Theory of mind and schizophrenia in young and middle-aged patients: Influence of executive functions.

Theory of Mind (ToM) is compromised in schizophrenia, and responsible for social disability. We aim to study the correlation between ToM deficits and Executive Functions (EF), using the Faux Pas Test (FPT) for ToM evaluation, Behavioral Assessment of the Dysexecutive Syndrome (BADS) and Wisconsin Card Sorting Test (WCST) for EF assessment. Two groups of patients with schizophrenia were included: 22 young (18-35 years-old) and 18 middle-aged (>50 years-old) Patients, compared to age-matched Controls. We found worst FPT performances in both groups of patients, but with a more generalized pattern of dysfunction in the middle-aged patient group. This group had worse EF scores than both controls and younger patients. The association of EF with FPT items was uneven. In young patients only empathy (Q6) remained significant after controlling for EF and level of education, while in middle-aged patients faux pas explanation (Q4), false belief (Q5) and total scores remained significant. In young patients only affective TOM was impaired. No correlation was found with clinical symptoms, nor age at onset of the disease. We conclude that ToM deficit arises early during the course of the illness (already present in young patients), increases in middle-aged patients, and relates only partially with EF.

Theory of mind in adolescents with early-onset schizophrenia: correlations with clinical assessment and executive functions.

OBJECTIVE: We examined Theory of Mind (ToM) abilities in adolescents with early-onset schizophrenia (EOS) and their correlation with clinical findings and Executive Functions (EF). METHODS: The ToM abilities of 12 adolescents with EOS were compared with those of healthy participants matched in age and educational level. The Moving Shapes Paradigm was used to explore ToM abilities in three modalities: random movement, goal-directed movement and ToM - scored on the dimensions of intentionality, appropriateness and length of each answer. EF was tested using Davidson's Battery and the clinical psychopathology with the Positive and Negative Syndrome Scale (PANSS). RESULTS: Adolescents with EOS were significantly more impaired than controls in the three dimensions evaluated for the goal-directed and ToM modalities. Regarding the random movement modality, the only difference was in appropriateness (p<0.01). No correlation with age or level of education was evident for ToM skills. Total PANSS score was negatively correlated with appropriateness score for the goal-directed (p=0.02) and ToM modalities (p=0.01). No correlation existed between performance in the ToM Animated Tasks and positive, negative or disorganisation PANSS subscores. No correlations were found among the three scores in the Moving Shapes Paradigm and any measures of the accuracy of the three tasks assessing EF. CONCLUSION: Our results confirm previous findings of ToM deficits in adult individuals with schizophrenia and attest the severity of these deficits in patients with EOS.

Major mental disorders, gender, and criminological circumstances of homicide.

OBJECTIVE: To examine the criminological circumstances of homicide in a group of French murderers with and without major mental disorders (MMD) stratified by the perpetrator's gender. METHODS: Sociodemographic, clinical, and criminological variables were collected from the psychiatric expert reports of 210 cases of homicide heard at the High Court of Angers, France. Murderers were categorized according to MMD diagnosis and gender. RESULTS: Among 210 murderers, 17.6% (n = 37) had a MMD (20% of the female perpetrators). Logistic regression models showed that being a murderer with a MMD was associated with younger age (adjusted Odds Ratio OR = 1.03, P = 0.034), high school education (OR = 2.48, P = 0.036), previous use of psychiatric services (OR = 4.75, P = 0.003), alcohol intoxication (OR = 2.71, P = 0.027), and delusional state (OR = 3.96, P = 0.002) at the time of the homicide. Multiple correspondence analyses showed that female murderers with a MMD were more prone to have depression and to use drowning as a method than those without a MMD, and that male murderers with a MMD more often had a high school education and delusional beliefs at the time of the homicide than those without a MMD. CONCLUSION: Specific profiles of criminological circumstances of homicide could help to explore the risk of homicide in female and male patients with a MMD.

Neurological soft signs in non-psychotic patients with cannabis dependence.

Psychomotor performance has consistently been found to be altered in chronic cannabis users. Neurological soft signs (NSS) reflect neurological dysfunction involving integrative networks, especially those involving the cerebellum, where cannabinoid receptors are particularly concentrated. Our objective was to study, for the first time, NSS in a group of patients with cannabis dependence compared with a of healthy control subjects, matched for age, gender and level of education. All outpatients seeking treatment for chronic cannabis use in the substance abuse department of Sainte-Anne Hospital in Paris between June 2007 and May 2009 and meeting the cannabis dependence DSM-IV criteria were included in the study (n = 45). Patients with psychotic disorders, bipolar 1 disorder and current alcohol, opioid or cocaine dependence were excluded. All patients and controls were assessed using the Diagnostic Interview for Genetic Studies, which screens for lifetime DSM-IV diagnoses, and the Standardized Neurological Examination of Neurological Soft Signs. NSS scores were significantly higher in patients with cannabis dependence compared with healthy subjects (8.90 ± 4.85 versus 6.71 ± 2.73, respectively, Mann-Whitney: U = 775.0, P = 0.05). Patients had particularly high scores on motor coordination and sensory integration NSS factors. Cannabis dependence is associated with more NSS and especially motor coordination and sensory integration signs. These results suggest that cannabinoids interact with the brain networks underlying NSS, known to be altered in schizophrenia.

Confirmation of the factorial structure of temperamental autoquestionnaire TEMPS-A in non-clinical young adults and relation to current state of anxiety, depression and to schizotypal traits.

BACKGROUND: The 39-item TEMPS-A self-rated questionnaire assesses affective temperaments. We examined the factorial structure of its French version in a large sample of young adults and examined the relation to schizotypy, depression and anxiety. METHOD: University students were enrolled during their mandatory preventive health visit in the University medical facility (n = 3807, 19.9 ± 2.5 y.o.). They answered to the 39-TEMPS-A questionnaire, the Schizotypal Personality Questionnaire (SPQ) and the Hospital Anxiety Depression Scale (HADS). We performed an exploratory Factorial Component Analysis (FCA) with varimax rotation of the 39-TEMPS-A in half of the sample, randomly selected, followed by a Confirmatory Factor Analysis (CFA) in the remaining subsample. TEMPS-A dimensions were correlated to HADS and SPQ sub-scores. RESULTS: A five-factor structure was found by PCA and confirmed by the confirmatory analysis. The scale showed a good internal consistency (whole scale Cronbach's α: 0.83 and from 0.78 to 0.59 for Cyclothymic, Depressive, Irritable, Hyperthymic, Anxious subscales). Depressive and Anxious TEMPS-A subscales were moderately correlated to HADS Depression and Anxiety subscales (Spearman ρ = 0.37 to 0.33). Cyclothymic and Depressive TEMPS-A subscales were respectively correlated to SPQ Paranoid (ρ = 0.53) and Negative dimensions (ρ = 0.52). LIMITATION: Representativity of the sample (higher education, response rate). CONCLUSION: We confirmed the five factor structure of the 39-item TEMPS-A in a large non-clinical population of young adults and found consistent correlations with anxiety - depression state markers and schizotypal traits.

Neurological soft signs in OCD patients with early age at onset, versus patients with schizophrenia and healthy subjects.

Compelling evidence suggests that both schizophrenia and obsessive compulsive disorder (OCD) are related to deviant neurodevelopment. Neurological soft signs (NSS) have been proposed to be a marker of abnormal brain development in schizophrenia. The purpose of this study is to examine whether NSS are also a marker in patients with OCD, in particular, in early-onset OCD. The authors included 162 subjects and compared patients with OCD, patients with schizophrenia (SCZ), and healthy control subjects. They were all examined for NSS (Krebs' Scale), extrapyramidal symptoms (Simpson-Angus Scale), and were rated on the Abnormal Involuntary Movements Scale (AIMS). The authors found no differences between NSS total scores and subscores in OCD versus controls, whereas total NSS, motor coordination, and motor integration were significantly lower in OCD than in SCZ. OCD patients with early-onset (before age 13) did not differ from those with later-onset OCD. These results support the idea that NSS, as determined by current scales, is relatively specific to schizophrenia, although they do not preclude the existence of a neurological dysfunction in OCD. Further studies are required to determine the type of neurological signs that could be useful trait-markers in the phenotypic characterization of subtype OCD.

Variable individual sensitivity to cannabis in patients with schizophrenia.

There is now compelling evidence that cannabis consumption might precipitate psychosis onset. The objective of the present study was to assess the role of individual sensitivity to the psychotogenic effect of cannabis in male patients with schizophrenia. The lifetime diagnosis, disease and substance-use history were determined using a standardized interview in 190 patients with schizophrenia. Of patients with lifetime cannabis use (n=121), 44 were characterized as Cannabis-sensitive (CS) patients if the onset of psychotic symptoms occurred within 1 month following the initiation of cannabis consumption, or following a marked rise of cannabis consumption, or marked aggravation of psychotic symptoms each time the subject used cannabis. Age at onset of psychosis was not different in patients with lifetime cannabis use compared to non-users. By contrast, the first psychotic episode occurred 2.6 yr earlier in CS compared to Non-cannabis-sensitive (NCS) patients (p=0.006). Moreover, a specific excess of family history of psychotic disorder was found in CS patients, but not of any other psychiatric disorder, as well as an earlier age at exposure to cannabis (16.7+/-2.5 yr, p=0.03). Sensitivity to psychotogenic effects of cannabis in schizophrenia patients could be related to both genetic vulnerability to schizophrenia and the influence of cannabis on brain maturation and could modulate the influence of cannabis on the onset of schizophrenia.

Deficit of inhibition motor control in untreated patients with schizophrenia: further support from visually guided saccade paradigms.

In addition to classical delusional, negative, and cognitive deficit, schizophrenia has consistently been associated with impairments in saccadic eye movements, e.g., an increased error rate in the antisaccade task. We hypothesized that a deficit in inhibitory control is a core defect in untreated patients with schizophrenia leading to impairment in different oculomotor paradigms. Ten drug-free or drug-naïve patients with schizophrenia were matched in age and gender to 11 healthy controls with no psychoactive substance use or abuse. They were explored using reflexive saccades with unpredictable targets with or without the gap procedure, predictive saccades and a fixation/distracter paradigm. Patients with schizophrenia displayed shorter latency in reflexive and predictive saccades. In the GAP condition, patients made more anticipatory saccades, fewer regular saccades, and had a shorter latency of express saccades than controls. In addition, patients had an increased error rate in the fixation/distracters task. Altogether, these results provide new evidence of reduced prefrontal inhibitory regulation of subcortical and brainstem systems involved in the control of saccades.

Impulsivity and sensation seeking in alcohol abusing patients with schizophrenia.

OBJECTIVE: Some studies have found that high levels of impulsivity and sensation seeking, particularly disinhibition are associated with substance abuse in patients with schizophrenia, as in the general population. However, no study has assessed impulsivity and sensation seeking specifically in schizophrenia patients with alcohol abuse or dependence. MATERIALS AND METHODS: We compared impulsivity and sensation seeking in a group of schizophrenia patients (DSM-III-R criteria) with lifetime alcohol abuse or dependence (n = 34) and in a group without lifetime substance abuse or dependence (n = 66). The patients were assessed using the composite international diagnostic interview (CIDI) for DSM-III-R disorders, the positive and negative syndrome scale (PANSS), the Barratt impulsivity scale (BIS), the Zuckerman seeking sensation scale (SSS), and the physical anhedonia scale (PAS). RESULTS: The mean scores for impulsivity and sensation seeking were higher in the group with lifetime alcohol abuse or dependence than in the group without substance abuse or dependence (BIS: 63.4 ± 18.7 vs 51.3 ± 14.2 respectively, ANOVA: F = 11.12, p = 0.001; SSS: 17.6 ± 5.9 vs 13.5 ± 6.7 respectively, ANOVA: F = 7.45, p = 0.008). There was no significant difference between the two groups on PAS score. CONCLUSION: Increased impulsivity or sensation seeking may be a link between schizophrenia and alcohol abuse or dependence.

Correlates between neurological soft signs and saccadic parameters in schizophrenia.

OBJECTIVE: Neurological Soft Signs (NSS) and impairments in oculomotor saccadic paradigms are both frequent in patients with schizophrenia but their correlation has never been explored. METHODS: 78 patients with DSM-IV schizophrenia (including 43 non-treated) and 41 matched healthy controls were tested for NSS, and on three saccadic tasks: prosaccades, predictive saccades and memory-guided saccades) using infrared oculometry. We analyzed correlations between NSS scores and latencies in all three tasks, rate of errors in memory-guided saccades, and rate of anticipated predictive saccades. RESULTS: No correlations were found in healthy controls. In the patient group, the NSS total and motor coordination scores were positively correlated with three saccadic variables: the latency of prosaccades (r=0.36, p<0.01 and r=0.36, p<0.01 respectively), of memory-guided saccades (r=0.35, p<0.01 and r=0.32, p<0.05 respectively) and, negative correlations were found, with the rate of anticipated predictive saccades (r=-0.33, p<0.01; r=-0.35, p<0.01 respectively). NSS total, motor coordination and sensory integration scores were correlated to the latency of non-anticipated predictive saccades (r=0.34, p<0.01; r=0.24, p<0.05 and r=0.40, p<0.001 respectively). The NSS total, motor integration and sensory integration scores were correlated with the rate of errors in memory-guided saccades (r=0.38, p<0.01; r=0.37, p<0.01 and r=0.34, p<0.01 respectively). CONCLUSIONS: These results support a common pathological mechanism with partial overlapping neural substrates between NSS and saccades in schizophrenia.

Neurological soft signs in patients with schizophrenia and their unaffected siblings: frequency and correlates in two ethnic and socioeconomic distinct populations.

Recent studies have suggested that ethnicity and socioeconomic status may have an impact on the frequency and significance of neurological soft signs (NSS). However, this impact has not been adequately assessed. The objectives were to determine the NSS scores in patients with schizophrenia and their unaffected siblings and to examine the clinical and therapeutic correlates of NSS in two ethnic and socioeconomic distinct populations. Two independent replicate studies were carried out: (1) a French Caucasian sample of 69 patients with schizophrenia, 43 of their unaffected siblings and 108 control subjects; (2) a Tunisian sample of 66 patients with schizophrenia, 31 of their unaffected siblings and 60 control subjects. NSS were assessed with a multidimensional scale, previously validated in drug-naïve and treated samples of patients with schizophrenia. Both patient groups were assessed with the positive and negative syndrome scale (PANSS), the clinical global impressions (CGI) and the global assessment of functioning. NSS total scores were significantly higher in patients with schizophrenia comparatively to siblings and to controls in both studies. The two sibling groups had also higher NSS scores than controls. In addition, NSS total scores were correlated to the PANSS negative and disorganization sub-scores, to the CGI-severity of illness and to a low educational level in both studies. These studies provide a confirmation in two distinct samples of the high prevalence of NSS in patients with schizophrenia, and in their biological relatives, independently of their respective ethnic and socioeconomic origins.

Bipolar disorders and quality of life: the impact of attention deficit/hyperactivity disorder and substance abuse in euthymic patients.

Patients with bipolar disorders (BPD) display high rates of comorbidities, especially substance abuse (20-40%) and attention deficit/hyperactivity disorder (ADHD) (6%-20%). However, there are virtually no data evaluating the role of current ADHD on the global functioning of patients with BPD. The recent literature suggests that impairments in quality of life are a key prognostic feature for predicting the long course of BPD. The aim of this study was to investigate the intrinsic impact of adult ADHD and substance abuse in patients with BPD on levels of social adaptation, functioning and vitality. Seventy-three outpatients with BPD I or II, all euthymic and being treated with mood stabilizers, were evaluated using the following measures: 1) the Diagnostic Interview of Genetics Study for DSM-IV criteria; 2) the ADHD Self-Report Scale (ASRS) (screening of adult ADHD); 3) measures of quality of life: social adaptation (Social Adjustment Scale Self-Report (SAS-SR)), well-being (Short Form 36 (SF-36) Health Survey), and the Brief Psychiatric Rating Scale. In this clinical sample, 30% met the ADHD criteria and 22% were substance abusers. The results showed that the presence of ADHD in BPD patients significantly predicted a low social functioning and adaptation by comparison with BPD patients without ADHD. By contrast, we failed to detect a significant impact of substance abuse on those functional outcomes. This is the first step towards improved screening for comorbidities and an understanding of their crucial role in the prognosis of the disorder, as well as in defining new multilevel therapeutic strategies.

Predictive saccades are impaired in biological nonpsychotic siblings of schizophrenia patients.

OBJECTIVE: Although impairments in predictive saccades have been reported in patients with schizophrenia, this has never been explored in their biological relatives. We examined predictive saccades in age-and sex-matched siblings of patients with schizophrenia. METHOD: Thirty siblings of schizophrenia patients, 30 healthy matched control subjects and 30 patients with schizophrenia performed a predictive saccades paradigm. Nonanticipated and anticipated saccades were analyzed separately. RESULTS: Compared with control subjects, primary saccades and final eye position were hypometric (they undershot the target) in siblings, as in patients. The proportion of anticipated saccades and latencies did not differ between the 3 groups. The maximum velocity was decreased only in patients. CONCLUSION: Alterations in predictive saccades observed in biological siblings are similar to those seen in patients, although they tend to be of a lesser degree. This finding supports predictive saccades as a valid endophenotypic marker. Further research is necessary to understand the physiopathological value of these disturbances and their link to a visuospatial representation deficit.

Polymorphisms TaqI A of the DRD2, BalI of the DRD3, exon III repeat of the DRD4, and 3' UTR VNTR of the DAT: association with childhood ADHD in male African-Caribbean cocaine dependents?

The conflicting results reported by genetic studies with the variants of the genes coding for the dopaminergic system in cocaine addicts could be partially explained by the difficulties to constitute homogenous sample of patients. Childhood attention-deficit/hyperactivity disorder (ADHD), and/or impulsivity are frequently associated with cocaine addiction and could participate in the heterogeneity of the samples in cocaine addicts. Accordingly, it is hypothesized that cocaine addiction would be associated with the variants of the genes coding for the dopamine system in an homogenized sample of cocaine addicts, especially in individuals with childhood ADHD comorbidity, or with a high impulsivity score. The potential association of the variants TaqI A of the DRD2, BalI of the DRD3, exon III repeat of the DRD4, and 3' UTR VNTR of the DAT was examined in African-Caribbean males, smoked-cocaine dependents. All the subjects were assessed with the Diagnostic Interview of Genetic Studies, the Barratt's impulsivity scale, and the Wender Utah rating scale for childhood ADHD. A positive association was found with the DRD2 and DRD4 polymorphisms in the subgroups of patients with childhood ADHD, or with a high impulsivity score, which represented, respectively, 53.3 and 73.0% of the patients. Conversely, no positive association was found for any of the polymorphisms studied when the group of patients was examined as a whole. Therefore, our results suggest that the clinical dimensions of childhood ADHD and of impulsivity could be taken into account to homogenize the samples of patients in cocaine association studies.

Validity of the CAGE questionnaire in schizophrenic patients with alcohol abuse and dependence.

The objective of the study was to assess the sensitivity and the specificity of the CAGE questionnaire in 114 schizophrenic patients. The Composite International Diagnostic Interview was used to assess the DSM-III-R diagnosis of abuse of or dependence on alcohol. The CAGE questionnaire can be reliably used to assess alcohol use disorders in schizophrenic patients: with a cutoff score of 1 or more, the sensitivity of the CAGE questionnaire was 0.91 and the specificity was 0.83. With a cutoff score of 2 or more, the sensitivity of the CAGE questionnaire was 0.82 and the specificity was 0.94. The post test probabilities (PPV) were high (PPV1=0.74; PPV2=0.85) compared to the primary probability of alcoholism (29.8%).

Specific pattern of attentional changes in impulsive individuals.

INTRODUCTION: Although impulsivity is recognised as a major psychopathological feature, its cognitive correlates remain controversial. We evaluated readiness to act induced by a warning signal and attentional engagement in healthy impulsive participants. METHODS: People with high impulsivity scores (HI) and low impulsivity (LI) scores on Barratt's Impulsivity Scale (BIS) were selected among 1250 students from top and bottom deciles. Subjects with personal or family of lifetime Axis I disorders were excluded. Motor preparation was evaluated by a Choice Reaction Time task (CRT) with a randomly presented warning signal with a delay before target of 500 ms or 2000 ms depending on the trial block. Attentional engagement and maintenance of fixation was evaluated by a Cued Target Detection task (CTD) comparing cued (valid, invalid, or double cue) and uncued trials and contrasting fixation offset (gap) or maintenance (overlap) conditions. RESULTS: HI, but not LI participants had a shortened reaction time in the 2000 ms condition of CRT with warning signal, indicating a persistent readiness to act. In contrast to LI, HI showed a decreased reinforcement of attention in the overlap condition of CTD with a hyperreactivity to all types of visual stimuli. CONCLUSIONS: Impulsivity per se appears to be associated with hyperreactivity to warning or cue signals and on inability to maintain attentional fixity.

Age at onset of schizophrenia: interaction between brain-derived neurotrophic factor and dopamine D3 receptor gene variants.

One of the main features of schizophrenia is its age at onset in early adulthood. Dopaminergic dysregulation is the most documented neurobiological factor that may be involved in triggering schizophrenia. Recent findings on neurodevelopmental processes show that the brain-derived neurotrophic factor plays a critical role in the development of mesolimbic dopaminergic-related systems and regulates the expression of dopamine D3 receptors. In this study, we examine whether an interaction between dopamine D3 receptors and brain-derived neurotrophic factor gene variants influences age at onset in patients with schizophrenia. Our findings show that this gene-gene interaction was significantly associated with an earlier emergence of psychosis by 3 years.

Population-based and family-based association study of 5'UTR polymorphism of the reelin gene and schizophrenia.

Reelin is a glycoprotein involved in the migration and positioning of proliferating neurons and synaptic connectivity during neurodevelopment. It may also modulate neuronal plasticity throughout life. Therefore, the reelin gene is a candidate gene for schizophrenia. We examined the association of the CGG repeat polymorphism in the 5'-untranslated region of the reelin gene with schizophrenia in 266 unrelated French Caucasian patients, 156 of their parents, and 103 controls. We found no difference in the allele distribution between patients and controls although there was a significant higher prevalence of the genotype 8-8 in controls (CLUMP T3: chi(2) = 6.3, P = 0.035). There was no significant transmission disequilibrium in intrafamilial analysis. To refine our phenotypic characterization and in accordance with converging evidence suggesting that treatment resistance is associated with indices of abnormal neurodevelopment, we studied the association between reelin gene polymorphism and response to antipsychotics. Patients who responded to antipsychotics had a higher frequency of both the (CGG)(10) allele and (CGG)(10)-containing genotypes (P = 0.02; P = 0.006, respectively), with an odd ratio for genotypes of 4.2 (CI = [1.4;12.4]). Our results weakly support an association of reelin gene variants with schizophrenia as a whole, yet suggest that reelin could be associated with treatment-resistant schizophrenia.