Olivier Lipp

Patterns of co-morbidity in male suicide completers

BACKGROUND Psychiatric co-morbidity is thought to be an important problem in suicide, but it has been little investigated. This study aims to investigate patterns of co-morbidity in a group of male suicide completers. METHOD One hundred and fifteen male suicide completers from the Greater Montreal Area and 82 matched community controls were assessed using proxy-based diagnostic interviews. Patterns of co-morbidity were investigated using latent class analysis. RESULTS Three subgroups of male suicide completers were identified (L2 = 171.62, df = 2012, P < 0.05). they differed significantly in the amount of co-morbidity (Kruskal-Wallis chi2 = 71.227, df = 2. P < 0.000) and exhibited different diagnostic profiles. Co-morbidity was particularly found in subjects with disorders characterized by impulsive and impulsive-aggressive traits, whereas subjects without those traits had levels of co-morbidity which were not significantly different from those of controls (chi2 = 8.17, df = 4, P = 0.086). CONCLUSIONS Suicide completers can be divided into at least three subgroups according to co-morbidity: a low co-morbidity group, a substance-dependent group and a group exhibiting childhood onset of psychopathology.

CANTAB explicit memory is less impaired in addicted schizophrenia patients

It has been suggested that in order to sustain the lifestyle of substance abuse, addicted schizophrenia patients would have less negative symptoms, better social skills, and less cognitive impairments. Mounting evidence supports the first two assumptions, but data lack regarding cognition in dual diagnosis schizophrenia. Seventy-six schizophrenia outpatients (DSM-IV) were divided into two groups: with (n = 44) and without (n = 32) a substance use disorder. Motor speed and visuo-spatial explicit memory were investigated using CANTAB. As expected, dual diagnosis patients showed a better cognitive performance. Our results suggest either that substance abuse relieves the cognitive deficits of schizophrenia or that the patients with less cognitive deficits are more prone to substance abuse.

Quetiapine in patients with comorbid schizophrenia-spectrum and substance use disorders: an open-label trial.

ABSTRACT Background: Preliminary evidence suggests that clozapine relieves the craving for psychoactive substances in schizophrenia patients. Quetiapine shares crucial pharmacological properties with clozapine. Promising results have been described with quetiapine therapy in patients with psychosis and substance use disorder. Methods: Based on Diagnostic and Statistical Manual of Mental Disorders – fourth edition (DSM‐IV) criteria, patients were diagnosed with comorbid schizophrenia-spectrum and substance use disorders. Patients were switched to quetiapine for a 12‐week open-label trial. Craving, quantities used, days of consumption, and severity of substance abuse were assessed every 3 weeks. Alcohol and Drug Use Scales were administered on baseline and end-point. Psychiatric symptoms, depressive symptoms, extrapyramidal symptoms, and cognition were also assessed at baseline, week 6 and week 12. Results: Twenty-four schizophrenia-spectrum patients were included in the last observation carried forward (LOCF) analyses, responding to one or more of the following substance use disorders: cannabis (15 patients), alcohol (10 patients), and other psychoactive substances (nine patients). Overall, severity of substance abuse improved during the study. Less weekly days were spent on drugs of abuse. A decrease in the weekly Canadian dollars spent on psychoactive substances was also observed. Cognition, psychiatric, depressive, and extrapyramidal symptoms also significantly improved ( p < 0.05). Conclusions: In this open-label, uncontrolled trial, significant improvements were noted in substance abuse, psychiatric symptoms, extrapyramidal symptoms, and cognition during quetiapine therapy. The study suffered from three main limitations: (1) the open-label design of the study; (2) the patients’ poor compliance; and (3) the small sample size involved. Controlled studies on the use of quetiapine in dual diagnosis schizophrenia are warranted to confirm that the effects are drug-related.

Suicide and serotonin: study of variation at seven serotonin receptor genes in suicide completers.

Suicide is an important public health problem, accounting for a significant proportion of total mortality among young people, particularly males. There is growing and consistent evidence suggesting that genetic factors play an important role in the predisposition to suicide. Based on several lines of evidence supporting a reduced serotonergic neurotransmission in subjects who committed suicide, we investigated variation at genes that code for serotonin receptor 1B (5‐HTR1B), 1Dα (5‐HTR1Dα), 1E (5‐HTR1E), 1F (5‐HTR1F), 2C (5‐HTR2C), 5A (5‐HTR5A), and 6 (5‐HTR6) in a total sample of 106 suicide completers and 120 normal controls. No differences were observed in allelic or genotypic distributions between groups for any of the loci investigated. Moreover, further analysis according to suicide method or psychopathology also failed to reveal differences between groups. Our results do not support a substantial role of these serotonergic receptors in suicide completion.

Increased extrapyramidal symptoms in patients with schizophrenia and a comorbid substance use disorder

Few data have been gathered about the impact of psychoactive substances on extrapyramidal symptoms (EPS) in schizophrenia, and so far, inconsistent results have been reported. We studied 41 outpatients with schizophrenia (based on DSM-IV criteria), who were divided into two groups: with (n = 17) and without (n = 24) a substance use disorder (alcohol, cannabis, and/or cocaine). Both groups were matched for sociodemographic data and psychiatric symptoms (Positive and Negative Syndrome Scale). EPS were evaluated with the Extrapyramidal Symptoms Rating Scale and the Barnes Akathisia Scale, and all patients were stable on either quetiapine or clozapine. Patients receiving anticholinergic drugs were excluded. Analyses of variance were conducted on both groups and showed that schizophrenia patients with a comorbid substance use disorder (especially cocaine) displayed more EPS compared with non-abusing patients.

Wolfram Syndrome and Suicide: Evidence for a Role of WFS1 in Suicidal and Impulsive Behavior

There is evidence suggesting that subjects affected with the Wolfram syndrome (WFS) and normal carriers present an increased risk of psychiatric disorders, particularly depression and suicidal behavior. We investigated a possible role of the gene involved in WFS (WFS1) in the neurobiology of suicide and the potential modulatory effect on traits associated to suicidal behavior. Genetic variation at WFS1 (H611R, R456H, and I333V) was investigated in 111 suicide victims and 129 normal controls. Possible effects on psychopathology and behavioral traits were investigated in a subsample of suicide cases (N = 31) for whom phenotyping was carried out by means of structured psychiatric interviews and questionnaires adapted for psychological autopsies. We found a significantly higher frequency of the 611R/611R genotype in suicide completers as compared to controls (χ2 = 19.21, df=2, P = 0.001). Suicide completers with this genotype had higher scores on measures of impulsivity (t = −3.15, df = 15.3, P = 0.006); novelty seeking (NS) (t = −3.35, df = 13.8, P = 0.005); and conversely, lower scores of persistence (t = 2.4, df = 16.6, P = 0.028). Scores of impulsivity and NS remained higher in subjects with the associated genotype after adjusting for age, gender, and psychopathology. These results suggest a role for WFS1 in the pathophysiology of impulsive suicide, and are consistent with previous clinical reports suggesting an increased risk of suicidal behavior in WFS homozygotes and heterozygotes. However, these findings are preliminary and should be confirmed in independent samples.

Endogenous cannabinoids in patients with schizophrenia and substance use disorder during quetiapine therapy

Disturbances in the endogenous cannabinoid (ECB) system in schizophrenia may contribute to their enhanced sensitivity to psychoactive substances, and the beneficial effects of second-generation antipsychotics for substance abuse in schizophrenia may involve modulatory effects on ECB. To verify these two assumptions, 29 patients (24 completers) with schizophrenia and substance use disorders (SUD) were treated with quetiapine for 12 weeks, and peripheral ECB levels were measured, using high-performance liquid chromatography/mass spectrometry, in patients (weeks 0, 6 and 12) and 17 healthy volunteers. Baseline anandamide levels were significantly higher in patients, relative to controls. This result is consistent with studies describing ECB dysfunctions in schizophrenia. SUD parameters improved during treatment, but no changes in ECB occurred over time. Improvements in substance abuse were probably not mediated by modulatory effects of quetiapine on ECB. Lastly, baseline anandamide predicted endpoint SUD scores (alcohol/ cannabis). Anandamide is a potential target for medications aimed at relieving SUD in schizophrenia.

Pain Perception in Schizophrenia: Evidence of a Specific Pain Response Profile

OBJECTIVE Ever since the characterization of schizophrenia, clinicians have noted abnormal pain sensitivity in their patients. The published literature, however, is inconsistent concerning the nature of the change reported. The objective of this study was to characterize the pain response profile of schizophrenic patients by providing both acute and prolonged (i.e., rapidly repeating) painful stimuli to schizophrenic participants and control subjects. PARTICIPANTS Twelve schizophrenic subjects and eleven controls were included in the final analysis. Diagnosis was made according to Diagnostic and Statistical Manual of mental disorders-4th edition, text revision (DSM-IV-TR) criteria. METHODS Intermittent, transcutaneous stimulations of the left sural nerve were administered to all participants. Painful sural nerve stimulations provoked a nociceptive flexion reflex response which was measured using an electromyographic recording of the bicep femoris muscle. Pain ratings were obtained using a 0-10 verbal numerical scale. Among schizophrenic participants, the relationship between subjective pain, reflex amplitude, and clinical features was investigated. The Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia, and Subjective Scale to Investigate Cognition in Schizophrenia were used to evaluate clinical features. RESULTS Compared with controls, schizophrenic subjects showed increased sensitivity to acute pain (i.e., lower pain thresholds; P = 0.019), but decreased subjective pain sensitization (P = 0.027). Group differences in subjective pain sensitization were not accompanied by group differences in nociceptive reflex activity (P = 0.260), suggesting supraspinal origins to the change in pain experienced by schizophrenic subjects. Moreover, positive symptoms correlated negatively with pain threshold values among schizophrenic participants (r = -0.696, P = 0.012), suggesting that distortions of thought and function relate to pain sensitivity in schizophrenic patients. CONCLUSION Results indicate that schizophrenic subjects present a specific experimental pain response profile, characterized by elevated sensitivity to acute pain but reduced sensitivity to prolonged pain.

Sensation-seeking, social anhedonia, and impulsivity in substance use disorder patients with and without schizophrenia and in non-abusing schizophrenia patients

Substance use disorders (SUDs) are common in patients with schizophrenia and this comorbidity is associated with a poorer prognosis, relative to non-abusing patients. One hypothesis that has been advanced in the literature is that dual diagnosis (DD) patients may have a different personality profile than non-abusing schizophrenia patients. The present case-control study aimed to characterize levels of personality traits (sensation-seeking, social anhedonia, and impulsivity) in substance abuse/dependence patients with (DD group; n=31) and without schizophrenia (SUD group; n=39), relative to non-abusing schizophrenia patients (SCZ group; n=23), and healthy controls (n=25). Impulsivity was assessed using the Barratt Impulsivity Scale. Sensation-seeking was assessed using the Zuckerman Sensation Seeking Scale. Social anhedonia was assessed with the Chapman Social Anhedonia Scale. We found that sensation-seeking was significantly higher in DD and SUD, relative to SCZ patients. We found that social anhedonia was significantly elevated in DD and SCZ, relative to healthy controls. We found that impulsivity was significantly higher in DD, SCZ and SUD patients, compared to healthy controls. The results suggest that sensation-seeking is prominent in substance abuse/dependence (irrespective of schizophrenia), social anhedonia is prominent in schizophrenia (irrespective of substance abuse/dependence), and impulsivity is prominent in all three populations.

Soluble interleukin-2 receptor levels correlated with positive symptoms during quetiapine treatment in schizophrenia-spectrum disorders.

BACKGROUND Some but not all antipsychotics have been shown to modulate plasma cytokine levels in schizophrenia patients. Thus far, the most consistent finding has been the increase in plasma levels of soluble interleukin (IL)-2 receptor (sIL-2R) associated with clozapine treatment. Quetiapine is a second-generation antipsychotic with a pharmacological profile similar to that of clozapine, but its immunomodulatory effects have not been investigated in schizophrenia yet. The purpose of this exploratory study was to examine the changes in plasma levels of sIL-2R in schizophrenia during quetiapine treatment and association with psychopathology. METHODS Participants were 29 schizophrenia-spectrum disorder patients (DSM-IV criteria), and 28 healthy controls. Patients had a comorbid substance use disorder (cannabis>alcohol>cocaine), since quetiapine is increasingly used in this population of dual diagnosis. No participant suffered from infection or overt inflammatory diseases. On baseline, patients taking mostly second-generation antipsychotics were switched to quetiapine for a 12-week open-label trial. Five patients were drop-outs. Mean dose of quetiapine for trial completers (n=24) was 466.6mg±227.3. Psychiatric variables were evaluated with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. Plasma sIL-2R levels were assessed at baseline, weeks 6 and 12 in patients, and in healthy controls, using sandwich immunoassay. Plasma IL-6 and IL-1 receptor antagonist (IL-1RA) were measured for comparison purposes. RESULTS On baseline, plasma sIL-2R, IL-6 and IL-1RA levels were higher in dual-diagnosis patients, compared to controls. Plasma sIL-2R further increased after quetiapine treatment (p=0.037), while plasma IL-6 and IL-1RA did not change. Clinical improvements were observed in positive, negative and depressive symptoms, and substance abuse severity (all p<0.01). Interestingly, changes in sIL-2R levels during treatment were inversely correlated with changes in positive symptoms (r=-0.524; p=0.009). That is, increases in sIL-2R levels were associated with reductions in positive symptoms. CONCLUSION These data show that quetiapine elevates, like clozapine, sIL-2R levels in schizophrenia. Furthermore, the results suggest that sIL-2R alterations in schizophrenia rely on complex interplays between antipsychotics and the positive symptoms of the disorder. Future randomized controlled trials involving larger samples of schizophrenia patients are warranted to determine whether changes in plasma sIL-2R are quetiapine-related.