Hippocampal volume change relates to clinical outcome in childhood-onset schizophrenia

BackgroundFixed hippocampal volume reductions and shape abnormalities are established findings in schizophrenia, but the relationship between hippocampal volume change and clinical outcome has been relatively unexplored in schizophrenia and other psychotic disorders. In light of recent findings correlating hippocampal volume change and clinical outcome in first-episode psychotic adults, we hypothesized that fewer decreases in hippocampal volume would be associated with better functional outcome and fewer psychotic symptoms in our rare and chronically ill population of childhood-onset schizophrenia (COS) patients.MethodWe prospectively obtained 114 structural brain magnetic resonance images (MRIs) from 27 COS subjects, each with three or more scans between the ages of 10 and 30 years. Change in hippocampal volume, measured by fit slope and percentage change, was regressed against clinical ratings (Children's Global Assessment Scale, Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms) at last scan (controlling for sex, time between scans and total intracranial volume).ResultsFewer negative symptoms were associated with less hippocampal volume decrease (fit slope: p = 0.0003, and percentage change: p = 0.005) while positive symptoms were not related to hippocampal change. There was also a relationship between improved clinical global functioning and maintained hippocampal volumes (fit slope: p = 0.025, and percentage change: p = 0.043).ConclusionsThese results suggest that abnormal hippocampal development in schizophrenia can be linked to global functioning and negative symptoms. The hippocampus can be considered a potential treatment target for future therapies.

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Negative Symptoms at Discharge and Outcome in Schizophrenia

The British Journal of Psychiatry ◽

10.1192/bjp.166.1.61 ◽

1995 ◽

Vol 166 (1) ◽

pp. 61-67 ◽

Cited By ~ 18

Author(s):

Hai-Gwo Hwu ◽

Happy Tan ◽

Chu-Chang Chen ◽

Ling-Ling Yeh

Keyword(s):

Clinical Outcome ◽

Social Functioning ◽

Symptom Score ◽

Negative Symptoms ◽

Positive Symptom ◽

Positive Symptoms ◽

Symptom Scores ◽

Schizophrenic Patients ◽

Positive And Negative Symptoms

BackgroundThe clinical significance in schizophrenia of positive and negative symptoms at discharge was assessed.MethodOf schizophrenic patients fulfilling DSM–III criteria, 113 were recruited for this study. Personal, social and psychopathological data were collected and all cases were followed up at one and two years after discharge.ResultsThe presence of positive symptoms (64 cases), without concomitant negative symptoms, did not predict the follow-up social function and positive symptom score. Conversely, the presence of negative symptoms (31 cases) predicted worse social functioning (P < 0.05 to P < 0.005) and higher positive symptom scores (P < 0.01) at follow-up using MANOVA. Eighteen cases (15.9%) had neither positive nor negative symptoms and had the best clinical outcome.ConclusionsNegative, but not positive, symptoms assessed at discharge are an important predictor of poor outcome. In addition, negative symptoms may themselves expose a biological vulnerability to the presence of positive symptoms.

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Hippocampal Volume Development in Healthy Siblings of Childhood-Onset Schizophrenia Patients

American Journal of Psychiatry ◽

10.1176/appi.ajp.2010.10050681 ◽

2011 ◽

Vol 168 (4) ◽

pp. 427-435 ◽

Cited By ~ 36

Author(s):

Anand Mattai ◽

Avinash Hosanagar ◽

Brian Weisinger ◽

Deanna Greenstein ◽

Reva Stidd ◽

...

Keyword(s):

Hippocampal Volume ◽

Childhood Onset ◽

Healthy Siblings ◽

Childhood Onset Schizophrenia

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Effectiveness of Integrated Neurocognitive Therapy on Cognitive Impairment and Functional Outcome for Schizophrenia Outpatients

Schizophrenia Research and Treatment ◽

10.1155/2018/2360697 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Andreana De Mare ◽

Miriam Cantarella ◽

Giovanni Galeoto

Keyword(s):

Cognitive Impairment ◽

Functional Outcome ◽

Effect Size ◽

Negative Symptoms ◽

Social Cognitive ◽

Meta Analysis ◽

Positive Symptoms ◽

Global Functioning ◽

Cognitive Domains ◽

Treatment Research

Cognitive impairment is highly prevalent in patients with schizophrenia and schizoaffective disorder. Many interventions have been developed to treat cognitive deficit, since it has a strong impact on functional outcome; however, there are no integrated interventions targeting multiple neuro- and social-cognitive domains with a particular focus on the generalization of the effects of therapy on the functional outcome. Recently, a group of experts has developed a cognitive remediation group therapy approach called Integrated Neurocognitive Therapy (INT), which includes exercises to improve the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) neuro- and social-cognitive domains. This systematic review and meta-analysis aimed to assess the efficacy of this approach. We conducted a search of PubMed, Scopus, Web of Science, and PsycINFO to select primary studies evaluating INT in schizophrenic and schizoaffective patients. The primary outcomes of the meta-analysis included negative and positive symptoms and global functioning. Two randomized controlled trials met inclusion criteria. A total of 217 participants were included. Based on the results from the Positive and Negative Syndrome Scale (PANSS), a significant pooled effect size was observed for negative symptoms, which demonstrated not only an improvement in the patients treated immediately after therapy but also a permanence of positive results at a 9–12-month follow-up. On the other hand, no significant effect size was observed for positive symptoms. In addition, a significant pooled effect size was found for Global Assessment of Functioning (GAF), which shows how INT’s integrated approach has lasting positive implications on patients’ functional outcome. We concluded that INT might be an effective treatment for negative symptoms and global functioning in patients with schizophrenia, compared to treatment as usual (TAU).

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Reduced Hippocampal Volume and Its Relationship With Verbal Memory and Negative Symptoms in Treatment-Naive First-Episode Adolescent-Onset Schizophrenia

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa092 ◽

2020 ◽

Author(s):

Xujun Duan ◽

Changchun He ◽

Jianjun Ou ◽

Runshi Wang ◽

Jinming Xiao ◽

...

Keyword(s):

Indirect Effect ◽

Verbal Memory ◽

Memory Impairment ◽

Negative Symptoms ◽

Clinical Symptoms ◽

Hippocampal Volume ◽

First Episode ◽

Intracranial Volume ◽

Hippocampal Morphometry ◽

The Relationship

Abstract Accumulating neuroimaging evidence has shown remarkable volume reductions in the hippocampi of patients with schizophrenia. However, the relationship among hippocampal morphometry, clinical symptoms, and cognitive impairments in schizophrenia is still unclear. In this study, high-resolution structural magnetic resonance imaging data were acquired in 36 patients with adolescent-onset schizophrenia (AOS, age range: 13–18 years) and 30 age-, gender-, and education-matched typically developing controls (TDCs). Hippocampal volume was assessed automatically through volumetric segmentation and measurement. After adjusting for total intracranial volume, we found reduced hippocampal volume in individuals with AOS compared with TDCs, and the hippocampal volume was positively correlated with verbal memory and negatively correlated with negative symptoms in AOS. In addition, mediation analysis revealed the indirect effect of hippocampal volume on negative symptoms via verbal memory impairment. When the negative symptoms were represented by 2 dimensions of deficits in emotional expression (EXP) and deficits in motivation and pleasure (MAP), the indirect effect was significant for EXP but not for MAP. Our findings provide further evidence of hippocampal volume reduction in AOS and highlight verbal memory impairment as a mediator to influence the relationship between hippocampal morphometry and negative symptoms, especially the EXP dimension of negative symptoms, in individuals with AOS.

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Faculty Opinions recommendation of Missense variants in ATP1A3 and FXYD gene family are associated with childhood-onset schizophrenia.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733445082.793547387 ◽

2018 ◽

Author(s):

Hans van Bokhoven

Keyword(s):

Gene Family ◽

Childhood Onset ◽

Missense Variants ◽

Childhood Onset Schizophrenia

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Performance of patients with different schizophrenia subtypes on the Synthetic House–Tree–Person Test

Social Behavior and Personality An International Journal ◽

10.2224/sbp.8408 ◽

2019 ◽

Vol 47 (11) ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

AiBao Zhou ◽

Pei Xie ◽

ChaoChao Pan ◽

Zhe Tian ◽

Junwei Xie

Keyword(s):

Negative Symptoms ◽

Positive Symptoms ◽

Study Results ◽

Symptom Type ◽

Positive And Negative Symptoms

We explored differences in performance on the Synthetic House–Tree–Person Test between people with mainly positive symptoms and those with mainly negative symptoms of schizophrenia and, further, aimed to provide a basis for the diagnosis of schizophrenia symptom type. Participants were 58 people receiving treatment for schizophrenia, and we asked them to complete the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, and the Synthetic House–Tree–Person Test. There were significant differences in results on the Synthetic House–Tree–Person Test between the group with positive symptoms, the group with a mix of positive and negative symptoms, and the group with negative symptoms. There were 12 features of participants' drawings, such as big hands, which were correlated with hallucinations and delusions in positive symptoms, and 9 features, such as trees in a landscape, which were correlated with avolition and anhedonia in negative symptoms. Our study results suggest differences in performance on the Synthetic House–Tree–Person Test between these different symptom subtypes of schizophrenia; hence, the features that appear in drawings made during the test may contribute to the diagnosis of symptoms of people with schizophrenia.

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Childhood-Onset Schizophrenia: Timely Neurobiological Research

Journal of the American Academy of Child & Adolescent Psychiatry ◽

10.1097/00004583-199407000-00001 ◽

1994 ◽

Vol 33 (6) ◽

pp. 771-781 ◽

Cited By ~ 49

Author(s):

KATHLEEN McKENNA ◽

CHARLES T. GORDON ◽

JUDITH L. RAPOPORT

Keyword(s):

Childhood Onset ◽

Childhood Onset Schizophrenia ◽

Neurobiological Research

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Evaluation of positive and negative symptoms in schizophrenia

Psychiatry and Psychobiology ◽

10.1017/s0767399x00003199 ◽

1986 ◽

Vol 1 (2) ◽

pp. 108-122 ◽

Cited By ~ 29

Author(s):

Nancy C. Andreasen ◽

William M. Grove

Keyword(s):

Negative Symptoms ◽

The United States ◽

Psychotic Symptoms ◽

Positive Symptoms ◽

University Of Iowa ◽

Normal Functions ◽

Subsequent Investigation ◽

The University ◽

The Relationship ◽

Positive And Negative Symptoms

SummaryMost investigators concur that schizophrenia is probably a heterogeneous group of disorders that share the common features of psychotic symptoms, partial response to neuroleptics, and a relatively poor outcome. The subdivision of schizophrenia into two subtypes, positive versus negative, has achieved wide acceptance throughout the world during recent years. This distinction has heuristic and theoretical appeal because it unites phenomenology, pathophysiology, and etiology into a single comprehensive hypothesis.In spite of its wide appeal, the distinction has a number of problems. These include the failure to distinguish between symptom syndromes and diseases; failure to deal with the mixed patient; failure to take longitudinal course into account; and failure to address conceptually and methodologically the distinction between positive and negative symptoms.This paper focuses primarily on the conceptual basis for two instruments designed to measure positive and negative symptoms, the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS), originally described in 1982. Since their description, these scales have been used in a variety of other centers. These scales are based on the hypothesis that negative symptoms represent a deficit or diminution in normal psychological functions wliile positive symptoms represent an excess or distortion of normal functions. Reliability data are now available from Italy, Spain, and Japan which suggest that these scales can be used reliably in cultural settings outside the United States. The results of these studies are summarized in this paper. In addition, a replication study involving a new sample of 117 schizophrenics collected at the University of Iowa is described. In this second study of the SANS and SAPS, internal consistency is found to be quite high in the SANS. Thus negative symptoms appear to be more internally correlated with one another than are positive symptoms. The implications of this result are discussed. A principal components analysis is used to explore the relationship between positive and negative symptoms. While the study reported in 1982 suggested that positive and negative symptoms are negatively correlated, in the present study they appear to be uncorrelated. Overall, the results suggest that the SANS and SAPS are useful comprehensive instruments for the evaluation of positive and negative symptoms. The relationship between these symptoms and external validators such as cognitive functioning or CT scan abnormalities will be reported in a subsequent investigation.

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Paliperidone to Treat Psychotic Disorders

Neurology International ◽

10.3390/neurolint13030035 ◽

2021 ◽

Vol 13 (3) ◽

pp. 343-358

Author(s):

Hormazd D. Minwalla ◽

Peter Wrzesinski ◽

Allison Desforges ◽

Joshua Caskey ◽

Brittany Wagner ◽

...

Keyword(s):

Cognitive Impairment ◽

Schizoaffective Disorder ◽

Negative Symptoms ◽

Psychotic Disorders ◽

Drug Information ◽

The United States ◽

Mental Illnesses ◽

Positive Symptoms ◽

Review Of The Literature ◽

Second Generation Antipsychotics

Purpose of Review: This is a comprehensive review of the literature regarding the use of paliperidone in the treatment of schizophrenia and schizoaffective disorder. It covers the background and presentation of schizophrenia and schizoaffective disorder, as well as the mechanism of action and drug information for paliperidone. It covers the existing evidence of the use of paliperidone for the treatment of schizophrenia and schizoaffective disorder. Recent Findings: Schizophrenia and schizoaffective disorder lead to significant cognitive impairment. It is thought that dopamine dysregulation is the culprit for the positive symptoms of schizophrenia and schizoaffective disorder. Similar to other second-generation antipsychotics, paliperidone has affinity for dopamine D2 and serotonin 5-HT2A receptors. Paliperidone was granted approval in the United States in 2006 to be used in the treatment of schizophrenia and in 2009 for schizoaffective disorder. Summary: Schizophrenia and schizoaffective disorder have a large impact on cognitive impairment, positive symptoms and negative symptoms. Patients with either of these mental illnesses suffer from impairments in everyday life. Paliperidone has been shown to reduce symptoms of schizophrenia and schizoaffective disorder.

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