Benzodiazepine long-term administration is associated with impaired attention/working memory in schizophrenia: results from the national multicentre FACE-SZ data set.

OBJECTIVE: The effect of benzodiazepine long-term administration (BLTA) in cognitive functioning of subjects with schizophrenia (SZ) has been partially explored to date. The objective was to assess BLTA-associated cognitive impairment with a comprehensive cognitive battery in a non-selected multicentric/national community-dwelling sample of stabilized SZ subjects. METHOD: 407 community-dwelling stabilized SZ subjects were consecutively included in the FondaMental Academic Centers of Expertise for Schizophrenia Cohort (FACE-SZ). Patients taking daily benzodiazepine were defined as BLTA+ as all patients examined by the Expert Center were clinically stabilized and under stable dose of treatment for at least 3 months. Each patient has been administered a 1-day long comprehensive cognitive battery (including The National Adult Reading Test, the Wechsler Adult Intelligence Scale, the Trail Making Test, the California Verbal Learning Test, the Doors test, and The Continuous Performance Test-Identical Pairs). RESULTS: In the multivariate analyses, results showed that BLTA was associated with impaired attention/working memory (OR 0.60, 95% confidence interval 0.42-0.86; p = 0.005) independently of socio-demographic variables and illness characteristics. Verbal and performance current IQ-[respectively, OR 0.98, 95% CI (0.96;0.99), p = 0.016 and 0.98, 95% CI(0.97;0.99), p = 0.034] but not premorbid IQ-(p > 0.05) have been associated with BLTA in a multivariate model including the same confounding variables. CONCLUSION: BLTA is associated with impaired attention/working memory in schizophrenia. The BLTA benefit/risk ratio should be regularly reevaluated. Alternative pharmacological and non-pharmacological strategies for comorbid anxiety disorders and sleep disorders should be preferred when possible. It seems reasonable to withdraw BLTA before the start of cognitive remediation therapy, as soon as possible, to improve the effectiveness of this therapy. Limits: the delay between the last benzodiazepine intake and testing, as well as the specific class of benzodiazepines (long half-life vs. short half-life), and the number of benzodiazepine daily intakes have not been recorded in the present study. The precise motive for BLTA prescription and sleep disturbances have not been reported, which is a limit for the interpretation of the present results.

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.

[The clinic of apathy in schizophrenia: a critical review of the issue]. / L'apathie dans la schizophrénie: une revue clinique et critique de la question.

INTRODUCTION: Today the concept of apathy is subject to many questions. This psychological state is present and predominant in different disorders such as neurodegenerative and psychiatric diseases or neurological acquired disorders. Apathy is a part of the clinical vocabulary, however, we can note that in the literature there remains confusion in its definition, and we can find an amalgam with other clinical symptoms. OBJECTIVES: The aim of this review is to provide a clarification of the concept of apathy in clinical practice in schizophrenia as well as to highlight the gaps that exist. LITERATURE FINDINGS: Apathy belongs to the negative symptoms of schizophrenia. For its understanding, it is necessary to define apathy as a multidimensional syndrome (cognitive, emotional, and behavioral) manifesting as a quantitative reduction of voluntary behaviors directed toward one or several goals. However, at present, we are witnessing a reductionist and simplistic conception of the syndrome of apathy and this especially in the Anglo-Saxon literature. Several authors reduce apathy to its behavioral component, so in other words, to avolition/amotivation. Avolition refers to a loss of self-initiated and spontaneous behaviors. In this definition only observable behavior is taken into account and not the underlying mechanisms (cognitive and emotional). In order to understand the syndrome of apathy, it is necessary to have a holistic and multidimensional outlook. Some authors have proposed diagnostic criteria for apathy by taking into account the different dimensions of apathy. Moreover not only is apathy confused with avolition, but it is also still difficult to distinguish it from depression. Apathy and depression share common clinical signs (i.e. loss of interest), but they also have distinct clinical signs (lack of motivation for apathy, and suicidal ideation for depression). Authors have shown that the presence of one symptom (apathy or depression) does not predict the presence of the other. An apathetic patient does not have to be necessarily in a depressive state and vice versa. However, to our knowledge, there is no data capable of distinguishing depression from apathy in schizophrenia, and knowing what is the part of one and the other when the patient has both symptoms. In addition, we can see that the confusion that persists between those two symptoms also stems from assessment tools. Indeed, some assessment tools such as the Montgomery and Asberg Depression Rating Scale (MARDS) have an apathy subscale. Therefore, this scale does not only evaluate depression. Regarding the assessment of apathy in schizophrenia, there are specific and nonspecific tools. Nonspecific tools define apathy differently. For this reason, authors have proposed to measure apathy by using analytic factors of negative symptoms. In this case, apathy is going to be assessed by the factor "motivation/pleasure" including anhedonia, asociality and avolition. This factor will provide the possibility of a better assessment of apathy. Concerning specific scales (like AES), there are gaps such as a lack of standardization in the execution and the quotation. Furthermore, no scale takes into account the factors causing apathy. CONCLUSION: Knowing the reasons for apathy is necessary because this syndrome is frequent in schizophrenia, and it is found in the different phases of this disease (prodromal, first episode psychosis, and chronic). In addition, apathy has significant functional consequences on the patient's quality of life, as well as on his or her global functioning. Indeed, apathy impacts on his or her social and professional life. Patients with schizophrenia have a loss of autonomy, less employment and social withdrawal. Consequently, interest in its drug or treatment it is obvious. However, drug and non-drug treatments are not specific to apathy and therefore little effective on this syndrome. Implications to stimulate future research are presented.

[Evolution of the concept of apathy: the need for a multifactorial approach in schizophrenia]. / Évolution du concept d'apathie: nécessité d'une approche multifactorielle dans la schizophrénie.

BACKGROUND: Schizophrenia is a chronic and severe mental illness that affects over 1% of the population, characterized by multiple symptom dimensions. One of this class of symptoms, "negative symptoms", have received more attention over the last few years. Negative symptoms, including among others blunted affect, withdrawal or apathy, are particularly important for recovery and are associated with negative functional outcomes, such as inability to get an employment and conduct normal daily living activities. While positive symptoms are usually treated by antipsychotic drugs, negative symptoms are usually persistent, which indicates the need for better treatment. The aim of this article is to highlight recent scientific progress on apathy and to explore current multidimensional approaches of this concept in schizophrenia. Apathy is a symptom frequently encountered in schizophrenia and in many neurological disorders. Therefore, it can be regarded as a transnosographic symptom. LITERATURE FINDINGS: A long time considered as a loss of motivation (psychological concept hard to define), recent descriptive and etiological models have proposed to consider apathy as a multidimensional phenomenon. Marin et al., have proposed a model of apathy in reference to the motivation concept. Marin et al.'s apathy model is composed of three dimensions: firstly, cognitive dimension, secondly, sensory-motor dimension and thirdly, affective dimension. These authors propose to differentiate "apathy syndrome" from "apathy symptom". "Apathy syndrome" resulting from a lack of motivation whereas "apathy symptom" results from cognitive and/or emotional/affective disorders. In addition, Marin et al. propose that apathy syndrome corresponds to the "lack of motivation" not attributable to diminished level of consciousness, cognitive impairment or emotional distress. Following this proposal, Levy and Dubois propose to define apathy as a quantitative reduction of self-generated, voluntary and purposeful behaviors. It is therefore observable and can be quantified. Levy and Dubois have proposed an apathy model considering: firstly, apathy as a syndrome related to reduction in goal-directed behaviors; secondly, anatomically, apathy can be secondary to dysfunctions or lesions of the prefrontal cortex. Since the prefrontal cortex is functionally and anatomically heterogeneous, subtypes of apathy occur in diseases affecting the basal ganglia, because these diseases disrupt associative and limbic pathways from/to the prefrontal cortex; thirdly, from a pathophysiological point of view, apathy may be explained by the impact of lesions or dysfunctions of the basal ganglia, because these lesions or dysfunctions lead to a loss of temporal and spatial focalization, both of which result in a diminished extraction of the relevant signal within the frontal cortex, thereby inhibiting the capacity of the frontal cortex to select, initiate, maintain and shift programs of action.