[Network analyses: Are we moving toward a new conceptualization and treatment of mental disorder?] / Les analyses par réseau : vers une nouvelle conceptualisation et prise en charge des troubles mentaux ?

In a break with categorical and dimensional approaches and thus the classical medical model, the network approach applied to psychopathology constitutes a holistic approach to mental disorders. In this approach, mental disorders are conceived as an interconnected system of symptoms in which symptoms are the cause of each other. It is suggested that the interaction between the different symptoms would result in a feedback loop that leads to the installation and maintenance of these symptoms/disorders. In addition, this approach proposes that co-morbidities are the result of symptom-symptom interactions that cross the diagnostic boundary and interact with symptoms from other psychiatric disorders. A growing number of studies have applied the network approach to elucidate causal interactions within the symptoms of depression, post-traumatic stress disorder, schizophrenia, or anxiety disorders. The overall objective of this review is to raise awareness among researchers and clinicians in psychiatry and clinical psychology of the network approach applied to psychopathology. To do this, we present the main concepts and principles of the network approach and its application in post-traumatic stress disorder. We also discuss recent criticisms of this approach and its clinical applications.

Clinical features of schizophrenia with enhanced carbonyl stress.

Accumulating evidence suggests that advanced glycation end products, generated as a consequence of facilitated carbonyl stress, are implicated in the development of a variety of diseases. These diseases include neurodegenerative illnesses, such as Alzheimer disease. Pyridoxamine is one of the 3 forms of vitamin B6, and it acts by combating carbonyl stress and inhibiting the formation of AGEs. Depletion of pyridoxamine due to enhanced carbonyl stress eventually leads to a decrease in the other forms of vitamin B6, namely pyridoxal and pyridoxine. We previously reported that higher levels of plasma pentosidine, a well-known biomarker for advanced glycation end products, and decreased serum pyridoxal levels were found in a subpopulation of schizophrenic patients. However, there is as yet no clinical characterization of this subset of schizophrenia. In this study, we found that these patients shared many clinical features with treatment-resistant schizophrenia. These include a higher proportion of inpatients, low educational status, longer durations of hospitalization, and higher doses of antipsychotic medication, compared with patients without carbonyl stress. Interestingly, psychopathological symptoms showed a tendency towards negative association with serum vitamin B6 levels. Our results support the idea that treatment regimes reducing carbonyl stress, such as supplementation of pyridoxamine, could provide novel therapeutic benefits for this subgroup of patients.

Recovery from serious mental illness: trajectories, characteristics, and the role of mental health care.

OBJECTIVE The objective was to identify trajectories of recovery from serious mental illnesses. METHODS A total of 177 members (92 women; 85 men) of a not-for-profit integrated health plan participated in a two-year mixed-methods study of recovery (STARS, the Study of Transitions and Recovery Strategies). Diagnoses included schizophrenia, schizoaffective disorder, bipolar disorder, and affective psychosis. Data sources included self-reported standardized measures, interviewer ratings, qualitative interviews, and health plan data. Recovery was conceptualized as a latent construct, and factor analyses and factor scores were used to calculate recovery trajectories. Individuals with similar trajectories were identified through cluster analyses. RESULTS Four trajectories were identified-two stable (high and low levels of recovery) and two fluctuating (higher and lower). Few demographic or diagnostic factors differentiated clusters at baseline. Discriminant analyses for trajectories found differences in psychiatric symptoms, physical health, satisfaction with mental health clinicians, resources and strains, satisfaction with medications, and mental health service use. Those with higher scores on recovery factors had fewer psychiatric symptoms, better physical health, greater satisfaction with mental health clinicians, fewer strains and greater resources, less service use, better quality of care, and greater satisfaction with medication. Consistent predictors of trajectories included psychiatric symptoms, physical health, resources and strains, and use of psychiatric medications. CONCLUSIONS Having access to good-quality mental health care-defined as including satisfying relationships with clinicians, responsiveness to needs, satisfaction with psychiatric medications, receipt of services at needed levels, support in managing deficits in resources and strains, and care for general medical conditions-may facilitate recovery. Providing such care may improve recovery trajectories.

Structural brain alterations associated with schizophrenia preceded by conduct disorder: a common and distinct subtype of schizophrenia?

Conduct disorder (CD) prior to age 15 is a precursor of schizophrenia in a minority of cases and is associated with violent behavior through adulthood, after taking account of substance misuse. The present study used structural magnetic imaging to examine gray matter (GM) volumes among 27 men with schizophrenia preceded by CD (SZ+CD), 23 men with schizophrenia but without CD (SZ-CD), 27 men with CD only (CD), and 25 healthy (H) men. The groups with schizophrenia were similar in terms of age of onset and duration of illness, levels of psychotic symptoms, and medication. The 2 groups with CD were similar as to number of CD symptoms, lifelong aggressive behavior, and number of criminal convictions. Men with SZ+CD, relative to those with SZ-CD, displayed (1) increased GM volumes in the hypothalamus, the left putamen, the right cuneus/precuneus, and the right inferior parietal cortex after controlling for age, alcohol, and drug misuse and (2) decreased GM volumes in the inferior frontal region. Men with SZ+CD (relative to the SZ-CD group) and CD (relative to the H group) displayed increased GM volumes of the hypothalamus and the inferior and superior parietal lobes, which were not associated with substance misuse. Aggressive behavior, both prior to age 15 and lifetime tendency, was positively correlated with the GM volume of the hypothalamus. Thus, among males, SZ+CD represents a distinct subtype of schizophrenia. Although differences in behavior emerge in childhood and remain stable through adulthood, further research is needed to determine whether the differences in GM volumes result from abnormal neural development distinct from that of other males developing schizophrenia.

Single-subject classification of schizophrenia using event-related potentials obtained during auditory and visual oddball paradigms.

In the search for the biomarkers of schizophrenia, event-related potential (ERP) deficits obtained by applying the classic oddball paradigm are among the most consistent findings. However, the single-subject classification rate based on these parameters remains to be determined. Here, we present a data-driven approach by applying machine learning classifiers to relevant oddball ERPs. Twenty-four schizophrenic patients and 24 matched healthy controls finished auditory and visual oddball tasks while high-density electrophysiological recordings were applied. The N1 component in response to standards and target as well as the P3 component following targets were submitted to different machine learning algorithms and the resulting ERP features were submitted to further correlation analyses. We obtained a classification accuracy of 72.4 % using only two ERP components. Latencies of parietal N1 components to visual standard stimuli at electrode positions Pz and P1 were sufficient for classification. Further analysis revealed a high correlation of these features in controls and an intermediate correlation in schizophrenia patients. These data exemplarily show how automated inference may be applied to classify a pathological state in single subjects without prior knowledge of their diagnoses and illustrate the potential of machine learning algorithms for the identification of potential biomarkers. Moreover, this approach assesses the discriminative accuracy of one of the most consistent findings in schizophrenia research by means of single-subject classification.

The Concord Centre for Mental Health's new 'phase of illness' model of care: are we on the right track?

OBJECTIVE: The aim of this study was to provide an overview of a new 'phase of illness' model of care after relocation of Rozelle Hospital to the new purpose built Concord Centre for Mental Health and discuss its implementation and progress thus far. METHOD: One year after relocation, staff were asked to provide feedback of their views of the new model of care in order to identify implementation barriers and ways forward. RESULTS: The new model has clear benefits for the consumer, but there are a number of practical challenges and dilemmas emerging that necessitate some refinement and evaluation. Feedback from staff provided a wide range of opinions indicating that some were quite cynical of the new model while others were very supportive and thought that patient care was enhanced. CONCLUSIONS: Further development and consolidation of the model is required, including more education sessions and a clear mission statement at unit, hospital and community levels. Further research is also required to assess the impact and ability of the new model to deliver better patient outcomes, especially in regard to continuity of care.

Two subgroups of schizophrenia identified by systematic cognitive neuropsychiatric mapping.

The description of the heterogeneous phenomenological, pathophysiological, and etiological nature of schizophrenia is under way; however, the relationships between heterogeneity levels are still unclear. We performed a robust cross-sectional study, including a systematic neuropsychological battery, assessment of clinical symptoms, neurological soft signs, morphogenetic anomalies and smell identification, and measurement of event-related potentials on 50 outpatients with schizophrenia in their compensated states. An explorative fuzzy cluster analysis revealed two subgroups in this sample that could be distinguished from each other on symptomatological, cognitive and neurological levels. The patterns of cognitive dysfunctions and neurological developmental anomalies equally indicate that there may be hemispherical differences between the patients belonging to the different clusters.

Classification of schizophrenia. Part 2: The nonsense of mental health illness.

The classification of schizophrenia is currently under review in a coordinated worldwide consultation for the Diagnostic and Statistical Manual of Mental Disorders (DSM V) and the International Classification of Diseases (ICD 11)--the standard manuals for psychiatric classification. Classification can seem remote from nurses by appearing to be the antithesis of person-centred approaches to recovery. This should not be the case. Nurses need to critically engage with methods of classification in order to better understand the biological, psychological, social and political assumptions underpinning them. It will be shown that these assumptions often compete, and some common objections to the construct of schizophrenia can be viewed as a function of this. However, it is argued here that a truly holistic approach to care needs to engage with all these factors. The alternative is to simply reject the process as irrelevant to mental health nursing. It will be shown that a corollary of this latter approach is the invention of nonsense terms such as 'mental health illness' as a function of trying to simultaneously deny yet acknowledge the existence of mental illness.

A psychoneuroimmunological perspective to Emil Kraepelins dichotomy: schizophrenia and major depression as inflammatory CNS disorders.

The Kraepelinian classification of psychiatric disorders, in particular the dichotomy of dementia praecox and manic-depressive psychosis is under discussion since a long time. In recent years, not only new research in the fields of psychopathology and clinical outcome, but also findings of biological markers in the areas of neurophysiology, neuroendocrinology, psychoneuroimmunology, genetics, or psychopharmacology show a big overlap between both groups of disorders. This overlap of symptoms and markers of both disorders intensified the discussion and the proposals for new criteria for the classification of psychiatric disorders. By means of findings from the field of psychoneuroimmunology and inflammation it will be shown that different pathological mechanisms in depression and schizophrenia may lead to the same final common pathway of inflammation. These mechanisms include the immunological balance between type-1 and type-2 immune activation which influences the tryptophan-degradating enzyme indoleamine 2,3-dioxygenase (IDO) in the CNS in opposite ways, leading to an altered availability of tryptophan and serotonin, and a disturbance of the kynurenine metabolism with an imbalance in favor of the production of the NMDA-receptor agonist quinolinic acid in depression and of the NMDA-receptor antagonist kynurenic acid in schizophrenia. In both disorders, however, an increased production of prostaglandin E2 and increased expression of cyclo-oxygenase-2 reflect a slight inflammatory process taking place probably in different regions of the CNS. Albeit this common inflammatory pathway--inflammation is a general pathway of the body as answer to a lot of different noxae and pathogens--the Kraepelinian dichotomy is important with respect to pathological mechanisms and therapeutic approaches, not only for further research in understanding the exact pathological mechanisms but also for the development of preventive strategies in high risk individuals and in patients. Opposite pathways regarding the immune activation, the neurotoxic versus neuroprotective kynurenine metabolites and the agonistic versus antagonistic effects on the NMDA receptor and the glutamatergic neurotransmission show despite a possible therapeutic advantage of anti-inflammatory therapy in both disorders that the Kraepelinian dichotomy still has a significant value from a biologic-psychiatric point of view.

Hallucinatory disorder, an original clinical picture? Clinical and imaging data.

OBJECTIVE: The aim of this study was to verify the existence of areas of clinical and neurofunctional homogeneity in a group of patients with auditory verbal hallucinations (AVHs) as an isolated symptom, attributable to what we have called "Hallucinatory Disorder" (HD) in an attempt to propose a clinical picture that is distinct from Schizophrenia. METHOD: Nine patients clinically characterised by chronic AVHs were compared with nine schizophrenic patients using the Structured Clinical Interview for DSM-III-R, BPRS, PANSS, SAPS, SANS, HRS-A, HRS-D, CDSS, MMSE, CGI and PSYRATS. Both groups of patients and nine healthy subjects underwent EEG and SPECT examinations. RESULTS: Considering the psychopathological dimensions of Schizophrenia, in the HD patients clinical evaluations revealed a mono-dimensional clinical profile, whereas all these dimensions contributed to the clinical picture of the schizophrenic patients. The SPECT data showed that the schizophrenic patients had a reduced rCBF in some areas of the right frontal lobe, while the HD patients did not show any area of hypoperfusion. The SPECT hyperperfusion data showed an activation pattern in the HD patients that was characterised by the involvement of various cortical and subcortical cerebral areas, similar to those found in studies of inner speech and auditory verbal imagery. CONCLUSIONS: The two groups of patients present significant differences that seem capable of supporting the proposed hypothesis that HD may be an independent nosographical entity.

Physiology of schizophrenia, bipolar disorder, and schizoaffective disorder.

OBJECTIVE: Endophenotypes have been proposed to identify the genetic and biological substrates of complex disorders. Three physiological inhibitory endophenotypes of large effect size in schizophrenia include suppression of P50 auditory evoked responses, inhibition of leading (small anticipatory) saccades during smooth pursuit eye movements, and cancellation of reflexive saccades in the antisaccade eye movement task. The aim of this study was to determine if the pattern of endophenotype abnormalities within individuals with schizophrenia differed from that within individuals with bipolar disorder. A second aim was to determine whether subjects with schizoaffective disorder, bipolar type, were neurophysiologically more similar to subjects with schizophrenia or subjects with bipolar disorder. METHOD: Endophenotypes were recorded for subjects diagnosed with schizophrenia (N=29), bipolar disorder (DSM-IV-TR) (N=40), and schizoaffective disorder, bipolar type (N=18). Data from normal comparison subjects were used to establish normal performance. RESULTS: Logistic regression determined that P50 ratio and frequency of leading saccades identified subjects with schizophrenia and bipolar disorder with a sensitivity of 95% and a specificity of 83%. The schizoaffective disorder group was split, with six subjects physiologically classified as schizophrenia-like and 12 subjects as bipolar-like. Those classified as schizophrenia-like were significantly younger at illness onset and had higher symptom ratings. CONCLUSION: A composite endophenotype of P50 ratio and frequency of leading saccades is consistent with the current clinical nosology of schizophrenia and bipolar disorder and parses patients with schizoaffective disorder, bipolar type, into two subgroups.

Characteristics of two alternative schizophrenia remission definitions: relationship to clinical and quality of life outcomes.

BACKGROUND: The goal of these secondary analyses of clinical trial data was to characterize clinical outcomes in patients with schizophrenia who met symptom severity or duration thresholds for two alternative definitions of remission, and to explore their relationships to improvement duration and quality of life outcomes. METHODS: Definition 1 used threshold criteria for selected PANSS items sustained over at least 6-months Definition 2 used Brief Psychiatric Rating Scale (BPRS) % change, a threshold score for the Clinical Global Improvement-Severity (CGI-S) maintained for at least 8 weeks, and threshold scores for selected BPRS items. Positive and Negative Symptom Scale (PANSS) and Quality of Life scale (QLS) total scores were pooled from 6 clinical trials. The extent to which the alternative severity thresholds from these two definitions and duration of clinical improvement were associated with different clinical and QLS outcomes was explored. Regression analysis also assessed the relative contribution of each of the components of the two definition severity thresholds to improvements in QLS Total score. RESULTS: Increases in QLS scores were greater for those patients who met either threshold criteria relative to those who met neither (p<.0001). Significantly greater improvements in QLS scores were observed for patients who met either threshold criteria at the 8-, 16- and 24-week visits relative to those who met criteria at weeks 16 and 24, or at week 24 only (p<0.001), as well as for the subset of patients who met threshold criteria at both 24 and 52 weeks relative to those who met criteria at only one of these 2 time points. Only 31% to 47% of patients meeting threshold criteria for either definition at the 8-, 16- or 24-week visits remained in remission at the 52-week visit. Among the severity threshold components analyzed, BPRS total % change from baseline was the strongest predictor of improvement in QLS scores. CONCLUSIONS: Quality of life improved most for patients who achieved severity thresholds associated with either remission criteria and who stayed improved for longer periods. Total BPRS change scores accounted for the greatest percentage of the QLS scores variance. Only a fraction of patients who meet severity criteria for either remission definition early in treatment will remain at that level of improvement within the subsequent 9-12 months.

Lista integrada de criterios diagnósticos para la esquizofrenia (LIDESQ) / Integrated list of criteria diagnoses for the schizophrenia (LIDESQ)

En el presente trabajo nosostros elaboramos un instrumento útil para el uso clínico y la investigación. El resultado es una lista de síntomas para facilitar el diagnóstico de esquizofrenia. Los ítems (55 en total) han sido creados tras la integración de los criterios para esquizofrenia de las clasificaciones internacionales CIE-10 y DSM-IV, pero se incluyen también otros criterios y clasificaciones como los de Kraepelin, Bleuler, Schneider, Langfeldt, Feighner, Astrachan y Taylor/Abraham (AU)

Defining the phenotype of schizophrenia: cognitive dysmetria and its neural mechanisms.

All research on schizophrenia depends on selecting the correct phenotype to define the sample to be studied. Definition of the phenotype is complicated by the fact that there are no objective markers for the disorder. Further, the symptoms are diverse, leading some to propose that the disorder is heterogeneous and not a single disorder or syndrome. This article explores an alternative possibility. It proposes that schizophrenia may be a single disorder linked by a common pathophysiology (a neurodevelopmental mechanism), which leads to a misconnection syndrome of neural circuitry. Evidence for disruption in a specific circuit is explored: the cortical-thalamic-cerebellar-cortical circuit (CCTCC). It is suggested that a disruption in this circuit leads to an impairment in synchrony, or the smooth coordination of mental processes. When synchrony is impaired, the patient suffers from a cognitive dysmetria, and the impairment in this basic cognitive process defines the phenotype of schizophrenia and produces its diversity of symptoms.

Delineation of acute and transient psychotic disorders in a developing country setting.

BACKGROUND: We examined whether acute transient psychoses can be distinguished from schizophrenia and the affective disorders. METHOD: We studied 46 cases of nonaffective acute psychosis in the Chandigarh Acute Psychosis Study. With respect to separation from schizophrenia, we examined the distribution of duration of the episode. With respect to separation from affective disorders, we assessed the frequency of affective symptoms. RESULTS: Duration was bimodal, suggesting the presence of two distinct conditions of short and long duration. Affective symptoms were minimal, suggesting that these were not atypical affective syndromes. CONCLUSIONS: Acute transient psychoses conform neither with schizophrenia of brief duration nor with atypical affective psychosis, and thus require separate classification as proposed in the ICD-10.

A selenium transport protein model of a sub-type of schizophrenia.

The model presented here suggests that a defect in a selenium transport protein may be a necessary but not sufficient precondition for a sub-type of schizophrenia--a type of schizophrenia that has been characterized by negative symptoms, brain damage, and a lack of primarily paranoid ideation. A defective selenium transport protein and consequent low levels of selenium might adversely affect multiple enzyme systems. Selenium-enzyme interreactions are discussed and the effect of selenium on arachidonic acid and its metabolites, especially 12-HPETE, are examined in light of the presented model. If the proffered model is essentially correct, selenoprotein P, a hypothesized selenium transport protein, is a likely candidate for a protein involved in the etiology of a form of schizophrenia.

Belief in the paranormal and its relationship to schizophrenia-relevant measures: a confirmatory study.

This study was an attempt to confirm previously reported findings that persons who believe in and claim experience of the paranormal tend to score higher on various measures relevant to schizophrenia. Level of belief in the paranormal was measured in a sample of university students. As predicted, those subjects whose scores indicated higher belief in the paranormal tended to score significantly higher on the Magical Ideation Scale, the Perceptual Aberration Scale, and the combined Perceptual Aberration-Magical Ideation (Per-Mag) Scale. However, the correlation with the MMPI's Schizophrenia Scale was significant for males only.

Social anxiety in schizophrenia.

The relationship between social anxiety and positive and negative symptomatology in schizophrenia was investigated. Thirty eight inpatients with schizophrenia completed a battery of self-report measures of anxiety, a modified Stroop task, and an unstructured role play. Positive symptoms were related to fear in a number of self-report domains (i.e., social and agoraphobic). Negative symptoms were related to global observational ratings of anxiety during the role play as well as specific behaviors associated with self-reported social anxiety (i.e., speech rate and fluency). Positive symptoms generally were not associated with role play ratings. Thus, specific behaviors related to social anxiety appear to be associated with negative symptoms, while self-report is associated with positive symptoms. Problems in the assessment of social anxiety in individuals with schizophrenia and implications of these findings for social skills training in this population are discussed.

A propósito de lo biológico en esquizofrenia / Biological alterations in Schizophrenia

Se exponen algunos hallazgos biologicos correspondientes a la alteracion de las estructuras cerebrales encontradas en esquizofrenicos. En los estudios post-mortem y enlos de imagenologia in vivo: se ha verificado disminucion del volumen cerebral, aumento de las cavidades ventriculares y de los surcos de la corteza, alteraciones neuronales y funcionales de los lobulos prefrontales y temporales medios, a predominio izquierdo y de sus conexiones, disminucion de la sustancia gris central, del numero de neuronas del nucleo dorsal del talamo y del nucleo accumbens. Es indudable la influencia del factor genetico, aunque los modelos del gen simple no son compatibles con los datos de los gemelos y familias. Es plausible la existencia de un desorden neurointegrativo asociado a un factor genetico y a circunstancias ambientales para la produccion de esquizofrenia. Acerca de la hipotesis dopaminergica, se ha aceptado mas para los sindromes positivos que muchos no los consideran propiamente esquizofrenicos, salvo los que se repiten y terminan en la cronicidad. Para los sindromes negativos "verdadera esquizofrenia", se propone la hipodopaminergia