Two-Injection Start Regimen of Long-Acting Aripiprazole in 133 Patients With Schizophrenia.

PURPOSE/BACKGROUND: Based on a population-pharmacokinetic model, the European Medicines Agency has recently approved a simplified starting strategy of aripiprazole once a month (AOM), injectable and long-acting antipsychotic, with two 400 mg injections and a single oral 20 mg dose of aripiprazole, administered on the same day, instead of 1 injection and 14 daily administrations of concurrent oral aripiprazole. However, to our knowledge, no previous study has reported the safety and tolerability of this regimen in real-world patients. METHODS/PROCEDURES: We retrospectively reviewed medical records of 133 patients who received the newly approved 2-injection start regimen as part of their standard care in 10 Italian clinical centers. FINDINGS/RESULTS: Adverse effects were mild or moderate, with no clinically evident difference from the adverse effects observed in previous trials where AOM was started with a single injection followed by 14 days of orally administered aripiprazole. None of the patients who started AOM after the 2-injection start regimen experienced severe adverse effects or severe adverse effects. IMPLICATIONS/CONCLUSIONS: The coadministration of 2 injections of 400 mg aripiprazole and 20 mg oral aripiprazole was not associated with safety concerns beyond those reported after a single injection followed by 14 days of orally administered aripiprazole. Our results should be interpreted with caution, due to the limited sample size and to the retrospective design of the study.

The 'dead man walking' disorder: an update on Cotard's syndrome.

In 1880, Jules Cotard described a peculiar syndrome after observing the case of a 43-year-old woman, which was characterized by melancholic anxiety, delusions of damnation or possession, a higher propensity to suicide ideation and deliberate self-harm, analgesia, hypochondriac thoughts of non-existence or ruin of several organs, of the whole body, of the soul, of divinity, and the idea of immortality or inability to die. Several expansions and reinterpretations have been made of the so-called Cotard's syndrome, which is often encompassed in different neurological and psychiatric disorders, complicating and worsening their symptomatic frameworks and making more difficult their treatments. However, the nosographic characterization of Cotard's syndrome remains elusive and is not now classified as a separate disorder in both ICD and DSM-5. Here, we try to give an update, as well as a putative systematization, of current views and opinions about this nosological entity in the light of the recent progress in the clinic, psychopathology and psycho-neurobiology.

Alexithymia, suicide ideation, affective temperaments and homocysteine levels in drug naïve patients with post-traumatic stress disorder: an exploratory study in the everyday 'real world' clinical practice.

Objective: The present exploratory study aimed to investigate relationships between alexithymia, suicide ideation, affective temperaments and homocysteine levels among drug-naïve adult outpatients with Post-Traumatic Stress Disorder (PTSD) in an everyday 'real world' clinical setting.Method: Sixty-four adult outpatients with PTSD were evaluated using the Davidson Trauma Scale (DTS), the Toronto Alexithymia Scale (TAS-20), the Scale of Suicide Ideation (SSI), the Temperament Evaluation of the Memphis, Pisa, Paris and San Diego-Autoquestionnaire. As well, homocysteine levels were measured.Results: Alexithymic subjects showed higher values on all scales but not homocysteine levels. Partial correlations showed that almost all studied variables were correlated with each other, except homocysteine levels. Regression analysis showed that higher disorder severity as measured by DTS and TAS-20 'Difficulty in Identifying Feelings' dimension was associated with higher SSI scores.Conclusions: In conclusion, alexithymic PTSD outpatients may be characterised by higher disorder severity and difficulty in identifying feelings that may be linked to increased suicide ideation, regardless of affective temperaments or homocysteine levels. Homocysteine levels were not related to any studied variable. However, study limitations are discussed and must be considered. KeypointsPatients with alexithymia showed increased PTSD severity, a higher score on TEMPS-A subscales, and more severe suicide ideation.The Difficulty in Identifying Feelings (DIF) dimension of TAS-20 was associated with suicide ideation in patients with PTSD.Homocysteine did not correlate with any studied variables.This study was exploratory and cross-sectional: further larger and prospective studies are needed.

Eradicating Suicide at Its Roots: Preclinical Bases and Clinical Evidence of the Efficacy of Ketamine in the Treatment of Suicidal Behaviors.

Despite the continuous advancement in neurosciences as well as in the knowledge of human behaviors pathophysiology, currently suicide represents a puzzling challenge. The World Health Organization (WHO) has established that one million people die by suicide every year, with the impressive daily rate of a suicide every 40 s. The weightiest concern about suicidal behavior is how difficult it is for healthcare professionals to predict. However, recent evidence in genomic studies has pointed out the essential role that genetics could play in influencing person's suicide risk. Combining genomic and clinical risk assessment approaches, some studies have identified a number of biomarkers for suicidal ideation, which are involved in neural connectivity, neural activity, mood, as well as in immune and inflammatory response, such as the mammalian target of rapamycin (mTOR) signaling. This interesting discovery provides the neurobiological bases for the use of drugs that impact these specific signaling pathways in the treatment of suicidality, such as ketamine. Ketamine, an N-methyl-d-aspartate glutamate (NMDA) antagonist agent, has recently hit the headlines because of its rapid antidepressant and concurrent anti-suicidal action. Here we review the preclinical and clinical evidence that lay the foundations of the efficacy of ketamine in the treatment of suicidal ideation in mood disorders, thereby also approaching the essential question of the understanding of neurobiological processes of suicide and the potential therapeutics.

Effect of agomelatine treatment on C-reactive protein levels in patients with major depressive disorder: an exploratory study in "real-world," everyday clinical practice.

OBJECTIVE: Agomelatine is a newer antidepressant but, to date, no studies have been carried out investigating its effects on C-reactive protein (CRP) levels in major depressive disorder (MDD) before and after treatment. The present study aimed (i) to investigate the effects of agomelatine treatment on CRP levels in a sample of patients with MDD and (ii) to investigate if CRP variations were correlated with clinical improvement in such patients. METHODS: 30 adult outpatients (12 males, 18 females) with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of MDD were recruited in "real-world," everyday clinical practice and treated with a flexible dose of agomelatine for 12 weeks. The Hamilton Rating Scale for Depression (HAM-D) and the Snaith-Hamilton Pleasure Scale (SHAPS) were used to evaluate depressive symptoms and anhedonia, respectively. Moreover, serum CRP was measured at baseline and after 12 weeks of treatment. RESULTS: Agomelatine was effective in the treatment of MDD, with a significant reduction in HAM-D and SHAPS scores from baseline to endpoint. CRP levels were reduced in the whole sample, with remitters showing a significant difference in CRP levels after 12 weeks of agomelatine. A multivariate stepwise linear regression analysis showed that higher CRP level variation was associated with higher baseline HAM-D scores, controlling for age, gender, smoking, BMI, and agomelatine dose. CONCLUSIONS: Agomelatine's antidepressant properties were associated with a reduction in circulating CRP levels in MDD patients who achieved remission after 12 weeks of treatment. Moreover, more prominent CRP level variation was associated with more severe depressive symptoms at baseline.

The Role of Inhaled Loxapine in the Treatment of Acute Agitation in Patients with Psychiatric Disorders: A Clinical Review.

Loxapine is a first generation antipsychotic, belonging to the dibenzoxazepine class. Recently, loxapine has been reformulated at a lower dose, producing an inhaled powder that can be directly administered to the lungs to treat the agitation associated with psychiatric disorders, such as schizophrenia and bipolar disorder. Thus, the aim of this narrative and clinical mini-review was to evaluate the efficacy and tolerability of inhaled loxapine in the treatment of acute agitation in patients with psychiatric disorders. The efficacy of inhaled loxapine has been evaluated in one Phase II trial on patients with schizophrenia, and in two Phase III trials in patients with schizophrenia and bipolar disorder. Moreover, there are two published case series on patients with borderline personality disorder and dual diagnosis patients. Inhaled loxapine has proven to be effective and generally well tolerated when administered to agitated patients with schizophrenia and bipolar disorder. Two case series have suggested that inhaled loxapine may also be useful to treat agitation in patients with borderline personality disorder and with dual diagnosis, but further studies are needed to clarify this point. However, the administration of inhaled loxapine requires at least some kind of patient collaboration, and is not recommended in the treatment of severe agitation in totally uncooperative patients. Moreover, the drug-related risk of bronchospasm must always be kept in mind when planning to use inhaled loxapine, leading to a careful patient assessment prior to, and after, administration. Also, the higher costs of inhaled loxapine, when compared to oral and intramuscular medications, should be taken into account when selecting it for the treatment of agitation.

Celecoxib Adjunctive Treatment to Antipsychotics in Schizophrenia: A Review of Randomized Clinical Add-On Trials.

Schizophrenia is a severe, chronic and debilitating mental disorder. Past literature has reported various hypotheses about the psychopathology of schizophrenia. Recently, a growing literature has been trying to explain the role of inflammation in the etiopathogenesis of schizophrenia. In the past, numerous immune modulation and anti-inflammatory treatment options have been proposed for schizophrenia, but sometimes the results were inconsistent. Electronic search was carried out in November 2015. PubMed and Scopus databases have been used to find studies to introduce in this review. Only randomized-placebo-controlled add-on trials were taken into account. In this way, six articles were obtained for the discussion. Celecoxib showed beneficial effects mostly in early stages of schizophrenia. In chronic schizophrenia, the data are controversial, possibly in part for methodological reasons.

Alexithymia, responsibility attitudes and suicide ideation among outpatients with obsessive-compulsive disorder: an exploratory study.

AIMS: Obsessive-compulsive disorder (OCD) is psychiatric disorder with a significant suicide risk, and the presence of alexithymia may increase this risk. As several studies attribute an important role, in OCD, to responsibility, the aims of this study were to evaluate possible clinical differences between patients positive or not for alexithymia concerning disorder severity, responsibility attitudes and suicide ideation and investigate which variables were associated with increased suicide ideation. METHODS: 104 adult outpatients with OCD were recruited. Alexithymia was measured with Toronto Alexithymia Scale (TAS-20), attitude about responsibility was tested with Responsibility Attitude Scale (RAS), suicide ideation was assessed with Scale of Suicide Ideation (SSI) and depressive symptoms were evaluated with Montgomery Åsberg Depression Rating Scale (MADRS). Score of item #11 on the Y-BOCS was considered as a measure of insight. RESULTS: Patients positive for alexithymia showed higher responsibility attitudes and more severe suicide ideation. In a blockwise regression model, the presence of lower insight, higher RAS scores and difficulty in identifying feelings dimension of TAS-20 were associated with higher SSI scores. CONCLUSIONS: OCD patients with alexithymia may show higher disorder severity, lower insight and inflated responsibility, all related to suicide ideation, independently from depressive symptoms. Implications were discussed and study limitations considered and reported.

Alexithymia, suicide risk and serum lipid levels among adult outpatients with panic disorder.

To elucidate the relationships between alexithymia, suicide ideation and serum lipid levels in drug-naïve adult outpatients with a DSM-IV diagnosis of Panic Disorder (PD), 72 patients were evaluated. Measures were the Panic Attack and Anticipatory Anxiety Scale, the Toronto Alexithymia Scale (TAS-20), the Scale of Suicide Ideation (SSI) and the Montgomery Åsberg Depression Rating Scale (MADRS). Alexithymic patients showed higher scores on all rating scales and altered serum lipid levels than non-alexithymics. In the hierarchical regression model, the presence of lower HDL-C and higher VLDL-C levels and Difficulty in Identifying Feelings dimension of TAS-20 were associated with higher suicide ideation. In conclusion, alexithymic individuals with PD may show a cholesterol dysregulation that may be linked to suicide ideation. The authors discuss study limitations and future research needs.

[Alexithymia and suicide risk among patients with schizophrenia: preliminary findings of a cross-sectional study]. / Alessitimia e rischio suicidario in pazienti affetti da schizofrenia: risultati preliminari di uno studio trasversale.

OBJECTIVE: The aim of the present study was to evaluate the prevalence of alexithymia and its relationships with psychopathological features and suicide risk in a sample of adult patients with a DSM-IV diagnosis of paranoid schizophrenia. METHODS: A mixed male-female sample of 60 subjects (30 males and 30 females) was evaluated with the following rating scales: Toronto Alexithymia Scale (TAS-20), Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS), Calgary Depression Scale for Schizophrenia (CDSS), Scale for Suicidal Ideation (SSI), State-Trait Anxiety Inventory (STAI). RESULTS: 22 subjects (36.7%) were categorized as alexithymic (TAS-20 scores > or =61). Alexithymics showed more severe negative and depressive symptoms and increased suicide risk than non alexithymics. However, the results of a linear regression with SSI score as dependent variable showed that Difficulty in Identifying and Describing Feelings dimensions of TAS-20 and higher CDSS scores were significantly associated with higher scores on the Scale for Suicide Ideation. CONCLUSIONS: The presence of alexithymia in schizophrenia may be related to higher risk of suicide ideation and more severe depressive symptoms, independently by the severity of positive and negative symptoms. However, results are preliminary and limitations must be considered.

Suicide in Healthcare Workers: Determinants, Challenges, and the Impact of COVID-19.

The Coronavirus disease-19 (COVID-19), which first appeared in Wuhan, China, and was later declared a pandemic, has caused significant morbidity and mortality worldwide. Numerous efforts have been made worldwide to understand the disease's physical manifestation. However, less emphasis has been placed on the pandemic's mental health challenges for healthcare workers (HCWs) who played a critical role in fighting the disease. Existing literature shows the detrimental psychological impact and increased incidence of depression and anxiety among HCWs. It is expected that the mental health crisis will become a serious issue affecting HCWs, with long-term negative consequences following COVID. Physicians and nurses already represent the highest risk groups of suicide among the general population, and suicide can be regarded as an occupational hazard in the healthcare industry. Increased workload, burnout and fatigue, multifaceted challenges women HCWs, and increased substance abuse are contributing factors to suicide ideation. In this article, we identify the risk factors of suicide among HCWs, discuss mental health challenges exacerbated by the pandemic and its impact on suicide ideation.

The effect of paliperidone palmitate long-acting injectable (PP-LAI) on "non-core" symptoms of schizophrenia: a retrospective, collaborative, multicenter study in the "real world" everyday clinical practice.

BACKGROUND: Schizophrenia is frequently complicated by the occurrence of depressive symptoms, anhedonia, obsessions and compulsions, suicidal ideation, and substance abuse, that causes exacerbations and remissions and, in several cases, sustained morbidity and disability. AIM: The present study aimed to evaluate the effect of paliperidone palmitate once-monthly long-acting injection (PP-LAI) mainly on "non-core" symptoms in persons with recent diagnosis schizophrenia, during a follow-up period of almost 12 months (T1) in the context of the "real world" everyday clinical practice. RESULTS: Concerning core symptoms of schizophrenia, PP-LAI was effective in reducing all symptoms at T1 as measured by Positive and Negative Syndrome Scale (PANSS), including depressive symptoms, and increased the functioning. Moreover, concerning the non-core symptoms of schizophrenia, PP-LAI treatment was effective in reducing scores of anhedonia, suicidal ideation and obsessive-compulsive symptoms at T1. However, the levels of alexithymia remained relatively stable, even if reduced. DISCUSSION: The present retrospective, multicenter, non-sponsored, collaborative study showed that early PP-LAI treatment was effective in improving almost all the core dimensions and "non-core" symptoms of schizophrenia, and this may have positive repercussions on both functioning and quality of life. CONCLUSIONS: PP-LAI treatment should be offered earlier as possible and was effective on "non-core" symptoms of schizophrenia at follow-up, but had a little effect on alexithymia. However, study' limitations must be considered and future researches are needed to confirm these interesting findings.

Adjunctive vortioxetine for SSRI-resistant major depressive disorder: a "real-world" chart review study.

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of treatment of major depressive disorder (MDD). However, non-response is common, often necessitating combination strategies. The present study assessed the efficacy of vortioxetine as an add-on therapy in patients with SSRI-resistant MDD. METHODS: The charts of 36 adult outpatients with DSM-IV-TR MDD who had not achieved a response after at least 8 weeks of treatment with an SSRI were reviewed retrospectively. Subjects were treated with vortioxetine (5-20 mg/day) for 8 weeks added to the current SSRI. The main outcome measures were change from baseline in total Hamilton Scale for Depression (HAM-D) score and the rate of response (a 50% or greater reduction in HAM-D score and a Clinical Global Impression - Improvement module [CGI-I] score of 1 or 2 at endpoint). HAM-D scores ≤ 7 were considered as remission. Additional outcome measures included the Snaith-Hamilton Pleasure Scale (SHAPS) and the Scale for Suicide Ideation (SSI). RESULTS: 32 patients completed the 8 weeks of treatment. At 8 weeks, a significant reduction in HAM-D score was observed (p ≤ 0.001), with response obtained by 41.7% and remission by 33.3% of patients. Significant reductions in SHAPS and SSI were also observed (p ≤ 0.001 for both scales). CONCLUSIONS: Adjunctive vortioxetine may be useful and well-tolerated in stage I treatment-resistant depression. However, the limitations of this study (such as small sample size, absence of randomization and control group, retrospective design, etc.) must be considered.

Alexithymia, resilience, somatic sensations and their relationships with suicide ideation in drug naïve patients with first-episode major depression: An exploratory study in the "real world" everyday clinical practice.

AIM: The present study is aimed at revaluating alexithymia, somatic sensations, resilience and their relationships with suicide ideation in drug naïve adult outpatients suffering from first episode major depression (MD). METHODS: Data of 103 adult outpatients (49 men, 56 women) with a diagnostic and statistical manual of mental disorders, 4th edition, text revision (DSM-IV-TR) diagnosis of MD were analysed. Alexithymia was measured using the 20-item Toronto Alexithymia Scale (TAS-20) and resilience with the 25 items Connor-Davidson Resilience Scale (CD-RISC) whereas depression was evaluated using the 17-item Hamilton Depression Rating Scale, somatic sensations with the Body Sensations Questionnaire and suicide ideation with Scale of Suicide Ideation (SSI). RESULTS: Gender comparisons between all demographic and clinical variables showed no significant differences in all variables. Subjects who were found positive for alexithymia showed higher scores on all clinical variables controlling for age, gender and duration of the current episode. In a linear regression model, lower scores on CD-RISC and Difficulty in Identifying Feelings dimension of TAS-20 were significantly predictive of higher scores on SSI. CONCLUSIONS: Alexithymia and low resilience were significant predictors of increased suicide ideation in a first MD episode. However, study limitations must be considered and future research needs are being discussed.

Religious Coping, Hopelessness, and Suicide Ideation in Subjects with First-Episode Major Depression: An Exploratory Study in the Real World Clinical Practice.

BACKGROUND: This study aimed to evaluate the potential relationships between religious coping, hopelessness, and suicide ideation in adult outpatients with the first episode of major depressive disorder (MDD). METHODS: Ninety-four adult outpatients with MDD were assessed through the Hamilton Depression Rating Scale (HAM-D), the Beck Hopelessness Scale (BHS), and the Scale of Suicide Ideation (SSI). Religious coping was assessed with the Italian version of the Brief RCOPE scale, consisting of seven positive coping items (PosCop) and seven negative coping items (NegCop). RESULTS: The results showed that the Brief RCOPE PosCop scale exhibited a strong inverse correlation with HAM-D, BHS, and SSI, whereas HAM-D and BHS were positively correlated with SSI. Brief RCOPE NegCop scores were positively correlated only with SSI. Regression analysis with SSI as the dependent variable showed that higher Brief RCOPE PosCop scores were associated with lower suicide ideation, whereas higher HAM-D and BHS scores were associated with higher suicide ideation. CONCLUSION: Positive religious coping may be a protective factor against the development of suicide ideation, perhaps counteracting the severity of depressive symptoms and hopelessness. The evaluation of religious coping should be performed in all subjects with MDD in everyday clinical practice. However, this study was preliminary, and limitations must be considered.

The FDA "Black Box" Warning on Antidepressant Suicide Risk in Young Adults: More Harm Than Benefits?

The decision made in the year 2004 by the U.S. Food and Drug Administration (FDA) to require a boxed warning on antidepressants regarding the risk of suicidality in young adults still represents a matter of controversy. The FDA warning was grounded on industry-sponsored trials carried one decade ago or earlier. However, within the past decade, an increasing number of reports have questioned the actual validity of the FDA warning, especially considering a decline in the prescription of the antidepressant drugs associated with an increase in the rate of suicidal events among people with severe depression. The present report provides an overview of the FDA black box warning, also documenting two Major Depressive Disorder patients whose refusal to undergo a pharmacological antidepressant treatment possibly led to an increased risk for suicidal behaviors. The concerns raised by the FDA black box warning need to be considered in real-world clinical practice, stating the associated clinical and public health implications.

Alexithymia, Suicide Ideation and Homocysteine Levels in Drug Naïve Patients with Major Depression: A Study in the "Real World" Clinical Practice

Objective: : This study was performed to elucidate relationships between alexithymia, suicide ideation and homocysteine levels in drug-naïve outpatients with major depressive disorder (MDD). Methods: : Sixty seven outpatients with MDD with melancholic features were evaluated by the means of the Hamilton Depression Rating Scale, the Toronto Alexithymia Scale (TAS-20), the Scale of Suicide Ideation, and homocysteine levels. Results: : Alexithymic subjects showed higher scores on all scales and higher homocysteine levels. Regression analysis shown higher homocysteine levels and TAS-20' "Difficulty in Describing Feelings" dimension, in turn being associated with higher suicide ideation. Conclusion: : In conclusion, alexithymic MDD outpatients may characterize for homocysteine dysregulation that may be linked to suicide ideation, regardless depression' severity. However, study limitations are discussed and must be considered.

Novel Pathways in the Treatment of Major Depression: Focus on the Glutamatergic System.

Depressive disorders represent protean psychiatric illnesses with heterogeneous clinical manifestations and a multitude of comorbidities leading to severe disability. In spite of decades of research on the pathophysiogenesis of these disorders, the wide variety of pharmacotherapies currently used to treat them is based on the modulation of monoamines, whose alteration has been considered the neurobiological foundation of depression, and consequently of its treatment. However, approximately one third to a half of patients respond partially or become refractory to monoamine-based therapies, thereby jeopardizing the therapeutic effectiveness in the real world of clinical practice. Recent scientific evidence has been pointing out the essential role of other biological systems beyond monoamines in the pathophysiology of depressive disorders, in particular, the glutamatergic neurotransmission. In the present review, we will discuss the most advanced knowledge on the involvement of glutamatergic system in the molecular mechanisms at the basis of depression pathophysiology, as well as the glutamate-based therapeutic strategies currently suggested to optimize depression treatment (e.g., ketamine). Finally, we will mention further "neurobiological targeted" approaches, based on glutamate system, with the purpose of promoting new avenues of investigation aiming at developing interventions that overstep the monoaminergic boundaries to improve depressive disorders therapy.

Alexithymia and its relationships with C-reactive protein and serum lipid levels among drug naïve adult outpatients with major depression.

Several studies have investigated the relationship between C-reactive protein (CRP) and serum lipid levels in Major Depression (MD), but no study has, to date, evaluated the impact of alexithymia on these parameters. Therefore, the aim of the present cross-sectional study was to evaluate the relationship between alexithymia, suicide risk, C-reactive protein (CRP) and serum lipid levels in adult outpatients suffering from moderate to severe MD. CRP and serum lipid levels data were analyzed in 145 drug-naïve adult outpatients (69 men, 76 women) with a DSM-IV diagnosis of MD. Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20), depression severity was evaluated with the 17-item Hamilton Depression Rating Scale (HAM-D) and suicide risk was determined using the Scale of Suicide Ideation (SSI). Alexithymics showed altered serum lipid levels and higher CRP than non-alexithymics. In the linear regression models, lower total cholesterol levels and "Difficulty in Identifying Feelings" dimension of TAS-20 were significantly associated with depression severity, whereas lower high-density lipoprotein levels and "Difficulty in Identifying and Describing Feelings" dimensions of TAS-20 were associated with higher suicide risk. Authors discuss study limitations and future research needs.

Protein-C Reactive as Biomarker Predictor of Schizophrenia Phases of Illness? A Systematic Review.

BACKGROUND: Schizophrenia is a complex illness in which genetic, environmental, and epigenetic components have been implicated. However, recently, psychiatric disorders appear to be related to a chronic inflammatory state, at the level of specific cerebral areas which have been found as well impaired and responsible for schizophrenia symptomatology. Hence, a role of inflammatory mediators and cytokines has been as well defined. Accordingly, the role of an acute inflammatory phase protein, the C-reactive protein (CRP) has been recently investigated. OBJECTIVE: The objective of the present study is to evaluate how PCR may represent a biomarker in schizophrenia, i.e. correlated with illness phases and/or clinical manifestation and/or psychopathological severity. METHODS: A systematic review was here carried out by searching the following keywords ((C-reactive protein AND ((schizophrenia) OR (psychotic disorder))) for the topics 'PCR' and 'Schizophrenia', by using MESH terms. RESULTS: An immune dysfunction and inflammation have been described amongst schizophrenic patients. Findings reported elevated CRP levels in schizophrenia, mainly correlated with the severity of illness and during the recrudescent phase. CRP levels are higher when catatonic features, negative symptomatology and aggressiveness are associated. CRP levels appeared not to be related to suicidal behaviour and ideation. CONCLUSION: CRP and its blood levels have been reported higher amongst schizophrenic patients, by suggesting a role of inflammation in the pathogenesis of schizophrenia. Further studies are needed to better understand if CRP may be considered a biomarker in schizophrenia.