Chronic Stages Of Schizophrenia Research Articles

Understanding the mechanisms underlying cognitive control in psychosis.

Cognitive control (CC) involves a top-down mechanism to flexibly respond to complex stimuli and is impaired in schizophrenia. This study investigated the impact of increasing complexity of CC processing in 140 subjects with psychosis and 39 healthy adults, with assessments of behavioral performance, neural regions of interest and symptom severity. The lowest level of CC (Stroop task) was impaired in all patients; the intermediate level of CC (Faces task) with explicit emotional information was most impaired in patients with first episode psychosis. Patients showed activation of distinct neural CC and reward networks, but iterative learning based on the higher-order of CC during the trust game, was most impaired in chronic schizophrenia. Subjects with first episode psychosis, and patients with lower symptom load, demonstrate flexibility of the CC network to facilitate learning, which appeared compromised in the more chronic stages of schizophrenia. These data suggest optimal windows for opportunities to introduce therapeutic interventions to improve CC.

Differential impacts of endogenous antioxidants on clinical symptoms and cognitive function in acute and chronic schizophrenia patients.

Impaired antioxidant defense is implicated in the pathophysiology of schizophrenia; and superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) are three first-line endogenous antioxidants. Various cognitive functions decline differently during schizophrenia course. The characteristic roles of the three antioxidants in clinical and cognitive profiles in acute and chronic phases of schizophrenia require study. We recruited 311 patients with schizophrenia, including 92 acutely exacerbated patients who had been off antipsychotics for at least 2 weeks and 219 chronic patients who had been stable on medication for at least 2 months. Blood SOD, CAT, and GSH, clinical symptoms, and nine cognitive tests were measured. Blood CAT levels were higher in the acute patients than in the chronic patients, while SOD and GSH levels were similar between them. Higher CAT levels were correlated with less positive symptoms, better working memory and problem solving in the acute phase, and less negative symptoms, less general psychopathology, better global assessment of function (GAF), and better cognitive function (in speed of processing, attention, problem solving) in the chronic period. Higher SOD levels were correlated with better GAF in the acute phase, and better speed of processing, working memory, and verbal learning and memory in the chronic period. GSH influenced neither clinical nor cognitive manifestations. This study showed that blood CAT affected different clinical and cognitive domains between acute and chronic stages of schizophrenia, SOD influenced cognitive functions in chronic state, but GSH impacted none. Further studies are needed to explore the underlying mechanisms.

Obsessions and Delusions: The Clinical Overlap and Differential Diagnosis of Obsessive-Compulsive and Psychotic Disorders

Obsessive-compulsive symptoms (OCS) are commonly observed in the pre-illness, prodromal, first-episode, and chronic stages of schizophrenia. Similarly, patients with obsessive-compulsive disorder (OCD) can present with delusional levels of conviction that border on psychosis. Transitions between OCD and schizophrenia spectrum disorders are also common. The phenomenological overlap between obsessions and delusions can be challenging for accurate diagnosis and treatment planning. Clinicians may struggle to differ entiate obsessions from delusions in severe OCD and similarly may not know if the emerging obsessive symptoms in schizophrenia require specialized OCD treatment. This review summarizes the current literature on comorbid obsessive-compulsive and psychotic disorders, transitions between these two disorders, the impact on prognosis, and the clinical strategies in differential diagnosis as well as treatment planning. [ Psychiatr Ann . 2023;53(5):199–203.]

Duration Mismatch Negativity Predicts Remission in First-Episode Schizophrenia Patients.

Objective: Remission in schizophrenia patients is associated with neurocognitive, social, and role functioning during both the early and chronic stages of schizophrenia. It is well-established that the amplitudes of duration mismatch negativity (dMMN) and frequency MMN (fMMN) are reduced in schizophrenia patients. However, the potential link between MMN and remission has not been established. In this study, we investigated the relationship between MMNs and remission in first-episode schizophrenia (FES) and their association with neurocognitive and social functioning.Method: dMMN and fMMN were measured in 30 patients with FES and 22 healthy controls at baseline and after a mean of 3 years. Clinical symptoms and cognitive and social functioning in the patients were assessed at the time of MMN measurements by using the Positive and Negative Syndrome Scale (PANSS), modified Global Assessment of Functioning (mGAF), Schizophrenia Cognition Rating Scale (SCoRS), and the Brief Assessment of Cognition in Schizophrenia (BACS). Remission of the patients was defined using the criteria by the Remission in Schizophrenia Working Group; of the 30 patients with FES, 14 achieved remission and 16 did not.Results: Baseline dMMN amplitude was reduced in FES compared to healthy controls. Further, baseline dMMN in the non-remitters had decreased amplitude and prolonged latency compared to the remitters. MMN did not change during follow-up period regardless of parameters, diagnosis, or remission status. Baseline dMMN amplitude in FES was correlated with future SCoRS and PANSS total scores. Logistic regression analysis revealed that dMMN amplitude at baseline was a significant predictor of remission.Conclusions: Our findings suggest that dMMN amplitude may be a useful biomarker for predicting symptomatic remission and improvement of cognitive and social functions in FES.

Stable habituation deficits in the early stage of psychosis: a 2-year follow-up study

Neural habituation, the decrease in brain response to repeated stimuli, is a fundamental, highly conserved mechanism that acts as an essential filter for our complex sensory environment. Convergent evidence indicates neural habituation is disrupted in both early and chronic stages of schizophrenia, with deficits co-occurring in brain regions that show inhibitory dysfunction. As inhibitory deficits have been proposed to contribute to the onset and progression of illness, habituation may be an important treatment target. However, a crucial first step is clarifying whether habituation deficits progress with illness. In the present study, we measured neural habituation in 138 participants (70 early psychosis patients (<2 years of illness), 68 healthy controls), with 108 participants assessed longitudinally at both baseline and 2-year follow-up. At follow-up, all early psychosis patients met criteria for a schizophrenia spectrum disorder (i.e., schizophreniform disorder, schizophrenia, schizoaffective disorder). Habituation slopes (i.e., rate of fMRI signal change) to repeated images were computed for the anterior hippocampus, occipital cortex, and the fusiform face area. Habituation slopes were entered into a linear mixed model to test for effects of group and time by region. We found that early psychosis patients showed habituation deficits relative to healthy control participants across brain regions, and that these deficits were maintained, but did not worsen, over two years. These results suggest a stable period of habituation deficits in the early stage of schizophrenia.

Karl Leonhard (1904-88) and his academic influence through the 'Erlangen School'.

The Erlangen University Psychiatric and Mental Clinic was an annexe to the Erlangen Mental Asylum, so when Leonhard worked there he became acquainted with acute and chronic stages of schizophrenia. This can be viewed as a decisive impulse for his later differentiated classification of types of schizophrenia. The suspicion that Leonhard suffered from attention deficit hyperactivity disorder cannot be supported. His reticence concerning social-psychiatric aspects is analysed in the context of his early professional contact with the 'Erlangen system' of open care and its Nazi perversion. Leonhard's role in National Socialism is still uncertain. His unsuccessful attempts to retain the Erlangen Chair of Psychiatry and Mental Illness in 1951 can be viewed as his first difficulty in the tensions between West Germany and East Germany.

Neuropsychological functioning in early and chronic stages of schizophrenia and psychotic bipolar disorder

BackgroundNeuropsychological impairment is common in schizophrenia and psychotic bipolar disorder. It has been hypothesized that the pathways leading to impairment differ between disorders. Cognitive impairment in schizophrenia is believed to result largely from atypical neurodevelopment, whereas bipolar disorder is increasingly conceptualized as a neuroprogressive disorder. The current investigation tested several key predictions of this hypothesis. MethodsCurrent neuropsychological functioning and estimated premorbid intellectual ability were assessed in healthy individuals (n = 260) and a large, cross-sectional sample of individuals in the early and chronic stages of psychosis (n = 410). We tested the following hypotheses: 1) cognitive impairment is more severe in schizophrenia in the early stage of psychosis; and 2) cognitive decline between early and chronic stages is relatively greater in psychotic bipolar disorder. Additionally, individuals with psychosis were classified as neuropsychologically normal, deteriorated, and compromised (i.e. below average intellectual functioning) to determine if the frequencies of neuropsychologically compromised and deteriorated patients were higher in schizophrenia and psychotic bipolar disorder, respectively. ResultsNeuropsychological impairment in the early stage of psychosis was more severe in schizophrenia. Psychotic bipolar disorder was not associated with relatively greater cognitive decline between illness stages. The frequency of neuropsychologically compromised patients was higher in schizophrenia; however, substantial portions of both schizophrenia and psychotic bipolar disorder patients were classified as neuropsychologically compromised and deteriorated. ConclusionsWhile schizophrenia is associated with relatively greater neurodevelopmental involvement, psychotic bipolar disorder and schizophrenia cannot be strictly dichotomized into purely neuroprogressive and neurodevelopmental illness trajectories; there is evidence of both processes in each disorder.

"Brain Connectivity Deviates by Sex and Hemisphere in the First Episode of Schizophrenia"-A Route to the Genetic Basis of Language and Psychosis?

Schizophrenia is genetic in origin and associated with a fecundity disadvantage. The deficits in schizophrenia have been attributed to variation related to the human capacity for language or brain laterality. How sex influences the relative connectivity of the 2 hemispheres is a route to understanding these 2 functions. Using resting-state functional magnetic resonance imaging (fMRI) we searched for sex- and hemisphere-specific changes in whole-brain functional-connectivity in multi-site datasets (altogether 672 subjects including 286 patients, all right-handed) in the first-episode schizophrenia (illness duration ≤ 1 year, mostly drug naive) and in chronic stages of schizophrenia (illness duration > 1 year), respectively. We used meta-analyses to integrate data from different sources concerning individuals at the same illness stage. We found first-episode male patients are predominantly left-lateralized in aberrant connectivity with a focus on Broca's area. Female patients show a lesser degree of lateralization than males, but to the right particularly in orbital frontal cortex. In the chronic stage, the focus of aberrant connectivity shifted from anterior to posterior structures with prominent involvement of the thalamus and pre- and post-central gyri bilaterally and in both sexes. While the "deviant connectivity" is right-sided in both the first-episode and the chronic stages in females, in males there is a shift between stages from the left to the right hemisphere. We hypothesized that the pathophysiology of schizophrenia may lie in the interaction between sex and lateralization, ie, in genetic mechanisms located on the X and Y chromosomes, intrinsic to the evolution of language.

Ginkgo biloba induced mood dysregulation: a case report

BackgroundImpairment of cognitive function as well as negative symptom is the major factor causing the decline of a patient’s functioning in chronic stages of schizophrenia. However, until now, there were no definite treatment options that could effectively reduce the impairment.Case presentationWe report a case of mood dysregulation associated with use of Ginkgo biloba in a patient with schizophrenia. After Ginkgo biloba was given, the patient experienced cluster symptoms of mood dysregulation including irritability, difficulty in controlling anger, agitation and restlessness. We estimated the possibility as “probable” according to Naranjo scale considering circumstantial evidence.ConclusionsThis case suggests that Ginkgo biloba may have caused mood dysregulation in this patient. Although it is generally accepted as safe, more attention should be given to the adverse effect when treating with Ginkgo biloba.

Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia.

Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functional-connectivity differences in prodromal, FE (mostly drug naïve), and chronic patients from their matched controls from 6 independent datasets involving a total of 789 participants (343 patients). Brain-wide functional-connectivity analysis was performed in different datasets and the results from the datasets of the same stage were then integrated by meta-analysis, with Bonferroni correction for multiple comparisons. Prodromal patients differed from controls in their pattern of functional-connectivity involving the inferior frontal gyri (Broca's area). In FE patients, 90% of the functional-connectivity changes involved the frontal lobes, mostly the inferior frontal gyrus including Broca's area, and these changes were correlated with delusions/blunted affect. For chronic patients, functional-connectivity differences extended to wider areas of the brain, including reduced thalamo-frontal connectivity, and increased thalamo-temporal and thalamo-sensorimoter connectivity that were correlated with the positive, negative, and general symptoms, respectively. Thalamic changes became prominent at the chronic stage. These results provide evidence for distinct patterns of functional-dysconnectivity across FE and chronic stages of schizophrenia. Importantly, abnormalities in the frontal language networks appear early, at the time of disease onset. The identification of stage-specific pathological processes may help to understand the disease course of schizophrenia and identify neurobiological markers crucial for early diagnosis.

Lack of progressive reduction in P3 amplitude after the first–episode of schizophrenia: A 6-year follow-up study

P3 event-related potential may track the course of neurophysiological pathology in schizophrenia. Reduction in the amplitude of the auditory P3 is a widely replicated finding, already present at the first psychotic episode, in schizophrenia. Whether a progressive deficit is present in auditory P3 in schizophrenia over the course of illness is yet to be clarified. Previous longitudinal studies did not report any change in P3 over time in schizophrenia. However, these studies have been inconclusive, because of their relatively short follow-up periods, lack of follow-up data on controls, and assessment of patients already at the chronic stages of schizophrenia. Auditory P3 potentials, elicited by an oddball paradigm, were assessed in 14 patients with first-episode schizophrenia and 22 healthy controls at baseline and at the 6-year follow-up. P3 amplitudes were smaller in patients with first-episode schizophrenia than in controls. Importantly, over the 6-year interval, the P3 amplitudes were reduced in controls, but they did not change in patients. The lack of P3 reduction over time in patients with schizophrenia might be explained by the maximal reduction in P3 already at baseline or by the alleviation of P3 reduction over time.

Karl Leonhard (21.03.1904-23.04.1988)

Introduction The procedure of meticulous description of the signs and symptoms of disease with ascription to localization applied was decisive to Leonhard's phenomenological approach to the classification of endogenous psychoses. Objectives/Aims Karl Leonhard is to be honored by the Department of Psychiatry at the University of Erlangen, the starting point and character-moulder of his clinical and academic career. Material and Methods Relevant Archive material as well as primary and secondary literature will be assessed. Results In 1930, in his contribution to the commemorative volume on Gustav Specht (1860-1940), the first Head of Psychiatry in Erlangen, Karl Leonhard presented a very detailed description of the hallucinatory pattern of a postencephalitic patient. Leonhard practised in this the differentiation between organic and endogenous psychoses. The Psychiatric and Neurological Hospital at the University of Erlangen being an adnexe to the Erlanger asylum for the mentally ill, Leonhard was also able to become acquainted with acute and chronic stages of schizophrenia. This can be viewed as the decisive impulse for his later differentiated classification of types of schizophrenia. Leonhard took from Gustav Specht the aspect of bipolarity, which is decisive for his cycloid psychoses. The prominent importance of anxiety, which Specht promulgated, was later used by Leonhard in the description of anxiety-happiness psychosis. Leonhard's unsuccessful efforts to retain the Erlanger Chair in 1955 can be viewed as his first difficulty in West-East- and East-West German tensions. Conclusion Appropriation of Leonard's diagnostics can contribute to differentiated pharmacotherapeutic strategies in cycloid psychoses.

Neurodevelopmental and neurodegenerative models of schizophrenia: white matter at the center stage.

Schizophrenia is a disorder of cerebral disconnectivity whose lifetime course is modeled as both neurodevelopmental and neurodegenerative. The neurodevelopmental models attribute schizophrenia to alterations in the prenatal-to-early adolescent development. The neurodegenerative models identify progressive neurodegeneration as its core attribute. Historically, the physiology, pharmacology, and treatment targets in schizophrenia were conceptualized in terms of neurons, neurotransmitter levels, and synaptic receptors. Much of the evidence for both models was derived from studies of cortical and subcortical gray matter. We argue that the dynamics of the lifetime trajectory of white matter, and the consistency of connectivity deficits in schizophrenia, support white matter integrity as a promising phenotype to evaluate the competing evidence for and against neurodevelopmental and neurodegenerative heuristics. We develop this perspective by reviewing normal lifetime trajectories of white and gray matter changes. We highlighted the overlap between the age of peak of white matter development and the age of onset of schizophrenia and reviewed findings of white matter abnormalities prior to, at the onset, and at chronic stages of schizophrenia. We emphasized the findings of reduced white matter integrity at the onset and findings of accelerated decline in chronic stages, but the developmental trajectory that precedes the onset is largely unknown. We propose 4 probable lifetime white matter trajectory models that can be used as the basis for separation between the neurodevelopmental and neurodegenerative etiologies. We argue that a combination of the cross-sectional and longitudinal studies of white matter integrity in patients may be used to bridge the neurodevelopment and degeneration heuristics to advance schizophrenia research.

General practitioners and schizophrenia: Results from a Swiss survey

General practitioners (GPs) have an important role in the care of patients with chronic schizophrenia and of those in the early phases of this disorder. To obtain information about the number of patients in the early and chronic stages of schizophrenia seen in general practice; the needs and attitudes of GPs, their diagnostic knowledge concerning early phases of schizophrenia and their knowledge and practice concerning treatment of patients with first-episode and multi-episode schizophrenia. A postal survey was conducted among randomly selected GPs in Switzerland. A total of 1089 GPs responded to the survey. Early psychosis had a low prevalence in general practice, and GPs expressed a wish for specialised, low-threshold referral services. Diagnostic and treatment knowledge showed inconsistencies. Most GPs said they would treat first-episode schizophrenia with antipsychotics, but only a third recommended maintenance treatment after a first episode of schizophrenia that would conform with international recommendations. Easily accessible, low-threshold referral services are pivotal in supporting GPs in the management and treatment of emerging schizophrenia in primary healthcare patients.

Auditory P300 in high-risk, recent-onset and chronic schizophrenia

Background The present study examined the integrity of the P300 component of the event-related potential (ERP) in patients at high imminent risk for schizophrenia in relation to healthy comparison subjects and patients in the recent-onset and chronic stages of schizophrenia. Methods The P300 was recorded by using an auditory oddball task in 10 patients clinically considered at risk of being prodromally symptomatic for schizophrenia, 10 patients with recent-onset schizophrenia, 14 patients with chronic schizophrenia, 14 young healthy comparison subjects, who were age-matched to the high-risk and recent-onset schizophrenia groups, and 14 older healthy comparison subjects, who were age-matched to the chronic schizophrenia group. Results High-risk subjects displayed smaller than normal P300 amplitudes at the parietal, centroparietal and central scalp locations. The observed P300 amplitude abnormalities in high-risk subjects were severe, being comparable in magnitude to the abnormalities seen in recent-onset and chronic schizophrenia subjects. However, whereas high-risk subjects showed P300 amplitude abnormalities that were bilaterally symmetrical, subjects with recent-onset schizophrenia and, particularly, subjects with chronic schizophrenia exhibited abnormalities that were markedly larger over the left temporal scalp sites. Conclusions Patients at high imminent risk for developing a first florid psychotic episode seem to manifest auditory P300 amplitude abnormalities that are similar, but not identical, to those observed in patients in the recent-onset and chronic stages of schizophrenia. These results support the idea that auditory P300 abnormalities in schizophrenia reflect a primary cognitive and pathophysiological feature of the illness.

Duration of untreated psychosis and treatment outcome in schizophrenia patients untreated for many years.

The duration of untreated psychosis (DUP) influences treatment outcome in schizophrenia but its relevance in untreated patients, ill for a very long duration, is not known. This study examined outcome and factors related to it after one year of treatment of schizophrenia patients who were ill for many years and not previously treated. Among 75 never-treated patients with schizophrenia detected in a community survey in Chennai, India, 49 took treatment and were followed up prospectively for one year. Evaluation at intake and outcome was carried out using standardized methods. A good clinical outcome in 29%, social outcome in 35%, occupational outcome in 51% and global outcome in 31% was observed at the end of one year. Patients with poor global outcome did not significantly differ from those with good outcome on demographic and clinical variables at intake but for the presence of delusions and formal thought disorder. The proportion with good outcome in clinical, work and global measures fell steadily with increasing DUP. This difference was significant for clinical and global outcomes after a DUP of 5 years. The relationship between DUP and response to treatment held good even in chronic stages of schizophrenia with longer DUP associated with poorer outcome.