H. Yazbek

Chronic Peripheral Inflammation is Associated With Cognitive Impairment in Schizophrenia: Results From the Multicentric FACE-SZ Dataset

OBJECTIVES Inflammation, measured by abnormal blood C-reactive protein (CRP) level, has been described in schizophrenia (SZ), being inconsistently related to impaired cognitive functions. The aim of the present study is to investigate cognitive impairment associated with abnormal CRP levels in a large multi-centric sample of community-dwelling SZ patients, using a comprehensive neuropsychological battery. METHOD Three hundred sixty-nine community-dwelling stable SZ subjects (76.2% men, mean age 32.7 y) were included and tested with a comprehensive battery of neuropsychological tests. Abnormal CRP level was defined as >3mg/L. RESULTS Multiple factor analysis revealed that abnormal CRP levels, found in 104 patients (28.2%), were associated with impaired General Intellectual Ability and Abstract Reasoning (aOR = 0.56, 95% CI 0.35-0.90, P = .014), independently of age, sex, education level, psychotic symptomatology, treatments, and addiction comorbidities. Abnormal CRP levels were also associated with the decline of all components of working memory (respectively effect size [ES] = 0.25, P = .033; ES = 0.27, P = .04; ES = 0.33, P = .006; and ES = 0.38, P = .004) and a wide range of other impaired cognitive functions, including memory (ES = 0.26, P = .026), learning abilities (ES = 0.28, P = .035), semantic memory (ES = 0.26, P = .026), mental flexibility (ES = 0.26, P = .044), visual attention (ES = 0.23, P = .004) and speed of processing (ES = 0.23, P = .043). CONCLUSION Our results suggest that abnormal CRP level is associated with cognitive impairment in SZ. Evaluating the effectiveness of neuroprotective anti-inflammatory strategies is needed in order to prevent cognitive impairment in SZ.

Metabolic syndrome, abdominal obesity and hyperuricemia in schizophrenia: Results from the FACE-SZ cohort

OBJECTIVE Abdominal obesity was suggested to be a better predictor than Metabolic Syndrome (MetS) for cardiovascular mortality, however this is has not been extensively studied in schizophrenia. Hyperuricemia (HU) was also suggested to be both an independent risk factor for greater somatic comorbidity and a global metabolic stress marker in patients with schizophrenia. The aim of this study was to estimate the prevalence of MetS, abdominal obesity and HU, to examine the association between metabolic parameters with HU in a cohort of French patients with schizophrenia or schizo-affective disorder (SZ), and to estimate the prevalence rates of treatment of cardio-vascular risk factors. METHOD 240 SZ patients (age=31.4years, male gender 74.3%) were systematically included. Metabolic syndrome was defined according to the International Diabetes Federation and HU if serum uric acid level was above 360μmol/L. RESULTS MetS, abdominal obesity and HU were found respectively in 24.2%, 21.3% and 19.6% of patients. In terms of risk factors, multiple logistic regression showed that after taking into account the potential confounders, the risk for HU was higher in males (OR=5.9, IC95 [1.7-21.4]) and in subjects with high waist circumference (OR=3.1, IC95 [1.1-8.3]) or hypertriglyceridemia (OR=4.9, IC95 [1.9-13]). No association with hypertension, low HDL cholesterol or high fasting glucose was observed. Only 10% of patients with hypertension received a specific treatment, 18% for high fasting glucose and 8% for dyslipidemia. CONCLUSIONS The prevalence of MetS, abdominal obesity and hyperuricemia is elevated in French patients with schizophrenia, all of which are considerably under-diagnosed and undertreated. HU is strongly associated with abdominal obesity but not with psychiatric symptomatology.

The Lille Apathy Rating Scale (LARS): Exploring its psychometric properties in schizophrenia

BACKGROUND Apathy in schizophrenia patients is linked to marked functional impairments and can be defined as a quantitative reduction of voluntary, goal-directed behaviors. If there are now convincing arguments to consider apathy as a multidimensional psychopathological state (cognitive, emotional, and behavioral), there is a lack of validated and standardized instruments for detecting apathy and assessing its multidimensional aspects in schizophrenia. The Lille Apathy Rating Scale (LARS) is a semi-structured interview, yielding a global score and composite subscores for the different domains of apathy and has been validated in several different contexts but not in schizophrenia patients. OBJECTIVE The aim of this study is to examine the psychometric properties of the LARS and identify the distinct components of apathy in a sample of schizophrenia patients. METHODS One hundred-and-twelve schizophrenia patients were included and they completed the LARS, The Calgary Depression Scale in Schizophrenia, the Positive and the Negative Syndrome Scale and the Scale for the Assessment of Negative Symptoms. The patient group was compared to 51 healthy control subjects. RESULTS Principal component analysis showed that the LARS proved a single construct which forms the root of an oblique factor structure reflecting four dimensions: novelty and social life, behavioral involvement, emotional involvement, and judgment skills. The main psychometric properties of the LARS were satisfactory. CONCLUSIONS Our findings show that the LARS has satisfactory psychometric properties when used in a different setting than the original version. The LARS is a promising instrument to examine apathy in schizophrenia through a multidimensional framework.

Akathisia: prevalence and risk factors in a community-dwelling sample of patients with schizophrenia. Results from the FACE-SZ dataset.

The main objective of this study was to determine the prevalence of akathisia in a community-dwelling sample of patients with schizophrenia, and to determine the effects of treatments and the clinical variables associated with akathisia. 372 patients with schizophrenia or schizoaffective disorder were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with validated scales. Akathisia was measured with the Barnes Akathisia Scale (BAS). Ongoing psychotropic treatment was recorded. The global prevalence of akathisia (as defined by a score of 2 or more on the global akathisia subscale of the BAS) in our sample was 18.5%. Patients who received antipsychotic polytherapy were at higher risk of akathisia and this result remained significant (adjusted odd ratio=2.04, p=.025) after controlling the influence of age, gender, level of education, level of psychotic symptoms, substance use comorbidities, current administration of antidepressant, anticholinergic drugs, benzodiazepines, and daily-administered antipsychotic dose. The combination of second-generation antipsychotics was associated with a 3-fold risk of akathisia compared to second-generation antipsychotics used in monotherapy. Our results indicate that antipsychotic polytherapy should be at best avoided and suggest that monotherapy should be recommended in cases of akathisia. Long-term administration of benzodiazepines or anticholinergic drugs does not seem to be advisable in cases of akathisia, given the potential side effects of these medications.

Childhood trauma, depression and negative symptoms are independently associated with impaired quality of life in schizophrenia. Results from the national FACE-SZ cohort

OBJECTIVES Depression and negative symptoms have been associated with impaired Quality of life (QoL) in schizophrenia (SZ). However, childhood trauma may influence both QoL and depression in SZ patients, with consequences for the management of impaired QoL in SZ patients. The aim of the present study was to determine if childhood trauma was associated with impaired QoL in schizophrenia. METHOD A sample of 544 community-dwelling stabilized SZ patients enrolled in FACE-SZ cohort were utilized in this study (74.1% males, mean aged 32.3years, mean illness duration 10.6years). QoL was self-reported with the S-QoL18 questionnaire. Childhood trauma was self-reported with the Childhood Trauma Questionnaire. Depression was measured by the Calgary Depression Rating Scale for Schizophrenia. Psychotic severity was measured by the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). Other clinical factors, treatments, comorbidities, functioning and sociodemographical variables were also recorded, with validated scales. RESULTS Overall, 151 participants (27.8%) had a current major depressive episode and 406 (82.5%) reported at least one episode of historical childhood trauma. In multivariate analyses, lower QoL total score was associated with a history of childhood trauma (β=-0.21, p<0.0001), psychotic negative symptoms (β=-0.11, p=0.04), current depression (β=-0.0.38, p<0.0001) and male gender (β=-0.16, p<0.0001). CONCLUSION Impaired QoL is independently associated with negative symptoms, depression and childhood trauma in schizophrenia.

Working Memory Deficit as a Risk Factor for Severe Apathy in Schizophrenia: A 1-Year Longitudinal Study

Apathy, described as impaired motivation and goal-directed behavior, is a common yet often overlooked multidimensional psychopathological state in schizophrenia. Its underlying cognitive processes remain largely unexplored. Data was drawn from a longitudinal hospital study of patients with a DSM-IV diagnosis of schizophrenia; 137 (82.5%) participated at the 1-month follow-up and 81 (59.1%) at the 1-year follow-up. Apathy was assessed with the Lille Apathy Rating Scale, validated in French and in schizophrenia. Severe apathy, overall (total score > -13) and on 4 previously identified distinct dimensions, was considered. Episodic verbal learning was assessed with the California Verbal Learning Test, executive functioning with the Trail Making Test, the Six Element Test and the Stop Signal Paradigm and working memory with the Letter-Number Sequencing Test. After controlling for confounding variables, only episodic verbal learning was associated with severe overall apathy in the cross-sectional study. At 1 year, working memory was associated with an increased risk of severe overall apathy, adjusting for baseline apathy. Using a dimensional approach to apathy, specific types of cognition were found to be associated with specific dimensions of apathy. Our findings confirm the need for a multidimensional approach of negative symptoms in schizophrenia. Moreover, cognitive functioning could be a risk factor for developing severe apathy. Cognitive remediation may thus be a useful non-pharmacological intervention for treating apathy in schizophrenia patients.

Influence of Venus and Mars in the cognitive sky of schizophrenia. Results from the first-step national FACE-SZ cohort

OBJECTIVES Sex differences can yield important clues regarding illness pathophysiology and its treatment. Schizophrenia (SZ) has a lower incidence rate, and a better prognosis, in women versus men. The present study investigated the cognitive profiles of both sexes in a large multi-centre sample of community-dwelling SZ patients. METHOD 544 community-dwelling stable SZ subjects (141 women and 403 men; mean age 34.5±12.1 and 31.6±8.7years, respectively) were tested with a comprehensive battery of neuropsychological tests. RESULTS Although community-dwelling SZ men had more risk factors for impaired cognition (including first-generation antipsychotics administration and comorbid addictive disorders), women had lower scores on a wide range of cognitive functions, including current and premorbid intellectual functioning, working memory, semantic memory, non-verbal abstract thinking and aspects of visual exploration. However, women scored higher in tests of processing speed and verbal learning, as well as having a lower verbal learning bias. No sex difference were evident for visuospatial learning abilities, cued verbal recall, sustained attention and tests of executive functions, including cognitive flexibility, verbal abstract thinking, verbal fluency and planning abilities. CONCLUSION Sex differences are evident in the cognitive profiles of SZ patients. The impact on daily functioning and prognosis, as well as longitudinal trajectory, should be further investigated in the FACE-SZ follow-up study. Sex differences in cognition have implications for precision-medicine determined therapeutic strategies. LIMITS Given the restricted age range of the sample, future research will have to determine cognitive profiles across gender in late onset SZ.

Cigarette smoking and schizophrenia: a specific clinical and therapeutic profile? Results from the FACE-Schizophrenia cohort

BACKGROUND Tobacco use is common in patients with schizophrenia (SZ) but little is known on the role of tobacco in the physiopathology or on the course of the disease. Only few studies embrace an extensive examination of clinical and therapeutic characteristics in stabilized patients. The objective of the present study was to determine the prevalence of tobacco smoking in stabilized SZ outpatients and the clinical and treatment characteristics associated with daily tobacco use in a large community-dwelling sample of patients. METHODS Three-hundred-and-sixty-one patients were included in the network of the FondaMental Expert Centers for Schizophrenia. Current tobacco status was self-declared. RESULTS 53.7% were smokers. Mean age at tobacco onset was 17.2years old. In multivariate analyses, after adjustment for confounding factors, positive symptoms and mean daily antipsychotic dose were associated with a higher frequency of tobacco use (OR=1.06 95%IC[1.02-1.12], for positive symptoms, OR=1.1, 95%IC[1.02-1.18] for daily antipsychotic dose). Education level, negative symptoms, anticholinergic agents, clozapine or aripiprazole administration were independently associated with a lower frequency of tobacco use (respectively OR=0.87, 95%IC [0.79, 0.95], OR=0.95, 95%IC[0.91-0.98], OR=0.41, 95%IC[0.22-0.76], OR=0.56, 95%IC=[0.32, 0.99] and OR=0.49, 95%IC [0.26-0.91]). CONCLUSION The prevalence of current tobacco smoking in a French community-dwelling SZ patients is higher that observed in the general population. Patients with tobacco use present clinical and therapeutic specificities that may involve interaction between cholinergic-nicotinic and dopaminergic systems. The present study suggests that some therapeutics may improve daily smoking behavior in smokers. These results should be confirmed in longitudinal studies.

Further insight into the role of metacognitive beliefs in schizophrenia and OCD patients: Testing a mediation model

This study explored the mediation effect of metacognitive beliefs on the relationship between intrusive thoughts and emotional distress in schizophrenia (N=49) and obsessive-compulsive disorder (OCD) (N=35). Intrusive thoughts impact on anxiety and depression through beliefs about uncontrollability and danger of thoughts in schizophrenia. Negative beliefs in general mediated the effect of intrusive thoughts on anxiety in obsessive-compulsive disorder. The results suggest that metacognitive beliefs may be a vulnerability factor for emotional and psychological disorder.

Psychiatric disability as mediator of the neurocognition-functioning link in schizophrenia spectrum disorders: SEM analysis using the Evaluation of Cognitive Processes involved in Disability in Schizophrenia (ECPDS) scale

The functional outcome in schizophrenia spectrum disorders is affected by multiple factors such as cognitive performance and clinical symptoms. Psychiatric disability may be another important determinant of functional outcome. The purpose of this study was to test whether schizophrenia symptoms and psychiatric disability mediated the association between cognition and functioning. Between April 2013 and July 2017, we included 108 community-dwelling adults with stable schizophrenia spectrum disorder in a multicenter study. Psychiatric disability was assessed with the Evaluation of Cognitive Processes involved in Disability in Schizophrenia (ECPDS) scale by relatives of patients. ECPDS focused on the broad array of motivational, neurocognitive, sociocognitive, and metacognitive impairments that result in activity restrictions. We used a battery of tests to assess seven cognition domains (processing speed, attention/vigilance, working, verbal and visual memory, reasoning and problem solving, and executive functioning) and cross-sectional structural equation modeling (SEM) for the mediation analyses. We estimated the one-year temporal stability of ECPDS scores in 45 participants. The model provided showed good fit and explained 43.9% of the variance in functioning. The effect of neurocognition on functioning was fully mediated by symptoms (proportion mediated: 36.5%) and psychiatric disability (proportion mediated: 31.3%). The ECPDS score had acceptable one-year temporal stability. The ECPDS scale has satisfactory psychometric properties, and shows significant convergence with neurocognition and functioning, suggesting a role for this tool in the routine evaluation of cognitive remediation needs. Our model validates psychiatric disability as a crucial step from cognitive impairment to restricted participation in life situations.