Knowledge of the treatment in schizophrenia and schizoaffective disorder and its relationship with nonadherence.

Despite its potential impor- tance for adherence, knowledge of the treatment has been little studied in patients with psychosis. We performed this study to assess the possible association between knowledge of the treatment and nonadherence, unintentional nonad- herence (UNA) and intentional nonadherence (INA).

Nonadherence after hospital discharge in patients with schizophrenia or schizoaffective disorder: A six-month naturalistic follow-up study.

BACKGROUND: Despite a wealth of studies seeking to identify factors associated with nonadherence few consistent predictors have been determined, and several gaps still exist in the literature. METHOD: We assessed 110 consecutively admitted patients diagnosed with schizophrenia or schizoaffective disorder according to ICD-10 criteria. Assessments were performed during hospitalization and at six-months follow-up. Evaluation included sociodemographic, clinical, psychopathologic and treatment-related variables. Prevalence of nonadherence, associated variables, reasons for nonadherence and possible subtypes were explored. Adherence was defined as the concurrence of adherence to antipsychotic treatment and adherence to outpatient follow-up, during the six-month period. RESULTS: Nonadherence was detected in 58.2% of patients. An identifiable profile was found in nonadherent patients. After multivariate logistic regression analysis, low socio-economic level (OR = 3.68; 95% CI = 1.42-9.53), current cannabis use or abuse (OR = 2.79; 95% CI = 1.07-7.28), nonadherence as a reason for relapse and admission (OR = 5.46; 95% CI = 2.00-14.90), and greater overall severity of symptoms at six months follow-up (OR = 2.00; 95% CI = 1.02-3.95) remained independently associated with nonadherence. Believing that medication is unnecessary was the most reported reason for nonadherence. For nonadherent patients (N = 64), two distinguishable subtypes were found: intentional nonadherence (N = 32; 50%), and unintentional nonadherence (N = 32; 50%). CONCLUSIONS: A large percentage of patients with schizophrenia or schizoaffective disorder did not adhere to their treatment in the post-discharge follow-up period. The profile identified may enable better prevention of this problem. Specific reasons for nonadherence should also be explored to provide individualized strategies.

Suicide Coverage in the Digital Press Media: Adherence to World Health Organization Guidelines and Effectiveness of Different Interventions Aimed at Media Professionals.

This study evaluated the characteristics of suicide news articles in the digital press, their adherence to World Health Organization (WHO) recommendations, and the effectiveness of interventions. We assessed adherence, avoidability, frequency and typology of suicide news over a six-month period in the four main digital media outlets of the Canary Islands (Spain). A brief training and information package intervention to the Canary Islands media outlets was carried out. We compared the quality of media reporting at both the pre-intervention and post-intervention timepoints, and compared the quality of reporting at the post-intervention timepoint in Victoria (Australia), where media interventions have been well-resourced and running for several years. We evaluated 339 suicide news articles: 38 from the pre-intervention period, 64 from the post-intervention period, and 237 from Victoria. News articles showed a very low degree of adherence to WHO recommendations, especially to those recommendations thought to have a protective effect. Post-intervention news articles showed better adherence than pre-intervention ones, but lower than those of Victoria, where constant interventions have been developed for years. We conclude that adherence to WHO recommendations is low. Simple interventions aimed at media professionals can improve adherence. However, constant and complex interventions seem to be more effective.

Prospective study of variables associated with nonadherence to psychotherapy.

Background: The identification of factors associated with nonadherence to psychotherapy would allow a better prevention of this problem.Aim: To investigate factors associated with nonadherence in psychotherapy, its possible effect on outcomes, and reasons for therapy dropout.Method: Prospective analytic observational study of patients who initiated psychotherapy (N = 144). Sociodemographic, general clinical, treatment-related, subjective, psychological, psychopathologic, and outcome variables were evaluated at baseline and 1, 3, 6, and 12 months later. Objective nonadherence (dropout and irregularity), subjective nonadherence (poor patient engagement), and global nonadherence (combination of both) were analyzed.Results: Global nonadherence was 66%. Global nonadherence was associated with substance use or abuse (OR = 2.64) and younger age (OR = 0.97). Objective nonadherence was associated with active working status (OR = 4.11), younger age (OR = 1.04) and substance use or abuse (OR = 2.35). Subjective nonadherence was associated with worse insight in psychotherapy (OR = 0.95) and poor pharmacologic adherence (OR = 0.55). Contextual reasons (25.8%) were the most commonly reported cause of dropout. Time in psychotherapy was associated with outcome variables.Conclusions: Nonadherence to psychotherapy is frequent. To reduce nonadherence in psychotherapy, specific interventions for reducing substance use and abuse, measures aimed at facilitating access to Community Mental Health Units, and enhancing insight in psychotherapy should be implemented.

Narcolepsy and psychosis; case report.

Narcolepsy is an infrequent neurological disorder, included in the catalog of rare diseases. Despite the existenceof precise diagnostic criteria, this entity remains underdiagnosed. It is characterized by excessive daytime sleepiness associated with cataplexy; in some cases, hypnagogic or hypnopompic hallucinations, auditory hallucinations, and/or delusional ideation may appear. The occurrence of psychotic symptoms makes differential diagnosis extremely difficult (narcolepsy, schizophrenia, or both). Furthermore, therapeutic management may be complex, since the treatment of one of the disorders may worsen the other. Here we describe the case of a patient with this rare comorbidity, which illustrates the major difficulties associated to both differential diagnosis and therapeutic management once a definitive diagnosis has been reached.

Suicidal risk, hopelessness and depression in patients with schizophrenia and internalized stigma.

BACKGROUND: Internalized stigma has negative consequences on subjective and objective aspects of the recovery in people diagnosed with mental disorders. Despite its relevance, it has been poorly studied in patients with schizophrenia. METHODS: A sample of 71 outpatients with a diagnosis of schizophrenia who attended Psychosocial Rehabilitation Centers of Gran Canaria, Spain, were evaluated. We assessed the prevalence of internalized stigma and its possible association with sociodemographic, clinical, psychological and psychopathological variables, as well as suicidal behaviour and suicidal ideation. RESULTS: 21.1% of the patients had internalized stigma. Internalized stigma was associated with higher prevalence of suicidal ideation during the last year, higher number of suicide attempts, higher current suicidal risk, worse self-compassion, higher self-esteem, higher scores on depression, higher prevalence of depression and higher hopelessness. After multivariate analysis, hopelessness and the existence of depression were independently associated with internalized stigma, although depression showed trend towards significance. CONCLUSIONS: The association between internalized stigma and higher hopelessness, depression and higher suicidal risk suggests the necessity to systematically assess internalized stigma in patients with schizophrenia, and to intervene to reduce it.

Variables associated with nonadherence in clinically stable patients with bipolar disorder.

INTRODUCTION: Nonadherence is an important and highly prevalent issue in bipolar disorder, which may have serious consequences. Surprisingly, few studies have been carried out in patients with clinical stability to explore risk factors for nonadherence. METHOD: Adherence was assessed in 76 bipolar disorder patients with clinical stability using objective and subjective methods, both with a cross-sectional approach and a 3-year retrospective period. Possible associations between nonadherence and sociodemographic, clinical, treatment-related, psychopathological, psychological-subjective and result variables were also assessed. RESULTS: 36.8% of patients were nonadherent. These patients showed greater concerns about medicines, worse functionality, a greater number of episodes and depressive episodes, higher prevalence of psychiatric comorbidities, present and/or past substance use or abuse and a history of depressive episodes with psychotic symptoms. A multivariate analysis revealed that concern about medicines, present and/or past substance use or abuse and psychiatric comorbidities were independently associated with nonadherence. CONCLUSIONS: Nonadherence is a frequent phenomenon in bipolar disorder, even in patients with clinical stability. Clinicians should assess patients’ beliefs and attitudes towards medicines and help them reevaluate those issues with a more realistic perspective. Clinicians should also take actions to prevent substance use or abuse. Identification of nonadherence risk profile in bipolar disorder patients in clinical stability, adds complementary information to the identified risk profile in acute phases of the disease.

A mathematical model for a T cell fate decision algorithm during immune response.

We formulate and analyze an algorithm of cell fate decision that describes the way in which division vs. apoptosis choices are made by individual T cells during an infection. Such model involves a minimal number of known biochemical mechanisms: it basically relies on the interplay between cell division and cell death inhibitors on one hand, and membrane receptors on the other. In spite of its simplicity, the proposed decision algorithm is able to account for some significant facts in immune response. At the individual level, the existence of T cells that continue to replicate in the absence of antigen and the possible occurrence of T cell apoptosis in the presence of antigen are predicted by the model. Moreover, the latter is shown to yield an emergent collective behavior, the observed delay in clonal contraction with respect to the end of antigen stimulation, which is shown to arise just from individual T cell decisions made according to the proposed mechanism.

Should full adherence be a necessary goal in schizophrenia? Full versus non-full adherence to antipsychotic treatment.

There is solid evidence of negative consequences of non-adherence in schizophrenia, and recently adherence has been defined as taking more than 80% of prescribed medication. However, the clinical relevance of different degrees of adherence in adherent patients has not been studied. We evaluated sociodemographic, clinical, treatment-related and psychopathological variables in 78 adherent outpatients with schizophrenia, who were classified into two groups: full-adherence (100% adherence) and non-full adherence (80-99.9%). Adherence was evaluated using electronic monitoring (MEMS®), and the injection record in case of injectable antipsychotics. Non-full adherence patients showed more extensive delusions and guilt feelings, as well as trends toward greater somatic concern, disorientation, general psychopathology, and lower number of prior psychiatric hospitalizations. These finding suggest that the 'fullness' of adherence to antipsychotic treatment is a relevant issue, impacting the psychopathological state of adherent patients with schizophrenia. We found that a large proportion of patients can achieve full adherence, and while 'adherence' is an appropriate objective to be pursued with non-adherent patients, 'full adherence' should be the goal among adherent patients.

Influence of antipsychotic treatment type and regimen on the functionality of patients with schizophrenia.

BACKGROUND: Enhanced functionality is a major goal in the treatment of schizophrenia. However, possible differences in the effectiveness of first- vs. second-generation antipsychotics or between depot/long-acting injectable (D/LAI) vs. D/LAI plus oral antipsychotics are not clear. AIMS: This study was designed to evaluate possible differences between the effects of different antipsychotic treatment types or regimens on the functionality of patients with schizophrenia. METHODS: 85 outpatients with schizophrenia, who were being treated with D/LAI antipsychotics--co-administered or not with oral antipsychotics--and had been adherent to the treatment during the previous year were evaluated. Socio-demographic, clinical, treatment-related, global severity and functionality variables were evaluated. Patients were grouped according to the type of antipsychotic drug (first- vs. second-generation) or according to the co-administration (or not) of oral antipsychotics. RESULTS: No differences were found between first- and second-generation antipsychotics in terms of global functionality. Patients treated with LAI risperidone showed better global functionality and better performance in their habitual social activities and personal-social relationships than patients treated with risperidone plus oral second-generation antipsychotics. Better functionality was also found to be associated with higher education level, paranoid subtype of schizophrenia, harmful use of nicotine, adherence to oral treatment and absence of concomitant oral anticholinergic or psychopharmacological treatment. CONCLUSIONS: Our results suggest that D/LAI antipsychotic treatments should be administered in monotherapy whenever possible and that the treatment schedule should be simple, in order to achieve better functionality.

A new role for erythropoietin in the homeostasis of red blood cells.

The regulation of red blood cell (RBC) homeostasis is widely assumed to rely on the control of cell production by erythropoietin (EPO) and the destruction of cells at a fixed, species-specific age. In this work, we show that such a regulatory mechanism would be a poor homeostatic solution to satisfy the changing needs of the body. Effective homeostatic control would require RBC lifespan to be variable and tightly regulated. We suggest that EPO may control RBC lifespan by determining CD47 expression in newly formed RBCs and SIRP-α expression in sinusoidal macrophages. EPO could also regulate the initiation and intensity of anti-RBC autoimmune responses that curtail RBC lifespan in some circumstances. These mechanisms would continuously modulate the rate of RBC destruction depending on oxygen availability. The control of RBC lifespan by EPO and autoimmunity emerges as a key mechanism in the homeostasis of RBCs.

Beliefs about illness and their relationship with hopelessness, depression, insight and suicide attempts in schizophrenia.

BACKGROUND: Although the negative appraisals of the illness may be related to suicidal thinking and behaviours in schizophrenia, this has been insufficiently studied. The aim of this study was to analyze the relationship between schizophrenic patients' cognitions about their illness and past suicidal behaviours. The relationship between patients' beliefs about their illness with potential mediators of suicidal behaviours such as depressive symptoms, hopelessness and insight was also investigated. SUBJECTS AND METHODS: A group of 60 patients diagnosed with schizophrenia according to ICD-10 criteria belonging to a follow-up study were assessed one year after their last psychiatric admission. Psychopathological variables were assessed by the Calgary Depression Scale, Beck Hopelessness Scale and the first three items of the Scale to Assess Unawareness of Mental Disorder. The appraisals of the illness were assessed by the Personal Beliefs about Illness Questionnaire. RESULTS: Negative appraisals were associated with hopelessness and depressive symptoms. Negative expectations and stigma showed the strongest associations. Contrary to our expectations, this scale was not able to differentiate between patients with and without past suicidal behaviour. CONCLUSIONS: Negative appraisals of the illness in patients with schizophrenia seem to have psychopathological consequences such as greater hopelessness and depression. Since these psychopathological features are linked to suicidal risk, the psychotherapeutic approach counteracting negative beliefs about the illness may reduce the risk of suicide.

Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behavior.

Insulin-like growth factor-I (IGF-I) exerts multiple actions, yet the role of IGF-I from different sources is poorly understood. Here, we explored the functional and behavioral consequences of the conditional deletion of Igf-I in the nervous system (Igf-I Δ/Δ), and demonstrated that long-term potentiation was impaired in hippocampal slices. Moreover, Igf-I Δ/Δ mice showed spatial memory deficits in the Morris water maze, and the significant sex-dependent differences displayed by Igf-I Ctrl/Ctrl mice disappeared in Igf-I Δ/Δ mice in the open field and rota-rod tests. Brain Igf-I deletion disorganized the granule cell layer of the dentate gyrus (DG), and it modified the relative expressions of GAD and VGLUT1, which are preferentially localized to inhibitory and excitatory presynaptic terminals. Furthermore, Igf-I deletion altered protein modules involved in receptor trafficking, synaptic proteins, and proteins that functionally interact with estrogen and androgen metabolism. Our findings indicate that brain IGF-I is crucial for long-term potentiation, and that it is involved in the regulation of spatial memory and sexual dimorphic behaviors, possibly by maintaining the granule cell layer structure and the stability of synaptic-related protein modules.

Hopelessness and suicidal risk in bipolar disorder. A study in clinically nonsyndromal patients.

OBJECTIVE: Attempted suicide and death due to suicide are not uncommon among patients with bipolar disorder. Although some risk factors for suicidality in bipolar patients have been identified, little is known about hopelessness and other possible trait or diathesis-related factors. Consequently, the objective of this study was to investigate variables associated with suicidal risk in clinically nonsyndromal bipolar patients. METHODS: A sample of 102 outpatients with a diagnosis of bipolar disorder according to International Classification of Diseases, 10th Revision criteria during nonsyndromal stage were evaluated. On the basis of suicidal history, patients were divided into suicide attempt, suicidal ideation, and nonsuicidal groups. Sociodemographic, clinical, and psychopathological variables were assessed. RESULTS: As compared with the nonsuicidal group, female sex, combined psychopharmacologic treatment, and hopelessness were independently associated with suicide attempt. Hopelessness and insight into having a mental disorder were independently associated with history of suicidal ideation. CONCLUSIONS: Patients with bipolar disorder and suicidal history are characterized by the presence of hopelessness, which probably confers greater vulnerability for suicidal behavior in the presence of stress factors. This identification of the risk profile for suicidal behavior in nonsyndromal bipolar patients adds complementary information to risk factors established for suicidality during acute phases of the disease, allows for differentiated preventive and treatment approaches of patients at risk, and suggests psychotherapy as an advisable intervention in this group of patients.

Killing the competition: a theoretical framework for liver-stage malaria.

The first stage of malaria infections takes place inside the host's hepatocytes. Remarkably, Plasmodium parasites do not infect hepatocytes immediately after reaching the liver. Instead, they migrate through several hepatocytes before infecting their definitive host cells, thus increasing their chances of immune destruction. Considering that malaria can proceed normally without cell traversal, this is indeed a puzzling behaviour. In fact, the role of hepatocyte traversal remains unknown to date, implying that the current understanding of malaria is incomplete. In this work, we hypothesize that the parasites traverse hepatocytes to actively trigger an immune response in the host. This behaviour would be part of a strategy of superinfection exclusion aimed to reduce intraspecific competition during the blood stage of the infection. Based on this hypothesis, we formulate a comprehensive theory of liver-stage malaria that integrates all the available knowledge about the infection. The interest of this new paradigm is not merely theoretical. It highlights major issues in the current empirical approach to the study of Plasmodium and suggests new strategies to fight malaria.

The coordination of anti-phage immunity mechanisms in bacterial cells.

Bacterial cells are equipped with a variety of immune strategies to fight bacteriophage infections. Such strategies include unspecific mechanisms directed against any phage infecting the cell, ranging from the identification and cleavage of the viral DNA by restriction nucleases (restriction-modification systems) to the suicidal death of infected host cells (abortive infection, Abi). In addition, CRISPR-Cas systems generate an immune memory that targets specific phages in case of reinfection. However, the timing and coordination of different antiviral systems in bacterial cells are poorly understood. Here, we use simple mathematical models of immune responses in individual bacterial cells to propose that the intracellular dynamics of phage infections are key to addressing these questions. Our models suggest that the rates of viral DNA replication and cleavage inside host cells define functional categories of phages that differ in their susceptibility to bacterial anti-phage mechanisms, which could give raise to alternative phage strategies to escape bacterial immunity. From this viewpoint, the combined action of diverse bacterial defenses would be necessary to reduce the chances of phage immune evasion. The decision of individual infected cells to undergo suicidal cell death or to incorporate new phage sequences into their immune memory would be determined by dynamic interactions between the host's immune mechanisms and the phage DNA. Our work highlights the importance of within-cell dynamics to understand bacterial immunity, and formulates hypotheses that may inspire future research in this area.

Morphological Diversity of Calretinin Interneurons Generated From Adult Mouse Olfactory Bulb Core Neural Stem Cells.

Neural stem cells (NSCs) in the olfactory bulb (OB) core can generate mature interneurons in the adult mice brain. The vast majority of these adult generated cells express the calcium-binding protein Calretinin (CalR), and they migrate towards different OB layers. However, these cells have yet to be fully characterized and hence, to achieve this we injected retroviral particles expressing GFP into the OB core of adult animals and found that the CalR+ neurons generated from NSCs mainly migrate to the granule cell layer (GCL) and glomerular layer (GL) in similar proportions. In addition, since morphology and function are closely related, we used three-dimensional imaging techniques to analyze the morphology of these adult born cells, describing new subtypes of CalR+ interneurons based on their dendritic arborizations and projections, as well as their localization in the GCL or GL. We also show that the migration and morphology of these newly generated neurons can be altered by misexpressing the transcription factor Tbr1 in the OB core. Therefore, the morphology acquired by neurons located in a specific OB layer is the result of a combination of both extrinsic (e.g., layer allocation) and intrinsic mechanisms (e.g., transcription factors). Defining the cellular processes and molecular mechanisms that govern adult neurogenesis might help better understand brain circuit formation and plasticity, as well as eventually opening the way to develop strategies for brain repair.

Testing the hypothesis of subtypes of nonadherence in schizophrenia and schizoaffective disorder: A prospective study.

BACKGROUND: Nonadherence is a major problem in the treatment of psychotic disorders. It has been hypothesized that nonadherent patients with schizophrenia are not a homogeneous population and subtypes of nonadherence might exist, but this hypothesis has not been specifically tested. AIM: To test the hypothesis of subtypes of nonadherence in schizophrenia and schizoaffective disorder. METHODS: This prospective study included 110 consecutively admitted patients diagnosed with schizophrenia or schizoaffective disorder. Assessments were performed at baseline and at 6 mo follow-up after discharge. Sociodemographic, clinical, psychopathological and treatment-related variables were evaluated. Adherence was defined as the concurrence of adherence to antipsychotic treatment and outpatient follow-up during the six-month period. Adherence to antipsychotic treatment was defined as the concurrence of objective and subjective adherence. Sixty-four patients (58%) fulfilled nonadherence criteria at the end of the follow-up period and were categorized according to their subtype of nonadherence. RESULTS: In nonadherent patients (n = 64), 32 (50%) fulfilled criteria of intentional nonadherence, and 32 (50%) of unintentional nonadherence (UNA). Unintentional nonadherent patients, as compared to intentional nonadherent patients, are characterized by older age, lower educational level, worse cognitive and negative symptoms, greater severity, worse knowledge of their treatment regimen, greater prevalence of supervision of the treatment, lower number of prior hospitalizations and greater use of nonpsychiatric treatment, anticholinergics and hypnotics. Low educational level (OR = 26.1; 95%CI: 2.819-241), worse treatment knowledge at six months (OR per unit = 0.904; 95%CI: 0.853-0.957) and nonpsychiatric treatment at six months (OR = 15.8; 95%CI: 1.790-139) were independently associated to UNA. CONCLUSION: Differentiated subtypes of nonadherence according to intentionality seem to exist in patients with schizophrenia and schizoaffective disorder. Our findings suggest the need for differentiated approach, both in future research and in clinical practice.

Painful insight vs. usable insight in schizophrenia. Do they have different influences on suicidal behavior?

BACKGROUND: Suicidal behavior is highly prevalent in schizophrenia. Among the risk factors, insight has been little studied and has yielded contradictory results. In addition, it has been studied neglecting relevant psychological aspects, such as beliefs about illness and coping styles. METHOD: We assessed 133 outpatients diagnosed with schizophrenia according to ICD-10 criteria. Evaluation included sociodemographic, general clinical, psychopathological, psychological and suicidal behavior variables. RESULTS: Neither insight nor insight coupled with negative beliefs and/or coping styles were associated with suicidal behavior. Nevertheless, insight coupled with negative beliefs and/or coping styles was associated with greater hopelessness and depression, internalized stigma, worse control over illness and greater global severity as compared to insight coupled with positive beliefs and coping styles. Suicide attempt and suicidal ideation groups showed greater depression and hopelessness, worse global beliefs and worse control over illness, higher socio-economic level, and greater number of previous psychiatric admissions compared to the non-suicidal group. CONCLUSIONS: Insight coupled with negative beliefs and/or coping style was not associated with suicidal behavior. Nevertheless, it was associated with greater depression and hopelessness, both of which are firmly established risk factors for suicide in schizophrenia. Prospective studies with long-term follow-up and large samples are needed to clarify this issue. Clinicians should assess these psychological features associated with insight, both in patients with insight and in those with poor insight when promoting it.

Evaluation of noncompliance in schizophrenia patients using electronic monitoring (MEMS) and its relationship to sociodemographic, clinical and psychopathological variables.

BACKGROUND: Noncompliance is common in patients with schizophrenia and can have serious consequences; therefore research of the variables associated with noncompliance is a priority. Although the MEMS device is regarded as the "reference standard" for evaluating compliance, it has been used in very few published studies. METHODS: Compliance was evaluated in 102 outpatients diagnosed with schizophrenia according to ICD-10 criteria. Compliance was evaluated with the MEMS device for 3 months in 79 patients who were on oral antipsychotic treatments. Baseline evaluations included sociodemographic, clinical, treatment-related and psychopathological variables. The psychiatrist, patients and relatives also provided compliance estimates. RESULTS: Noncompliant behaviors were observed in 42.3% of patients. Agreement between estimations by the psychiatrist and the MEMS findings was fair, and agreements between those of both patients and relatives and the MEMS findings were slight. Noncompliant patients showed poor insight, conceptual disorganization, stereotyped thinking and poor attention as compared to compliant patients. CONCLUSIONS: A large percentage of schizophrenic patients failed to adequately comply with their prescribed treatment. Compliance was overestimated by the psychiatrist, by patients and by relatives. Poorer insight and increased conceptual disorganization were independently associated with noncompliance. Identification of factors associated with noncompliance and strategies to reduce these behaviors would help improve the prognosis of schizophrenia.