Gender, age at onset, and duration of being ill as predictors for the long-term course and outcome of schizophrenia: an international multicenter study.

BACKGROUND: The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia. METHODS: Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects. RESULTS: There was a 3-year later age at onset for females (P < .001) and lower rates of negative symptoms (P < .01) and higher depression/anxiety measures (P < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness. DISCUSSION: Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.

Building a neurocognitive profile of suicidal risk in severe mental disorders.

BACKGROUND: Research on the influence of neurocognitive factors on suicide risk, regardless of the diagnosis, is inconsistent. Recently, suicide risk studies propose applying a trans-diagnostic framework in line with the launch of the Research Domain Criteria Cognitive Systems model. In the present study, we highlight the extent of cognitive impairment using a standardized battery in a psychiatric sample stratified for different degrees of suicidal risk. We also differentiate in our sample various neurocognitive profiles associated with different levels of risk. MATERIALS AND METHODS: We divided a sample of 106 subjects into three groups stratified by suicide risk level: Suicide Attempt (SA), Suicidal Ideation (SI), Patient Controls (PC) and Healthy Controls (HC). We conducted a multivariate Analysis of Variance (MANOVA) for each cognitive domain measured through the standardized battery MATRICS Consensus Cognitive Battery (MCCB). RESULTS: We found that the group of patients performed worse than the group of healthy controls on most domains; social cognition was impaired in the suicide risk groups compared both to HC and PC. Patients in the SA group performed worse than those in the SI group. CONCLUSION: Social cognition impairment may play a crucial role in suicidality among individuals diagnosed with serious mental illness as it is involved in both SI and SA; noteworthy, it is more compromised in the SA group fitting as a marker of risk severity.

Modeling psychological function in patients with schizophrenia with the PANSS: an international multi-center study.

BACKGROUND: The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model. METHODS: Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed. RESULTS: The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage. CONCLUSIONS: The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct "cores" of schizophrenia, the "Positive" and the "Negative," while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.

Schizophrenia and Dental Health: A Systematic Review.

ABSTRACT: Schizophrenia is characterized not only by psychopathological symptoms but also by medical comorbidities. Among the latter, there are limited data on dental health. We conducted a systematic review with the primary aim of clarifying the extent of the relationship between dental diseases and schizophrenia. The second aim was to delineate an intervention program based on illness-related factors that influence dental health. The preferred reporting items for systematic reviews and meta-analyses statement for reporting systematic reviews was used. Only articles published in English language peer-reviewed journals were considered; we excluded case reports, meta-analyses, and systematic reviews, as well as studies that did not clearly report statistical analysis, diagnostic criteria, or the number of patients included. Twenty-one studies comprising 13,110 patients with schizophrenia and 9025 healthy controls were included. Negative symptomatology, long duration of illness, smoking habit, drug-induced xerostomia, and neuroinflammation are the most critical areas. We suggest an intervention program for prevention and treatment of dental diseases in schizophrenia.

The COVID-19 Outbreak and Subjects With Mental Disorders Who Presented to an Italian Psychiatric Emergency Department.

ABSTRACT: We performed a retrospective study from January to May 2020 to establish the sociodemographic and clinical characteristics of patients with mental health problems who arrived at an Italian emergency department during the COVID-19 outbreak. We divided the sample into two groups taking as a watershed March 11, when the World Health Organization announced COVID-19 outbreak as a pandemic. Chi-square/t-tests, adjusted p values (Bonferroni method), and regression analysis were performed. Patients who arrived at the emergency department during the lockdown decreased by 56%; showed greater active suicidal ideation, more tension, and more severe psychopathological state; were living alone more frequently; and were taking home treatment mainly based on second-generation antipsychotics. According to our study, it seems that patients with mental disorders have consulted psychiatric services less frequently during the pandemic, but the economic, health, and social distress may be linked with an increase in suicidal risk and the severity of the psychopathological state.

The Complex Relationship Among Formal Thought Disorders, Neurocognition, and Functioning in Nonacutely Ill Schizophrenia Patients.

The aims of the present study were to 1) evaluate clinical differences between patients suffering from schizophrenia (SZ) with mild versus moderate/severe formal thought disorder (FTD); 2) explore relationships between dimensions of FTD, neuropsychological domains, and global functioning; and 3) compare clinical dimensions of FTD in early and late SZ. One hundred thirty-six individuals with schizophrenia were recruited and evaluated during a nonacute phase of illness. FTD was assessed with the Thought, Language, and Communication Scale. Partial correlations, t-tests, and stepwise regression were undertaken to address the study aims. Patients with moderate/severe FTD performed worse than those with mild FTD for processing speed, reasoning and problem solving, and social cognition, and demonstrated poorer global functioning. Early SZ did not differ from late SZ in terms of negative FTD and difficulty in abstract thinking (DAT). Negative FTD was correlated with reasoning and problem solving; DAT was correlated with social cognition. All clinical dimensions of FTD, regardless of neurocognitive impairment, accounted for a significant amount of variance in global functioning. FTD predicted global functioning, regardless of neurocognitive factors. Due to their stability in different phases of the course of the disease and their strong relationship with other core variables, Neg-FTD and DAT should be investigated as an intermediate phenotype of the illness.

Staging of Schizophrenia With the Use of PANSS: An International Multi-Center Study.

INTRODUCTION: A specific clinically relevant staging model for schizophrenia has not yet been developed. The aim of the current study was to evaluate the factor structure of the PANSS and develop such a staging method. METHODS: Twenty-nine centers from 25 countries contributed 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Analysis of covariance, Exploratory Factor Analysis, Discriminant Function Analysis, and inspection of resultant plots were performed. RESULTS: Exploratory Factor Analysis returned 5 factors explaining 59% of the variance (positive, negative, excitement/hostility, depression/anxiety, and neurocognition). The staging model included 4 main stages with substages that were predominantly characterized by a single domain of symptoms (stage 1: positive; stages 2a and 2b: excitement/hostility; stage 3a and 3b: depression/anxiety; stage 4a and 4b: neurocognition). There were no differences between sexes. The Discriminant Function Analysis developed an algorithm that correctly classified >85% of patients. DISCUSSION: This study elaborates a 5-factor solution and a clinical staging method for patients with schizophrenia. It is the largest study to address these issues among patients who are more likely to remain affiliated with mental health services for prolonged periods of time.

Predictive factors of overall functioning improvement in patients with chronic schizophrenia and schizoaffective disorder treated with paliperidone palmitate and aripiprazole monohydrate.

BACKGROUND: Long-acting injectable (LAI) antipsychotics can improve medication adherence and reduce hospitalisation rates compared with oral treatments. Paliperidone palmitate (PAL) and aripiprazole monohydrate (ARI) LAI treatments were associated with improvements in global functioning in patients with schizophrenia. OBJECTIVE: The objective of this study was to assess the predictive factors of better overall functioning in patients with chronic schizophrenia and schizoaffective disorder treated with PAL and ARI. METHOD: Enrolled were 143 (97 males, 46 females, mean age 38.24 years, SD = 12.65) patients with a diagnosis of schizophrenia or schizoaffective disorder, whom we allocated in two groups (PAL and ARI treatments). We assessed global functioning, amount of oral medications, adherence to oral treatment, and number of hospitalisations before LAI introduction and at assessment time point. RESULTS: Longer treatment time with LAIs (p < .001), lower number of oral drugs (p < .001), and hospitalisations (p = .002) before LAI introduction, and shorter duration of illness (p = .038) predicted better Global Assessment of Functioning scores in the whole sample (R2  = 0.337). CONCLUSION: Early administration and longer duration of ARI or PAL treatments could play a significant role in improving global functioning of patients with schizophrenia and schizoaffective disorder. Better improvement in functioning could be achieved with ARI in young individuals with recent illness onset and PAL in patients at risk for recurrent hospitalisations.

The relationships of personal resources with symptom severity and psychosocial functioning in persons with schizophrenia: results from the Italian Network for Research on Psychoses study.

The relationships of personal resources with symptom severity and psychosocial functioning have never been tested systematically in a large sample of people with schizophrenia. We applied structural equation models to a sample of 921 patients with schizophrenia collected in a nationwide Italian study, with the aim to identify, among a large set of personal resources, those that may have an association with symptom severity or psychosocial functioning. Several relevant demographic and clinical variables were considered concurrently. Poor service engagement and poor recovery style, as well as older age and younger age at onset, were related to greater symptom severity and poorer social functioning. Higher resilience and higher education were related to better social functioning only. Poor problem-focused coping and internalized stigma, as well as male gender and depression, were related to symptom severity only. The explored variables showed distinctive and partially independent associations with symptom severity and psychosocial functioning. A deeper understanding of these relationships may inform treatment decisions.

Anomalous self-experiences and their relationship with symptoms, neuro-cognition, and functioning in at-risk adolescents and young adults.

Empirical and theoretical studies support the notion that anomalous self-experience (ASE) may constitute a phenotypic aspect of vulnerability to schizophrenia, but there are no studies examining the relationship of ASE with other clinical risk factors in a sample of ultra-high risk (UHR) subjects. The aim of the present study was to explore the relationship between ASE, prodromal symptoms, neurocognition, and global functioning in a sample of 45 UHR adolescents and young adults (age range 15-25years) at first contact with Public Mental Health Services. Prodromal symptoms and global functioning were assessed through the SIPS interview. ASE was evaluated through the Examination of Anomalous Self-Experience (EASE); for neurocognition, we utilized a battery of tests examining seven cognitive domains as recommended by the Measurement And Treatment Research to Improve Cognition in Schizophrenia. In the UHR group, higher levels in two domains of the EASE (stream of consciousness and self-awareness) were found in comparison with help-seeking subjects. Correlational analysis corrected for possible confounding variables showed a strong association (p>0.001) between higher EASE scores and global functioning. A principal factor analysis with Varimax rotation yielded a two-factor solution, jointly accounting for 70.58% of the total variance in the UHR sample. The first factor was comprised of SOPS domains, while the second was comprised of EASE-total, EASE-10, and GAF variables. Our findings provide support for the notion that disorders of self-experience are present early in schizophrenia and are related to global functioning. As such, they may constitute a potential marker of risk supplementing the UHR approach.

Basic symptoms and psychotic symptoms: their relationships in the at risk mental states, first episode and multi-episode schizophrenia.

In the field of the early psychosis two main approaches attempt to develop rating tools, one investigating the basic symptoms domain, and the other the attenuated psychotic symptoms. To explore the relationship between basic symptoms (BSs) and other symptom domains in different phases of the psychotic illness 32 at ultra-high risk (UHR), 49 first episode schizophrenia (FES), 42 multiple episode schizophrenia (MES), and 28 generalized anxiety disorder (GAD) patients were enrolled. Participants were assessed using the SIPS/SOPS and the FCQ scales. Analyses of covariance taking into account socio-demographic and clinical variables significantly different between groups were applied to compare FCQ and SOPS scores. Finally FCQ and SOPS principal component analysis was carried out in the schizophrenia spectrum group. SOPS scores were higher in the UHR, FES and MES groups compared to the GAD control group. Concordantly, FES and MES groups had a higher number of basic symptoms in comparison with the GAD group, whereas UHR did not differ from the control group. The largest number of correlations between BSs and psychotic symptoms was found in the GAD group. According to the principal component analysis (PCA) five factors were extracted, with the BSs loading on a unique factor. Our findings imply that the boundary between psychotic and non-psychotic conditions cannot be outlined on the basis of the presence/absence of basic and psychotic symptoms.

Symptom correlates of facial emotion recognition impairment in schizophrenia.

BACKGROUND: The ability to facial emotion recognition (FER), a key component of socioemotional competence, is often impaired in schizophrenic disorders. The purpose of the present study was to examine the relationship between emotion recognition performance and symptoms in a group of patients with schizophrenia spectrum disorders. SAMPLING AND METHODS: Seventy-nine patients meeting DSM-IV-TR criteria for schizophrenia, schizophreniform disorder and schizoaffective disorder were assessed by the Positive and Negative Syndrome Scale and a FER task. In schizophrenia patients and healthy control subjects, FER performance was compared. In order to avoid a possible confounding role of cognitive impairment, we carried out partial correlations corrected for an index of global cognition. RESULTS: Patients performed worse than a healthy control group on all negative emotions. Partial correlations showed that cognitive/disorganized symptoms correlated with a worse performance in the FER task, whereas no correlations were found with positive, negative, excitement and depressive symptoms. CONCLUSIONS: Our findings support that in schizophrenia FER impairment is specific for negative emotions and that there is a relationship between this deficit and cognitive/disorganized symptoms, regardless of the general cognitive level.

A case of rapid conversion to psychosis of delusional misidentification associated with derealisation, verbal memory impairment and FDG-PET imaging abnormalities.

The delusional misidentification syndromes, occurring within the context of different nosological settings, such as schizophrenia, are psychopathological phenomena related to the experience of depersonalisation/derealisation. Extensive research indicates that individuals meeting specific "prodromal" criteria, such as attenuated psychotic symptoms, brief intermittent psychotic symptoms, or functional decline and family history of schizophrenia have increased risk for impending psychosis. Despite depersonalisation and/or derealisation often precede psychotic onset, they are not included among the prodromal criteria of the Australian-American approach. A 17-year-old boy with acute agitation, violent behaviour and aggression, and dissociative amnesia had a mild verbal memory impairment and temporo-limbic hypometabolism on the positron-emission tomography. The patient was assessed with both the ultra-high risk (UHR) and the basic symptom approaches and was not found to be prodromal with imminent risk of transition to psychosis. He was hospitalised briefly and 2 weeks after discharge he developed delusional misidentification. This case shows that even the integration of both UHR and basic symptoms criteria may give false negatives in the prediction of psychosis, especially in those cases in which a long prodromal phase is absent.

Relationships between psychopathological variables and insight in psychosis risk syndrome and first-episode and multiepisode schizophrenia.

Insight may vary across psychosis risk syndrome (PRS), first-episode schizophrenia (FES), or multiepisode schizophrenia (MES). We aimed to compare insight domains (awareness, relabeling, and compliance) in PRS, FES, and MES groups and to correlate scores with psychopathological measures. Insight was assessed in 48 (14 PRS, 16 FES, and 18 MES) patients using the Schedule for the Assessment of Insight-Expanded Version. We conducted psychopathological assessment through the Brief Psychiatric Rating Scale (BPRS). In the whole group, the BPRS psychosis factor correlated with all insight domains. In the MES group, the more severe the anxiety/depression, the higher the insight score in the symptom relabeling domain. Insight did not differ significantly between the PRS, FES, and MES groups. Our results suggest that, across different phases of the illness, lack of insight behaves like a trait and is modulated by positive symptom severity. Anxiety and depression may be associated with increased insight in patients with chronic schizophrenia.

Clinical experiences with intranasal esketamine for major depressive disorder resistant to treatment and with a psychiatric emergency: case presentations.

Recently, esketamine became availableas an intranasal formulation, proposed for treatment-resistant depression (TRD). Three cases of TRD are presented, two with features of a psychiatric emergency. The first case is a 35-year-old man with MDD onset at the age of 27 years, with five previous failed therapies. The second patient is a middle-aged man with a 21-year MDD onset and six previous antidepressant treatments discontinued for poor therapeutic effects and tolerability. He also presented suicidal ideation with intent and a history of a failed suicide attempt by self-cutting his forearms. The third case is a 28-year-old female with a first MDD episode in 2020, treated first with amitriptyline and then with intravenous clomipramine. She had a history of a previous suicide attempt by self-cutting and, by her admission, showed active suicidal ideation with intent. In all three cases, a rapid reduction of depressive symptoms was observed with a subsequent complete resolution of suicidal ideation and intent in the two patients with such risk. Intranasal esketamine treatment was carried out with concomitant oral antidepressant therapy. The third patient reported the only recorded side effect: dissociation 20 min after every esketamine administration. Our preliminary experience proved esketamine's effectiveness on TRD symptoms and successful outcomes in psychiatric emergencies such as suicide risk.

Neurocognition, psychopathology, and subjective disturbances in schizophrenia: a comparison between short-term and remitted patients.

Patients with schizophrenia present deficits in multiple domains of cognition. The study of the relationship between cognitive performance and symptoms of schizophrenia has yielded heterogeneous results. The purposes of this study were to examine the extent of the relationship between psychopathologic symptoms, cognitive function, and subjective disturbances in a group of patients affected by schizophrenia spectrum disorders and to compare short-term with remitted patients. Seventy-nine patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for schizophrenia, schizophreniform disorder, and schizoaffective disorder were assessed through the Positive and Negative Syndrome Scale, the Frankfurt Complaint Questionnaire, and a neuropsychologic battery exploring the 7 Measurement and Treatment Research to improve Cognition in Schizophrenia cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition) plus executive control. Neuropsychologic and psychopathologic variables were compared and correlated. Treatment groups did not differ in neuropsychologic and psychopathologic measures. The cognitive factor of the Positive and Negative Syndrome Scale correlated with worse performance on cognitive tasks and with higher scores on the Frankfurt Complaint Questionnaire 24 in the short-term, remitted, and combined groups. Subjective disturbances correlated with impaired executive control, reasoning and problem solving, and social cognition but not during the short-term phase. Both "objective" and subjective psychopathology are intertwined with cognitive function, suggesting some common underlying neural bases. The condition of being in a short-term or a remitted phase of the illness influences this interrelationship, regardless of the type of antipsychotic medication taken.

Differentiation and comorbidity of bipolar disorder and attention deficit and hyperactivity disorder in children, adolescents, and adults: A clinical and nosological perspective.

Bipolar Disorder (BD) and Attention Deficit and Hyperactivity Disorder (ADHD) are mental disorders with high degree of lifetime comorbidity. Both BD and ADHD are disorders with onset in childhood and early adolescence. Both disorders are often undiagnosed, misdiagnosed, and sometimes overdiagnosed, leading to high rates of morbidity and disability. The psychiatric and behavioral symptoms associated with ADHD and BD have significant overlap. Albeit the existence of a large body of literature, it is far from being clear whether comorbidity can be explained by the confounding overlap of operationally defined criteria or whether it reflects a genuine comorbidity of two biologically distinct disorders. The aim of this paper is to recognize and/or differentiate the pattern of ADHD across the course of BD from a nosological point of view, focusing on specific clinical and neurobiological dimensions. We found that some critical issues may help to fulfill the purpose of our perspective. We suggest that the relationship between ADHD and BD, based on clinical, developmental, and epidemiological commonalities, can be better clarified using four different scenarios.

Subjective disturbance of perception is related to facial affect recognition in schizophrenia.

To examine the relationship between facial affect recognition (FAR) and subjective perceptual disturbances (SPDs), we assessed SPDs in 82 patients with DSM-IV schizophrenia (44 with first-episode psychosis [FEP] and 38 with multiple episodes [ME]) using two subscales of the Frankfurt Complaint Questionnaire (FCQ), WAS (simple perception) and WAK (complex perception). Emotional judgment ability was assessed using Ekman and Friesen's FAR task. Impaired recognition of emotion correlated with scores on the WAS but not on the WAK. The association was significant in the entire group and in the ME group. FAR was more impaired in the ME than in the FEP group. Our findings suggest that there is a relationship between SPDs and FAR impairment in schizophrenia, particularly in multiple-episode patients.

Bipolar disorder presenting as stalking--a case report.

BACKGROUND: Stalking behaviour may find its roots in an individual's psychological development and culture-related factors that facilitate it. Psychiatric disorders may underlie some stalking cases, but no reports exist of the relationship of actual psychiatric status with the expression of stalking behaviour. CASE REPORT: A 22-year-old adoptive woman perpetrated stalking towards her gynaecologist, who took legal action to protect herself. She was admitted to a general hospital psychiatric department and diagnosed with bipolar disorder-I, manic phase, and personality disorder, not otherwise specified. She was prescribed lithium and valproate combination and followed-up as an outpatient. She underwent cognitive-behavioural therapy incorporating Bowlby's concepts. Stalking behaviour did not reemerge. CONCLUSION: Exacerbations of psychiatric episodes may trigger stalking behaviour. Drug treatment may prevent its clinical expression, but underlying ideation and affect may need long-term psychotherapy focusing on attachment.

Mismatch Negativity and P3a Impairment through Different Phases of Schizophrenia and Their Association with Real-Life Functioning.

Impairment in functioning since the onset of psychosis and further deterioration over time is a key aspect of subjects with schizophrenia (SCZ). Mismatch negativity (MMN) and P3a, indices of early attention processing that are often impaired in schizophrenia, might represent optimal electrophysiological candidate biomarkers of illness progression and poor outcome. However, contrasting findings are reported about the relationships between MMN-P3a and functioning. The study aimed to investigate in SCZ the influence of illness duration on MMN-P3a and the relationship of MMN-P3a with functioning. Pitch (p) and duration (d) MMN-P3a were investigated in 117 SCZ and 61 healthy controls (HCs). SCZ were divided into four illness duration groups: ≤ 5, 6 to 13, 14 to 18, and 19 to 32 years. p-MMN and d-MMN amplitude was reduced in SCZ compared to HCs, independently from illness duration, psychopathology, and neurocognitive deficits. p-MMN reduction was associated with lower "Work skills". The p-P3a amplitude was reduced in the SCZ group with longest illness duration compared to HCs. No relationship between P3a and functioning was found. Our results suggested that MMN amplitude reduction might represent a biomarker of poor functioning in SCZ.