Although evidence from psychosis patients demonstrates the adverse effects of cannabis use (CU) at a young age and that the rate of CU is high in subgroups of young violent patients with psychotic disorders, little is known about the possible effect of the age of onset of CU on later violent behaviors (VB). So, we aimed to explore the impact of age at onset of CU on the risk of displaying VB in a cohort of early psychosis patients.

Data were collected prospectively over a 36-month period in the context of an early psychosis cohort study. A total of 265 patients, aged 18–35 years, were included in the study. Logistic regression was performed to assess the link between age of onset of substance use and VB.

Among the 265 patients, 72 had displayed VB and 193 had not. While violent patients began using cannabis on average at age 15.29 (0.45), nonviolent patients had started on average at age 16.97 (0.35) (p = 0.004). Early-onset CU (up to age 15) was a risk factor for VB (odds ratio = 4.47, confidence interval [CI]: 1.13–20.06) when the model was adjusted for age group, other types of substance use, being a user or a nonuser and various violence risk factors and covariates. History of violence and early CU (until 15) were the two main risk factors for VB.

Our results suggest that early-onset CU may play a role in the emergence of VB in early psychosis.

Patients with schizophrenia display experiential anomalies in their feelings and cognitions arising in the domain of their lived body. These abnormal bodily phenomena (ABP) are not part of diagnostic criteria for schizophrenia. One of the reasons is the difficulty to assess specific ABP for schizophrenia spectrum disorders. The present study aimed to explore the presence in patients with schizophrenia of specific ABP.

We used a semistructured interview—the Abnormal Bodily Phenomena questionnaire (ABPq), an instrument devised to detect and measure ABP specific to patients with schizophrenia. Fifty-one outpatients affected by schizophrenia and 28 euthymic outpatients affected by bipolar disorder type I with psychotic features (BD-pf-e) were recruited. Before assessing the specificity for schizophrenia of the observed ABP, we tested the internal consistency and the convergent validity of the ABPq in patients with schizophrenia. Specificity was assessed by examining potential differences in ABPq among the patients with schizophrenia in remission (SCZ-r) and BD-pf-e.

The ABPq shows strong internal consistency and convergent validity. As to the specificity, ABP measured by ABPq were more frequent and severe in SCZ-r than in BD-pf-e. In particular, all ABPq dimensions, except “Coherence,” had at least mild severity in over 50% of SCZ-r, while dimensions with at least mild severity were observed in 5–10% of the BD-pf-e.

These findings can contribute to establish more precise phenomenal boundaries between schizophrenia and bipolar disorder, to explore the borders between nonpsychotic and psychotic forms of ABP, between ABP and negative and disorganized symptoms, and to enlighten core aspects of schizophrenia.

Seasonal patterns in hospitalizations have been observed in various psychiatric disorders, however, it is unclear whether they also exist in schizophrenia. Previous studies found mixed results and those reporting the presence of seasonality differ regarding the characteristics of these patterns. Further, they are inconclusive whether sex is an influencing factor. The aim of this study was therefore to examine if seasonal patterns in hospitalizations can be found in schizophrenia, with special regard to a possible influence of sex, by using a large national dataset.

Data on all hospital admissions within Austria due to schizophrenia (F20.0–F20.6) for the time period of 2003–2016 were included. Age standardized monthly variation of hospitalization for women and men was analyzed and the level of significance adjusted for multiple testing.

The database comprised of 110,735 admissions (59.6% men). Significant seasonal variations were found in the total sample with hospitalization peaks in January and June and a trough in December (p < 0.0001). No significant difference in these patterns was found between women and men with schizophrenia (p < 0.0001).

Our study shows that schizophrenia-related hospitalizations follow a seasonal pattern in both men and women. The distribution of peaks might be influenced by photoperiod changes which trigger worsening of symptoms and lead to exacerbations in schizophrenia. Further research is necessary to identify underlying factors influencing seasonal patterns and to assess whether a subgroup of patients with schizophrenia is especially vulnerable to the impact of seasonal variations.

Despite apparent clinical remission, individuals with psychotic disorders often experience significant impairments across functional domains. Thus, there is a need to search beyond management of core symptoms to optimize treatment outcomes. Affective dysregulation is considered a risk factor for poor clinical and functional outcomes in many mental disorders, but research investigating such features in psychosis, particularly in schizophrenia, is limited. We aimed to investigate the level of affective lability (AL) in participants with schizophrenia- and bipolar spectrum disorders (n = 222) compared to healthy controls (n = 140), as well as clinical correlates of AL in the diagnostic groups.

The Affective Lability Scale (ALS-SF) was used to measure total score of AL and subscores covering the domains of anxiety/depression, depression/elation, and anger. An analysis of covariance was performed to compare the ALS-SF total score between groups, correcting for potential confounders, as well as standard multiple regression analyses for diagnosis-specific investigations of the relationship between AL and demographic and clinical features.

Both the schizophrenia- and bipolar spectrum group had significantly higher ALS-SF total score compared to controls (p < 0.001), and no significant differences between the patient groups were found. In the schizophrenia group, current psychotic and depressive symptoms were significantly and independently associated with AL (p = 0.012 and p = 0.024, respectively).

The findings indicate that AL is elevated in psychotic disorders and that it transcends diagnostic boundaries. Further research into the causal relationship between psychotic and affective symptoms and AL, as well as its role as a potential therapeutic target in psychosis spectrum disorders, is warranted.

Greater levels of insight may be linked with depressive symptoms among patients with schizophrenia, however, it would be useful to characterize this association at symptom-level, in order to inform research on interventions.

Data on depressive symptoms (Calgary Depression Scale for Schizophrenia) and insight (G12 item from the Positive and Negative Syndrome Scale) were obtained from 921 community-dwelling, clinically-stable individuals with a DSM-IV diagnosis of schizophrenia, recruited in a nationwide multicenter study. Network analysis was used to explore the most relevant connections between insight and depressive symptoms, including potential confounders in the model (neurocognitive and social-cognitive functioning, positive, negative and disorganization symptoms, extrapyramidal symptoms, hostility, internalized stigma, and perceived discrimination). Bayesian network analysis was used to estimate a directed acyclic graph (DAG) while investigating the most likely direction of the putative causal association between insight and depression.

After adjusting for confounders, better levels of insight were associated with greater self-depreciation, pathological guilt, morning depression and suicidal ideation. No difference in global network structure was detected for socioeconomic status, service engagement or illness severity. The DAG confirmed the presence of an association between greater insight and self-depreciation, suggesting the more probable causal direction was from insight to depressive symptoms.

In schizophrenia, better levels of insight may cause self-depreciation and, possibly, other depressive symptoms. Person-centered and narrative psychotherapeutic approaches may be particularly fit to improve patient insight without dampening self-esteem.

Functional capacity (FC) has been identified as a key outcome to improve real-world functioning in schizophrenia. FC is influenced by cognitive impairments, negative symptoms, self-stigma and reduced physical activity (PA). Psychosocial interventions targeting FC are still under-developed.

we conducted a quasi-experimental study evaluating the effects of an exercise-enriched integrated social cognitive remediation (SCR) intervention (RemedRugby [RR]) compared with an active control group practicing Touch Rugby (TR). To our knowledge, this is the first trial to date evaluating the effectiveness of such a program provided in a real-life environment.

Eighty-seven people with schizophrenia were included and allocated to either the RR group (n = 57) or the TR group (n = 30) according to the routine clinical practice of the recruiting center. Outcomes were evaluated at baseline and post-treatment in both groups and after 6 months of follow-up in the RR group using standardized scales for symptom severity, social functioning, self-stigma, and a large cognitive battery. After treatment we observed moderate to large improvements in social function (Personal and Social Performance Scale [PSP], p < 0.001, d = 1.255), symptom severity (Positive and Negative Syndrome Scale [PANSS] negative, p < 0.001, d = 0.827; PANSS GP, p < 0.001, d = 0.991; PANSS positive, p = 0.009, d = 0.594), verbal abstraction (p = 0.008, d = 0.554), aggression bias (p = 0.008, d = 0.627), and self-stigma (stereotype endorsement, p = 0.019, d = 0.495; discrimination experiences, p = 0.047; d = 0.389) that were specific to the RR group and were not observed in participants playing only TR. Effects were persistent over time and even larger between post-treatment and follow-up.

Exercise-enriched integrated SCR appears promising to improve real-life functioning in schizophrenia. Future research should investigate the potential effects of this intervention on neuroplasticity and physical fitness.

Premorbid adjustment (PA) abnormalities in psychotic disorders are associated with an earlier age at onset (AAO) and unfavorable clinical outcomes, including treatment resistance. Prior family studies suggest that familial liability, likely reflecting increased genetic risk, and socioeconomic status (SES) contribute to premorbid maladjustment. However, their joint effect possibly indicating gene–environment interaction has not been evaluated.

We examined whether family history of psychosis (FHP) and parental SES may predict PA and AAO in unrelated cases with first-episode psychosis (n = 108) and schizophrenia (n = 104). Premorbid academic and social functioning domains during childhood and early adolescence were retrospectively assessed. Regression analyses were performed to investigate main effects of FHP and parental SES, as well as their interaction. The relationships between PA, AAO, and response to antipsychotic medication were also explored.

Positive FHP associated with academic PA difficulties and importantly interacted with parental SES to moderate social PA during childhood (interaction p = 0.024). Positive FHP and parental SES did not predict differences in AAO. Nevertheless, an earlier AAO was observed among cases with worse social PA in childhood (β = −0.20; p = 0.005) and early adolescence (β = −0.19; p = 0.007). Further, confirming evidence emerged for an association between deficient childhood social PA and poor treatment response (p = 0.04).

Familial risk for psychosis may interact with parental socioeconomic position influencing social PA in childhood. In addition, this study supports the link between social PA deviations, early psychosis onset, and treatment resistance, which highlights premorbid social functioning as a promising clinical indicator.

Earlier studies examining structural brain abnormalities associated with cognitively derived subgroups were mainly cross-sectional in design and had mixed findings. Thus, we obtained cross-sectional and longitudinal data to characterize the extent and trajectory of brain structure abnormalities underlying distinct cognitive subtypes (“preserved,” “deteriorated,” and “compromised”) seen in psychotic spectrum disorders.

Data from 364 subjects (225 patients with psychotic conditions and 139 healthy controls) were first used to determine the relationship of cognitive subtypes with cross-sectional measures of subcortical volume and cortical thickness. To probe neurodevelopmental abnormalities, brain structure laterality was examined. To examine whether neuroprogressive abnormalities persist, longitudinal brain structural changes over 5 years were examined within a subset of 101 subjects. Subsequent discriminant analysis using the identified brain measures was performed on an independent subject group.

Cross-sectional comparisons showed that cortical thinning and limbic volume reductions were most widespread in “deteriorated” cognitive subtype. Laterality comparisons showed more rightward amygdala lateralization in “compromised” than “preserved” subtype. Longitudinal comparisons revealed progressive hippocampal shrinkage in “deteriorated” compared with healthy controls and “preserved” subtype, which correlated with worse negative symptoms, cognitive and psychosocial functioning. Post-hoc discrimination analysis on an independent group of 52 subjects using the identified brain structures found an overall accuracy of 71% for classification of cognitive subtypes.

These findings point toward distinct extent and trajectory of corticolimbic abnormalities associated with cognitive subtypes in psychosis, which can allow further understanding of the biological course of cognitive functioning over illness course and with treatment.

Childhood traumatic events are risk factors for psychotic-like experiences (PLEs). However, the mechanisms explaining how trauma may contribute to the development of PLEs are not fully understood. In our study, we investigated whether cannabis use and cognitive biases mediate the relationship between early trauma and PLEs.

A total sample of 6,772 young adults (age 26.6 ± 4.7, 2,181 male and 3,433 female) was recruited from the general population to participate in an online survey. We excluded 1,158 individuals due to a self-reported lifetime diagnosis of any mental disorder. The online survey included selected items from the following questionnaires: Traumatic Experience Checklist (TEC, 3 items), Childhood Experience of Care and Abuse Questionnaire (CECA.Q, 3 items), Cannabis Problems Questionnaire (CPQ, 10 items), Davos Assessment of Cognitive Biases Scale (DACOBS-18, 9 items), and Prodromal Questionnaire-16 (PQ-16). Mediation analyses were performed with respect to different categories of traumatic experiences (emotional, physical and sexual abuse as well as emotional neglect).

Our results showed significant associations of any time of childhood trauma with higher scores of cannabis use (CPQ), cognitive biases (DACOBS), and PLEs (PQ-16) (p < 0.001). We found a direct effect of childhood trauma on PLEs as well as significant indirect effect mediated through cannabis use and cognitive biases. All models tested for the effects of specific childhood adversities revealed similar results. The percentage of variance in PQ-16 scores explained by serial mediation models varied between 32.8 and 34.2% depending on childhood trauma category.

Cannabis use and cognitive biases play an important mediating role in the relationship between childhood traumatic events and the development of PLEs in a nonclinical young adult population.

Formal thought disorder (FTD) and social functioning impairments are core symptoms of schizophrenia. Although both have been observed for over a century, the strength of the relationship between FTD and social functioning remains unclear. Furthermore, a variety of methodological approaches have been used to assess these constructs—which may contribute to inconsistency in reported associations. This meta-analysis aimed to: (a) systematically test the relationship between FTD and social functioning and (b) determine if the methodology used to assess FTD and/or social functioning moderates this relationship.

Following Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines, a targeted literature search was conducted on studies examining the relationship between FTD and social functioning. Correlations were extracted and used to calculate weighted mean effect sizes using a random effects model.

A total of 1,478 participants across 13 unique studies were included in this meta-analysis. A small-medium inverse association (r = −0.23, p < 0.001) was observed between FTD and social functioning. Although heterogeneity analyses produced a significant Q-statistic (Q = 52.77, p = <0.001), the relationship between FTD and social functioning was not moderated by methodology, study quality, demographic variables, or clinical factors.

Findings illustrate a negative association between FTD and social functioning. Despite differences in the methodological approach used and type of information assessed, measurement type and clinical factors did not moderate the relationship between FTD and social functioning. Future studies should explore whether other variables, such as cognitive processes (e.g., social cognition), may account for variability in associations between these constructs.

Schizophrenia is a leading cause of disability. People living with schizophrenia (PLWS) present unemployment, social isolation, excess mortality and morbidity, and poor quality of life. Early recognition and appropriate treatment reduce the risk of chronicity and comorbidity. Personalization and integration of pharmacological and psychosocial interventions, as well as accurate identification and management of psychiatric and somatic comorbidities, can significantly improve mental and physical health of PLWS, promoting recovery.

A three-step Delphi approach was used to explore consensus on the essential components of early recognition and intervention, personalization, and integration of care to improve schizophrenia outcome, and on barriers and challenges to close treatment gaps. The consensus involved 8 Italian experts of schizophrenia, 100 psychiatrists from academic and nonacademic settings, including representatives of Italian Society of Psychiatry, and 65 trainees in psychiatry.

A strong consensus (from mostly agree to totally agree) emerged on the importance of early diagnosis (97%), standardized assessments (91%), correct management of somatic and psychiatric comorbidities (99%), and personalization and integration of care (94%). Lack of time, human resources, and training were identified as the main barriers and challenges to the translation of knowledge into clinical practice.

The results of this Delphi study demonstrated a strong consensus on main components of schizophrenia care, as well as on unmet needs to promote best practice and gaps between knowledge and clinical practice. The involvement of a large group of professionals and trainees in this in-depth consensus process might contribute to raise awareness and stimulate innovative strategies to improve the outcome of PLWS.

Sex differences in cognitive functioning have long been recognized in schizophrenia patients and healthy controls (HC). However, few studies have focused on patients with an at-risk mental state (ARMS) for psychosis. Thus, the aim of the present study was to investigate sex differences in neurocognitive performance in ARMS patients compared with HC.

The data analyzed in this study were collected within the multicenter European Gene–Environment Interactions study (11 centers). A total of 343 ARMS patients (158 women) and 67 HC subjects (33 women) were included. All participants completed a comprehensive neurocognitive battery. Linear mixed effects models were used to explore whether sex differences in cognitive functioning were present in the total group (main effect of sex) and whether sex differences were different for HC and ARMS (interaction between sex and group).

Women performed better in social cognition, speed of processing, and verbal learning than men regardless of whether they were ARMS or HC. However, only differences in speed of processing and verbal learning remained significant after correction for multiple testing. Additionally, ARMS patients displayed alterations in attention, current IQ, speed of processing, verbal learning, and working memory compared with HC.

Findings indicate that sex differences in cognitive functioning in ARMS are similar to those seen between healthy men and women. Thus, it appears that sex differences in cognitive performance may not be specific for ARMS, a finding resembling that in patients with schizophrenic psychoses.

We studied the cumulative incidence of physical illnesses, and the effect of early environmental factors (EEFs) on somatic comorbidity in schizophrenia, in nonschizophrenic psychosis and among nonpsychotic controls from birth up to the age of 50 years.

The sample included 10,933 members of the Northern Finland Birth Cohort 1966, of whom, 227 had schizophrenia and 205 had nonschizophrenic psychosis. Diagnoses concerning physical illnesses were based on nationwide registers followed up to the end of 2016 and classified into 13 illness categories. Maternal education and age, family type at birth and paternal socioeconomic status were studied as EEFs of somatic illnesses.

When adjusted by gender and education, individuals and especially women with nonschizophrenic psychosis had higher risk of morbidity in almost all somatic illness categories compared to controls, and in some categories, compared to individuals with schizophrenia. The statistically significant adjusted hazard ratios varied from 1.27 to 2.42 in nonschizophrenic psychosis. Regarding EEFs, single-parent family as the family type at birth was a risk factor for a higher somatic score among men with schizophrenia and women with nonschizophrenic psychosis. Maternal age over 35 years was associated with lower somatic score among women with nonschizophrenic psychosis.

Persons with nonschizophrenic psychoses have higher incidence of somatic diseases compared to people with schizophrenia and nonpsychotic controls, and this should be noted in clinical work. EEFs have mostly weak association with somatic comorbidity in our study.

There is consistent evidence that theory of mind (ToM) is impaired in schizophrenia (SZ); however, it remains unclear whether such deficits are trait- or state-dependent. We evaluated ToM in patients with schizophrenia spectrum disorders (SSDs), their healthy first-degree relatives, and controls to test its suitability as an endophenotypic marker. We also studied the modifying effect of markers of clinical and genetic liability to SZ (schizotypy and genetic variability in the oxytocin receptor gene: OXTR) on ToM in healthy individuals.

The sample included 38 stable SSD patients, 80 unaffected first-degree relatives, and 81 controls. ToM was assessed using the Hinting Task (HT) and schizotypy via the Schizotypal Personality Questionnaire-Brief (SPQ-B), which generates interpersonal (SPQ-IP), cognitive-perceptual (SPQ-CP), and disorganization (SPQ-D) scores. The polymorphism rs53576 of OXTR was genotyped.

Patients presented poorer HT performance than relatives and controls (p = 0.003 and p < 0.001). High SPQ-IP and SPQ-CP scores correlated with poorer ToM performance in relatives (p = 0.010 and p = 0.030), but not in controls. OXTR was not associated with HT scores, but it showed a modifying effect within controls; high SPQ-CP was related to HT poorer performance conditional to GG genotype (p = 0.007).

ToM deficits were present in patients but not in unaffected relatives or controls. However, our data indicate the usefulness of clinical and genetic liability markers to characterize differences in ToM abilities within healthy individuals. Then, the observed link between ToM and SZ liability suggests the putative role of ToM as an endophenotypic marker. Nevertheless, new analyses in larger samples are needed.

Distinguishing prodromes of bipolar disorder (BD) specific to children/adolescents, adults, and elderly patients is essential. The primary objective of this systematic review was to determine initial and relapse prodromes identifying adult patients with BD.

PubMed, PsycINFO, and Web of Science databases were searched using a predetermined strategy. A controlled process of study selection and data extraction was performed.

The 22 articles selected included 1,809 adult patients with BD. Initial prodromes cited most frequently in these studies showed low specificity. Among relapse prodromes cited most frequently, more talkative than usual, increased energy/more goal-directed behavior, thoughts start to race, increased self-esteem, strong interest in sex, increase in activity, and spending too much were identified exclusively before a manic/hypomanic episode, while loss of interest and hypersomnia were detected only before a depressive episode. Initial prodromal phases lasted longer than prodromal relapse phases. In the selected studies, the most used prodrome identification procedure was the clinical interview.

For adult patients with BD, initial and relapse prodromes of manic, hypomanic, and depressive episodes were identified. It is proposed that the most frequent prodromes found in this review be incorporated into a smartphone app that monitors the functioning of people at risk of BD and patients who have already been diagnosed. Data from this app would constitute a relevant source of big data.

Operational definitions of mania are based on expert consensus rather than empirical data. The aim of this study is to identify the key domains of mania, as well as the relevance of the different signs and symptoms of this clinical construct.

A review of latent factor models studies in manic patients was performed. Before extraction, a harmonization of signs and symptoms of mania and depression was performed in order to reduce the variability between individual studies.

We identified 12 studies fulfilling the inclusion criteria and comprising 3039 subjects. Hyperactivity was the clinical item that most likely appeared in the first factor, usually covariating with other core features of mania, such as increased speech, thought disorder, and elevated mood. Depressive–anxious features and irritability–aggressive behavior constituted two other salient dimensions of mania. Altered sleep was frequently an isolated factor, while psychosis appeared related to grandiosity, lack of insight and poor judgment.

Our results confirm the multidimensional nature of mania. Hyperactivity, increased speech, and thought disorder appear as core features of the clinical construct. The mood experience could be heterogeneous, depending on the co-occurrence of euphoric (elevated mood) and dysphoric (irritability and depressive mood) emotions of varying intensity. Results are also discussed regarding their relationship with other constitutive elements of bipolar disorder, such as mixed and depressive states.

There is limited research on the interaction of both positive and negative daily-life environments with stress-related genetic variants on psychotic experiences (PEs) and negative affect (NA) across the extended psychosis phenotype. This study examined whether the FK506 binding protein 51 (FKBP5) variability moderates the association of positive and negative experiences in the moment with PEs and NA in participants with incipient psychosis and their nonclinical counterparts.

A total of 233 nonclinical and 86 incipient psychosis participants were prompted for a 1-week period to assess their day-to-day experiences. Participants were genotyped for four FKBP5 single nucleotide polymorphisms (rs3800373, rs9296158, rs1360780, and rs9470080).

Multilevel analyses indicated that, unlike the risk haplotype, the protective FKBP5 haplotype moderated all the associations of positive experiences with diminished PEs and NA in incipient psychosis compared with nonclinical group.

Participants with incipient psychosis showed symptomatic improvement when reporting positive appraisals in the interpersonal domain, which suggests that these act as a powerful coping mechanism. The fact that this occurred in daily-life underscores the clinical significance of this finding and pinpoints the importance of identifying protective mechanisms. In addition, results seem to concur with the vantage sensitivity model of gene–environment interaction, which poses that certain genetic variants may enhance the likelihood of benefiting from positive exposures.

Studying offspring of schizophrenia (SZo) and bipolar disorder patients (BDo) provides important information on the putative neurodevelopmental trajectories underlying development toward severe mental illnesses. We compared intracranial volume (ICV), as a marker for neurodevelopment, and global and local brain measures between SZo or BDo and control offspring (Co) in relation to IQ and psychopathology.

T1-weighted magnetic resonance imaging (MRI) brain scans were obtained from 146 participants (8–19 years; 40 SZo, 66 BDo, 40 Co). Linear mixed models were applied to compare ICV, global, and local brain measures between groups. To investigate the effect of ICV, IQ (four subtests Wechsler Intelligence Scale for Children/Wechsler Adult Intelligence Scale-III) or presence of psychopathology these variables were each added to the model.

SZo and BDo had significantly lower IQ and more often met criteria for a lifetime psychiatric disorder than Co. ICV was significantly smaller in SZo than in BDo (d = −0.56) and Co (d = −0.59), which was largely independent of IQ (respectively, d = −0.54 and d = −0.35). After ICV correction, the cortex was significantly thinner in SZo than in BDo (d = −0.42) and Co (d = −0.75) and lateral ventricles were larger in BDo than in Co (d = 0.55). Correction for IQ or lifetime psychiatric diagnosis did not change these findings.

Despite sharing a lower IQ and a higher prevalence of psychiatric disorders, brain abnormalities in BDo appear less pronounced (but are not absent) than in SZo. Lower ICV in SZo implies that familial risk for schizophrenia has a stronger association with stunted early brain development than familial risk for bipolar disorder.

The implications of cannabis use in the onset of early psychosis and the severity of psychotic symptoms have resulted in a proliferation of studies on this issue. However, few have examined the effects of cannabis use on the cognitive symptoms of psychosis (i.e., neurocognitive functioning) in patients with first-episode psychosis (FEP). This systematic review and meta-analysis aim to assess the neurocognitive functioning of cannabis users (CU) and nonusers (NU) with FEP.

Of the 110 studies identified through the systematic review of 6 databases, 7 met the inclusion criteria, resulting in 14 independent samples and 78 effect sizes. The total sample included 304 CU with FEP and 369 NU with FEP. The moderator variables were age at first use, duration of use, percentage of males, and age.

Effect sizes were not significantly different from zero in any neurocognitive domain when users and NU were compared. Part of the variability in effect sizes was explained by the inclusion of the following moderator variables: (1) frequency of cannabis use (β = 0.013, F = 7.56, p = 0.017); (2) first-generation antipsychotics (β = 0.019, F = 34.46, p ≤ 0.001); and (3) country where the study was carried out (β = 0.266, t = 2.06, p = 0.043).

This meta-analysis indicates that cannabis use is not generally associated with neurocognitive functioning in patients with FEP. However, it highlights the deleterious effect of low doses of cannabis in some patients. It also stresses the importance of the type of antipsychotic prescription and cannabis dose as moderator variables in the neurocognitive functioning of CU with FEP.