The Role of Untreated Psychosis in Neurodegeneration: A Review of Hypothesized Mechanisms of Neurotoxicity in First-Episode Psychosis

Anderson, Kelly K.; Voineskos, Aristotle N.; Mulsant, Benoit H.; George, Tony P.; McKenzie, Kwame

doi:10.1177/070674371405901003

Cited by 40 publications

(27 citation statements)

References 39 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Given the established association between DUP and FEP outcomes, exposure to preonset STPS may represent an "extended DUP" (combining both threshold and subtheshold psychotic symptoms). The extended DUP concept, acting through biological and/or psychosocial mechanisms, [63][64][65] could further explain the poorer recovery seen in the STPSp group, whereas patients with STPSa may have a relatively acute-onset psychosis with a shorter threshold-level DUP followed by rapid recovery. The association between STPS and poorer 1-year outcomes is strengthened by the fact that our analyses addressed potential confounders of this association.…”

Section: Discussionmentioning

confidence: 99%

Association of Pre-onset Subthreshold Psychotic Symptoms With Longitudinal Outcomes During Treatment of a First Episode of Psychosis

et al. 2019

View full text Add to dashboard Cite

The clinical high-risk state in psychosis is most often characterized by subthreshold psychotic symptoms (STPS) and represents a target for psychosis prevention. However, evidence suggests that between 30% and 50% of patients with a first episode of psychosis (FEP) report no prior history of STPS, indicating that not all patients with FEP experience a previous clinical high-risk phase. As with other early characteristics of illness onset, this diversity in the early course of symptoms may offer prognostic value for subsequent clinical trajectories. OBJECTIVE To determine whether a history of pre-onset STPS is associated with differential 1-year treatment outcomes in an early intervention service for FEP. DESIGN, SETTING, AND PARTICIPANTS Data on 195 patients 15 to 35 years of age who were recruited between January 17, 2003, and October 17, 2013, were collected from a catchment-based specialized early intervention service for FEP. Patients who reported experiencing at least 1 STPS prior to the onset of FEP were identified as STPS present (STPSp; n = 135); those who reported no such history were identified as STPS absent (STPSa; n = 60). Statistical analysis was conducted from December 15, 2016, to February 15, 2018. MAIN OUTCOMES AND MEASURES Summary scores on the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms, Calgary Depression Scale for Schizophrenia, Hamilton Anxiety Rating Scale, Global Assessment of Functioning scores, and Social and Occupational Functioning Assessment Scale scores at baseline and after 1 year of treatment were analyzed to evaluate 1-year outcomes. RESULTS Individuals in the STPSp group (39 female and 96 male participants; mean [SD] age, 23.4 [4.2] years) and the STPSa group (20 female and 40 male participants; mean [SD] age, 23.9 [5.1] years) did not differ in symptom severity or functioning at baseline. Although both groups improved by 1 year of treatment, mixed analyses of covariance (controlling for duration of untreated psychosis) revealed group-by-time interactions for scores on the Scale for the Assessment of Negative Symptoms (F 1,192 = 6.17; P = .01), the Global Assessment of Functioning (F 1,188 = 7.54; P = .006), and the Social and Occupational Functioning Assessment Scale (F 1,192 = 3.79; P = .05). Mixed analyses of covariance also revealed a group effect for scores on the Scale for the Assessment of Positive Symptoms (F 1,192 = 5.31; P = .02). After controlling for multiple comparisons, all significant results indicate poorer 1-year outcomes for patients with STPSp compared with patients with STPSa. CONCLUSIONS AND RELEVANCE A history of pre-onset STPS consistent with a prior clinical high-risk state is associated with poorer outcomes in psychotic symptoms and global functioning for patients after 1 year of treatment for FEP. The presence or absence of pre-onset STPS therefore has prognostic value for treatment outcomes, even during a later stage of psychotic illness.

show abstract

Section: Discussionmentioning

confidence: 99%

Association of Pre-onset Subthreshold Psychotic Symptoms With Longitudinal Outcomes During Treatment of a First Episode of Psychosis

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Research into the transition process from schizotypy to schizophrenia has found no influence of sex (Addington et al ., ), or more commonly, does not investigate sex as a variable of interest (Borgwardt et al ., ; Gee and Cannon, ; Simon et al ., , ). Similarly, studies of brain anomalies in first episode psychosis, which may help in understanding the nature of the relationship between schizotypy and schizophrenia, also tend to omit sex as a variable of interest (De Peri et al ., ; Anderson et al ., ; Kahn and Sommer, ; Nenadic et al ., ; Tao et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Chinese version of the Schizotypal Personality Questionnaire: Factor structure replication and invariance across sex

Bernardo

Zaroff

2015

Asia-Pacific Psychiatry

View full text Add to dashboard Cite

show abstract

“…There is ample evidence from brain imaging studies of schizophrenics that have shown significant gray matter loss and reduced cortical volume following onset of the disease. [3] This has been recently been ascribed to glutamatergic neurotoxicity in what has been called the "glutamate hypothesis". [4] However, the glutamate hypothesis does not specify a cause of glutamate dysregulation nor does it completely explain the degenerative changes in the schizophrenic neocortex.…”

Section: A Theory Of Initial Causementioning

confidence: 99%

A Theoretical Model to Explain the Symptoms and Progression of Schizophrenia

Overholt¹

2018

Preprint

View full text Add to dashboard Cite

Through the use of a simplified model of consciousness this paper illustrates the symptoms of schizophrenia linked to neocortical structures and functions.  It makes the case that the bewildering and varied presentation of symptoms in schizophrenia can be analyzed and explained using such models.  The model is used to illustrate the central thesis of the paper, that schizophrenia is a disorder of neurogenesis which leads to progressive neurochemical, functional and neurophysiological changes that create the characteristic behaviors of the disease.

show abstract

The Role of Untreated Psychosis in Neurodegeneration: A Review of Hypothesized Mechanisms of Neurotoxicity in First-Episode Psychosis

Cited by 40 publications

References 39 publications

Association of Pre-onset Subthreshold Psychotic Symptoms With Longitudinal Outcomes During Treatment of a First Episode of Psychosis

Association of Pre-onset Subthreshold Psychotic Symptoms With Longitudinal Outcomes During Treatment of a First Episode of Psychosis

Chinese version of the Schizotypal Personality Questionnaire: Factor structure replication and invariance across sex

A Theoretical Model to Explain the Symptoms and Progression of Schizophrenia

Contact Info

Product

Resources

About