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Background: Cannabinoids are proposed in a wide array of medical indications. Yet, the evaluation of adverse effects in controlled clinical studies, following the evidence-based model, has partly been bypassed. On the other hand, studies on the consequences of recreational use of cannabis and experimental studies bring some insights on the potential long-term consequences of cannabinoids use., Results: Epidemiological studies have consistently demonstrated that cannabis use is associated with a risk of persistent cognitive deficits and increased risk of schizophrenia-like psychoses. These risks are modulated by the dose and duration of use, on top of age of use and genetic factors, including partially shared genetic predisposition with schizophrenia. Experimental studies in healthy humans showed that cannabis and its principal psychoactive component, the delta-9-tetrahydrocannabinol (THC), could produce transient, dose-dependent, psychotic symptoms as well as cognitive effects, which can be attenuated by cannabidiol (CBD). Studies in rodents have confirmed these effects and shown that adolescent exposure results in structural changes and impaired synaptic plasticity, impacting fronto-limbic systems that are critically involved in higher brain functions. The endocannabinoid system plays an important role in brain maturation. Its over-activation by cannabinoid receptor type 1 agonists (e.g., THC) during adolescence and the resulting changes in neuroplasticity could alter brain maturation and cause long-lasting changes that persist in the adult brain., Conclusions: Exposure to cannabinoids can have long-term impact on the brain, with an inter-individual variability that could be conveyed by personal and family history of psychiatric disorders and genetic background. Adolescence and early adulthood are critical periods of vulnerability., Significance: The assessment of benefice-risk balance of medical use of cannabis and cannabinoids needs to carefully explore populations that could be more at-risk of psychiatric and cognitive complications., (© 2019 European Pain Federation - EFIC®.)

Purpose: Cognitive deficits in schizophrenia mainly affect memory, attention and executive functions. Cognitive remediation is a technique derived from neuropsychology, which aims to improve or compensate for these deficits. Working memory, verbal learning, and executive functions are crucial factors for functional outcome. Our purpose was to assess the impact of the cognitive remediation therapy (CRT) program on cognitive difficulties in patients with schizophrenia, especially on working memory, verbal memory, and cognitive flexibility., Methods: We collected data from clinical and neuropsychological assessments in 24 patients suffering from schizophrenia (Diagnostic and Statistical Manual of mental Disorders-Fourth Edition, DSM-IV) who followed a 3-month (CRT) program. Verbal and visuo-spatial working memory, verbal memory, and cognitive flexibility were assessed before and after CRT., Results: The Wilcoxon test showed significant improvements on the backward digit span, on the visual working memory span, on verbal memory and on flexibility. Cognitive improvement was substantial when baseline performance was low, independently from clinical benefit., Conclusions: CRT is effective on crucial cognitive domains and provides a huge benefit for patients having low baseline performance. Such cognitive amelioration appears highly promising for improving the outcome in cognitively impaired patients.

Several studies have shown that Δ-9-THC the main psychoactive constituent of cannabis, can impair cognitive functions, especially attention, episodic memory, working memory and executive functions. These impairments have been related to the duration, frequency, dose and age at onset of cannabis use. Cognitive deficits may disappear with abstinence, but abnormalities may be long-lasting in subjects who began smoking cannabis before age 15. The lifetime prevalence of cannabis use disorders is about 1% in the general population. The main characteristics of cannabis use disorders are craving, persistent desire or unsuccessful efforts to cut down or control cannabis use, and persistent avoidance of familial, social occupational or recreational activities because of cannabis use. Nine prospective longitudinal studies in the generalpopulation have shown that cannabis use is associated with a two-fold increase in the risk of psychotic disorders, particularly schizophrenia, compared to controls. The risk of psychosis increases in a dose-related fashion. A higher risk of schizophrenia is predicted by earlier onset of cannabis use. The effects of cannabis are exerted primarily through THC interaction with cannabinoid (CB) 1 receptors in the brain. Cannabis exposure may disrupt the last steps of brain maturation, through the endocannabinoid system, thereby increasing the risk of psychosis during adolescence.

In Ultra High Risk (UHR) studies, intellectual functioning is commonly assessed using premorbid IQ tools as a covariate. The aim of this study was to show that the use of the Wechsler Adult Intelligence Scale (WAIS) could yield accurate neuropsychological profiling and that an alternative approach such as a multiple-case study could be a more interesting way to isolate discrete cognitive processes in the early stage of illness. The studied population consisted of 198 adolescents and young adults (16-30 y.o.) referred to our outpatient clinic. After the CAARMS' interview, we defined 3 subgroups: UHR (N=104), First Episode (FE; N=30), and Help-Seekers (HS; N=64) who were neither UHR nor psychotic. Intellectual functioning was assessed by the WAIS-III (9 subtests version) and 'heterogeneous' intellectual profiles were defined based on the existence of a 3-point difference in scoring at subtests constitutive of the same WAIS index. While UHR did not differ from FE or HS on WAIS' scores and sub-scores, the multiple-case study indicated a higher proportion of 'heterogeneous' profiles in the Verbal Comprehension Index in the UHR sample than in FE and HS (p=0.04). The disease progression could heterogeneously impact on specific domains, in patterns depending on the stage of the illness. This approach exploring intra-subject WAIS performances might be more relevant than the use of global scores in detecting the subtle cognitive alteration of emerging psychosis., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Rationale: During cerebral development, adolescence is a critical phase in which the endocannabinoid system plays an important role in regulating various neurotransmitters. Moreover, evidence from both human and animal studies suggests that chronic cannabinoid exposure during this vulnerable period can induce persistent brain and behavioural alterations., Objectives: The aim of this study was to compare the long-term cognitive consequences of chronic adolescence cannabinoid exposure between Lister Hooded rats and Wistar rats., Methods: Rats of both strains were injected daily throughout their adolescent or adult periods with vehicle or with incremental doses of the synthetic cannabinoid CB1 receptor agonist CP55,940 (CP). Short-term and spatial working memories were assessed using the object recognition and object location, tasks respectively. For both tasks, the effect of a 30- or 120-min delay between the learning and the testing phase was investigated., Results: In the object recognition task, adolescent CP exposure impaired short-term memory after both delays in both strains. In contrast, in the object location task, adolescent CP exposure impaired spatial working memory in the Wistar rats after a 30-min delay, whereas the Lister Hooded rats exhibited a similar effect only after a 120-min delay. In these tests, no long-term deleterious effects were found following adult CP exposure in either strain., Conclusions: Our results confirm that adolescence is a critical period for the deleterious effects of cannabinoids on cognition and that these deleterious effects on spatial working memory are more strain-dependent than the effects observed on short-term memory.

Investigations of memory impairment in schizophrenia have frequently revealed a strategic processing deficit at encoding. The authors studied an early encoding process, refreshing (in this case, thinking of a stimulus that has just-previously been presented), and its impact on recognition memory in schizophrenia. Following simultaneous presentation of three words or a single word in the top, middle, or bottom position of the screen, 25 patients with schizophrenia and 25 control participants saw and read a new word (read condition), or a word presented on the previous screen (repeat condition), or saw a dot indicating that they should think of and say the last word to have appeared in that position (refresh condition). Later, on a surprise test, participants were asked to recognize words seen previously and give a Remember, Know, or Guess response according to whether they recognized each on the basis of conscious recollection, familiarity, or guessing. The cognitive operation of refreshing was impaired in schizophrenia: patients were slower on 1-word trials and less accurate on 3-word trials to refresh a word, and their Remember responses did not benefit from refreshing., (Copyright 2009 APA, all rights reserved.)

The role of the cerebellum in schizophrenia has been highlighted by Andreasen's hypothesis of "cognitive dysmetria," which suggests a general dyscoordination of sensorimotor and mental processes. Studies in schizophrenic patients have brought observations supporting a cerebellar impairment: high prevalence of neurological soft signs, dyscoordination, abnormal posture and propioception, impaired eyeblink conditioning, impaired adaptation of the vestibular-ocular reflex or procedural learning tests, and lastly functional neuroimaging studies correlating poor cognitive performances with abnormal cerebellar activations. Despite those compelling evidences, there has been, to our knowledge, no recent review on the clinical, cognitive, and functional literature supporting the role of the cerebellum in schizophrenia. We conducted a Medline research focusing on cerebellar dysfunctions in schizophrenia. Emphasis was given to recent literature (after 1998). The picture arising from this review is heterogeneous. While in some domains, the role of the cerebellum seems clearly defined (ie, neurological soft signs, posture, or equilibrium), in other domains, the cerebellar contribution to schizophrenia seems limited or indirect (ie, cognition) if present at all (ie, affectivity). Functional models of the cerebellum are proposed as a background for interpreting these results.

Schizophrenia is associated with impairments in many cognitive domains on which the influence of antipsychotics, whether conventional or atypical, remains unclear. We conducted a study of recent-onset schizophrenic patients (DSM IV) that included unmedicated (n=19), and medicated (n=19) patients matched for age and IQ. Both groups of patients had comparably low extra-pyramidal symptoms (EPS). Cognitive tasks included attentional tasks (alertness and divided attention tests), a working memory task (a verbal n-back test) and the Wisconsin Card Sorting Test (WCST). After adjustment for the Total PANSS score, we found no significant difference between the two groups of patients in any of the cognitive tasks. When compared to a group of healthy controls (n=20) matched for IQ level, unmedicated patients performed significantly worse in all cognitive tasks, with significantly longer reaction times for alertness, divided attention and working memory. These results confirm the presence of cognitive impairments in attentional and executive functions in recent-onset patients whether or not they are medicated. There was no evidence that either conventional or atypical antipsychotics had an influence on patients when EPS were excluded. Altogether, our results further support the idea that cognitive deficits in schizophrenia are enduring features per se and cannot be considered as secondary to psychiatric symptoms or to the adverse effects of medication. In addition our results suggest that antipsychotics do not have a major effect on these impairments.

Background: Neurological soft signs (NSS) and minor physical anomalies (MPA) are frequent in patients with schizophrenia and their biological relatives. We examined whether the NSS and MPA are related to the genetic loading in schizophrenia., Methods: Patients with schizophrenia (DSM-IV) (n=61), nonpsychotic parents of these patients (n=76) and healthy comparison subjects (n=44) took part in the study. Parents were further classified as "presumed carriers" of the genetic loading (n=26) if they had a second relative with schizophrenia in their ascendants and/or collaterals (first or second degree) or as "presumed noncarriers" (n=50). NSS and MPA were compared in these groups., Results: A multivariate analysis indicated that total NSS and MPA scores, adjusted for age and gender, were significantly related to group status. Univariate tests showed higher scores in motor coordination and integration subscores (p=0.005 and 0.008, respectively) in presumed carriers than in presumed noncarriers. In addition, a discriminant function analysis based on total NSS and MPA scores correctly classified 71% of nonpsychotic parents in presumed carriers or presumed noncarriers., Conclusions: Neurological impairments and slight morphological anomalies seem to be associated with the genetic risk for schizophrenia, even when the disease itself is absent. Their presence might be a valuable composite intermediate phenotype for genetic studies.

The aim of this study is to circumscribe the cognitive deficits according to schizophrenic syndromes in a population of sub-acute untreated patients. We have studied the cross-sectional correlation between cognitive deficits and schizophrenic symptoms, in a group of 24 untreated patients (including 17 neuroleptic-naive patients) with recent onset of the disease. A task of alertness, a working memory (WM) test (including two levels of difficulty) and an abbreviated version of the Wisconsin Card Sorting Test (WCST) were selected. WM deficits and poor performance on the WCST were highly correlated with disorganized symptoms, modestly with the positive syndrome and not with the negative syndrome. Thus, disorganized symptoms, more than any other, appear to be related to the impairment of executive function and WM in recent onset unmedicated patients with schizophrenia.