Growing evidence suggests that cannabis abuse/dependence is paradoxically associated with better cognition in schizophrenia. Accordingly, we performed a functional magnetic resonance imaging (fMRI) study of visuospatial abilities in 14 schizophrenia patients with cannabis abuse (DD), 14 nonabusing schizophrenia patients (SCZ), and 21 healthy controls (HCs). Participants performed a mental rotation task while being scanned. There were no significant differences in the number of mistakes between schizophrenia groups, and both made more mistakes on the mental rotation task than HC. Relative to HC, SCZ had increased activations in the left thalamus, while DD patients had increased activations in the right supramarginal gyrus. In both cases, hyper-activations are likely to reflect compensatory efforts. In addition, SCZ patients had decreased activations in the left superior parietal gyrus compared to both HC and DD patients. This latter result tentatively suggests that the neurophysiologic processes underlying visuospatial abilities are partially preserved in DD, relative to SCZ patients, consistently with the findings showing that cannabis abuse in schizophrenia is associated with better cognitive functioning. Further fMRI studies are required to examine the neural correlates of other cognitive dysfunctions in schizophrenia patients with and without comorbid cannabis use disorder.
Neuropsychological studies have shown that 70% to 75% of patients with schizophrenia have significant cognitive deficits [
The cognitive deficits of schizophrenia may be further amplified by the chronic use of psychoactive substances. In schizophrenia, the lifetime prevalence of substance use disorders approaches 50%; this estimate represents a 3- to 5-fold increased risk relative to the general population [
In nonpsychiatric smokers, cannabis intoxication has been consistently shown to impair working memory, executive functions, and attention as well as (verbal) episodic memory [
Despite the reliable evidence discussed above, only one functional imaging study (to our knowledge) has examined the neural correlates of cognitive functioning in cannabis smoking patients with schizophrenia. Using an attention task (auditory dichotic listening), this functional magnetic resonance imaging (fMRI) study revealed that schizophrenia patients with previous cannabis use (
In healthy controls, various fMRI studies have shown that visuospatial abilities, as measured commonly with mental rotation tasks, depend closely on the recruitment of frontal, premotor, thalamic, and parietal regions [
Twenty-eight outpatients meeting DSM-IV criteria for schizophrenia (APA) [
Patients were evaluated by experienced psychiatrists using DSM-IV criteria [
In agreement with the
Our version of the mental rotation task consisted of an 8-minute run of alternating 38-second blocks of experimental and control conditions with 20-second periods of rest separating the blocks from one another. Both types of blocks (experimental and control) were repeated four times during the course of the functional run and involved presentations of pairs of 3D shapes, adopted from Shepard and Metzler’s [
We recorded blood oxygenation level dependent (BOLD) signals using a single-shot, gradient-recalled echo-planar imaging sequence (repetition time (TR) = 3000 ms, echo time (TE) = 30 ms, flip angle = 90°, matrix size = 64 × 64 voxels, and voxels size = 3.5 × 3.5 × 3.5 mm3) on a Siemens TRIO MRI system at 3.0 Tesla at the
We analyzed fMRI data using a statistical parametric mapping software (SPM5: Wellcome Department of Cognitive Neurology, London, UK) according to the methods outlined by Friston [
We used a standard peak-detection approach and the general linear model implemented in SPM5 for our statistical analyses in order to identify the dynamic cerebral changes associated with mental rotation. Block design analyses were performed with SPM-5 using a 2-level procedure. At the first level, a separate general linear model was specified for each participant to investigate individual brain activation maps associated with the mental rotation contrast (experimental minus control condition). Second-level random-effects models were then implemented to investigate the pattern of activations during the mental rotation contrast (experimental minus control condition) in each group, using one-sample student’s
To examine between-group differences in sociodemographic, clinical, and cognitive variables, we conducted one-way analyses of variance with diagnosis (HC, DD, and SCZ) as the independent variable. Where we detected group effects, we further investigated the source of these effects by performing multiple comparisons. For dichotomic variables, we performed Pearson’s chi-square tests. The level of significance was set at
The three groups were matched for age and handedness. HC were more educated than both groups of patients (
Sociodemographic and clinical data.
Control group ( |
SCZ group ( |
DD group ( |
|
---|---|---|---|
Age (years) | 30.3 (7.9) | 32.6 (8.4) | 30.9 (11.5) |
Lefthanded | 4 | 4 | 1 |
Education level (years) | 18.0 (2.9)** | 11.1 (2.9) | 10.0 (1.9) |
Parental SES | 2.4 (1.1)** | 2.9 (0.7)* | 3.8 (1.2) |
Clinical | |||
Age of onset (years) | — | 20.8 (4.6) | 20.3 (4.4) |
Duration of illness (years) | — | 11.9 (9.0) | 10.6 (12.2) |
Total medication (mg/day) | — | 568 (276) | 553 (392) |
PANSS positive | — | 17.1 (4.7) | 16.4 (6.0) |
PANSS negative | — | 19.9 (6.2) | 18.9 (5.3) |
PANSS general | — | 37.3 (5.2) | 32.5 (8.7) |
Calgary Depression Scale | — | 3.7 (2.1) | 3.8 (4.1) |
Antipsychotics | — | risperidone (6), |
risperidone (7), |
DD: dualdiagnosis; SCZ: schizophrenia; SES: socioeconomic status; total medication is in chlorpromazine equivalents; (SD in parentheses);
As shown in Table
Mental rotation performance in schizophrenia and dual-diagnosis patients and healthy controls.
Score | Control group ( |
SCZ group ( |
DD group ( |
Statistics | Multiple comparisons* |
---|---|---|---|---|---|
Accuracy (%) | 94.6 (5.5) | 76.7 (11.0) | 72.4 (14.4) |
|
Controls > SCZ & DD |
Reaction time (s) | 1.5 (0.4) | 2.0 (0.2) | 1.9 (0.4) |
|
Controls < SCZ & DD |
DD: dualdiagnosis; SCZ: schizophrenia;
ROI analyses revealed significant loci of activations in the left inferior and superior parietal gyrus, the right supramarginal gyrus, and the left superior frontal gyrus as well as the bilateral precentral gyrus in the HC group. In the SCZ group, we observed significant activations restricted to the left thalamus. Finally, the DD group presented significant loci of activations in the bilateral superior parietal gyrus, the left inferior parietal gyrus, the right supplementary motor area, the left precentral gyrus, and the left and right supramarginal gyrus (Table
ROI activations during the mental rotation task (experimental relative to control condition) in the 3 groups (1-sample student’s
Brain region | R/L | MNI coordinates |
|
Voxels |
|
||
---|---|---|---|---|---|---|---|
|
|
| |||||
Control group | |||||||
Inferior parietal | L | −35 | −42 | 46 | 5.30 | 120 | 0.001 |
Supramarginal | R | 38 | −35 | 42 | 5.14 | 86 | 0.001 |
Superior parietal | L | −24 | −60 | 63 | 4.97 | 169 | 0.001 |
Precentral | L | −28 | −14 | 49 | 4.32 | 36 | 0.003 |
Superior frontal | L | −24 | −7 | 63 | 4.00 | 43 | 0.003 |
Precentral | R | 32 | −7 | 56 | 4.30 | 80 | 0.001 |
SCZ group | |||||||
Thalamus | L | −7 | −4 | 10 | 3.37 | 31 | 0.050 |
DD group | |||||||
Superior parietal | L | −18 | −63 | 49 | 3.97 | 198 | 0.002 |
Supplementary motor area | R | 14 | 4 | 70 | 3.71 | 17 | 0.013 |
Precentral | L | −35 | −10 | 46 | 3.64 | 27 | 0.012 |
Inferior parietal | L | −38 | −35 | 38 | 3.45 | 27 | 0.010 |
Supramarginal | L | −49 | −38 | 28 | 3.42 | 19 | 0.018 |
R | 56 | −28 | 52 | 3.21 | 15 | 0.036 | |
Superior parietal | R | 21 | −56 | 56 | 3.44 | 43 | 0.008 |
R: right; L: left;
ROI brain activity when processing the mental rotation task in the 3 groups. HC: healthy control group; SCZ = schizophrenia group; DD = dual-diagnosis group; L = left; R = right.
Between-group analyses revealed increased loci of activations in the left superior parietal cortex in HC relative to the SCZ group (MNI coordinates:
In view of the literature showing that cannabis smoking/abuse is associated in schizophrenia with better performance in various cognitive domains, including visuospatial abilities [
More importantly, our between-group comparisons revealed increased activations in the left superior parietal gyrus in both HC and DD, relative to SCZ patients, while the comparison between DD patients and HC revealed no between-group differences regarding brain region (despite the fact that DD patients had lower parental SES status). In fMRI studies examining the neural processes underlying mental rotation and visuospatial processing in healthy subjects, the superior parietal gyrus is one of the regions that have been most consistently activated [
To the best of our knowledge, our study is only the second one to examine the neural correlates of cognitive functioning in schizophrenia patients with comorbid cannabis use/abuse using functional imaging. Indeed, in a recent fMRI study, Løberg et al. [
Our results need to be discussed cautiously. On one hand, the finding of a spared functioning of the left superior parietal gyrus in DD relative to SCZ patients tentatively suggests that cannabis has neuroprotective effects in schizophrenia. Cannabis produces its effects on the brain via the endogenous cannabinoid system, which is composed of (at least) two principal ligands, anandamide, and 2-arachidonoylglycerol, which bind (at least) two cannabinoid receptors (CB1 and CB2) [
As an alternative to the above-mentioned neuro-protection hypothesis, it has been proposed that in order to sustain the lifestyle of substance abuse (make deals, find money, etc.), patients with schizophrenia have to be able to maintain minimal social contacts and apply at least some organizational strategies. According to this view, one would expect substance-abusing schizophrenia patients to have relatively spared cognitive abilities [
Our study comprised a few limitations. First, we did not scan a group of nonpsychosis patients with cannabis abuse/dependence. The inclusion of such a group may have clarified aspects of our results. However, here, we found that cannabis abuse/dependence was associated with spared superior parietal functioning in schizophrenia, whereas chronic smoking is known to impair, not to improve, the neurophysiologic processes underlying various cognitive functions in otherwise healthy subjects [
Together with the literature on cognition, the results of the current fMRI study provide preliminary evidence that some cognitive-related neurophysiologic processes are partially spared in cannabis-smoking schizophrenia patients. Future fMRI studies in the field will need to examine the neural correlates of cognitive functions other than visuospatial abilities in larger sample of patients. Studies will also need to determine whether our results hold true for female DD patients. Finally, longitudinal studies will need to be performed in order to find out if the relatively preserved superior parietal functioning of DD patients is primary or secondary to cannabis smoking. Such studies would measure cognition and their neural correlates when patients are in the active smoking phase and after prolonged abstinence. Studies initiated during the prodromal phase of psychosis are also warranted.
All authors declare that they have no conflict of interests.
This study was supported by a catalyst Grant (SP) and an operating Grant (AM) from the