COMT but not 5HTTLPR Gene is associated with depression in First-Episode Psychosis: the role of stressful life events

Serotonergic and dopaminergic systems are involved in the regulation of mood and reactivity to psychological stress. This study explores, in a sample of first episode psychosis (FEP) patients, whether more severe depressive symptoms were found in those who: (1) experienced a major stressful event in the 6 months preceding illness onset; and (2) were homozygous for the COMT Val158 allele or carrying the S allele of 5-HTTLPR. A total of 186 FEP patients recruited were assessed using the Hamilton Rating Scale for Depression (HAMD) for depressive symptoms. Stressful life events (SLEs) were collected by the List of Events Scale. The genotypes of 5-HTTLPR, rs25531, and COMT Val158 Met were performed. It has been found that higher levels of depression is associated with the presence of SLEs (p = 0.019) and with COMT Val158 allele homozygosity (p = 0.029), but not with carrying the S allele of 5-HTTLPR. The COMT gene moderates the association between depression and SLEs as Val158 allele homozygote patients experiencing SLEs had the highest level of depressive symptoms compared to the others (p = 0.002). The present study provides initial evidence for an effect of the COMT Val158 homozygosity and severe stressful life events on the severity of depressive symptoms in first episode psychosis

Caratteristiche premorbose, cliniche e sociali dei pazienti all'esordio psicotico valutati nell'ambito del PROGETTO PICOS-VENETO. L'impatto delle "gender differences"

La schizofrenia \ue8 un disturbo psichico cronico, grave e molto debilitante che colpisce in vario modo il comportamento, il pensiero e le emozioni. I sintomi comunemente iniziano nella tarda adolescenza o al principio dell\u2019et\ue0 adulta. Approssimativamente l\u20191% della popolazione sviluppa questa malattia nel corso della vita (Tansella et al., 1991). Nonostante i molti studi, il problema riguardante il peso relativo giocato da fattori di diversa natura nel determinare l\u2019insorgenza del disturbo e nel condizionarne il successivo decorso ed esito resta da chiarite. Secondo l\u2019ipotesi eziopatogenetica attualmente pi\uf9 accreditata, la schizofrenia viene considerata come il risultato dell\u2019interazione di fattori genetici e ambientali, che opererebbero in combinazione nel determinare una condizione di suscettibilit\ue0 alla malattia. Innumerevoli sono i fattori che sono stati individuati come potenziali elementi di rischio per l\u2019insorgenza della schizofrenia. Fra questi, l\u2019appartenere al sesso maschile o femminile \ue8 risultato essere in numerosi studi un fattore in grado di modulare il ricorso al trattamento, le caratteristiche della sintomatologia ed il decorso del disturbo stesso, con un chiaro svantaggio da parte del sesso maschile. Da quando Kraepelin (Kraepelin, 1919) fece le prime ricerche sulle differenze di genere molti altri studiosi hanno posto la loro attenzione su questo argomento. Gli studi pi\uf9 recenti riportano che gli uomini schizofrenici hanno un\u2019et\ue0 d\u2019esordio pi\uf9 precoce rispetto alle donne (Hafner et al., 1998), una storia premorbosa caratterizzata da maggiori difficolt\ue0, un pi\uf9 alto tasso di ricaduta, un peggiore esito e una risposta ai farmaci ridotta (Addington et al., 2003; Kelley et al., 1992). Vi \ue8, inoltre, una caratterizzazione della malattia diversa in base al genere: alcuni studi hanno riscontrato una maggior presenza di sintomi negativi negli uomini 6 rispetto alle donne, mentre queste ultime possono avere una prevalenza di sintomi affettivi come disforia, depressione e ostilit\ue0 (Leung & Chue, 2000; Addington et al., 2003). Sono state messe in evidenza altre importanti differenze che caratterizzano la malattia al momento dell\u2019esordio. Si \ue8 visto che le donne sono pi\uf9 spesso sposate e che gli uomini hanno un livello di istruzione pi\uf9 basso. Negli uomini, inoltre, il tempo che intercorre tra la comparsa dei primi sintomi e il primo contatto con un Servizio di Salute Mentale \ue8 pi\uf9 lungo (Larsen et al., 1996). Le implicazioni di tale svantaggio ai fini del funzionamento sociale delle persone affette, dei trattamenti che possono essere messi in atto e dell\u2019organizzazione dei servizi non sono ancora state adeguatamente studiate. A tutt\u2019oggi non e\u2019 stato chiarito se le \u201cgender differences\u201d siano patognomoniche della schizofrenia o riguardino in generale la caratterizzazione e l\u2019evoluzione delle psicosi in generale. Infine, nessuno studio \ue8 stato a tutt\u2019oggi effettuato in Italia su campioni rappresentativi di pazienti all\u2019esordio psicotico che consentano di verificare, nel nostro contesto socio-culturale, quanto effettivamente le differenze di genere incidano sulle manifestazioni ed il decorso delle psicosi. Questa tesi e\u2019 articolata in pi\uf9 sezioni. Specificatamente: 1. analisi della letteratura che indaga l\u2019et\ue0 d\u2019esordio, le complicanze ostetriche, il funzionamento premorboso, la durata di psicosi non trattata, l\u2019utilizzo di cannabis e le differenze di genere nell\u2019espressione della malattia; 2. obiettivi della Ricerca svolta e delle ipotesi che si intendono testare; 3. illustrazione dei Metodi utilizzati nel Progetto di Ricerca e descrizione del Progetto PICOS, con particolare attenzione alla parte della ricerca che si occupa dell\u2019ambito relativo all\u2019et\ue0 d\u2019esordio, le complicanze ostetriche, il funzionamento premorboso, la durata di psicosi non trattata, l\u2019utilizzo di cannabis e le differenze di genere nell\u2019espressione della malattia; 4. sintesi dei dati raccolti all\u2019interno del Progetto PICOS, analizzati attraverso il filtro delle differenze di genere.not availabl

Outcome of patients dropping out from community-based mental health care: A 6-year multiwave follow-up study

OBJECTIVE: To test three hypotheses: i) is dropping out of community mental health care due to dissatisfaction? ii) Do those who appropriately interrupt mental health care need any more help? iii) Do those who need treatment continue to receive it? METHOD: A cohort from a Community Mental Health Service in Verona, Italy, was followed up for 6 years, interviewing patients at follow-up who are both in contact and not in contact with the service. RESULTS: The main reason for dropping out was service dissatisfaction. Patients still in contact with the service were more often psychotic. Many patients no longer in contact had mild-to-moderate problems, especially anxiety and depression and some social disability. Patients out of contact rarely sought help from other agencies. CONCLUSION: Comprehensive community mental health services seem to offer good continuity of mental health care to patients with psychosis, but dedicate less attention to patients with less severe problems. Some of these patients will go on experiencing a burden of symptoms and disability, over the years

Dietary habits and physical activity in first-episode psychosis patients treated in community services. Effect on early anthropometric and cardio-metabolic alterations

People with psychosis often develop metabolic and cardiovascular disorders, due to several factors including unhealthy lifestyle and antipsychotic treatment. This study aims to evaluate in a sample of first episode psychosis (FEP) patients lifestyle factors, with a specific emphasis on dietary habits and physical activity, and cardio-metabolic and anthropometric profile at illness onset and at 9 months. Moreover, this study aims to evaluate the impact of lifestyle factors on short term changes in cardio-metabolic and anthropometric profile. A 9-month follow-up study was conducted on a sample of 96 FEP patients recruited within the context of the GET UP program. Standardised assessments of dietary habits (EPIC) and physical activity (IPAQ) were retrospectively performed at 9 months; cardiovascular measures (blood pressure, heart rate), metabolic parameters (glucose, cholesterol, triglycerides), BMI and antipsychotic treatment were assessed at illness onset and at 9 months. We found that most FEP patients (60%) displayed poor dietary habits, as defined in terms of adherence to the Mediterranean diet. A significant increase for both BMI and cholesterol levels was found in the overall sample over 9 months. However, when considering the effect of lifestyle factors, BMI and total cholesterol were specifically raised in patients with low adherence to Mediterranean diet. The association with antipsychotic medication was found for SGA only, with a significant increase in both BMI and total cholesterol overtime. Our findings confirm the need to implement specific and early strategies to promote healthy lifestyle in people with FEP, since metabolic alterations occur within the first months of treatment

Effect of COMT genotype on aggressive behaviour in a community cohort of schizophrenic patients

Although the etiology of aggression is multifactorial, many studies have associated the Val158Met polymorphism of the COMT with aggression in schizophrenia. This study tests the hypothesis that Met/Met patients display more episodes of aggression and violent behaviour than Val/Val patients in a 6 year follow-up cohort of subjects with schizophrenia in contact with the South-Verona Community-based Mental Health Service. Out of the 141 subjects with an ICD-10 SCAN-confirmed diagnosis of schizophrenia, 115 completed both baseline and follow-up assessments (81.6% of the baseline cohort). Of these, 80 subjects (70%) were genotyped and rated for aggression using the Overt Aggression Scale. Met/Met homozygous patients had higher aggressive behaviour compared to Val/Val homozygous subjects. Antipsychotic dosage, alcohol and drug abuse were taken into account as confounders. The Met/Met genotype of COMT may have an effect on aggressive behaviour in schizophrenia because norepinephrine is less effectively inactivated. \ua9 2011 Elsevier Ireland Ltd.Although the etiology of aggression is multifactorial, many studies have associated the Val158Met polymorphism of the COMT with aggression in schizophrenia. This study tests the hypothesis that Met/Met patients display more episodes of aggression and violent behaviour than Val/Val patients in a 6 year follow-up cohort of subjects with schizophrenia in contact with the South-Verona Community-based Mental Health Service. Out of the 141 subjects with an ICD-10 SCAN-confirmed diagnosis of schizophrenia, 115 completed both baseline and follow-up assessments (81.6% of the baseline cohort). Of these, 80 subjects (70%) were genotyped and rated for aggression using the Overt Aggression Scale.Met/Met homozygous patients had higher aggressive behaviour compared to Val/Val homozygous subjects. Antipsychotic dosage, alcohol and drug abuse were taken into account as confounders. The Met/Met genotype of COMT may have an effect on aggressive behaviour in schizophrenia because norepinephrine is less effectively inactivated

Childhood adversity, symptoms, and cortisol in first episode psychosis: a cross-sectional, secondary, observational analysis of a subsample of FEP patients

Background: Although it has been proposed that childhood adversities (CAs) may affect the hypothalamic-pituitary-adrenal (HPA) axis activity and psychotic symptoms severity, these associations have not been fully confirmed in first-episode psychosis (FEP). This study explored the association between CA, cortisol and psychotic symptoms in FEP patients. Methods: 81 FEP patients were enrolled. CAs were evaluated by the Childhood Experience of Care and Abuse Questionnaire and a semi-structured interview. Psychotic symptoms were evaluated by the Positive and Negative Syndrome Scale. Cortisol level was collected using saliva samples. ANCOVA and partial correlation analyses were run. Results: FEP patients with childhood abuse reported severe positive symptoms than those without CA. FEP patients with at least one CA had higher levels of cortisol awaking, cortisol at 12 a.m., and cortisol at 8 p.m. Morning cortisol levels were negatively correlated with the severity of negative symptoms and positively correlated with the severity of general psychopathology. Evening cortisol levels were positively correlated with severity of general psychopathology. Conclusion: FEP patients with CAs, compared with those without CA, might report more severe positive symptoms and higher cortisol, even though these findings as prone to bias due to the small sample size, and should be seen in the larger perspective of conflicting evidence in the field

COMT but Not 5HTTLPR Gene Is Associated with Depression in First-Episode Psychosis: The Role of Stressful Life Events

Serotonergic and dopaminergic systems are involved in the regulation of mood and reactivity to psychological stress. This study explores, in a sample of first episode psychosis (FEP) patients, whether more severe depressive symptoms were found in those who: (1) experienced a major stressful event in the 6 months preceding illness onset; and (2) were homozygous for the COMT Val158 allele or carrying the S allele of 5-HTTLPR. A total of 186 FEP patients recruited were assessed using the Hamilton Rating Scale for Depression (HAMD) for depressive symptoms. Stressful life events (SLEs) were collected by the List of Events Scale. The genotypes of 5-HTTLPR, rs25531, and COMT Val158 Met were performed. It has been found that higher levels of depression is associated with the presence of SLEs (p = 0.019) and with COMT Val158 allele homozygosity (p = 0.029), but not with carrying the S allele of 5-HTTLPR. The COMT gene moderates the association between depression and SLEs as Val158 allele homozygote patients experiencing SLEs had the highest level of depressive symptoms compared to the others (p = 0.002). The present study provides initial evidence for an effect of the COMT Val158 homozygosity and severe stressful life events on the severity of depressive symptoms in first episode psychosis

The influence of gender on clinical and social characteristics of patients at psychosis onset: A Report from the Psychosis Incident Cohort Outcome Study (PICOS)

BACKGROUND: This paper examined the hypothesis that males with first-episode psychosis (FEP) experience lower pre-morbid adjustment, greater social disability and more self-perceived needs at illness onset than females (by controlling for duration of untreated psychosis, diagnosis, age and symptoms at onset). Results disconfirming this hypothesis were thought to suggest the potentially mediating role of social context in determining the impact of symptoms and disability on the everyday lives of male patients in the early phase of psychosis.MethodA large epidemiologically representative cohort of FEP patients (n=517) was assessed within the Psychosis Incident Cohort Outcome Study (PICOS) framework - a multi-site research project examining incident cases of psychosis in Italy's Veneto region.RESULTS: Despite poorer pre-morbid functioning and higher social disability at illness onset, males reported fewer unmet needs in the functioning domain than females did. An analysis of help provided by informal caregivers showed that males received more help from their families than females did. This finding led us to disconfirm the second part of the hypothesis and suggest that the impact of poorer social performance and unmet needs on everyday life observed in male patients might be hampered by higher tolerance and more support within the family context.CONCLUSIONS: These findings shed new light on rarely investigated sociocultural and contextual factors that may account for the observed discrepancy between social disability and needs for care in FEP patients. They also point to a need for further research on gender differences, with the ultimate aim of delivering gender-sensitive effective mental health care