted 136.61 (85.65) vs 178.35 (128.02); p=0.24) per raggiungere il criterio necessario a superare gli stage e un maggior numero di stage completati (IED stages completed 7.79 (2.11) vs 6.85 (3.12); p=0.35) Al test di Ekman il gruppo degli abusatori (media=41.86 (7.50)) mostra un punteggio statisticamente più alto (p=0.02) rispetto ai non abusatori (media=35.29 (11.79). All’IED (stage completati), controllando per la PANSS, il genotipo Met-Met rispetto al genotipo Val-Val è diverso nel gruppo di abuso rispetto allo stesso confronto nel gruppo di non abuso (interazione con coefficiente -4.09 CI [-8.06, -0.13]; p=0.043): Met-Met mostra una performance peggiore rispetto a Val-Val nel gruppo di abuso. Lo stesso tipo di interazione è confermata anche per quanto riguarda il test di Ekman, pur non raggiungendo la significatività statistica (interazione con coefficiente -6.46 CI [-0.83, 13.76]; p=0.081). CONCLUSIONI: I soggetti schizofrenici con abuso si sono dimostrati tendenzialmente meno compromessi sotto il profilo neuropsicologico rispetto a quelli senza abuso. Inoltre si è evidenziata un’interazione tra il polimorfismo per il gene COMT e la condizione di abuso di alcol e sostanze per quanto riguarda le performance relative alle FE e alla FER.
BACKGROUND: cognitive and genetic features are increasingly important in the study of schizophrenia. The impairment of executive function (FE) and facial emotion recognition, are central issues in schizophrenic disease. To date, however, the paradigm of the (dis) cognitive functioning in schizophrenia is based on studies that excluded subjects with schizophrenia and a history of substance abuse (SUD)(5), which is actually a phenomenon that showed a derogatory impact on cognition in the population with substance use disorder. The literature has also over the years defined polymorphisms potentially implicated in both schizophrenia and in alcohol and substance use disorders, such as the one (rs4680) related to the gene of catechol-O-methyltransferase (COMT). Given the prevalence of the phenomenon and the association between cognition, functional outcome and genetic polymorphisms, the study of these related in schizophrenic patients with substance abuse is an important issue for a more precise stratification diagnosis, prognosis and treatment. AIM: to evaluate the impact of the COMT polymorphism and alcohol and substance abuse on cognitive performance in a population of subjects with schizophrenia. MATERIALS AND METHODS: this is a observational study. We recruited 62 subjects (M = 50, F = 12) diagnosed with schizophrenia according to DSM-IV (assessed by the Structured Clinical Interview for DSM-IV, SCID I). The sample was subdivided according to the presence or not of alcohol abuse and related substances (evaluated with the Alcohol and Drug Use Scale -Aus and DUS) into two groups (SKZ+SUD and SKZ-SUD), which were then compared with regard to socio-demographic and clinical characteristics (Positive and Negative Syndrome Scale - PANSS). It was then analysed the association between the condition of abuse, COMT polymorphism and score on Intra-Extra Dimensional Shift September (IED), which evaluates the FE and on test Ekman, evaluating the FER, controlling for socio-demographic and clinical variables. RESULTS: the two groups SKZ+SUD (n= 8) and SKZ-SUD (n = 34) show a statistically significant difference by age with mean (SD) of 47.21 (9.41) in abusers and 36.04 (10.09) in non-abusers (p <0.001). Abusers tend to make fewer errors on IED (IED errors adjusted Total 47.32 (47.77) vs 70.59 (70.84); p = 0:26), fewer trials (IED trials Total Adjusted 136.61 (85.65) vs 178.35 (128.02); p = 0:24) to reach the criterion to overcome the stage and a greater number of stages completed (IED stages completed 7.79 (2.11) vs 6.85 (3.12), p = 0:35). Abusers (mean = 41.86 (7:50)) show a score statistically higher (p = 0.02) compared with non-abusers (mean = 35.29 (11.79) on Ekman test. On IED (stage completed), checking for the PANSS, the Met-Met genotype compared with Val-Val genotype was different in the group of abuse compared with the group not abusing (interaction coefficient -4.09 CI [-8.06, -0.13]; p = 0.043): Met-Met show a worse performance than in the group of Val-Val. The same type of interaction is confirmed also with regard to the Ekman , although not reaching statistical significance (interaction with coefficient -6.46 CI [-0.83, 13.76]; p = 0.081). CONCLUSIONS: subjects with schizophrenia and substance abuse seems to be less compromised from a neuropsychological point of view than those without abuse. Furthermore it is shown an interaction between the polymorphism for COMT gene and the condition of alcohol and substance abuse with regard to the FE and FER performance.

Catechol-O-methyltransferase (COMT) metabolises catechol-containing compounds, including dopamine. The aim of this thesis was to investigate whether COMT is involved in hippocampal function. This thesis also explored the role of functional polymorphisms within the COMT gene in the pathogenesis of schizophrenia and schizophrenia-related phenotypes. First, as part of a study investigating the role of COMT in schizophrenia, human hippocampal COMT mRNA levels were shown to be neither altered in schizophrenia or bipolar disease, nor affected by COMT genotype. Hence, functional COMT polymorphisms do not appear to operate by altering gross COMT mRNA expression. Importantly, this study showed that COMT is expressed in the human hippocampus. Second, the role of COMT in hippocampal neurochemistry was explored by studying the effect of pharmacological COMT inhibition on catecholamines and metabolites in rat hippocampal homogenates, and extracellularly, using microdialysis. Both demonstrated that COMT modulates hippocampal dopamine metabolism. Thus, hippocampal COMT is of functional significance with respect to dopamine. Third, the effect of COMT inhibition on hippocampus-dependent behaviour was investigated. The results suggested a memory-enhancing effect of pharmacological COMT inhibition on hippocampus-dependent associative and non-associative forms of short-term memory in rats. In contrast, acute COMT inhibition appeared to have no effect on behavioural correlates of ventral hippocampal function i.e. anxiety-like behaviour. In summary, the expression of COMT mRNA in the human hippocampus, as well as the effect of COMT inhibition on rat hippocampal neurochemistry and hippocampus-dependent behaviour provide evidence for a functional role of COMT in the hippocampus. Moreover, changes in COMT activity alter hippocampal dopamine metabolism, which could be a potential mechanism for the role of COMT in hippocampus-dependent short-term memory.

Studies conducted over many decades consistently demonstrate that schizophrenia presents a broad spectrum of possible outcomes and course patterns, ranging from complete or nearly complete recovery after acute episodes of psychosis to continuous, unremitting illness leading to progressive deterioration of cognitive performance and social functioning. Between these extremes, a substantial proportion of patients show an episodic course with relapses of psychotic symptoms and partial remissions during which affective and cognitive impairments become increasingly conspicuous and may progress to gross deficits. Although no less than one-third of all patients with schizophrenia have relatively benign outcomes, in the majority the illness still has a profound, lifelong impact on personal growth and development. The initial symptoms of the disorder are not strongly predictive of the pattern of course but the mode of onset (acute or insidious), the duration of illness prior to diagnosis and treatment, the presence or absence of comorbid substance use, as well as background variables such as premorbid adjustment (especially during adolescence), educational and occupational achievement, marital status, and availability of a supportive social network allow a reasonable accuracy of prediction in the short- to medium-term (2–5 years). One of the most striking aspects of the longitudinal course of schizophrenia is the so-called ‘terminal improvement’. A relatively high proportion of patients tend to improve substantially with ageing. What determines this long-term outcome is far from clear but the stereotype view of schizophrenia as an invariably progressive, deteriorating disorder does not accord well with the evidence. Similarly, a model of schizophrenia as a static neurodevelopmental encephalopathy decompensating post-adolescence under the influence of a variety of stressors fits only part of the spectrum of course patterns. In a significant proportion of cases, the disorder exhibits the unmistakable features of a shift-like process with acute exacerbations and remissions which may progress to severe deterioration or come to a standstill at any stage. Whether a single underlying pathophysiology can explain the variety of clinical outcomes, or several different pathological processes are at work, remains obscure. It has been suggested that the longitudinal course of schizophrenia should be seen as an open-ended, dynamic life process with multiple, interacting biological and psychosocial determinants. Obviously, such issues cannot be resolved by clinical follow-up studies alone, and require a strong involvement of neurobiological research in prospective investigations of representative samples of cases spanning the entire spectrum of course and outcomes. No such studies have been possible until recently, both because of the technical complexity of such an undertaking and because of the tendency to selectively recruit for biological investigations patients from the severe, deteriorating part of the spectrum. Overcoming such limitations will be essential to the uncovering of the mechanisms driving the ‘natural history’ of schizophrenia.

Cognitive capability impacts individual functioning in every life domain such as social, emotional, academic, and occupational. Understanding the mechanism through which cognitive impairment can influence an individual’s susceptibility to homelessness is essential to providing effective services for improving health outcomes among this population. This chapter details the relationship between cognitive impairment and homelessness, with a focus on defining the clinical descriptions and diagnostic guidelines. It also discusses the bidirectional cause-and-effect association between homelessness and cognitive impairment, particularly reviewing disorders of cognition including schizophrenia, bipolar disorder, intellectual disability, autism spectrum disorder, childhood trauma, malnutrition, traumatic brain injury, and substance abuse. Lastly, this chapter uses the clinical correlations taken from available literature between homelessness and cognitive impairment to make recommendations on potential interventions that aim to address an individual’s cognitive skills as a relevant determinant of one’s functional capacity.

INTRODUCCIÓN Más del 70% de los pacientes con esquizofrenia son dependientes a la nicotina. (Buckley, 1998). Los pacientes con esquizofrenia tienen un estilo de vida menos saludable en comparación con la población general, ya que presentan tasas más elevadas de consumo de tabaco, tienen una alimentación menos sana y son más sedentarios. (Costa et al., 2019). Esta es el primer estudio que analiza un modelo predictivo del consumo de tabaco en estos pacientes. METODOLOGIA Estudio transversal sobre 590 pacientes (60,1% hombres y 39,7% mujeres) diagnosticados de un trastorno del espectro de la esquizofrenia (edad media 43,19 + 13,58 años). Evaluamos la gravedad de la enfermedad (PANSS y GAF), el estado cognitivo (SCIP y CRASH) y los hábitos de vida (PREDIMED e IPAQ). Medimos el consumo de tabaco en todos los pacientes (nºcig/d). Se realiza una regresión logística por pasos hacia atrás con el consumo de tabaco como variable dependiente, con el resto de variables como independientes. RESULTADOS El consumo cigarrillos medio fue de 9,50+-10,71. El modelo de regresión por pasos hacia atrás fue estadísticamente significativo (F=4,6; p= 0,001). Las variables que contribuyen significativamente al modelo son: PANSS positiva (p=0,011), CRASH (p=0,028) y PREDIMED (p=0,032). CONCLUSIONES Una mayor gravedad de la enfermedad, una menor reserva cognitiva y una menor adherencia a la dieta mediterránea, predicen un mayor consumo de cigarrillos. FEDER, PI17/00246 Buckley, P. F. (1998). Substance abuse in schizophrenia: a review. The Journal of Clinical Psychiatry, 59 Suppl 3, 26–30. http://www.ncbi.nlm.nih.gov/pubmed/9541335 Costa, R., Teasdale, S., Abreu, S., Bastos, T., Probst, M., Rosenbaum, S., Ward, P. B., & Corredeira, R. (2019). Dietary Intake, Adherence to Mediterranean Diet and Lifestyle-Related Factors in People with Schizophrenia. Issues in Mental Health Nursing, 40(10), 851–860. https://doi.org/10.1080/01612840.2019.1642426