New dopaminergic and non-dopaminergic theories in schizophrenia and their therapeutic impact

1997 ◽  
Vol 9 (2) ◽  
pp. 64-67
Author(s):  
R.S. Kahn
Keyword(s):  
Cognitive Deficits ◽  
Negative Symptoms ◽  
Dopamine Neurons ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
The Core ◽  
Schizophrenic Patients ◽  
Core Symptoms ◽  
Influential Theory

The dopamine (DA) hypothesis of schizophrenia, postulating that schizophrenia is characterized by increased dopamine function, has been the most influential theory on the pathogenesis of schizophrenia. It has recently been revised based on the appreciation that the core symptoms of schizophrenia may not be the positive (psychotic) symptoms, but rather the negative symptoms and the cognitive deficits found in schizophrenic patients. This revision has prompted the hypothesis that schizophrenia is characterized by both decreased prefrontal dopamine activity (causing deficit symptoms) and increased dopamine activity in mesolimbic dopamine neurons (causing positive symptoms).Notwithstanding this revision of a role for dopamine in schizophrenia, it has become increasingly evident that dysfunction of other monoaminergic systems may be as important in contributing to the pathophysiology of schizophrenia. Specifically, the putative role of serotonin (5-hydroxytryptamine, 5-HT) in schizophrenia is gaining considerable attention. Several observations, such as the ability of the 5-HT antagonist, ritanserin, to alleviate schizophrenic symptoms and, when added to haloperidol (Haldol®), to decrease its extrapyramidal side-effects (EPS), have stimulated studies into a role of 5-HT in schizophrenia. The finding that clozapine (Leponex®), clinically superior to conventional neuroleptics, is a weak DA2 antagonist but a potent 5-HT1c and 5-HT2 antagonist has further stimulated 5-HT-related research in schizophrenia.

scholarly journals Not Just a Bystander: The Emerging Role of Astrocytes and Research Tools in Studying Cognitive Dysfunctions in Schizophrenia

2021 ◽  
Vol 22 (10) ◽  
pp. 5343
Author(s):  
Chia-Yuan Chang ◽  
Da-Zhong Luo ◽  
Ju-Chun Pei ◽  
Ming-Che Kuo ◽  
Yi-Chen Hsieh ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Negative Symptoms ◽  
Brain Disorders ◽  
Serotoninergic Neurons ◽  
Schizophrenic Patients ◽  
Core Symptoms ◽  
Behavioral Methods ◽  
The Brain ◽  
Insight Into

Cognitive dysfunction is one of the core symptoms in schizophrenia, and it is predictive of functional outcomes and therefore useful for treatment targets. Rather than improving cognitive deficits, currently available antipsychotics mainly focus on positive symptoms, targeting dopaminergic/serotoninergic neurons and receptors in the brain. Apart from investigating the neural mechanisms underlying schizophrenia, emerging evidence indicates the importance of glial cells in brain structure development and their involvement in cognitive functions. Although the etiopathology of astrocytes in schizophrenia remains unclear, accumulated evidence reveals that alterations in gene expression and astrocyte products have been reported in schizophrenic patients. To further investigate the role of astrocytes in schizophrenia, we highlighted recent progress in the investigation of the effect of astrocytes on abnormalities in glutamate transmission and impairments in the blood–brain barrier. Recent advances in animal models and behavioral methods were introduced to examine schizophrenia-related cognitive deficits and negative symptoms. We also highlighted several experimental tools that further elucidate the role of astrocytes. Instead of focusing on schizophrenia as a neuron-specific disorder, an additional astrocytic perspective provides novel and promising insight into its causal mechanisms and treatment. The involvement of astrocytes in the pathogenesis of schizophrenia and other brain disorders is worth further investigation.

Cocaine Use and Liability to Psychotic Symptoms

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
E.J. Franzek
Keyword(s):  
Negative Symptoms ◽  
Cocaine Addiction ◽  
Stress Factors ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
Cocaine Use ◽  
Cycloid Psychoses ◽  
Schizophrenia Spectrum ◽  
Schizophrenic Patients ◽  
Core Symptoms

In a pilot study with 55 inpatients, primarily admitted for cocaine addiction, the following hypotheses were found: Patients with cocaine addiction and comorbide core schizophrenia (according to Kreapelin, n=17) respond completely different on cocaine use than all other groups of patients including a schizophrenia spectrum group (without core schizophrenia according to Kraepelin). When using cocaine the schizophrenic patients do not experience new psychotic symptoms and existing symptoms do not get worse. Most of them are less bothered of negative symptoms and some of them are, even more, less bothered of positive symptoms. In all other patients with various comorbidity (n=28) and without comorbide psychiatric disorders (n=10) positive psychotic symptoms occur dependent on the dosage of cocaine. In some of them the positive symptoms are also triggered by stress alone. The symptoms occurred in a dosage dependent hierarchical structure: mistrust - delusions of reference with fear - delusions of persecution and illusions with anxiety or panic - threatening voices and noises - disorganized and catatonic behavior.The psychopathology induced by cocaine prooved to be similar to one of the core symptoms of cycloid psychoses.The hypothesis is raised that there is an individual genetically and/or environmentally caused liability to the developing of positive psychotic symptoms under various stress factors including drugs. These reactive psychoses have to be distinguished from schizophrenia. Their relationship to the spectrum of cycloid psychoses is discussed.

Impact of Lithium Therapy on Core Psychotic Symptoms of Schizophrenia

1984 ◽  
Vol 144 (1) ◽  
pp. 64-69 ◽  
Author(s):  
Frank P. Zemlan ◽  
Jack Hirschowitz ◽  
Frederic J. Sautter ◽  
David L. Garver
Keyword(s):  
Early Identification ◽  
Lithium Treatment ◽  
Lithium Therapy ◽  
Thought Disorder ◽  
Psychotic Symptoms ◽  
Formal Thought Disorder ◽  
The Core ◽  
Schizophrenic Patients ◽  
Core Symptoms

SummaryThe authors have previously reported that a sub-group of schizophrenic-like patients respond favorably to lithium therapy: furthermore, psychotic patients who respond to lithium demonstrate appreciable improvement during the first seven days of treatment. The present study investigated which symptoms of schizophrenia improved quickly during lithium treatment. We found that patients who do respond to lithium show significant improvement in the core symptoms of psychosis—hallucinations, delusions and formal thought disorder—during the first seven days of treatment, thus allowing early identification of 88 per cent of schizophrenic patients who ultimately respond to lithium and 91 per cent of those who do not.

scholarly journals Efficacy of Memantine in Schizophrenic Patients: A Systematic Review

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Giuseppe Di Iorio ◽  
Gaia Baroni ◽  
Marco Lorusso ◽  
Chiara Montemitro ◽  
Maria Chiara Spano ◽  
...  
Keyword(s):  
Systematic Review ◽  
Negative Symptoms ◽  
Positive Symptoms ◽  
Cognitive Symptoms ◽  
Review Of The Literature ◽  
Excitatory Neurotransmitter ◽  
Aspartate Receptor ◽  
Schizophrenic Patients ◽  
Promising Treatment

Several evidences support the hypothesis that glutamatergic dysfunction may be implicated in the pathogenesis of schizophrenia and in the last few years great interest has been focused on the role of the N-methyl-D-aspartate receptor (NMDAR). Glutamate is the main excitatory neurotransmitter in human CNS and it plays a prominent role in synaptic plasticity, learning, and memory and other cognitive functions. Increasing interest in memantine add-on therapy in schizophrenic patients with negative and cognitive symptoms may suggest that memantine could be a new promising treatment in schizophrenia. The aim of this update was to evaluate clinical data about the memantine effectiveness in schizophrenic patients. Our systematic review of the literature highlights that memantine therapy in schizophrenic patients seems to improve mainly negative symptoms while positive symptoms and cognitive symptoms did not improve significantly.

Efficacy of memantine in schizophrenic patients: A systematic review

2017 ◽  
Vol 41 (S1) ◽  
pp. s824-s824
Author(s):  
C. Montemitro ◽  
M.C. Spano ◽  
M. Lorusso ◽  
G. Baroni ◽  
G. Di Iorio ◽  
...  
Keyword(s):  
Negative Symptoms ◽  
Positive Symptoms ◽  
Aspartate Receptor ◽  
Sigma 1 ◽  
Schizophrenic Patients ◽  
Promising Treatment ◽  
High Concentrations ◽  
Competing Interest ◽  
Image Position

IntroductionSeveral evidences support the hypothesis that glutamatergic dysfunction may be implicated in the pathogenesis of schizophrenia and in the last few year great interest has been focused on the role of the N-methyl-D-aspartate receptor (NMDAR). Memantine is a noncompetitive NMDARs antagonist, binds the same site of NMDARs of Mg2+, endogenous blocker of NMDARs, with moderate affinity, rapid unblocking kinetics and strong functional voltage-dependency. Memantine does not affect the physiological activation of NMDARs whereas it blocks the sustained activation under pathological conditions. Preclinical studies have demonstrated that memantine at high concentrations targets many receptors, including serotonin, nicotinic acetylcholine, sigma-1 and serotonin and dopamine receptors.ObjectivesIncreasing interest in memantine add-on therapy in schizophrenic patients with negative and cognitive symptoms may suggest that memantine could be a new promising treatment in schizophrenia.AimsThe aim of this update was to evaluate clinical data about the memantine effectiveness in schizophrenic patients.MethodsWe searched on PubMed to identify original studies about the use of memantine in treatment of schizophrenic patients. The search conducted on June 16th, 2016 yielded 135 records. Neuf papers met our inclusion criteria.ResultsNegative symptoms improved in the large majority of patients treated, however there is not a clear evidence on cognitive and positive symptoms (Table 1)ConclusionsMemantine therapy in schizophrenic patients has given unclear results. It seems that memantine improves mainly negative symptoms, while cognitive and positive symptoms did not improve significantly. Further trials with a more numerous sample are required obtain an objective result.Table 1Observation during Memantime administration.↓: reduction in severity of symptoms; -: no relevant modifications; +: onset of new symptomsDisclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Cariprazine in the management of negative symptoms of schizophrenia: state of the art and future perspectives

2020 ◽  
Vol 15 (4) ◽  
pp. FNL52
Author(s):  
Christoph U Correll ◽  
Koen Demyttenaere ◽  
Andrea Fagiolini ◽  
Göran Hajak ◽  
Stefano Pallanti ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Negative Symptoms ◽  
State Of The Art ◽  
Dorsal Striatum ◽  
Psychotic Symptoms ◽  
D3 Receptor ◽  
Future Perspectives ◽  
Clinical Issue ◽  
Cortical Regions

In schizophrenia, dopaminergic hyperactivity in the mesolimbic regions, or possibly even selectively so in the dorsal striatum, seems to cause the emergence of psychotic symptoms, whereas dopaminergic hypoactivity in cortical regions underlies the negative symptoms and cognitive deficits. Managing the negative symptoms is a major current challenge in the treatment of schizophrenia with a dearth of novel modalities to address this clinical issue. Cariprazine is a novel second-generation antipsychotic that specifically targets the D3 receptor mainly associated to negative symptoms. The review summarizes the main issues regarding negative symptom management and the role of cariprazine treatment.

III. Clinical Findings. Abnormalities of the Mental State and Movement Disorder and their Correlates

1991 ◽  
Vol 159 (S13) ◽  
pp. 21-25 ◽  
Author(s):  
Eve C. Johnstone ◽  
D. G. C. Owens ◽  
C. D. Frith ◽  
J. Leary
Keyword(s):  
Movement Disorder ◽  
Mental State ◽  
Negative Symptoms ◽  
Clinical Evidence ◽  
Treatment Resistance ◽  
Clinical Findings ◽  
Psychotic Symptoms ◽  
Positive Symptoms ◽  
Schizophrenic Patients ◽  
Unselected Sample

Persisting positive symptoms largely unresponsive to treatment (Tuma & May, 1979; Macmillan et al, 1986; May et al, 1989) occur in about 7% of patients with schizophrenia but lesser degrees of treatment resistance are common (Hogarty, 1988; Johnstone, 1990) and problems of recurrence of positive symptoms and deterioration of negative symptoms are well known (Johnstone, 1990). Schizophrenic patients have also been found to have persisting non-psychotic symptoms, particularly depression (Cheadle et al, 1978). Disorders of movement in relation to schizophrenia and their treatment have been found to be disabling in a few patients and to cause lesser problems for many (Kane et al, 1985). The assessment of the mental state and of clinical evidence of movement disorder in the patients who form the subjects of the Harrow study was therefore clearly of interest, as it is rarely possible to examine these issues in a large, unselected sample.

Evaluation of positive and negative symptoms in schizophrenia

1986 ◽  
Vol 1 (2) ◽  
pp. 108-122 ◽  
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.

Symptômes Positifs Et Négatifs De La Schizophrénie: Une Mise à jour

1994 ◽  
Vol 39 (7) ◽  
pp. 407-414 ◽  
Author(s):  
Marc-André Roy ◽  
Xavier Devriendt
Keyword(s):  
Cognitive Deficits ◽  
Negative Symptoms ◽  
Three Dimensions ◽  
Positive Symptoms ◽  
Research Questions

The purpose of this article is to summarize the results of studies examining the validity of the positive and negative sub-types of schizophrenia as proposed by Crow. The authors summarized Crow's model's predictions in the form of 12 research questions and examined whether its predictions were confirmed. The following predictions are generally confirmed by the data collected: (i) it is possible to measure negative symptoms with accuracy; (ii) the negative symptoms predict a deterioration; (Hi) the negative symptoms are generally correlated with overall cognitive deficits; (iv) each dimension appears to have distinct neurobiological substrata. However, several elements of the Crow model are not supported by the data collected. Among the necessary modifications, the most important are as follows: (i) it appears more productive to conceive of the negative symptoms as distinct dimensions, rather than distinct diseases; (ii) at least three dimensions exist for describing the symptoms of schizophrenia; (Hi) the negative symptoms are not necessarily intrinsic to the schizophrenic process, and they may be due to other causes; (iv) the negative symptoms are not necessarily irreversible, and can be improved under ataractics; (v) the positive symptoms, in particular those relating to disorganization, can also be correlated with cognitive deficits.

Combination Treatments for Schizophrenia

CNS Spectrums ◽  
2004 ◽  
Vol 9 (S9) ◽  
pp. 19-23 ◽  
Author(s):  
Alexander L. Miller
Keyword(s):  
Electroconvulsive Therapy ◽  
Cognitive Deficits ◽  
Negative Symptoms ◽  
Current Evidence ◽  
Positive Symptoms ◽  
Combination Therapies ◽  
Safety And Efficacy ◽  
Combination Treatments ◽  
Improved Outcomes ◽  
Expert Recommendations

ABSTRACTCombination treatments, especially combinations of antipsychotics, are used frequently for schizophrenia, despite a paucity of evidence regarding their safety and efficacy. Because the literature basis is weak and expert recommendations are largely lacking, providers should be vigilant in documenting improved outcomes for patients thought to benefit from combination treatments. Target symptoms that have been studied include psychosis, cognitive deficits, and negative symptoms. The strongest evidence is for augmentation of clozapine with another antipsychotic or with electroconvulsive therapy for persistent positive symptoms. Combination treatments for cognitive deficits and negative symptoms are being actively investigated, but current evidence is insufficient to recommend available agents for these components of schizophrenia. It is important that appropriate monotherapies be given adequate trials before resorting to combination therapies.

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