Aetiopathological mechanisms of negative symptoms in schizophrenia

2016 ◽  
Vol 13 (03) ◽  
pp. 121-129
Author(s):  
F. Caputo ◽  
G. M. Giordano ◽  
A. Mucci ◽  
S. Galderisi

Summary Background: Negative symptoms represent core features of schizophrenia and have an unfavorable impact on the disease outcome. Unfortunately, their aetiopathology has not been elucidated yet and the effectiveness of available treatments is not satisfactory. Aims: This review aims to provide a critical overview of research findings concerning negative symptom aetiopathology, highlighting limitations and future perspectives. Results: Enduring and transient negative symptoms, as well as motivation-related and expression-related domains of negative symptoms, have different risk factors and clinical correlates, and are associated to distinct brain abnormalities. Enduring negative symptoms seem to be related to subtle, pervasive deviations in neurodevelopmental trajectories. Expression deficit, as compared with avolition, shows a stronger association with neurological soft signs, cognitive impairment and diffuse disconnectivity. Avolition/apathy is a multifaceted construct probably related to deficits of reward and action valuation and instrumental learning, subtended by cortico-striatal dysfunctions. Conclusions: Research findings support the heterogeneity of negative symptoms and are likely to pave the way for the discovery of more effective treatments.

1992 ◽  
Vol 22 (4) ◽  
pp. 923-927 ◽  
Author(s):  
K. W. Brown ◽  
T. White

SynopsisSyndromes of dyskinetic movements in subjects (N = 70) with chronic schizophrenia were investigated, using principal components analysis of AIMS ratings. Consonant with previous research, three discrete groupings were found, namely dyskinetic movements of lips-jaw-tongue, limb-truncal and facial movements. These were then related to demographic, psychological and movement disorder variables. The limb-truncal, but neither the lips-jaw-tongue nor facial movements components, were associated with negative symptoms and cognitive impairment.


1990 ◽  
Vol 157 (1) ◽  
pp. 41-49 ◽  
Author(s):  
A. M. Mortimer ◽  
C. E. Lund ◽  
P. J. McKenna

Two studies are reported. In the first, of 62 schizophrenic patients, no correlation between negative symptom scores (rated blindly) and any measure of positive symptoms was found. This independence was confirmed by factor and cluster analyses, which left the question of a third ‘disorganisation’ class of schizophrenic symptoms open. In the second study, of 80 patients, formal thought disorder separated unequivocally into ‘positive formal thought disorder’ and ‘alogia’ syndromes on the basis of correlations with positive and negative symptoms. Catatonic motor disorder also showed evidence of a corresponding positive: negative division, although this only emerged when severity or chronicity of illness was controlled for. Cognitive impairment showed a broad range of affiliations and its particular correlation with negative symptoms was perhaps artefactual.


1991 ◽  
Vol 158 (6) ◽  
pp. 770-775 ◽  
Author(s):  
D. J. King ◽  
A. Wilson ◽  
S. J. Cooper ◽  
J. L. Waddington

Among 16 chronic schizophrenic in-patients, all had at least one neurological soft sign (NSS), and 6 (40%) had definite neurodysfunction. NSS and TD scores were highly intercorrelated, and NSS were significantly correlated with neuroleptic drug exposure. NSS correlated positively with both positive and negative symptoms and cognitive impairment but not with cerebral ventricular size on CT. Patients with neurodysfunction had more positive and negative psychopathology, cognitive impairment and TD than those without. Cerebral ventricular sizes and family histories of schizophrenia were similar in both NSS groups. The presence of NSS may be a simple but important way of identifying a subgroup of schizophrenics with neurodevelopmental predisposing abnormalities, and vulnerability to TD.


2020 ◽  
Vol 17 ◽  
Author(s):  
Hyung-Ji Kim ◽  
Jae-Hong Lee ◽  
E-nae Cheong ◽  
Sung-Eun Chung ◽  
Sungyang Jo ◽  
...  

Background: Amyloid PET allows for the assessment of amyloid β status in the brain, distinguishing true Alzheimer’s disease from Alzheimer’s disease-mimicking conditions. Around 15–20% of patients with clinically probable Alzheimer’s disease have been found to have no significant Alzheimer’s pathology on amyloid PET. However, a limited number of studies had been conducted this subpopulation in terms of clinical progression. Objective: We investigated the risk factors that could affect the progression to dementia in patients with amyloid-negative amnestic mild cognitive impairment (MCI). Methods: This study was a single-institutional, retrospective cohort study of patients over the age of 50 with amyloidnegative amnestic MCI who visited the memory clinic of Asan Medical Center with a follow-up period of more than 36 months. All participants underwent brain magnetic resonance imaging (MRI), detailed neuropsychological testing, and fluorine-18[F18]-florbetaben amyloid PET. Results: During the follow-up period, 39 of 107 patients progressed to dementia from amnestic MCI. In comparison with the stationary group, the progressed group had a more severe impairment in verbal and visual episodic memory function and hippocampal atrophy, which showed an Alzheimer’s disease-like pattern despite the lack of evidence for significant Alzheimer’s disease pathology. Voxel-based morphometric MRI analysis revealed that the progressed group had a reduced gray matter volume in the bilateral cerebellar cortices, right temporal cortex, and bilateral insular cortices. Conclusion: Considering the lack of evidence of amyloid pathology, clinical progression of these subpopulation may be caused by other neuropathologies such as TDP-43, abnormal tau or alpha synuclein that lead to neurodegeneration independent of amyloid-driven pathway. Further prospective studies incorporating biomarkers of Alzheimer’s diseasemimicking dementia are warranted.


Author(s):  
Victoria J. Williams ◽  
Steven E. Arnold ◽  
David H. Salat

Throughout the lifespan, common variations in systemic health and illness contribute to alterations in vasculature structure and function throughout the body, significantly increasing risk for cardiovascular and cerebrovascular disease (CVD). CVD is a prevalent cause of mortality in late life; it also promotes brain alterations, contributing to cognitive decline and, when severe, vascular dementia. Even prior to diseased states, individual variation in CVD risk is associated with structural and functional brain alterations. Yet, how cumulative asymptomatic alterations in vessel structure and function contribute to more subtle changes in brain tissue integrity and function that emerge in late life is unclear. Finally, vascular risk factors are associated with the clinical progression of neurodegenerative diseases such as Alzheimer’s disease (AD); however, recent theory posits that vascular degeneration may serve a contributory role in these conditions. This chapter reviews how lifespan changes in vascular health contribute to degenerative changes in neural tissue and the subsequent development of cognitive impairment and/or vascular dementia. It first discusses associations between vascular risk factors and cognition and also how declining vascular health may lead to cognitive impairment and dementia. Next, it identifies basic aspects of cerebrovascular anatomy and physiology sustaining tissue health and discusses how vulnerabilities of this system contribute to neurodegenerative changes. Finally, it reviews evidence of vascular contributions to AD and presents ideas for future research to better understand the full spectrum of cerebrovascular contributions to brain aging, cognitive decline, and dementia.


2019 ◽  
Vol Volume 15 ◽  
pp. 167-175 ◽  
Author(s):  
Oana Albai ◽  
Mirela Frandes ◽  
Romulus Timar ◽  
Deiana Roman ◽  
Bogdan Timar

2021 ◽  
Vol 79 (1) ◽  
pp. 401-414
Author(s):  
Max Toepper ◽  
Philipp Schulz ◽  
Thomas Beblo ◽  
Martin Driessen

Background: On-road driving behavior can be impaired in older drivers and particularly in drivers with mild cognitive impairment (MCI). Objective: To determine whether cognitive and non-cognitive risk factors for driving safety may allow an accurate and economic prediction of on-road driving skills, fitness to drive, and prospective accident risk in healthy older drivers and drivers with MCI, we examined a representative combined sample of older drivers with and without MCI (N = 74) in an observational on-road study. In particular, we examined whether non-cognitive risk factors improve predictive accuracy provided by cognitive factors alone. Methods: Multiple and logistic hierarchical regression analyses were utilized to predict different driving outcomes. In all regression models, we included cognitive predictors alone in a first step and added non-cognitive predictors in a second step. Results: Results revealed that the combination of cognitive and non-cognitive risk factors significantly predicted driving skills (R2adjusted = 0.30) and fitness to drive (81.2% accuracy) as well as the number (R2adjusted = 0.21) and occurrence (88.3% accuracy) of prospective minor at-fault accidents within the next 12 months. In all analyses, the inclusion of non-cognitive risk factors led to a significant increase of explained variance in the different outcome variables. Conclusion: Our findings suggest that a combination of the most robust cognitive and non-cognitive risk factors may allow an economic and accurate prediction of on-road driving performance and prospective accident risk in healthy older drivers and drivers with MCI. Therefore, non-cognitive risk factors appear to play an important role.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
T. Muhammad ◽  
Shobhit Srivastava ◽  
T. V. Sekher

Abstract Background Greater cognitive performance has been shown to be associated with better mental and physical health and lower mortality. The present study contributes to the existing literature on the linkages of self-perceived income sufficiency and cognitive impairment. Study also provides additional insights on other socioeconomic and health-related variables that are associated with cognitive impairment in older ages. Methods Data for this study is derived from the 'Building Knowledge Base on Population Ageing in India'. The final sample size for the analysis after removing missing cases was 9176 older adults. Descriptive along with bivariate analyses were presented to show the plausible associations of cognitive impairment with potential risk factors using the chi-square test. Also, binary logistic regression analysis was performed to provide the relationship between cognitive impairment and risk factors. The software used was STATA 14. Results About 43% of older adults reported that they had no source of income and 7.2% had income but not sufficient to fulfil their basic needs. Older adults with income but partially sufficient to fulfil their basic needs had 39% significantly higher likelihood to suffer from cognitive impairment than older adults who had sufficient income [OR: 1.39; OR: 1.21–1.59]. Likelihood of cognitive impairment was low among older adults with asset ownership than older adults with no asset ownership [OR: 0.83; CI: 0.72–0.95]. Again, older adults who work by compulsion (73.3%) or felt mental or physical stress due to work (57.6%) had highest percentage of cognitive impairment. Moreover, older adults with poor self-rated health, low instrumental activities of daily living, low activities of daily living, low subjective well-being and low psychological health were at increased risk for cognitive impairment. Conclusion The study highlights the pressing need for care and support and especially financial incentives in the old age to preserve cognitive health. Further, while planning geriatric health care for older adults in India, priority must be given to financially backward, with no asset ownership, with poor health status, older-older, widowed, and illiterate older individuals, as they are more vulnerable to cognitive impairment.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Gregory P. Strauss ◽  
Lisa A. Bartolomeo ◽  
Philip D. Harvey

AbstractNegative symptoms have long been considered a core component of schizophrenia. Modern conceptualizations of the structure of negative symptoms posit that there are at least two broad dimensions (motivation and pleasure and diminished expression) or perhaps five separable domains (avolition, anhedonia, asociality, blunted affect, alogia). The current review synthesizes a body of emerging research indicating that avolition may have a special place among these dimensions, as it is generally associated with poorer outcomes and may have distinct neurobiological mechanisms. Network analytic findings also indicate that avolition is highly central and interconnected with the other negative symptom domains in schizophrenia, and successfully remediating avolition results in global improvement in the entire constellation of negative symptoms. Avolition may therefore reflect the most critical treatment target within the negative symptom construct. Implications for targeted treatment development and clinical trial design are discussed.


2021 ◽  
Vol 13 (3) ◽  
pp. 343-358
Author(s):  
Hormazd D. Minwalla ◽  
Peter Wrzesinski ◽  
Allison Desforges ◽  
Joshua Caskey ◽  
Brittany Wagner ◽  
...  

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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