Isabel Morales-Muñoz

Characterizing cannabis-induced psychosis: A study with prepulse inhibition of the startle reflex

Cannabis-induced psychotic disorder (CIPD) refers to psychotic symptoms that arise in the context of cannabis intoxication. Prepulse inhibition (PPI) deficits have been extensively identified in schizophrenia and in cannabis abusers. We aimed to characterize PPI in CIPD patients. We used a sample of 48 CIPD patients, 54 schizophrenia patients and cannabis abuse (SCHZ), 44 cannabis dependents (CD), and 44 controls. CIPD, SCHZ and CD were abstinent of cannabis consumption for 9 months. Participants were assessed with PPI at 30, 60, and 120 ms. At 30 ms, CIPD showed lower PPI levels than controls, and SCHZ obtained worse functioning than controls and CD. At 60 ms, only SCHZ exhibited worse PPI percentages (of object) than controls. Finally, at 120 ms, CIPD showed higher PPI levels than SCHZ, and SCHZ obtained lower percentages than controls. We found that CIPD and SCHZ patients showed deficits at the most pre-attentional levels, whereas CIPD patients performed better than SCHZ at higher attentional levels. These results suggest that CIPD constitutes a different group of patients than that of SCHZ. Deficits in PPI functioning at 30 ms could be a useful psychophysiological measure to detect CIPD patients, who are frequently confused with cannabis abusers whose symptoms may mimic that of schizophrenia.

The course of negative symptoms in first-episode schizophrenia and its predictors: A prospective two-year follow-up study

AIMS This study aimed to investigate the course of negative symptoms and its stability over a two-year period following a first-episode schizophrenia (FES) and the possible predictors of higher severity in this symptomatology after this period. METHODS In this longitudinal two-year prospective follow-up study we included 268 patients with a FES, according to DSM-IV. Analysis of variance was conducted in patients who completed the full follow-up to study changes in negative symptoms over three visits. Regression analyses were conducted to show correlates and potential predictors of negative symptoms at two-year follow-up. RESULTS There was a significant effect for time in negative symptomatology, which was less severe at one-year follow-up after a FES and remained stable up to two years (Time 1>Time 2>Time 3); F(2,151)=20.45, p<0.001. Poorer premorbid adjustment (p=0.01) and higher negative symptoms at baseline (p<0.001) made a significant contribution to the changes in the negative symptoms severity at two-years after a FES (R2=0.21, p<0.001). CONCLUSIONS We found a reduction in the negative symptomatology at one-year after a FES. This change remained stable at two-year. Our results suggested that the presence of this symptomatology early in the course of the illness, together with a poorer premorbid adjustment, predict more severe negative symptoms at mid-term outcome.

Relationship between measures of inhibitory processes in patients with schizophrenia: Role of substance abuse disorders

Disruption of prepulse inhibition of the startle response (PPI) has been widely identified in patients with schizophrenia, as well as impairment in many domains of cognitive functioning. However, there is some controversy regarding the relationship between PPI and the different neuropsychological tasks assessing inhibition. This controversy may be due to the influence of other variables, such as substance abuse. We aimed to determine whether differences in inhibition in schizophrenia subjects were related to their pattern of substance use and whether there was a correlation between the changes in each process. PPI and neuropsychological functioning were studied in three groups of subjects with schizophrenia (N=73): tobacco dependents (ToD; n=22), multiple substance abusers (MSUD; n=31) and non-substance abusers (non-SUD; n=20). All subjects were assessed using PPI and neuropsychological tests (Stroop and Wisconsin Card Sorting Test [WCST]). ToD showed better pre-attentive inhibitory function compared to the other two groups, and MSUD showed lower resistance to interference. Furthermore, significant correlations were found between PPI, Stroop, and WCST. Our data suggest that there is a relationship between the different tasks assessing inhibition in schizophrenia, being affected by substance abuse history. We also found differences in inhibition capacity depending on substance abuse in patients with schizophrenia.

Pharmacogenetic study of antipsychotic induced acute extrapyramidal symptoms in a first episode psychosis cohort: role of dopamine, serotonin and glutamate candidate genes

This study investigated whether the risk of presenting antipsychotic (AP)-induced extrapyramidal symptoms (EPS) could be related to single-nucleotide polymorphisms (SNPs) in a naturalistic cohort of first episode psychosis (FEP) patients. Two hundred and two SNPs in 31 candidate genes (involved in dopamine, serotonin and glutamate pathways) were analyzed in the present study. One hundred and thirteen FEP patients (43 presenting EPS and 70 non-presenting EPS) treated with high-potency AP (amisulpride, paliperidone, risperidone and ziprasidone) were included in the analysis. The statistical analysis was adjusted by age, gender, AP dosage, AP combinations and concomitant treatments as covariates. Four SNPs in different genes (DRD2, SLC18A2, HTR2A and GRIK3) contributed significantly to the risk of EPS after correction for multiple testing (P<1 × 10−4). These findings support the involvement of dopamine, serotonin and glutamate pathways in AP-induced EPS.

Sensory Gating Deficits in First-Episode Psychosis: Evidence From Neurophysiology, Psychophysiology, and Neuropsychology.

Abstract Sensory gating deficits are commonly found in patients with schizophrenia. However, there is still scarce research on this issue. Thirty-eight patients with first-episode psychosis (FEP) were compared to thirty-eight controls. A condition-test paradigm of event-related potentials (ERP), prepulse inhibition (PPI), and some specific tasks of the MATRICS Consensus Cognitive Battery (MCCB) were used (i.e., TMT, BACS-SC, and Fluency for processing speed and CPT-IP for attention and vigilance). The ERP components measured were P50, N1, and P2. The PPI intervals examined were 30, 60, and 120 msec. Regarding the MCCB, processing speed and attention/vigilance cognitive domains were selected. FEP patients showed significant deficits in N1 and P2 components, at 30 and 60 PPI levels and in all the MCCB subtests selected. We obtained significant relationships in N1 with PPI-60, and with one MCCB subtest for processing speed. In addition, this same subtest showed significant association with P2. Therefore, sensory gating functioning is widely impaired since the very early stages of schizophrenia.

Cognitive impairments in patients with first episode psychosis: The relationship between neurophysiological and neuropsychological assessments.

Cognitive deficits in schizophrenia have been widely reported. Neurophysiological and neuropsychological assessments have been conducted to study these impairments. Event-related potentials (ERPs) are relevant markers of cognitive deficits in schizophrenia, and reductions in specific ERP components have been found. The MATRICS Consensus Cognitive Battery (MCCB) was developed to obtain a consensus battery for the assessment of cognitive deficits in schizophrenia. Here, we aimed to study modulations of several ERP components in first episode psychosis (FEP). We also examined neuropsychological deficits using the MCCB, and correlations between ERP and MCCB impairments. Thirty-eight FEP patients were compared to thirty-eight healthy controls. The following ERP components were examined: P1, N1, MMN, P2, early-P3 and late-P3. We used an auditory three-stimulus oddball paradigm, with standard (60%), target (20%) and distractor (20%) stimuli. FEP patients showed significantly lower amplitudes of P2, early-P3 and late-P3 components. FEP patients also showed significant deficits in all the MCCB cognitive domains. Finally, correlational analyses found strong associations between amplitudes of P2, early-P3 and late-P3 components and MCCB tests for attention and speed of processing. These findings indicate that deficits in late auditory ERP components are present in FEP, whereas early components are preserved. These reductions in late ERP components were related to attentional deficits in FEP as assessed by MCCB. These findings indicate that MCCB is a valid battery for studying cognitive impairments in the initial stages of schizophrenia, and highlight the utility of converging neurophysiological and neuropsychological measures to examine attentional impairments in schizophrenia.

Cannabis Abuse Effects on Prepulse Inhibition in Patients With First Episode Psychosis in Schizophrenia

Deficits in prepulse inhibition (PPI) and cannabis abuse are consistently found in schizophrenia. The authors studied PPI deficits in first episode psychosis (FEP) with schizophrenia and cannabis abuse influence. Thirty-five patients with FEP and 22 control subjects were examined. Patients were divided into cannabis use disorder (CUD) (N=21) and non-CUD (N=14). Startle measures were as follows: PPI at 30, 60, and 120 msec. Patients with CUD and patients without CUD showed lower PPI at 30 msec than control subjects. At 60 msec, patients with CUD obtained higher %PPI than patients without CUD, and patients without CUD obtained lower levels than control subjects. These findings show that cannabis abuse may improve PPI in patients with FEP at some levels.

Critical dynamics of endogenous fluctuations predict cognitive flexibility in the Go/NoGo task

Fluctuations with power-law scaling and long-range temporal correlations (LRTCs) are characteristic to human psychophysical performance. Systems operating in a critical state exhibit such LRTCs, but phenomenologically similar fluctuations and LRTCs may also be caused by slow decay of the system’s memory without the system being critical. Theoretically, criticality endows the system with the greatest representational capacity and flexibility in state transitions. Without criticality, however, slowly decaying system memory would predict inflexibility. We addressed these contrasting predictions of the ‘criticality’ and ‘long-memory’ candidate mechanisms of human behavioral LRTCs by using a Go/NoGo task wherein the commission errors constitute a measure of cognitive flexibility. Response time (RT) fluctuations in this task exhibited power-law frequency scaling, autocorrelations, and LRTCs. We show here that the LRTC scaling exponents, quantifying the strength of long-range correlations, were negatively correlated with the commission error rates. Strong LRTCs hence parallel optimal cognitive flexibility and, in line with the criticality hypothesis, indicate a functionally advantageous state. This conclusion was corroborated by a positive correlation between the LRTC scaling exponents and executive functions measured with the Rey-Osterrieth Complex Figure test. Our results hence support the notion that LRTCs arise from critical dynamics that is functionally significant for human cognitive performance.

Psychological symptomatology and impaired prepulse inhibition of the startle reflex are associated with cannabis-induced psychosis

Background: Cannabis-induced psychotic disorder (CIPD) is a psychiatric disorder induced by cannabis consumption. The psychological and psychophysiological features of this disorder are still unknown. We aimed to examine the psychological, personality and psychophysiological features of patients with CIPD. This study is an analytical extension of our previously published data, which previously found prepulse inhibition (PPI) deficits in the CIPD group used in this current paper. Methods: We used a sample of 45 patients with CIPD. After 9 months of follow up, these patients were assessed with a Symptom Checklist-90-R (SCL-90-R) questionnaire of psychopathology, with the Eysenck Personality Questionnaire, and with a psychophysiological paradigm of inhibition of the startle reflex (PPI). These results were compared with a group of patients with schizophrenia and cannabis abuse (SCHZ) (n = 54); patients with cannabis dependence (CD) (n = 21); and healthy controls (n = 50). Results: CIPD patients obtained significant higher scores in the SCL-90-R subscale of neuroticism. These patients showed PPI percentages similar to SCHZ patients within early attentional levels (30 ms). The variables with greater correlation, and that appeared in the CIPD group were interpersonal sensitivity, depression and phobia. Conclusions: Neurotic symptomatology and difficulties in inhibition of the startle reflex might be risk factors for developing CIPD.

Smoking does not impact social and non-social cognition in patients with first episode psychosis

BACKGROUND Many studies having shown significant improvements in non-social and social cognitive performance in smoking FEP patients compared to non-smoking FEP patients. The findings are controversial. This study analyzed the effects of tobacco use on non-social and social cognitive function in a large group of FEP patients and a matched healthy control group. METHODS A sample of 335 patients with FEP and 253 healthy controls was divided into four subgroups: control tobacco users (CTU), control non-tobacco users (CNTU), patient tobacco users (PTU) and patient non-tobacco users (PNTU). Demographic variables, tobacco use variables (presence or absence, frequency and duration of tobacco use), neurocognitive (non-social) performance and social cognition were assessed. RESULTS Comparison of 4 subgroups in non-social cognitive function revealed significant differences after controlling for covariables in executive functions (F=13.45; p≤0.001) and working memory domains (F=4.30; p=0.005). CTU and CNTU subgroups scored higher in all the domains compared to the PTU and the PNTU subgroups respectively. Social cognitive function was also significantly different within the four subgroups, with control subgroups showing better social cognition than patient subgroups. Significant differences in the executive functions domain were observed when comparing PTU and CTU groups (F=19.60; p≤0.001). No significant differences were revealed in the comparison between the patient groups. CONCLUSIONS This large study suggests that tobacco use in FEP patients is not related to better non-social or social cognitive performance.