On the interplay between state-dependent reconfigurations of global signal correlation and BOLD fluctuations: An fMRI study.

BACKGROUND: The dynamics of global, state-dependent reconfigurations in brain connectivity are yet unclear. We aimed at assessing reconfigurations of the global signal correlation coefficient (GSCORR), a measure of the connectivity between each voxel timeseries and the global signal, from resting-state to a stop-signal task. The secondary aim was to assess the relationship between GSCORR and blood-oxygen-level-dependent (BOLD) activations or deactivation across three different trial-conditions (GO, STOP-correct, and STOP-incorrect). METHODS: As primary analysis we computed whole-brain, voxel-wise GSCORR during resting-state (GSCORR-rest) and stop-signal task (GSCORR-task) in 107 healthy subjects aged 21-50, deriving GSCORR-shift as GSCORR-task minus GSCORR-rest. GSCORR-tr and trGSCORR-shift were also computed on the task residual time series to quantify the impact of the task-related activity during the trials. To test the secondary aim, brain regions were firstly divided in one cluster showing significant task-related activation and one showing significant deactivation across the three trial conditions. Then, correlations between GSCORR-rest/task/shift and activation/deactivation in the two clusters were computed. As sensitivity analysis, GSCORR-shift was computed on the same sample after performing a global signal regression and GSCORR-rest/task/shift were correlated with the task performance. RESULTS: Sensory and temporo-parietal regions exhibited a negative GSCORR-shift. Conversely, associative regions (ie. left lingual gyrus, bilateral dorsal posterior cingulate gyrus, cerebellum areas, thalamus, posterolateral parietal cortex) displayed a positive GSCORR-shift (FDR-corrected p < 0.05). GSCORR-shift showed similar patterns to trGSCORR-shift (magnitude increased) and after global signal regression (magnitude decreased). Concerning BOLD changes, Brodmann area 6 and inferior parietal lobule showed activation, while posterior parietal lobule, cuneus, precuneus, middle frontal gyrus showed deactivation (FDR-corrected p < 0.05). No correlations were found between GSCORR-rest/task/shift and beta-coefficients in the activation cluster, although negative correlations were observed between GSCORR-task and GO/STOP-correct deactivation (Pearson rho=-0.299/-0.273; Bonferroni-p < 0.05). Weak associations between GSCORR and task performance were observed (uncorrected p < 0.05). CONCLUSION: GSCORR state-dependent reconfiguration indicates a reallocation of functional resources to associative areas during stop-signal task. GSCORR, activation and deactivation may represent distinct proxies of brain states with specific neurofunctional relevance.

Poor sleep quality may contribute to dysfunctional illness perception, physical and emotional distress in hospitalised patients: results of a national survey of the Italian Society of Consultation-Liaison Psychiatry.

Distress associated with physical illness is a well-known risk factor for adverse illness course in general hospitals. Understanding the factors contributing to it should be a priority and among them dysfunctional illness perception and poor sleep quality may contribute to it. As poor sleep quality is recognised as a major risk factor for health problems, we aimed to study its association with illness perception and levels of distress during hospitalisation. This cross-sectional study included a consecutive series of 409 individuals who were hospitalised in medical and surgical units of different hospitals located throughout the Italian national territory and required an assessment for psychopathological conditions. Sleep quality was assessed with the Pittsburgh (Sleep Quality Index), emotional and physical distress with the Edmonton Symptom Assessment System (ESAS), and illness perception with the Brief Illness Perception Questionnaire (BIPQ). Differences between groups, correlations and mediations analyses were computed. Patients with poor sleep quality were more frequently females, with psychiatric comorbidity, with higher scores in the ESAS and BIPQ. Poor sleep quality was related to dysfunctional illness perception, and to both emotional and physical distress. In particular, by affecting cognitive components of illness perception, poor sleep quality may, directly and indirectly, predict high levels of distress during hospitalisation. Poor sleep quality may affect >70% of hospitalised patients and may favour dysfunctional illness perception and emotional/physical distress.Assessing and treating sleep problems in hospitalised patients should be included in the routine of hospitalised patients.

Self-reported interoception and exteroception are atypical and excessively coupled in psychosis compared to healthy controls.

Although psychotic disorders are characterized by an impaired ability to discriminate internal and external worlds, the role of interoceptive and exteroceptive perceptions in determining this alteration is still unclear. This observational study aimed at investigating (a) increases/decreases in interoceptive and exteroceptive perceptions in patients with psychosis (PSY) compared to healthy controls (HC); (b) the association between interoception and exteroception in HC and PSY. Two hundred and ten HC and 72 PSY completed the Multidimensional Assessment of Interoceptive awareness (MAIA, 8 domains) and the Adolescent-Adult Sensory Profile (AASP, 4 domains). MAIA/AASP differences were evaluated with MANOVA, Kruskal-Wallis and Mann-Whitney tests. MAIA and AASP scores were correlated to quantify the interoceptive-exteroceptive coupling as Spearman's rho coefficients. Subgroup analyses were performed dividing PSY in schizophrenia/schizoaffective versus other psychosis. Compared to HC, PSY showed increased mean scores in four MAIA and two AASP domains (Bonferroni-p < 0.01). The interoceptive-exteroceptive coupling followed two correlation patterns in HC. A first pattern displayed negative correlations between MAIA not-worrying and AASP sensory sensitivity/sensation avoidance, while the second pattern highlighted positive correlations between MAIA scores and AASP sensation seeking. The two correlation patterns between HC and other-PSY subgroup were similar. However, schizophrenia/schizoaffective PSY did not show positive correlations in the second pattern, rather displaying negative correlations between MAIA scores and AASP domains related to passive behavioral responses. Correlation values were more extreme in PSY subgroups, indicating stronger interoceptive-exteroceptive coupling compared to HC. This study demonstrates that interoception and exteroception are atypical and excessively coupled in psychosis compared to the general population.Clinical Trials Registration: Protocol Number 20210003663 (Pavia, Ethical Committee IRCCS Policlinico San Matteo).

Gender differences in clinical and biochemical parameters among patients hospitalized for schizophrenia: towards precision medicine.

BACKGROUND: The scientific literature shows some gender differences in the clinical course of schizophrenia. The aim of this study is to identify gender differences in clinical and biochemical parameters in subjects affected by schizophrenia. This would allow for the implementation of individualized treatment strategies. METHODS: We examined a large set of clinical and biochemical parameters. Data were obtained from clinical charts and blood analyses from a sample of 555 schizophrenia patients consecutively admitted for exacerbation of symptoms to the inpatient clinic of Fondazione IRCCS Policlinico (Milan) or ASST Monza in Italy from 2008 to 2021. Univariate analyses, binary logistic regression, and a final logistic regression model were performed with gender as dependent variable. RESULTS: The final logistic regression models showed that male patients (compared to females) were more prone to lifetime substance use disorders (p = 0.010). However, they also had higher GAF (global functioning) mean scores (p < 0.001) at the time of hospitalization. Univariate analyses showed that male patients (with respect to females) had an earlier age at onset (p < 0.001), a more frequent family history of multiple psychiatric disorders (p = 0.045), were more often smokers (p < 0.001), had a more frequent comorbidity with at least one psychiatric disorder (p = 0.001), and less often suffered from hypothyroidism (p = 0.011). In addition, men had higher levels of albumin (p < 0.001) and bilirubin (t = 2.139, p = 0.033), but lower levels of total cholesterol (t = 3.755, p < 0.001). CONCLUSIONS: Our analyses indicate a less severe clinical profile in female patients. This is evident especially in the early years of the disorder, as suggested by less comorbidity with psychiatric disorders or later age at onset; this is consistent with the related literature. In contrast, female patients seem to be more vulnerable to metabolic alterations as demonstrated by more frequent hypercholesterolemia and thyroid dysfunction. Further studies are needed to confirm these results in the framework of precision medicine.

Progressive Voxel-Wise Homotopic Connectivity from childhood to adulthood: Age-related functional asymmetry in resting-state functional magnetic resonance imaging.

Homotopic connectivity during resting state has been proposed as a risk marker for neurologic and psychiatric conditions, but a precise characterization of its trajectory through development is currently lacking. Voxel-Mirrored Homotopic Connectivity (VMHC) was evaluated in a sample of 85 neurotypical individuals aged 7-18 years. VMHC associations with age, handedness, sex, and motion were explored at the voxel-wise level. VMHC correlates were also explored within 14 functional networks. Primary and secondary outcomes were repeated in a sample of 107 adults aged 21-50 years. In adults, VMHC was negatively correlated with age only in the posterior insula (false discovery rate p < .05, >30-voxel clusters), while a distributed effect among the medial axis was observed in minors. Four out of 14 considered networks showed significant negative correlations between VMHC and age in minors (basal ganglia r = -.280, p = .010; anterior salience r = -.245, p = .024; language r = -.222, p = .041; primary visual r = -.257, p = .017), but not adults. In minors, a positive effect of motion on VMHC was observed only in the putamen. Sex did not significantly influence age effects on VMHC. The current study showed a specific decrease in VMHC for minors as a function of age, but not adults, supporting the notion that interhemispheric interactions can shape late neurodevelopment.

Childhood adversity, symptoms, and cortisol in first episode psychosis: a cross-sectional, secondary, observational analysis of a subsample of FEP patients.

BACKGROUND: Although it has been proposed that childhood adversities (CAs) may affect the hypothalamic-pituitary-adrenal (HPA) axis activity and psychotic symptoms severity, these associations have not been fully confirmed in first-episode psychosis (FEP). This study explored the association between CA, cortisol and psychotic symptoms in FEP patients. METHODS: 81 FEP patients were enrolled. CAs were evaluated by the Childhood Experience of Care and Abuse Questionnaire and a semi-structured interview. Psychotic symptoms were evaluated by the Positive and Negative Syndrome Scale. Cortisol level was collected using saliva samples. ANCOVA and partial correlation analyses were run. RESULTS: FEP patients with childhood abuse reported severe positive symptoms than those without CA. FEP patients with at least one CA had higher levels of cortisol awaking, cortisol at 12 a.m., and cortisol at 8 p.m. Morning cortisol levels were negatively correlated with the severity of negative symptoms and positively correlated with the severity of general psychopathology. Evening cortisol levels were positively correlated with severity of general psychopathology. CONCLUSION: FEP patients with CAs, compared with those without CA, might report more severe positive symptoms and higher cortisol, even though these findings as prone to bias due to the small sample size, and should be seen in the larger perspective of conflicting evidence in the field.

Not a matter of quantity: quality of relationships and personal interests predict university students' resilience to anxiety during CoViD-19.

During the CoViD-19 pandemic, University students may have suffered from increased anxiety due to interferences in their relationships and in academic requirements, as didactic activities have moved to distance learning systems. However, being surrounded by supportive relationships and being motivated to cultivate personal interests might have decreased anxiety. In this pilot study, we collected the responses of 174 students from Italian University merit colleges to an online questionnaire, investigating their perceived anxiety, the quality of surrounding relationships, whether they were cultivating any personal interests and whether they had spent the period of lockdown in college or at home. Regression analyses indicated that both quality of relationships and personal interests predicted low levels of anxiety (p < 0.001). However, simple slope analyses showed that personal interests were negatively related to anxiety only at medium and high quality of relationships (p < 0.001), while no association was found at low quality of relationships. No differences were found between students who stayed in college or at home. These results suggest that Universities should promote accessibility to relationships and cultivation of personal interests to protect students' mental health during mass emergencies such as the current pandemic, in the perspective of improving community resilience.

Missed diagnoses and misdiagnoses of adults with autism spectrum disorder.

Autism spectrum disorder (ASD) is a group of life-long neurodevelopmental disorders affecting 1.5% of the general population. The present study aimed to evaluate the psychiatric history of a group of adults who received the first diagnosis of ASD in two Italian university centers. Diagnoses of ASD were confirmed by a team of psychiatrists with wide expertise in the field, after the administration of standardized tools (i.e., ADOS-2, ADI-R). The sample comprised 161 participants, of which 114 (79.5%) were males. The median age of diagnosis was 23 years (range 18-55), with a median IQ of 100 (range 30-145). The first evaluation by a mental health professional was performed at a median age of 13 years, with a gap of 11 years between the first evaluation and the diagnosis of ASD. 33.5% of participants had never received a psychiatric diagnosis, while the rest of the sample had received one or more diagnoses different from ASD. The most common past diagnoses were intellectual disability, psychoses, personality disorders, and depression. Sex differences were detected in the age of diagnosis and ADOS-2 scores. Our results provide important information for both child and adult psychiatrists. Given the prevalence of autism and the high rates of co-occurrent psychiatric conditions, it is important for clinicians to consider ASD in the differential diagnostic process.

COVID-19 lockdown impact on familial relationships and mental health in a large representative sample of Italian adults.

PURPOSE: Benefits of national-level stay-at-home order imposed in Italy to prevent SARS-CoV-2 transmission need to be carefully weighed against its impact on citizens' health. In a country with a strong familial culture and where welfare relies on households, confinement drastically decreased support provided by elder relatives, which may have resulted in mental health worsening. METHODS: A web-based cross-sectional study (LOST in Italy) was conducted on a representative sample of Italian adults during lockdown (27th of April-3rd of May 2020). We asked 3156 subjects to report on reduced help in housework and childcare from retired parents to assess the impact of confinement on mental health, through validated scales before and during lockdown. RESULTS: Overall, 1484 (47.0%) subjects reported reduced housework help from parents, and 769 (64.0%, of the 1202 subjects with children) diminished babysitting support. Subjects reporting reduced housework help had worsened sleep quality (multivariate odds ratio, OR = 1.74, 95% confidence interval, CI 1.49-2.03) and quantity (OR = 1.50, 95% CI 1.28-1.76), depressive (OR = 1.32, 95% CI 1.14-1.53) and anxiety symptoms (OR = 1.53, 95% CI 1.32-1.78), compared to those reporting unreduced help. Worsening in sleep quality (OR = 2.32, 95% CI 1.76-3.05), and quantity (OR = 1.80, 95% CI 1.36-2.37), depressive (OR = 1.79, 95% CI 1.39-2.31) and anxiety symptoms (OR = 1.90, 95% CI 1.48-2.46) was also associated with reduced babysitting help. Mental health outcomes were worse in subjects with poorer housing and teleworking during lockdown. CONCLUSION: Confinement came along with reduced familial support from parents, negatively impacting household members' mental health. Our findings might inform evidence-based family and welfare policies to promote population health within and beyond pandemic times.

Understanding source monitoring subtypes and their relation to psychosis: a systematic review and meta-analysis.

AIMS: Source monitoring (SM) is the metacognitive ability to determine the origin of one's experiences. SM is altered in primary psychiatric psychosis, although relationships between SM subtypes, other cognitive domains and symptoms are unclear. Our aims were to synthesize evidence comparing psychosis -with and without hallucinations- and healthy controls classifying SM subtypes by source discrimination (internal/external/reality monitoring) and stimulus modality (visual/auditory/imagined/performed). METHODS: This systematic review adopted Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Meta-analyses Of Observational Studies in Epidemiology and Population, Intervention, Comparison and Outcomes guidelines. Core demographical and clinical parameters were extracted. Newcastle-Ottawa Scale was used as quality check. SM differences between (i) psychosis patients versus healthy controls and (ii) patients with versus without hallucinations were investigated via random-effect model meta-analysis. The primary effect size measure was standardized mean difference (SMD) in each SM subtype performance (error or accuracy). Heterogeneity, publication biases and meta-regressions were assessed. RESULTS: Five thousand two hundred and fifty-six records were screened to finally include 44 studies (1566 patients, 1175 controls). Mean Newcastle-Ottawa score was 7.41 out of 9. Few studies measured SM associations with cognition (n = 9) and symptoms (n = 19), with heterogeneous findings. SM performance across all measures was reduced in psychosis versus healthy controls (SMD = 0.458). Internal SM (SMD: errors = 0.513; accuracy = 0.733) and imagined stimuli (SMD: errors = 0.688; accuracy = 0.978) were specifically impaired. Patients with versus without hallucinations showed SM deficits only for externalizing (SMD = 0.410) and imagined/auditory (SMD = 0.498/0.277) errors. CONCLUSION: The proposed classifications highlight specific SM deficits for internal/imagined stimuli in psychosis, providing evidence-based indications to design and interpret future studies.

Impaired Quality of Life in Patients with Autoimmune Atrophic Gastritis.

BACKGROUND: Autoimmune atrophic gastritis (AAG) leads to vitamin B12 deficiency that may manifest with neuropsychiatric disorders, such as emotional instability, cognitive deficits, depression, and personality changes. AIMS: To evaluate the quality of life (QoL) in patients with AAG and the interplay between QoL, psychopathological symptoms, and demographic factors. METHODS: This is an observational, cross-sectional study including 102 patients with AAG (mean age 62 ± 13 years), 100 with functional gastrointestinal disorders (mean age 38.3 ± 17 years), 100 with other chronic organic gastrointestinal diseases (mean age 50.9 ± 21.4 years), and 100 healthy controls (mean age 37.5 ± 18.9 years). The 36-Item Short Form Health Survey questionnaire (SF-36) and the General Health Questionnaire-12 were administered. The results of the scales were compared among the study groups. Linear regression analyses were fitted to identify independent predictors of QoL in AAG patients. RESULTS: QoL was significantly different among the four groups in all subdomains. In particular, the AAG group was significantly (P < 0.01) more impaired than the functional gastrointestinal disorder group in the physical functioning and it was significantly more impaired than the control group in all the quality of life subdomains with exception of vitality. Vitamin B12 serum level was a significant (P < 0.04) independent predictor of physical functioning. CONCLUSIONS: Patients with AAG have a decreased QoL compared to healthy controls, but in line with that of patients with organic gastrointestinal disorders. Physical component is responsible for worsening QoL. Vitamin B12 supplementation may positively affect patient's perception of body functioning.

Beneath the surface: hyper-connectivity between caudate and salience regions in ADHD fMRI at rest.

Attention-Deficit/Hyperactivity Disorder (ADHD) comprises disturbances in attention, emotional regulation, and reward-related processes. In spite of the active efforts in researching neurofunctional correlates of these symptoms, how the activity of subcortical regions-such as basal ganglia-is related to ADHD has yet to be clarified. More specifically, how age may influence the critical changes observed in functional dynamics from childhood to adulthood remains relatively unexplored. We hence selected five core subcortical regions (amygdala, caudate, putamen, pallidum and hippocampus) as regions of interest from the previous literature, measuring their whole-brain voxel-wise rsFC in a sample of 95 ADHD and 90 neurotypical children and adolescents aged from 7 to 18. The only subcortical structure showing significant differences in rsFC was the caudate nucleus. Specifically, we measured increased rsFC with anterior cingulate and right insula, two mesolimbic regions pertaining to the Salience Network. The degree of hyper-rsFC positively correlated with ADHD symptomatology, and showed different patterns of evolution in ADHD vs neurotypical subjects. Finally, the rsFC scores allowed a fair discrimination of the ADHD group (Area Under the Curve ≥ 0.7). These findings shed further light on the fundamental role covered by subcortical structures in ADHD pathogenesis and neurodevelopment, providing new evidence to fill the gap between neurofunctional and clinical expressions of ADHD.

The Hippocratic Risk: Epidemiology of Suicide in a Sample of Medical Undergraduates.

In spite of the growing awareness on medical students' mental health in recent years, epidemiologic literature about the topic is scarce, particularly for what concerns suicide. Here, we collected cases of suicides among medical students enrolled at a local University in Italy and compared it to the general population of the same age group. Our sample was collected using records of suicides in the city of Pavia, Italy between the years of 2014 and 2019. This record was cross-referenced with enrolment numbers to the Medical Faculty of the city in order to select cases that involved medical students A time-window of 6 years was chosen for the evaluation. The odds ratio of suicide in medical students in comparison to the general population was of 14.58 (p value at the exact Poisson test <0.001). We then differentiated between native Italians and students from abroad. In this case, an odds ratio of 6.81 was observed (p value at the exact Poisson test 0.011). Our estimated suicide rates exceeded what was previously reported for the general population. We call for a closer attention on mental health in medical students, and an increased effort in collecting objective data on the topic.

Defining the Optimal Threshold Scores for Adult Autism Subthreshold Spectrum (AdAS Spectrum) in Clinical and General Population.

BACKGROUND: The Adult Autism Subthreshold Spectrum (AdAS Spectrum) is a recently developed instrument tailored to assess the broad range of full-threshold as well as sub-threshold manifestations related to the autism spectrum. Although it has proved to be a valuable instrument for quantitative assessment of autistic symptoms, the AdAS Spectrum still lacks validated diagnostic thresholds. OBJECTIVE: The aim of this study was to define the best cut-off scores of the AdAS Spectrum for determining the presence of subthreshold autistic traits as well as a clinically significant autism spectrum disorder (ASD). METHODS: Our sample was composed of 39 patients with full-blown ASD, 73 subjects with autistic traits, and 150 healthy controls. Subjects were evaluated by trained psychiatrists, who performed a clinical diagnosis according to DSM-5 and then assessed with the AdAS Spectrum and the Autism Spectrum Quotient. RESULTS: Our results showed that the most discriminant cut-off scores were 70 for identifying subjects with full-blown ASD, and 43 for determining the presence of significant autistic traits. CONCLUSION: The threshold values proposed here showed satisfying levels of specificity and sensibility, as well as a good agreement with the diagnosis according to DSM-5 criteria, confirming the validity of the AdAS Spectrum as a psychometric tool for measuring ASD-related conditions in the clinical and general population.

The institution of a Multi-disciplinary Italian Breast Unit: Reflections of the first psychosocial research study results on distress and quality of life.

Breast cancer affects patients both emotionally and physically. It is time to consider distress as the sixth vital sign in breast cancer patients in Europe. Between 2012 and 2015, our EUSOMA-certified multi-disciplinary group conducted a study on emotional distress and quality-of-life in breast cancer patients at diagnosis, and observed their trend over the first 8 months of treatment. One hundred and forty-nine patients concluded the program. The psycho-oncologist and the breast nurses gave out SF36, Hospital Anxiety and Depression Scale and Distress Thermometer. Our Italian data go along with the reported literature on distress and quality-of-life. Despite modern advances, experiencing breast cancer impacts on overall quality-of-life.

Clinical effectiveness of parenteral trazodone for the management of psychomotor activation in patients with bipolar disorder.

OBJECTIVES: Trazodone is a multifunctional triazolopyridine drug with antidepressant, anxiolytic, sedative, and hypnotic properties. The current retrospective study was designed to investigate the effectiveness of trazodone for reducing acute psychomotor activation (PA) in patients with bipolar disorder (BD). We specifically reasoned that a parenteral route of administration could offer potential advantages in this clinical setting. METHODS: We assessed the effectiveness and safety of parenteral trazodone in a retrospective study conducted in 64 inpatients with BD and acute PA. The effectiveness assessment was the Clinical Global Impression Scale - Severity Of Illness (CGI-S) rated before the administration of parenteral trazodone (baseline) and at the end of treatment. A post-treatment reduction in CGI-S score ≥ 20% compared with baseline was considered as the primary outcome measure. RESULTS: Administration of parenteral trazodone was associated with significant improvements in CGI-S scores from baseline (5.4 ± 0.9) to the end of the study (4.2 ± 1.0; p < 0.001, Wilcoxon matched-pairs signed-ranks test). A total of 34 patients (53.1%) showed a post-treatment reduction in CGI-S score ≥ 20% compared to baseline. Multivariable binary logistic regression analysis using a forward selection procedure identified treatment duration (in days) as the only independent predictor of post-treatment reduction in CGI-S score ≥ 20% (odds ratio: 1.28; 95% confidence interval: 1.02-1.60, p <0.05). Adverse effects occurred in 13 (20.3%) patients. CONCLUSIONS: Parenteral trazodone is well-tolerated and effective in 53.1% of patients with BP and acute PA. Treatment duration was identified as an independent predictor of response in our sample.

Treating Depression: What Patients Want; Findings From a Randomized Controlled Trial in Primary Care.

OBJECTIVE: To highlight clinical and sociodemographic factors associated with patients' preference in the treatment of depression, we conducted a randomized controlled trial comparing the efficacy of selective serotonin reuptake inhibitors and interpersonal counseling in patients with a major depressive episode. METHODS: Patients, recruited from a psychiatric consultation service in the primary care setting, were asked to express their preference for the type of treatment before randomization to one of the 2 intervention arms. Severity of depressive symptoms and functional impairment was assessed using the 21-item Hamilton Rating Scale for Depression and the Work and Social Adjustment Scale, respectively. RESULTS: A total of 170 patients were evaluated, 87 (51.2%) patients expressed their preference for interpersonal counseling and 83 (48.8%) for selective serotonin reuptake inhibitors. Depression severity and treatment preference showed significant correlations. Preference for interpersonal counseling was related to mild depression and greater functional impairment, whereas patients with moderate or severe depression were more likely to prefer medication. Remission rates and functional level were not related to treatment preference at the end of the study. CONCLUSION: Treatment preference is a critical factor, influenced by clinical and sociodemographic characteristics, and further studies are needed to improve its clinical relevance.

Disorder, not just state of risk: meta-analysis of functioning and quality of life in people at high risk of psychosis.

BACKGROUND: The nosology of the psychosis high-risk state is controversial. Traditionally conceived as an 'at risk' state for the development of psychotic disorders, it is also conceptualised as a clinical syndrome associated with functional impairment. AIMS: To investigate meta-analytically the functional status of patients at high clinical risk for psychosis and its association with longitudinal outcomes. METHOD: Three meta-analyses compared level of functioning (n = 3012) and quality of life (QoL) (n = 945) between a high-risk group, a healthy control group and group with psychosis, and baseline functioning in people in the high-risk group who did or did not have a transition to psychosis at follow-up (n = 654). RESULTS: People at high risk had a large impairment in functioning (P<0.001) and worse QoL (P = 0.001) than the healthy control group, but only small to moderately better functioning (P = 0.012) and similar QoL (P = 0.958) compared with the psychosis group. Among the high-risk group, those who did not develop psychosis reported better functioning (P = 0.001) than those who did. CONCLUSIONS: Our results indicate that the high-risk state is characterised by consistent and large impairments of functioning and reduction in QoL similar to those in other coded psychiatric disorders.