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.

Parental separation is a very common childhood adversity. The association between other adverse childhood experiences and an increased risk of psychosis has been reported. However, the evidence on the risk of psychosis for children of separated parents is limited. In this systematic review, cohort, case–control, and cross-sectional studies, comparing the risk of psychotic disorders for people with and without separated parents, were searched, critically appraised, and summarized.

Studies were searched in PubMed, EMBASE, PsycINFO, and the Web of Science, from database inception to September 2019. A meta-analysis, using random-effects models, was undertaken to obtain pooled estimates of the risk of psychosis among participants with separated parents.

Twelve studies, with 305,652 participants from 22 countries, were included in the review. A significantly increased risk of psychosis for those with separated parents was observed, with a pooled odds ratio: 1.53 (95% confidence interval [CI]: 1.29–1.76), p < 0.001. The association remained significant when cohort, case–control, and cross-sectional studies were analyzed separately. The five cohort studies included in this review showed and increased risk of psychosis with odds ratio: 1.47 (95% CI: 1.26–1.69), p < 0.001.

Parental separation is a common childhood adversity associated with an increased risk of psychosis. Although the risk for an individual child of separated parents is still low, given the high proportion of couple that separate, the increased rates of psychosis may be substantial in the population. Further studies on the risk of psychosis in those with separated parents, and the explanatory factors for this association, are required.

Research has consistently shown that language abilities represent a core dimension of psychosis; however, to date, very little is known about syntactic comprehension performance in the early stages of psychosis. This study aims to compare the linguistic abilities involved in syntactic comprehension in a large group of First Episode Psychosis (FEP) patients and healthy controls (HCs).

A multiple choice test of comprehension of syntax was administered to 218 FEP patients (166 non-affective FEP patients [FEP-NA] and 52 affective FEP patients [FEP-A]) and 106 HCs. All participants were asked to match a sentence they listen with one out of four vignettes on a pc screen. Only one vignette represents the stimulus target, while the others are grammatical or non-grammatical (visual) distractors. Both grammatical and non-grammatical errors and performance in different syntactic constructions were considered.

FEP committed greater number of errors in the majority of TCGB language domains compared to HCs. Moreover, FEP-NA patients committed significantly more non-grammatical (z = −3.2, p = 0.007), locative (z = −4.7, p < 0.001), passive-negative (z = −3.2, p = 0.02), and relative (z = −4.6, p < 0.001) errors compared to HCs as well as more passive-affirmative errors compared to both HCs (z = −4.3, p < 0.001) and FEP-A (z = 3.1, p = 0.04). Finally, we also found that both FEP-NA and FEP-A committed more grammatical (FEP-NA: z = −9.2, p < 0.001 and FEP-A: z = −4.4, p < 0.001), total (FEP-NA: z = −8.2, p < 0.001 and FEP-A: z = 3.9, p = 0.002), and active-negative (FEP-NA: z = −5.8, p < 0.001 and FEP-A: z = −3.5, p = 0.01) errors compared to HCs.

This study shows that the access to syntactic structures is already impaired in FEP patients, especially in those with FEP-NA, ultimately suggesting that language impairments represent a core and inner feature of psychosis even at early stages.

Somatic diseases have been associated with an increased risk for subsequent schizophrenia; however, it is unknown whether prior somatic diseases negatively affect early treatment outcomes after a first-time schizophrenia diagnosis.

We included all individuals born in Denmark after January 1st, 1977 and first-time diagnosed with schizophrenia between January 1st, 1996 and December 31st, 2015. We identified all life-time somatic hospital contacts and all prescriptions within the year before the first-time schizophrenia diagnosis and followed patients for up to five years regarding risk for schizophrenia (re)-hospitalization (relapse). We performed Cox regression analyses calculating hazard rate ratios (HRR) including 95%-confidence intervals (CI) and adjusted for relevant confounders.

We followed a total of 11,856 patients with a first-time schizophrenia diagnosis (58.7% male, mean age 23.1 (SD = 4.7) years) for 39,033 person-years, whereof 5506 (46.4%) had relapse with schizophrenia re-hospitalization during 5-year of follow-up. Somatic hospital contacts ever before (95.4%; HRR = 1.30; 95%-CI = 1.07–1.59), and specifically during the year before schizophrenia diagnosis (42.5%; HRR = 1.36; 95%-CI = 1.11–1.66) were associated with an increased risk of schizophrenia relapse as were a greater number of prior somatic hospital contacts (p < 0.001). Individuals with up to four different prescriptions for somatic medications showed a trend towards a slightly lower risk of relapse.

Somatic diseases and health seeking patterns might have an impact on the course of schizophrenia, where severe somatic comorbidity, specifically during the year before first-time schizophrenia diagnosis, seem to negatively affect early treatment course, whereas previous somatic medication use may indicate a better compliance and help-seeking behavior.

We analyzed the association of cannabinoid receptor CNR1 genotypes with changes in neurocognitive performance in patients with first-episode psychosis (FEP) after 18 months of treatment. Our secondary aim was to analyze the association of CNR1 genotypes with changes of perceived levels of stress.

We enrolled a sample of 159 patients with FEP from two Croatian psychiatric hospitals between 2014 and 2017. Patients were assessed at baseline and after 18 months. We analyzed the associations of changes in neurocognitive test results and the perceived levels of stress with CNR1 polymorphic loci (rs7766029 and rs12720071) in 121 patients.

In the analysis adjusted only for baseline neurocognitive test scores, carriers of rs7766029 CC genotype had significantly (with false discovery rate, FDR < 15%) higher improvement in verbal memory (Wechsler, Wechsler 30′) and attention (Digit span F) compared with other participants. In such analysis, rs12720071 carriers of AG genotype had significantly (FDR < 15%) higher improvement in executive functions (Block design), but lower improvement in language functions than AA carriers. In the fully adjusted analysis for age, sex, cannabis use and negative symptoms, only the association of rs7766029 genotypes with the change in the Weschler 30′ score was significant (FDR < 15%). In the analysis adjusted only for the baseline neurocognitive tests’ scores, both rs7766029 and rs12720071 genotypes were significantly associated with the change in perceived levels of stress (FDR < 15%). In the fully adjusted analysis, only the association with rs7766029 genotype remained significant.

The rs7766029 CNR1 variants may moderate changes in neurocognitive performance as well as in perceived levels of stress of patients with FEP over time.