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.

Insight of patients and their parents into schizophrenia: Exploring agreement and the influence of parental factors.

Poor insight is found in up to 80% of schizophrenia patients and has been associated with multiple factors of which cognitive functioning, social and environmental factors. Few studies have explored associations between patient insight and that of their biological parents', and the influence of parental factors. Insight was assessed in 41 patients and their biological parents with Amador's Scale for the assessment of Unawareness of Mental Disorder (SUMD). Parents' knowledge about schizophrenia and critical attitudes were assessed with validated self-report questionnaires. Both groups underwent cognitive assessments for working memory and executive functioning. Insight in patients and their parents was not associated for any of the SUMD dimensions but a significant correlation was found between patient and parent awareness of treatment effect for patient-parent dyads with frequent daily contact. Low parental critical attitude was associated with higher patient awareness of symptoms and a high parental memory task score with high patient insight. Our study is the first to suggest a possible influence of parental factors such as critical attitudes and cognitive performance on patient insight.

Social priming enhances interpersonal synchronization and feeling of connectedness towards schizophrenia patients.

What leads healthy individuals to abnormal feelings of contact with schizophrenia patients remains obscure. Despite recent findings that human bonding is an interactive process influenced by coordination dynamics, the spatiotemporal organization of the bodily movements of schizophrenia patients when interacting with other people is poorly understood. Interpersonal motor coordination between dyads of patients (n = 45) or healthy controls (n = 45), and synchronization partners (n = 90), was assessed with a hand-held pendulum task following implicit exposure to pro-social, non-social, or anti-social primes. We evaluated the socio-motor competence and the feeling of connectedness between participants and their synchronization partners with a measure of motor coordination stability. Immediately after the coordination task, all participants were also asked to rate the likeableness of their interacting partner. Our results showed greater stability during interpersonal synchrony in schizophrenia patients who received pro-social priming, inducing in their synchronization partner greater feelings of connectedness towards patients. This greater feeling of connectedness was positively correlated with stronger motor synchronization between participants suggesting that motor coordination partly underlies patients' social interactions and feelings of contact with others. Pro-social priming can have a pervasive effect on abnormal social interactions in schizophrenia patients.

Psychological distress over time in early rheumatoid arthritis: results from a longitudinal study in an early arthritis cohort.

OBJECTIVE: RA is a chronic disease with frequent psychological co-morbidities, of which depression and anxiety are two common manifestations. We aimed to identify predictive factors of psychological distress in a large prospective cohort of very early RA patients. METHODS: ESPOIR (Etude et Suivi des Polyarthrites Indifférenciées Récentes) is a multicentre, longitudinal and prospective cohort study of patients with early arthritis (<6 months disease duration). The study sample comprised 641 patients with very early RA according to the 2010 ACR/European League Against Rheumatism RA criteria from the ESPOIR cohort. Psychological distress was assessed over 3 years by the five-item Mental Health Inventory questionnaire at various time points (baseline, 6, 12, 18, 24 and 36 months). Logistic regression with a generalized estimating equation model was used to analyse the association of disease variables and risk of psychological distress. RESULTS: At baseline, 46.9% of RA patients were screened as positive for psychological distress. Over 3 years, psychological distress decreased significantly, with a prevalence of 25.8% at 36 months. The HAQ Disability Index (HAQ-DI) score was the most important factor predicting psychological distress over 3 years [odds ratio 2.10 (95% CI 1.41, 3.14)-3.59 (2.29, 5.63)]. Baseline biological and radiological variables and treatment regimens were not associated with distress. CONCLUSION: Psychological distress in very early RA is frequent and the HAQ-DI score is a predictor of depression and anxiety in these patients. A psychological evaluation in patients with early RA is important for further individual psychiatric diagnosis and management.

Social priming increases nonverbal expressive behaviors in schizophrenia.

Semantic priming tasks are classically used to influence and implicitly promote target behaviors. Recently, several studies have demonstrated that prosocial semantic priming modulated feelings of social affiliation. The main aim of this study was to determine whether inducing feelings of social affiliation using priming tasks could modulate nonverbal social behaviors in schizophrenia. We used the Scrambled Sentence Task to prime schizophrenia patients according to three priming group conditions: pro-social, non-social or anti-social. Forty-five schizophrenia patients, diagnosed according to DSM-IV-TR, were randomly assigned to one of the three priming groups of 15 participants. We evaluated nonverbal social behaviors using the Motor-Affective subscale of the Motor-Affective-Social-Scale. Results showed that schizophrenia patients with pro-social priming had significantly more nonverbal behaviors than schizophrenia patients with anti-social and non-social priming conditions. Schizophrenia patient behaviors are affected by social priming. Our results have several clinical implications for the rehabilitation of social skills impairments frequently encountered among individuals with schizophrenia.

Cognitive insight in schizophrenia patients and their biological parents: a pilot study.

BACKGROUND: Clinical insight in schizophrenia patients is partly associated with familial environment but has been poorly studied to date. We aimed to explore (1) the relationship between parents' cognitive insight and their offspring's; (2) the relationship between parents' cognitive insight and their clinical insight into the disease of their offspring; and (3) the clinical and cognitive determinants of cognitive insight in parents. METHODS: Cognitive insight was assessed in 37 patient-biological parent pairs/dyads with the Beck Cognitive Insight Scale (BCIS). Other measures included the Scale to assess Unawareness of Mental Disorder and cognitive assessments. RESULTS: We found no significant association between parents' cognitive insight and their offspring's. Conversely, a positive association between parents' cognitive insight and parents' insight into their offspring's symptoms was found. Better awareness of their offspring's specific symptoms was associated with lower levels of overconfidence in one's beliefs and with BCIS total score. BCIS Self-Certainty and BCIS total score were associated with better executive functioning and verbal comprehension. CONCLUSIONS: Better insight into their offspring's symptoms is associated with cognitive insight in biological parents of schizophrenia patients. Our results support the integration of cognitive intervention targeting parents' cognitive flexibility in family psychoeducational programs and provide an important first step towards developing a more refined understanding of the factors involved in insight into symptoms of illness in parents of schizophrenia patients.

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.

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.

Memory self-efficacy in schizophrenia.

The positive association between memory self-efficacy (MSE), defined as the beliefs about one's ability to use memory effectively, and memory performance is highly documented in the literature but has not yet been explored in schizophrenia. In the current study the relationship between MSE and objective memory measures was explored in thirty schizophrenia patients and twenty healthy controls. Compared to healthy controls, schizophrenia patients presented lower MSE, which was associated with depression. Among controls, but not patients, MSE was positively related to memory performance. This result suggests that normal relationship between MSE and memory functioning is disrupted in schizophrenia.

Can individuals with schizophrenia be instructed to deliberately feign memory deficits?

INTRODUCTION: Neuropsychological tests are increasingly applied in research studies and clinical practice in psychiatry. In this context, the detection of poor effort is crucial to adequately interpret data. We measured schizophrenia patients' performance on a memory test designed to detect excessive malingering (the "21-Item Test"), before examining whether a second group of schizophrenia patients would excessively malinger on this test when given an incentive to feign memory impairment. METHODS: Two independent studies including respectively 49 schizophrenia patients and 100 controls (study 1) and 25 schizophrenia patients and 25 controls (study 2) were conducted. In study 1, participants were asked to complete the 21-Item Test to the best of their ability. In study 2, participants were given a hypothetical scenario in which having a memory impairment would be financially advantageous for them, before completing the 21-Item Test. RESULTS: In study 1, no participant scored at levels indicative of excessive malingering. In study 2, 84% of controls but only 36% of patients scored at excessive levels of malingering, and these patients had higher executive functioning than patients who did not excessively malinger, although it should be noted that a significantly greater proportion of patients excessively malingered in study 2 compared to study 1. CONCLUSIONS: These results indicate that schizophrenia patients do not normally feign excessive memory impairment during psychological testing. Furthermore, they are less able and/or less inclined to excessively malinger than controls in situations where a memory impairment would be advantageous, perhaps indicating a better ability to malinger without detection. Potential clinical implications are discussed.

Difficulty leading interpersonal coordination: towards an embodied signature of social anxiety disorder.

Defined by a persistent fear of embarrassment or negative evaluation while engaged in social interaction or public performance, social anxiety disorder (SAD) is one of the most common psychiatric syndromes. Previous research has made a considerable effort to better understand and assess this mental disorder. However, little attention has been paid to social motor behavior of patients with SAD despite its crucial importance in daily social interactions. Previous research has shown that the coordination of arm, head or postural movements of interacting people can reflect their mental states or feelings such as social connectedness and social motives, suggesting that interpersonal movement coordination may be impaired in patients suffering from SAD. The current study was specifically aimed at determining whether SAD affects the dynamics of social motor coordination. We compared the unintentional and intentional rhythmic coordination of a SAD group (19 patients paired with control participants) with the rhythmic coordination of a control group (19 control pairs) in an interpersonal pendulum coordination task. The results demonstrated that unintentional social motor coordination was preserved with SAD while intentional coordination was impaired. More specifically, intentional coordination became impaired when patients with SAD had to lead the coordination as indicated by poorer (i.e., more variable) coordination. These differences between intentional and unintentional coordination as well as between follower and leader roles reveal an impaired coordination dynamics that is specific to SAD, and thus, opens promising research directions to better understand, assess and treat this mental disorder.

Efficacy and safety of vortioxetine (Lu AA21004), 15 and 20 mg/day: a randomized, double-blind, placebo-controlled, duloxetine-referenced study in the acute treatment of adult patients with major depressive disorder.

This study assessed the efficacy, tolerability and safety of vortioxetine versus placebo in adults with recurrent major depressive disorder. This double-blind, randomized, placebo-controlled study included 608 patients [Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥ 26 and Clinical Global Impression - Severity score ≥ 4]. Patients were randomly assigned (1 : 1 : 1 : 1) to vortioxetine 15 mg/day, vortioxetine 20 mg/day, duloxetine 60 mg/day or placebo. The primary efficacy endpoint was change from baseline in MADRS total score at week 8 (mixed model for repeated measurements). Key secondary endpoints were: MADRS responders; Clinical Global Impression - Improvement scale score; MADRS total score in patients with baseline Hamilton Anxiety Rating Scale ≥ 20; remission (MADRS ≤ 10); and Sheehan Disability Scale total score at week 8. On the primary efficacy endpoint, both vortioxetine doses were statistically significantly superior to placebo, with a mean difference to placebo (n = 158) of -5.5 (vortioxetine 15 mg, P < 0.0001, n = 149) and -7.1 MADRS points (vortioxetine 20 mg, P < 0.0001, n = 151). Duloxetine (n = 146) separated from placebo, thus validating the study. In all key secondary analyses, both vortioxetine doses were statistically significantly superior to placebo. Vortioxetine treatment was well tolerated; common adverse events (incidence ≥ 5%) were nausea, headache, diarrhea, dry mouth and dizziness. No clinically relevant changes were seen in clinical safety laboratory values, weight, ECG or vital signs parameters. Vortioxetine was efficacious and well tolerated in the treatment of patients with major depressive disorder.

Social motor coordination in unaffected relatives of schizophrenia patients: a potential intermediate phenotype.

Intermediate endophenotypes emerge as an important concept in the study of schizophrenia. Although research on phenotypes mainly investigated cognitive, metabolic or neurophysiological markers so far, some authors also examined the motor behavior anomalies as a potential trait-marker of the disease. However, no research has investigated social motor coordination despite the possible importance of its anomalies in schizophrenia. The aim of this study was thus to determine whether coordination modifications previously demonstrated in schizophrenia are trait-markers that might be associated with the risk for this pathology. Interpersonal motor coordination in 27 unaffected first-degree relatives of schizophrenia patients and 27 healthy controls was assessed using a hand-held pendulum task to examine the presence of interpersonal coordination impairments in individuals at risk for the disorder. Measures of neurologic soft signs, clinical variables and neurocognitive functions were collected to assess the cognitive and clinical correlates of social coordination impairments in at-risk relatives. After controlling for potential confounding variables, unaffected relatives of schizophrenia patients had impaired intentional interpersonal coordination compared to healthy controls while unintentional interpersonal coordination was preserved. More specifically, in intentional coordination, the unaffected relatives of schizophrenia patients exhibited coordination patterns that had greater variability and in which relatives did not lead the coordination. These results show that unaffected relatives of schizophrenia patients, like the patients themselves, also present deficits in intentional interpersonal coordination. For the first time, these results suggest that intentional interpersonal coordination impairments might be a potential motor intermediate endophenotype of schizophrenia opening new perspectives for early diagnosis.

A multi-dimensional approach to insight and its evolution in first-episode psychosis: a 1-year outcome naturalistic study.

The aim of the study was to describe the evolution of the different dimensions of insight at 1 year and its associations with psychopathology and symptomatic remission. Participants included 55 patients hospitalized for a first psychosis episode and followed up at 6 and 12 months after discharge. Measures included the Scale to Assess Unawareness of Mental Disorder and the Positive and Negative Syndrome Scale (PANSS). Six dimensions of insight were evaluated, for current episode at hospital discharge and at 6 and 12 month FUs and past episode (at 6 and 12 month follow-ups). Our results show that concerning the current episode, only awareness of the social consequences and of the positive symptoms significantly improved during follow-up. Insight into the past episode improved for awareness of having a mental disorder, the social consequences and the positive symptoms of mental illness. Cross-sectional associations between insight and PANSS show weak to moderate, albeit significant, associations. Most of the dimensions of insight are positively and significantly associated with remission. Our findings suggest that the main underlying dimensions of insight evolve differently over time, which could suggest different inherent processes. This could be useful for developing psychotherapeutic programmes acting upon the different aspects of insight.

Impaired ability to imagine future pleasant events is associated with apathy in schizophrenia.

Recent research has established that schizophrenia patients have difficulties envisioning the future. Although mental simulations have a clear adaptive value, little is known about the function of simulating future episodes, particularly emotional events. The aim of this study was to explore the relationships between apathy and future projection in schizophrenia. Twenty-five schizophrenia patients and 25 healthy controls were asked to imagine pleasant and unpleasant episodes that might happen to them in the future. Verbal descriptions were scored for specificity, and participants also completed the Memory Characteristics Questionnaire, which assesses phenomenal characteristics of imagined future events. Apathy was assessed with the Lille Apathy Rating Scale and the apathetic/social withdrawal item of the Positive and Negative Syndrome Scale. Results showed that schizophrenia patients' pleasant and unpleasant imagined future events were less specific and contained fewer phenomenal characteristics (e.g., amount of sensory details) than those of controls. In the schizophrenia group, difficulties imagining future pleasant events, and particularly poor self-referential information for future pleasant events, were specifically associated with apathy, even after controlling for working memory. These results suggest that episodic future thinking impairments, especially for future events of pleasure, may partly underlie the motivational deficits characteristic of schizophrenia.

Early maladaptive schemas predict positive symptomatology in schizophrenia: a cross-sectional study.

Recent literature has shown the role of social factors, such as childhood negative experiences and attachment styles, in the genesis of psychotic symptoms. So far, despite this association with childhood negative experiences and a wide range of psychiatric disorders, no study has yet attempted to assess early maladaptive schemas (EMSs) in patients with schizophrenia as primary diagnosis. A sample of 48 patients diagnosed with schizophrenia and 44 control participants answered the schema questionnaire short form's French validation, and were assessed with the positive and negative syndrome scale as well as a scale of depression symptomatology. Results showed that, after controlling for depression, patients with schizophrenia achieved higher scores than control subjects on six EMSs. The EMSs were associated with positive, but not negative, symptomatology. After controlling for depression, only the Mistrust/Abuse schema was a significant predictor of positive symptoms accounting for a small portion (12.4%) of the variance. The results highlight the importance of focusing not only on the schizophrenic symptoms but also on the person and his or her subjective development of self. Therefore, these results suggest that Young's schema theory may be applied to schizophrenic patients.

Extended duration of hospitalization in first episode psychosis: an evaluation of its clinical justification.

Short periods of hospitalization for first episode psychosis are generally considered preferable, although research evidence is inconsistent. Clinical and social determinants of length of hospital stay (LOS) were examined in 121 admissions for first episode psychosis using standardized assessment measures, in five clinical units of a French psychiatric hospital. LOS varied from 4 to 371 days, and considerably between units. LOS was examined both as a continuous variable and dichotomized comparing short (<31 days) to long (>31 days) stays. In the multivariate analyses, change in antipsychotic medication and the unit head psychiatrist's preference for longer stays were significantly associated with both measures of LOS, indicating effects on LOS per SE and not only with respect to a threshold duration of stay. Of the clinical factors at admission, the only borderline significant association found was between the severity of negative symptoms and LOS on a continuum. Despite some justification for longer stays with respect to discharge conditions, the persisting association with the head psychiatrist's preference for long or short stays strongly suggests a need for greater evidence-based rationalization of practice.

A further evaluation of decision-making under risk and under ambiguity in schizophrenia.

Abnormal decision-making has been described as a key-concept to understand some behavioral disturbances in schizophrenia. However, whether schizophrenia patients display impairments in profitable decision-making on experimental designs is still controversial (1) to assess performance on decision-making paradigms under ambiguity and under risk conditions in a large sample of schizophrenia patients and (2) to study the impact of clinical variables on decision-making performance in schizophrenia. The Iowa gambling task (IGT) and the game of dice task (GDT) were administered to assess, respectively, decision-making under ambiguity and under risk in 63 schizophrenia patients and 67 healthy controls. In addition, clinical variables (e.g., schizophrenic symptoms, self-reported depression, and impulsivity) were evaluated using appropriate questionnaires the same day. Pharmacological treatments were reported. Schizophrenia patients had impaired performances on both IGT and GDT tasks. No correlation between the decision-making tasks performance and clinical variables was found. Lower gains on the GDT were associated with executive dysfunctioning in schizophrenia. These findings give evidence that schizophrenia patients display impairments in both decision-making under ambiguity and under risk.

Frequent attendance in family practice and common mental disorders in an open access health care system.

UNLABELLED: Frequent attenders in family practice are known to have higher rates of mental disorder. However little is known about specific psychiatric disorders and whether this behavior extends to specialist services, in an open access fee-for-service health care system. METHODS: 1060 patients from 46 family practices completed the Patient Health Questionnaire and the Client Service Receipt Inventory. During the consultation, family practitioners blind to the questionnaire responses rated the severity of mental health and physical disorders. The 10% of patients with the highest number of 6-month consultations in six age and sex stratified groups were defined as frequent attenders. RESULTS: After adjustments for sociodemographic variables, physical health and other psychiatric diagnoses, patients with a somatoform disorder were more likely to be frequent attenders, with an odds ratio of 2.3 (95% CI: 1.3-3.8, p=.002). CONCLUSION: When adjusting for confounders, among the four psychiatric diagnoses investigated only somatoform disorders remain significantly associated with frequent attendance. Physical health and chronic disease were no longer associated with frequent attendance which does not support the hypothesis that in an open access fee-for-service system, patients will consult for a wider range of health problems. Greater investigation into unexplained somatic symptoms could help reduce the frequency of attendance in both primary and secondary care, as this behaviour appears to be a general health-seeking drive than extends beyond family practice.

A randomized clinical study of Lu AA21004 in the prevention of relapse in patients with major depressive disorder.

The efficacy and tolerability of Lu AA21004 in the prevention of relapse of major depressive disorder (MDD) in patients in remission after acute treatment was evaluated. Patients (n=639) aged 18-75 years with a primary diagnosis of MDD with a current major depressive episode (MDE) ≥4 weeks' duration, at least one prior MDE and a MADRS total score ≥26 received 12-week, open-label Lu AA21004 at 5 or 10mg/day. Patients in remission (MADRS ≤10) at both weeks 10 and 12 were assigned to double-blind treatment with either placebo or Lu AA21004 (fixed dose from Week 8).Patients (n=396) were treated, after random assignment to placebo (n=192) or Lu AA21004 (n=204). The primary analysis of time to relapse (full-analysis set, Cox proportional hazard model) showed a statistically significant difference in favour of Lu AA21004 versus placebo with a hazard ratio of 2.01 (95% confidence interval: 1.26-3.21; p=0.0035). The proportion of patients who relapsed was 13% in the Lu AA21004 group (n=27) and 26% in the placebo group (n=50). The withdrawal rates due to adverse events were 8% (open-label), and 3% (placebo) and 8% (Lu AA21004) (double-blind). Thus, Lu AA21004 was effective in preventing relapse of MDD and was well tolerated as maintenance treatment.