Reappraisal of Dementia Praecox: focus on clinical psychopathology.

One century of investigation in schizophrenia is still not enough to elucidate all the complex issues related to the essential symptomatology, clinical boundaries, aetiology, pathogenesis, outcome, treatment and prevention. Despite the extraordinary progress in the neuroscience field, no definitive data is available for schizophrenia. On the other hand, after the successful activity of the psychopharmacological era, the clinical psychopathological investigations were reduced and almost replaced by the mechanistic operational diagnosis. This has caused an impoverishment in psychiatry. Tracing some historical aspects of schizophrenia since the kraepelinian Dementia Praecox, this article intends to demonstrate the failure of the current model of diagnosis and current limitation of neuroscience. It advocates the reinforcement of Clinical Psychopathology as the foundation for correct and appropriate first steps in the investigation of schizophrenia. The splitting disease is still a challenge to biological psychiatry.     

The Psychopathology and Neuroanatomical Markers of Depression in Early Psychosis

Depression frequently occurs in first-episode psychosis (FEP) and predicts longer-term negative outcomes. It is possible that this depression is seen primarily in a distinct subgroup, which if identified could allow targeted treatments. We hypothesize that patients with recent-onset psychosis (ROP) and comorbid depression would be identifiable by symptoms and neuroanatomical features similar to those seen in recent-onset depression (ROD). Data were extracted from the multisite PRONIA study: 154 ROP patients (FEP within 3 months of treatment onset), of whom 83 were depressed (ROP+D) and 71 who were not depressed (ROP−D), 146 ROD patients, and 265 healthy controls (HC). Analyses included a (1) principal component analysis that established the similar symptom structure of depression in ROD and ROP+D, (2) supervised machine learning (ML) classification with repeated nested cross-validation based on depressive symptoms separating ROD vs ROP+D, which achieved a balanced accuracy (BAC) of 51%, and (3) neuroanatomical ML-based classification, using regions of interest generated from ROD subjects, which identified BAC of 50% (no better than chance) for separation of ROP+D vs ROP−D. We conclude that depression at a symptom level is broadly similar with or without psychosis status in recent-onset disorders; however, this is not driven by a separable depressed subgroup in FEP. Depression may be intrinsic to early stages of psychotic disorder, and thus treating depression could produce widespread benefit.     

Dementia praecox to schizophrenia: The first 100 years

The historical roots of dementia praecox and schizophrenia are described in the context of current nosology and continuing controversies surrounding this nosology. Relevant books and journal articles were reviewed. The information was obtained through computer searches and cross-references from previously published papers. If English translations of foreign language articles were available, they were used; if not, the cross-references were consulted. The psychoses have existed as diagnostic categories from ancient times although their names have changed. Initially, these disorders were considered diseases of the brain, a concept that was swept aside in the United States, influenced by European-derived psychodynamic theories. American clinicians and investigators simply accepted these theories, showing little interest in testing their underlying principles. In contrast, a narrower Kraepelinian approach was adopted outside the United States, and attempts were made to refine its nosology. Because current data supports a central nervous system aetiology for schizophrenia, the concept of dementia praecox warrants resurrection. The authors suggest abandoning the term schizophrenia in favour of the more broad and generic term dementia praecox. Replacing 'schizophrenia' with 'dementia praecox' in the 21st century will facilitate further research and help clarify the nosology of various brain disorders currently included in the schizophrenias.     

Psychopathology and treatment responsiveness of patients with first-episode schizophrenia

One hundred and four male patients hospitalized for the first time with the diagnosis of first-episode schizophrenia were comprehensively assessed on admission and discharge. Psychopathology, treatment response, and remission rates were evaluated (based on the Positive and Negative Syndrome Scale (PANSS), severity of symptoms only). On admission, the most frequently observed symptoms were lack of judgment and insight (87.6%), suspiciousness/feelings of persecution (82.3%), delusions (77%), poor attention (70%), disturbance of volition (65.4%), conceptual disorganization (64.7%), and active social avoidance (64%). Except for delusions and hallucinations, the positive items of the PANSS correlated significantly with negative symptoms, and conceptual disorganization correlated with the greatest number of negative symptoms. Individual negative symptoms were present in about half the patients. At discharge, the most frequent symptoms were again lack of judgment and insight (in 55.7%), and for negative symptoms they were blunted affect (22.1%), emotional withdrawal (21.2%), and passive/apathetic social withdrawal (19.5%). The positive symptoms of suspiciousness/feelings of persecution and grandiosity persisted in 20.6% of patients. On average, all symptoms were significantly reduced 44 days after admission. The negative symptoms improved less, compared with the positive ones. At discharge there was a high rate of responders (response defined as minimal 30% reduction of total PANSS): 73% and 74% of patients fulfilled the criteria for remission. On admission, the responders (n = 76) had significantly higher scores of most symptoms, both positive and negative ones than nonresponders (n = 28).     

Psychopathology and outcome of first-admission schizophrenic patients: hypochondriac-cenestopathic symptoms as predictors of an unfavorable outcome

The outcome of first-admission schizophrenic patients at Jichi Medical School Hospital was investigated to identify outcome predictors of schizophrenia among the symptoms at the time of the first hospitalization. The subjects were 62 schizophrenic patients, 29 females and 33 males, consecutively discharged from the Department of Psychiatry, Jichi Medical School Hospital, between June 1983 and May 1988. The mean interval between first admission and follow-up was 13 years. Eguma's Social Adjustment Scale was used to measure social outcome. The subjects were divided into two groups according to their rating on Eguma's Scale; a favorable outcome group and an unfavorable outcome group. Information on premorbid status and psychopathology at the time of the first hospitalization was obtained from clinical records and analyzed by comparing them between the two groups. Of the 62 patients, 56 were followed-up. Nine of the 56 patients followed-up had died. While 47 patients were alive; 39 were receiving psychiatric treatment and eight were not. The 47 patients who were still living were divided into two groups; a favorable outcome group (n = 22), and an unfavorable outcome group (n = 25). No significant differences in premorbid status were found. Comparison of psychopathology at the time of the first hospitalization between the outcome groups revealed significant differences in lack of spontaneity and hypochondriac-cenestopathic symptoms. Lack of spontaneity may reflect negative symptomatology, while hypochondriac-cenestopathic symptoms may reflect a serious disturbance of ego function. There is a strong possibility that evaluation of body-related symptoms in schizophrenia will be helpful in predicting outcome.     

Testing the Psychopathology of Psychosis: Evidence for a General Psychosis Dimension

Background: Psychiatric taxonomists have sometimes argued for a unitary psychosis syndrome and sometimes for a pentagonal model, including 5 diagnostic constructs of positive symptoms, negative symptoms, cognitive disorganization, mania, and depression. This continues to be debated in preparation for impending revisions of the Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Diseases. We aimed to identify general and specific dimensions underlying psychopathological features of psychosis. Methods: The samples comprised 309 patients admitted to psychiatric services in the acute phase of their first or second episode of psychosis and 507 patients with enduring psychosis recruited from community mental health teams. Patients’ symptoms were assessed on the Positive and Negative Symptom Scale. Analyses compared unitary, pentagonal, and bifactor models of psychosis. Results: In both samples, a bifactor model including 1 general psychosis factor and, independently, 5 specific factors of positive symptoms, negative symptoms, disorganization, mania, and depression gave the best fit. Scores of general and specific symptom dimensions were differentially associated with phase of illness, diagnosis, social functioning, insight, and neurocognitive functioning. Conclusions: The findings provide strong evidence for a general psychosis dimension in both early and enduring psychosis. Findings further allowed for independent formation of specific symptom dimensions. This may inform the current debate about revised classification systems of psychosis.     

Searching for bridges between psychopathology and real-world functioning in first-episode psychosis: A network analysis from the OPTiMiSE trial

BackgroundNetwork analysis has been used to explore the interplay between psychopathology and functioning in psychosis, but no study has used dedicated statistical techniques to focus on the bridge symptoms connecting these domains. The current study aims to estimate the network of depressive, negative, and positive symptoms, general psychopathology, and real-world functioning in people with first-episode schizophrenia or schizophreniform disorder, focusing on bridge nodes.MethodsBaseline data from the OPTiMiSE trial were analyzed. The sample included 446 participants (age 40.0 ± 10.9 years, 70% males). The network was estimated with a Gaussian graphical model, using scores on individual items of the positive and negative syndrome scale (PANSS), the Calgary depression scale for schizophrenia, and the personal and social performance scale. Stability, strength centrality, expected influence (EI), predictability, and bridge centrality statistics were computed. The top 20% scoring nodes on bridge strength were selected as bridge nodes.ResultsNodes from different rating scales assessing similar psychopathological and functioning constructs tended to cluster together in the estimated network. The most central nodes (EI) were Delusions, Emotional Withdrawal, Depression, and Depressed Mood. Bridge nodes included Depression, Conceptual Disorganization, Active Social Avoidance, Delusions, Stereotyped Thinking, Poor Impulse Control, Guilty Feelings, Unusual Thought Content, and Hostility. Most of the bridge nodes belonged to the general psychopathology subscale of the PANSS. Depression (G6) was the bridge node with the highest value.ConclusionsThe current study provides novel insights for understanding the complex phenotype of psychotic disorders and the mechanisms underlying the development and maintenance of comorbidity and functional impairment after psychosis onset.     

Is violence at presentation by patients with first-episode psychosis associated with duration of untreated psychosis?

Introduction Violence in first episode psychosis poses significant challenges for mental health staff and patients’ families. Violence has been shown to be related to psychopathology. Duration of untreated psychosis (DUP) has been shown to influence psychopathology at presentation in first-episode psychosis, but little is known about the direct relationship between violence at presentation and DUP. We therefore sought to examine the relationship between these two variables. Methods Patients were all individuals aged between 16 and 65 years, with a DSM-III-R diagnosis of psychotic illness, taking part in a First Episode study. We used the Structured Clinical Interview (SCID-I), Positive and Negative Symptom Scale (PANSS), Beiser Scale and the Modified Overt Aggression Scale (MOAS) to evaluate diagnosis, psychopathology, DUP and violent behaviour respectively. Data for each case were retrospectively examined for violence, for the week prior to and week following first contact with psychiatric services, blind to diagnosis, DUP and psychopathology scores. Results We assessed 157 patients. About 46 patients (29%) were violent. Violence rates did not differ across diagnostic groups, while DUP varied significantly across diagnostic groups (P = 0.001). Violence was not associated with DUP across all psychoses (P = 0.41). In the schizophrenia subgroup (n = 94), thirty individuals (32%) were violent. In a logistic regression, logDUP was not associated with violence (P = 0.11). Violence was predicted by involuntary admission status (P = 0.04) and global positive symptoms (P = 0.03). DUP was associated weakly with negative symptoms (P = 0.01) but not associated with positive or general psychopathology. Neither pre nor post-contact violence was associated (P = 0.79 and P = 0.09 respectively) with DUP. Discussion Contrary to a recent study, we did not find an association between violence at presentation and DUP. The relationships between violence, DUP and psychopathology are complex and may be compounded by potential difficulties inherent in the PANSS. Conclusion Programs to reduce DUP may not impact on rates of violence at presentation in First Episode Psychosis (FEP).     

Endorphins in human cerebrospinal fluid: Clinical correlations to some psychotic states

The significance of endorphins, endogenous morphine-like agents, in some psychiatric disorders was investigated. Samples of cerebrospinal fluid were taken by lumbar puncute from healthy volunteers and from patients with schizophrenic, manic-depressive and puerperal psychosis and analyzed for two major fractions of endorphins (Fractions I and II). In 19 healthy volunteers the levels of the two fracstions fell within a fairly narrow range. In constrast, six out of nine drug-free and symptom-rich schizophrenics showed elevated levels of Fracstion I, which returned to normal or slightly supranormal values after treatment with neuroleptics or propranolol. This decrement was paralleled by a clinical improvement in four of six responding patients. In four manic-depressive patients, serial samples of cerebrospinal fluid revelaed elevated endorphin levels, particularly Fraction I during the manic stage. In three out of four patients with puerperal psychosis, the levels of endorphins (either Fraction I or II) were elevated in the acute drug-free stage. During a later symjptomfree stage, after treatment with ECT and/or neuroleptics, the endorphin levles were within the normal range. The present data lend credit to the hypothesis that endorphins are involved in some psychotic states in the human.     

Clinical interventions for women with schizophrenia: pregnancy

Objective: A comprehensive treatment program for schizophrenia needs to include services to women of childbearing age that address contraception, pregnancy, and postpartum issues, as well as safe and effective parenting. To update knowledge in these areas, a summary of the recent qualitative and quantitative literature was undertaken. Method: The search terms ‘sexuality,’‘contraception,’‘pregnancy,’‘postpartum,’‘custody,’ and ‘parenting’ were entered into PubMed, PsycINFO, and SOCINDEX along with the terms ‘schizophrenia’ and ‘antipsychotic.’ Publications in English for all years subsequent to 2000 were retrieved and their reference lists further searched in an attempt to arrive at a distillation of useful clinical recommendations. Results: The main recommendations to care providers are as follows: take a sexual history and initiate discussion about intimate relationships and contraception with all women diagnosed with schizophrenia. During pregnancy, adjust antipsychotic dose to clinical status, link the patient with prenatal care services, and help her prepare for childbirth. There are pros and cons to breastfeeding while on medication, and these need thorough discussion. During the postpartum period, mental health home visits should be provided. Parenting support is critical. Conclusion: The comprehensive treatment of schizophrenia in women means remembering that all women of childbearing age are potential new mothers.     

Offspring of women with nonorganic psychosis: mother-infant interaction at one year of age

Mother-infant interaction during feeding and in an unstructured play situation was studied in the home at 1 year of age in 46 index mother-infant pairs in which the mother had a history of nonorganic psychosis and in 80 demographically similar control pairs. As was true at the five previous observation ages, some aspects of the interaction were significantly more negative in index than control pairs. Index mothers showed increased tension and uncertainty regarding the infant's needs, increased physical contact during feeding and a discrepancy between the intonation and content of the mother's verbal contact with the infant. Index infants did not differ from controls in behavior in interaction. Across the entire first year, the Cycloid and Schizophrenic mothers deviated most frequently from controls, while the Affectives' interaction was more negative than controls' for the first time at the 1-year observation.     

A prospective study of postpartum psychoses in a high-risk group. 1. Clinical characteristics of the current postpartum episodes

Postpartum psychotic episodes (PPPs) occurring during the first 6 months after delivery were prospectively studied in 88 pregnant index women with a history of nonorganic psychosis and 104 pregnant controls with no such history. While no control developed a PPP, PPPs were found following 28% of the index deliveries, almost all of these 25 cases being psychiatrically hospitalized. PPPs were especially frequent among cases with total illness diagnoses of Cycloid Psychosis and Affective Illness. More than half of the 25 cases had symptom onset within 3 weeks of delivery, and these early onset cases represented predominantly affective disorders, many of whom were manic in this episode. Cases with onset after 3 weeks were predominantly schizophrenic. Confusion was part of the current episode symptomatology in about one third of the cases and was well distributed across the different diagnostic groups.     

Integrated genetic and genomic approach in the SingaporeTranslational and Clinical Research in Psychosis Study: an overview

Aims: Schizophrenia is a severe mental disorder with onset frequently in adolescence and followed by a chronic and disabling course. Although the exact pathophysiology of this devastating disorder has not been clearly elucidated, a large part of it has been attributed to genetic influences. This article seeks to provide an overview on what our group has embarked on – to elucidate genetic risk factors for schizophrenia within the Chinese ethnic group. Methods: We plan to conduct an integrated approach to interrogate comprehensively the genome from different angles and in stages. The first stage involves a genome‐wide association study of 1000 cases of schizophrenia‐control pairs, with a follow‐up replication study in another 1000 cases of schizophrenia and in 1000 controls, and combination analyses with groups from other places including China and Hong Kong. Other than the genome‐wide association study, gene sequencing for purported candidate genes and copy number variation analysis will be performed. Neurocognitive intermediate phenotypes will be employed to deconstruct the complex schizophrenia phenotype in a bid to improve association findings. Promising leads from longitudinal gene and protein expression in ultra‐high‐risk subjects who develop psychosis and schizophrenia (in a parallel study) will be followed up as candidate genes and sequenced in the genetic analysis. Functional analysis forms the last stage of this integrated approach. Conclusion: This integrated genetic and genomic approach will hopefully help in further characterizing and deepening our understanding of molecular pathophysiological mechanisms underlying schizophrenia.