1,721,163 research outputs found
The impact of cannabis use on age of onset in first-episode psychotic patients
No full textThe present study, conducted in a first-episode psychotic sample, aims totest whether substance misuse, particularly cannabis use 1) is more frequent in patients than the general population, 2) is associated with a higher level of positive symptoms, a lower level of depressive symptoms and a worse premorbid adjustment atthe onset, 3) is associated with an earlier age of onset and a better premorbid IQ. The study was conducted within the broader framework of the PICOS (Psychosis Incident Cohort Outcome Study), a multi-site collaborative research on incident cases of psychosis attending psychiatric services in the Veneto Region, Italy
The role of genetics in the vulnerability to psychosis and in predicting clinical outcome. Data from the Psychosis Incident Cohort Outcome Study (PICOS)
No full textNonostante ci siano forti evidenze che sostengono una base genetica per la schizofrenia e il disturbo bipolare, non sono stati ancora identificati i geni responsabili di tali patologie che sono malattie complesse e multifattoriali, in cui la componente genetica interagisce con fattori ambientali. Inoltre, i risultati deludenti e contraddittori degli ultimi anni degli studi di genetica in ambito delle psicosi posso essere dovuti alle intrinseche caratteristiche del fenotipo studiato: la “diagnosi” di schizofrenia e di disturbo bipolare. Infatti benché la diagnosi fatta secondo i criteri DSM o ICD è indubbiamente di enorme utilità clinica, non fornisce informazioni circa la natura fondamentale della schizofrenia che è stata concettualizzata come un disturbo eterogeneo. Di conseguenza, per ottenere una classificazione corretta delle psicosi, è importante capire se il gruppo eterogeneo di sindromi che vengono diagnosticate come schizofrenia sono una o più patologie e per fare ciò, dovrebbe essere studiata la relazione tra il fenotipo e il genotipo, per determinare se una specifica variazione in un gene aumenta il rischio per una specifica forma di malattia. Un possibile approccio per affrontare la questione è quella si esaminare la relazione tra le caratteristiche cliniche della psicosi e le varianti genetiche, e non solo selezionare i casi sulla base della diagnosi di schizofrenia o disturbi bipolare.
Su tali presupposti teorici si è svolto il lavoro di ricerca, che ha avuto l’obiettivo di studiare, all’interno di una coorte di pazienti all’esordio psicotico, se alcune varianti genetiche sono responsabili dell’insorgenza delle psicosi e di determinare uno specifico pattern clinico di presentazione. È stata inoltre studiata l’associazione tra un endofenotipo (i Neurological Soft Signs, NSS) e la presentazione clinica.
Lo studio si è svolto all’interno del progetto PICOS (Psychosis Incident Cohort Outcome Study). Quest’ultimo è uno dei più ampi progetto di ricerca multicentrici mai svolti in Italia sui pazienti all’esordio psicotico. È stato svolto in Veneto e circa l’80% dei Dipartimenti di Salute Mentale ha aderito. Nel periodo compreso tra il 1 gennaio 2005 e il 31 dicembre 2008, è stata reclutata una coorte di pazienti che si sono presentati per la priva volta ai Centri di Salute Mentale per un episodio psicotico e caratterizzata attraverso una serie di valutazioni cliniche, demografiche, ambientali, neuropsicologiche e biologiche. È stato effettuato il follow up ad un anno ed è in corso il follow up a 2 e 5 anni. I pazienti sono stati valutati attraverso una serie di strumenti standardizzati tra cui: Schedule for Clinical Assessment in Neuropsychiatry (SCAN), Scale for the Assessment of Positive and Negative Symptoms (PANSS), Bech-Rafaelsen Mania Rating Scale (BRMRS), Hamilton Rating Scale for Depression (HAM-D), Global Assessment of Functioning Scale (GAF), Premorbid Adjustment Scale (PAS); Test d’Intelligenza Breve (TIB, Sartori et al, 1997), the Italian version of the New Adult Reading Test (NART), Neurological Evaluation Scale (NES); Family Interview For Genetic Studies (FIGS). A ciascun paziente è stato chiesto di sottoporsi a prelievo ematico per l’estrazione del DNA, che è stato successivamente genotipizzato utilizzando diverse SNPs dei seguenti geni candidati: DTNBP1, NRG1, DISC1, COMT, DAOA/G30, BDNF, DRD2, DRD3, MAOA.
Nel contesto del progetto PICOS sono stati reclutati e valutati 351 pazienti: il 24% ha ricevuto una diagnosi di schizofrenia, il 55% di psicosi non affettiva non schizofrenia, il 21% di psicosi affettiva. Di questi 213 hanno dato il loro consenso all’analisi genetica. Inoltre, per effettuare lo studio caso-controllo, è stato reclutato presso il Servizio Trasfusionale di Verona il gruppo di controllo costituito da 514 soggetti, simili ai pazienti per caratteristiche etniche e area di residenza. È stato trovato che alcuni aplotipi nei geni DISC1, NRG1 e DAOA sono maggiormente presenti nei pazienti che nei controlli, rappresentando un fattore di rischio per lo sviluppo della psicosi. Inoltre 62 pazienti sono stati sottoposti a valutazione neurologica con la scheda NES. È stato riscontrato che i pazienti con più NSS nelle sottoscale “capacità di effettuare atti motori in sequenza” e “capacità sensoriale” sono quelli che hanno più sintomi negativi e che in generale hanno punteggi più elevati alla PANSS. Lo studio PICOS indica che i NSS non sono un artefatto o un epifenomeno della gravità delle psicosi e che sono presenti già all’esordio della malattia. Per il fatto che è ancora da chiarire se i NSS sono un segno di tratto o di stato delle psicosi, o entrambi, è necessario effettuare studi longitudinali per confermare la loro stabilità durante il decorso della malattia.
In conclusione, le difficoltà nel definire in modo chiaro e definitivo la componente genetica alla base delle psicosi rispecchia la loro marcata eterogeneità clinica e neurobiologica. Manca ancora un modello complessivo in grado di studiare tale eterogeneità. In futuro sarà necessario condurre studi che definiscano quali aspetti persistenti del profilo psicotico possono avere una patogenesi biologica, da contrapporre a sintomi fluttuanti mediati dalla componente ambientale.While the evidence for a genetic contribution to schizophrenia and bipolar disorder is strong, the genetics is complex with environmental factors contributing as well.
The inconsistent results and disappointing findings of genetic research into functional psychosis may be due to the intrinsic characteristics of the phenotypes under investigation: the “diagnosis of schizophrenia” and the “diagnosis of bipolar disorder”. Although the DSM/ICD definition of schizophrenia/bipolar disorder has an undoubtedly high clinical utility, it does not provide information about the fundamental nature of the illness. For example, the manifest clinical heterogeneity of schizophrenia, combined with a failure, to date, to demonstrate the existence of a unitary disease process, has led to the conceptualization of schizophrenia as a heterogeneous disorder. Consequently, to obtain a correct classification of psychosis, it is important to understand whether the heterogeneous group of syndromes placed under schizophrenia specific diagnosis is one, or many, diseases. To achieve this aim, the relationship between phenotype and genotype pattern should be ascertained, to detect whether specific variation in a gene imparts risk for a specific form of the illness. One approach to resolve this controversy is to examine the relationship between the clinical features of illness and genetic factors, in addition to selecting cases on the basis of a specific ICD-10 or DSM IV diagnosis of schizophrenia or bipolar alone.
The present study aims, in a cohort of first episode psychosis, to study whether genetic variants are associated with functional psychosis and with one endophenotype (Neurological Soft Signs). Moreover it will be studied whether genetic polymorphisms can determine the clinical profile of psychosis at the onset of the illness.
The present research was conducted within the broader framework of the PICOS study. The PICOS (Psychosis Incident Cohort Outcome Study) is one of the most comprehensive and largest multisite collaborative research projects ever done in Italy. It was performed in Veneto Region: among the Departments of Mental Health the vast majority has accepted to participate in the study, covering 81.4% of the total regional population (about 3.685.000 inhabitants).
A representative cohort of subjects presenting with psychotic symptoms from January 1st 2005 till December 31st 2008 to Community Mental Health Services in the participating catchment areas has been characterized at baseline and then followed-up for 1 year: a comprehensive set of biological, environmental, demographic, clinical and neuropsychological variables were collected by interviewing both the individuals themselves and their carers.
Patients were assessed with a set of standardized measures which include: Schedule for Clinical Assessment in Neuropsychiatry (SCAN), Scale for the Assessment of Positive and Negative Symptoms (PANSS), Bech-Rafaelsen Mania Rating Scale (BRMRS), Hamilton Rating Scale for Depression (HAM-D), Global Assessment of Functioning Scale (GAF), Premorbid Adjustment Scale (PAS); Test d’Intelligenza Breve (TIB, Sartori et al, 1997), the Italian version of the New Adult Reading Test (NART), Neurological Evaluation Scale (NES); Family Interview For Genetic Studies (FIGS). For each subject, venous blood samples (15 ml) were collected in EDTA-containing tubes and DNA was extracted. Several SNPs in DTNBP1, NRG1, DISC1, COMT, DAOA/G30, BDNF, DRD2, DRD3, MAOA genes were genotyped.
In the context of PICOS, 351 patients, with a diagnosis of schizophrenia (24%), non affective (55%), and affective psychoses (21%) were assessed at baseline. Within this group, 213 patients gave their DNAs for the genetic analysis. In addition, 514 controls selected from a population similar to the patients with regard to ethnicity and area of residence were recruited from the Blood Transfusion Service in Verona and were genotyped.
In the PICOS sample, it was found that some haplotypes in DISC1, NRG1 and DAOA occurred more often in cases compared to controls than expected by chance.
Sixty-two subjects with a first-episode psychosis underwent the NSS evaluation. It was found that there is a relationship between having “high” NSS in “sensory” and “sequencing” neurological dysfunction scale and the severity of psychopathology and the negative dimensions. Moreover, patients with “high” NSS in the total score of NES have greater score in the negative dimension and in the total score of the PANSS. The PICOS study indicates that the NSS are not artefacts or epiphenomena of the severity of the illness and that they are present at the very onset of psychosis. Due to the fact that it remains inconclusive whether NSS could be a trait or state marker, or both, for schizophrenia, longitudinal studies are required to confirm the stability of NSS over the course of illness.
In conclusion, the difficulties in gaining a consistent and clear-cut picture of the genetics of schizophrenia and bipolar disorder mirror the marked clinical and neurobiological heterogeneity of the disorder. A comprehensive global model to understand clinical heterogeneity in schizophrenia is still lacking. It will be necessary in the future to conduct studies that define persistent aspects of the psychotic profile which are more likely to represent an underlying biological pathogenesis as opposed to fluctuating, possibly environmentally mediated symptoms
Epigenetics and gene expression profile in First-Episode Psychosis: the role of Childhood Trauma
No full textChildhood Trauma (CT) mediation of the epigenome and its impact on gene expression profile could provide a mechanism for the gene-environment interaction underling psychosis. We reviewed the evidence concerning epigenetic and gene expression modifications associated with CT in both First-Episode Psychosis (FEP) and healthy subjects. In order to explore the relative role of psychosis itself in determining these modifications, evidence about FEP and epigenetics/gene expression was also summarized. We performed a systematic search on PubMed, last updated in December 2016. Out of 2966 potentially relevant records, only 41 studies were included. CT resulted associated: in FEP subjects, with global DNA hypo-methylation and reduced BDNF gene-expression; in healthy subjects, with hyper-methylation of SLC6A4, NR3C1, KITLG, and OXTR; hypo-methylation of FKBP5, IL-6, and BDNF; increased IL1B, IL8, and PTGS gene expression; and decreased SLC6A4 gene expression. FEP showed global DNA hypo-methylation; increased methylation and reduced gene expression of GCH1; hyper-expression of MPB, NDEL1, AKT1, and DICER1; and hypo-expression of DROSHA, COMT, and DISC1 in comparison with healthy controls
The psychopathology of schizophrenia and the presence of neurological soft signs: a review
No full textPurpose of review: The symptoms of schizophrenia cluster in at least three subtypes: positive, negative, and disorganized. The study of these subtypes and their phenotypic markers may help our understanding of the pathophysiology of schizophrenia. Among the markers of schizophrenia are minor neurological signs, which are abnormalities in sensory and motor performance elicited by clinical examination. Evidence on whether neurological abnormalities are associated with a specific symptom subtype is considered. As recent studies have often evaluated individuals at their first psychotic episode who are antipsychotic naive, a review would help to clarify whether neurological soft signs are part of a neurodysfunction that underlies schizophrenia rather than the consequence of degenerative processes or of long-term pharmacological treatment.Recent findings: A consistent association seems to emerge between an excess of neurological soft signs and severe negative symptoms. Signs associated with negative symptoms remain stable over time, and may characterize a subgroup of patients with poor illness course and outcome. Some signs, such as motor dysfunction, may be associated with a worse profile of positive symptoms, and may improve as symptoms improve. Too few studies have evaluated the association between neurological soft signs and disorganization symptoms to suggest or disconfirm any relationship.Summary: Finding an association between neurological soft signs and one (or more) dimension(s) of schizophrenia in never treated patients may explain which neurological dysfunction is an intrinsic characteristic of the illness. The comparability of future studies can be improved by using the same structured rating scale for neurological soft signs and psychopathology, and by a better characterization of patient samples
Child maltreatment, migration and risk of first-episode psychosis: results from the multinational EU-GEI study
Full text linkThe EU-GEI Project was funded by grant agreement Health-F2-2010-241909 from the European Community’s Seventh
Framework program. The Brazilian study was funded by grant 2012-0417-0 from the São Paulo Research FoundationD'Andrea, Giuseppe; Lal, Jatin; Tosato, Sarah;Gayer-Anderson, Charlotte;Jongsma, Hannah E.;Stilo, Simona A.; van der Ven, Els;Quattrone, Diego;Velthorst, Eva;Berardi, Domenico;Rossi Menezes, Paulo; Arango, Celso; Parellada, Mara; Lasalvia, Antonio; La Cascia, Caterina; Ferraro, Laura; La Barbera, Daniele; Sideli, Lucia; Bobes, Julio; Bernardo, Miguel; Sanjuan, Julio; Santos, Jose Luis; Arrojo, Manuel; Marta Del-Ben, Cristina; Tripoli, Giada; Llorca, Pierre-Michel; de Haan, Lieuwe; Selten, Jean-Paul; Tortelli, Andrea; Szoke, Andrei; Muratori, Roberto; Rutten, Bart P.; van Os, Jim; Jones, Peter B.; Kirkbride, James B.; Murray, Robin M.; di Forti, Marta; Tarricone, Ilaria; Morgan, Crai
Can the role of genetic factors in schizophrenia be enlightened by studies of candidate gene mutant mice behaviour?
No full textSchizophrenia is one of the most severe psychiatric disorders. Despite the knowledge accumulated over years, aetiology and pathophysiology remain uncertain. Research on families and twins suggests that genetic factors are largely responsible for the disease and implies specific genes as risk factors. Genetic epidemiology indicates a complex transmission mode, compatible with a multi-locus model, with single genes accounting for specific traits rather than for the entire phenotype. To better understand every single gene contribution to schizophrenia, the use of intermediate endophenotypes has been proposed. A straight communication between preclinical and clinical researchers could facilitate research on the association between genes and endophenotypes. Many behavioural tasks are available for humans and animals to measure endophenotypes. Here, firstly, we reviewed the most promising mouse behavioural tests modelling human behavioural tasks altered in schizophrenia. Secondly, we systematically reviewed animal models availability for a selection of candidate genes, derived from linkage and association studies. Thirdly, we systematically reviewed the studies which tested mutant mice in the above behavioural tasks. Results indicate a large mutant mice availability for schizophrenia candidate genes but they have been insufficiently tested in behavioural tasks. On the other hand, multivariate and translational approach should be implemented in several behavioural domains
Prevalence of non-psychotic disorders in ultra-high risk individuals and transition to psychosis: A systematic review
Full text linkDespite the growing interest in the prodromes of psychosis, the proper identification of those Ultra High Risk (UHR) subjects who will convert to psychosis remains an unresolved issue. It remains to be fully understood whether the risk of transition to psychosis is incremented by the concomitant presence of non-psychotic symptoms. We performed a systematic review in order to estimate: prevalence rates of non-psychotic disorders in UHR individuals and whether any comorbid disorder impacts on the risk of transition to frank psychosis. The review was conducted using the PRISMA guidelines by searching PubMed until August 2017. The inclusion criteria were: studies with appropriate definition of UHR/ ARMS (At Risk Mental States for psychosis); cross-sectional design (for prevalence rates) or longitudinal design (for transition rates to psychosis); adolescents and/or adults; specified instrument/interview for the diagnosis of mental disorder/symptoms. We included 46 English-language articles. We found that non-psychotic symptoms are a prevalent concern in UHR individuals, and this is true for all comorbid disorders examined. None of the mental disorder examined appear to be a marker for transition to psychosis. Our systematic review found that the great majority of UHR individuals actually has a highly prevalent clearly defined, above-the-threshold mental disorder that should constitute the primary focus of intervention
Association between the Neuregulin 1 Gene and schizophrenia: A systematic review
No full textChromosome 8p22-p11 has been identified as a locus for schizophrenia in several genome-wide scans, which has been confirmed by meta-analysis of published linkage data. It appears to be 1 of the most robust linkage findings in psychosis. Several attempts have been made to identify the underlying genetic variation that gives rise to this linkage peak, including systematic fine mapping using extended Icelandic pedigrees that have identified an associated haplotype (HAP(ICE)) in the gene neuregulin 1, also known as heuregulin, glial growth factor, NDF43, and ARIA. Neuregulin 1 (NRG1) is a plausible susceptibility gene because of its involvement in neurodevelopment, regulation of glutamate and other neurotransmitter receptor expression, and synaptic plasticity. Encouragingly, this finding was quickly and directly replicated in a Scottish case-control sample by the same investigators with the same approximately 300 kb associated haplotype. Although in Caucasian populations subsequent attempts at replication of this finding have been difficult to interpret, and no individual functional or causative genetic variants have yet been identified, a summary of HAP(ICE) association results in about 4,500 subjects is consistent with a small (odds ratio approximately 1.5) but significant effect of this haplotype on schizophrenia risk. In Chinese Han populations, where HAP(ICE) is not found, there is good evidence from several studies of association with other markers in the same region. Overall, there is convincing but not yet compelling evidence for a role for NRG1 in susceptibility to schizophrenia. Other genes from this region have also been implicated in schizophrenia, not by systematic mapping but by positional candidate gene analysis; these include MSTP131, frizzled-3, and the calcineurin A gamma subunit gene. Not only are these alternative explanations for the linkage seen between chromosome 8p and schizophrenia, but it is equally possible that there is more than 1 susceptibility gene at this locu
Targeting metabolic abnormalities in mental health prevention strategies
No full textPeople with severe mental disorders (SMI) have a shorter life expectancy of 10–20 years than the general population, mainly due to physical comorbidities, predominantly cardiovascular disease (CVD) and type 2 diabetes (T2D). Patient lifestyle-related risk factors (e.g., smoking, alcohol abuse, lack of physical activity, sedentary lifestyle, unhealthy diet) as well as the use of antipsychotics and antidepressants are likely to be involved. Furthermore, recent evidence shows that cardio-metabolic alterations are present at the beginning of psychosis and major depressive disorder, are probably related to the disease, and worsen with drugs, especially if taken for a long time. Therefore, it is of paramount importance to develop and implement strategies that can prevent and address the problem of physical comorbidity in mental disorders, and it is also essential to raise awareness among health professionals about these insidious and life-threatening conditions. The interventions that can be implemented are both pharmacological and non-pharmacological and can be applied to prevent the development of cardio-metabolic diseases or to reduce their effects in those who have already manifested alterations. The most effective interventions will be presented in the chapter. Despite the evidence that various interventions (e.g., improving physical activity) work and different editorials have required action, “lifestyle interventions” are still limited in routine clinical care
Psychiatric disorders
No full textThis chapter summarizes the most significant gender influences on mental health in terms of illness incidence and prevalence, clinical presentation, course, and response to treatment. Several mental disorders including major depression, bipolar disorder, anxiety disorders, schizophrenia, and eating disorders are considered in different sections. Depression is twice more frequent in women than in men. Moreover, men and women show differences regarding presentation, course, treatment response, and outcome. Women affected by depression show higher recurrence and atypical features; they have generally an earlier onset, more severe, longer, and recurrent depressive episodes, and a lower quality of life than men do. Women are also more likely to have a comorbid anxiety, eating or somatoform disorder, and more frequently than men, they attempt suicide (although lethal suicide is more probable to happen in men). Psychopharmacological treatment of depression also might present significant gender dissimilarities; still, there is no clear consensus on whether there are gender-related differences in antidepressant efficacy. There is a significant gender difference in terms of lifetime prevalence of bipolar disorder type II, with more affected women, while both genders show a similar prevalence of bipolar disorder type I. Women usually have an older age of onset and they typically manifest a depressive polarity at the onset and a predominance of depression phases during lifetime. Women are also more likely to undergo mixed and seasonal episodes and have an increased risk of developing rapid cycling mood disturbances. Bipolar disorder in men is characterized by manic onset, recurrence of manic phases, and by lower treatment adherence. Comorbidity of psychiatric (eating and anxiety disorders) and medical (thyroid disease, migraine, obesity) conditions are more common in women, while substance use disorder is more common in men. There is no evidence that women and men suffering from bipolar disorder differ significantly in treatment response to mood stabilizers. Schizophrenia also has significant gender differences: affected males, normally younger at the onset than females, present more severe negative symptoms, worse cognitive impairment, more frequent hospitalizations, and are more likely to commit acts of severe violence. In detail, incidence rate of early onset is higher in males than females, while at older onset women predominate. Until the mid-30s, rates are estimated to be approximately 1.5–2 times greater in males than females. Later, rates decrease for both sexes, with a narrowing sex ratio, until the mid-40s when there is a minor secondary peak for women. Male patients are likely to have more cognitive impairment and poorer premorbid functioning, more negative symptoms, and more severe deterioration over time. Female patients experienced more severe positive symptoms (hallucinations and persecutory delusions) and commit a greater number of suicide attempts. Women also show a considerably less severe course of the illness: they show a better social functioning and have fewer hospitalizations with shorter inpatient stays. Gender differences have also been well recognized in the response to antipsychotic treatment, with women being better responders than men are. Eating disorders in the past were considered as almost exclusively female disorders (F:M = 20:1), but that is changing rapidly. One million men have been shown to suffer from eating disorders in the USA. Males accounted for roughly 10.0–25.0% of eating disorder patients, with the number of men struggling from bulimia nervosa being more than those who struggle with anorexia. Research and knowledge on the topic are expanding rapidly, and recent literature elucidates gender-specific issues in terms of age of onset, weight history and compensatory exercise behavior, frequency of abuse record, and substance use rates. A later age of onset, premorbid obesity, and over-exercise are more likely in men. Around 30% of subjects suffering from an eating disorder were victims of sexual abuse (1:3 in women vs. 1:7 in men) and a substance use disorder is generally more frequent in subjects with eating disorder (particularly the use of steroids and growth hormones in affected men) in comparison to the general population
- …
