Volumetric and morphological characteristics of the hippocampus are associated with progression to schizophrenia in patients with first-episode psychosis

Sauras-Quetcuti, R.B.; Keymer, A.; Alonso-Solís, Anna; Díaz, Adrián Plaza; Molins, Conrad; Núñez, Fidel; Rabella, Mireia; Roldán, Alexandra; Grasa, Eva; Álvarez, Enric; Portella, Marı́a J.; Corripio, Iluminada

doi:10.1016/j.eurpsy.2017.06.006

Cited by 28 publications

(17 citation statements)

References 43 publications

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“…As part of the limbic circuitry, the hippocampus and prefrontal cortex were also analyzed here. In addition, deficits in neuronal network synchrony in these regions are also classically associated with SCZ 49 – 52 . Since, in addition to the prefrontal cortex, the striatum showed the highest expression of NDEL1 in the brain 17 , 53 , this brain region was also included in the present study.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics

Nani

Lee

Yonamine

et al. 2020

Sci Rep

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Nuclear distribution element-like 1 (NDEL1) enzyme activity is important for neuritogenesis, neuronal migration, and neurodevelopment. We reported previously lower NDEL1 enzyme activity in blood of treated first episode psychosis and chronic schizophrenia (SCZ) compared to healthy control subjects, with even lower activity in treatment resistant chronic SCZ patients, implicating NDEL1 activity in SCZ. Herein, higher NDEL1 activity was observed in the blood and several brain regions of a validated animal model for SCZ at baseline. In addition, long-term treatment with typical or atypical antipsychotics, under conditions in which SCZ-like phenotypes were reported to be reversed in this animal model for SCZ, showed a significant NDEL1 activity reduction in blood and brain regions which is in line with clinical data. Importantly, these results support measuring NDEL1 enzyme activity in the peripheral blood to predict changes in NDEL1 activity in the CNS. Also, acute administration of psychostimulants, at levels reported to induce SCZ-like phenotype in normal rat strains, increased NDEL1 enzyme activity in blood. Therefore, alterations in NDEL1 activity after treatment with antipsychotics or psychostimulants may suggest a possible modulation of NDEL1 activity secondary to neurotransmission homeostasis and provide new insights into the role of NDEL1 in SCZ pathophysiology.

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Section: Discussionmentioning

confidence: 99%

Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics

Nani

Lee

Yonamine

et al. 2020

Sci Rep

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“…Most earlier brain imaging studies on outcome prediction have used univariate methods. Univariate findings which may predict outcomes include alterations in rhythmic activity in electroencephalogram (EEG) ( 62 ); a prefrontal MRI spectroscopic marker of neuronal integrity ( 63 ); striatal dopamine-2 receptor binding potential ( 64 ); the integrity of the frontotemporal white matter tracts ( 65 ); abnormal gyrification of the cerebral cortex ( 66 , 67 ); white matter network organization ( 68 ); and the volumes of the ventricles ( 69 ) and the temporal lobe in general ( 70 ), and the volumes of the hippocampus ( 71 , 72 ) and the superior temporal gyrus ( 73 ) in particular. For a review on structural MRI measures as predictors of outcome, see Dazzan et al ( 74 ).…”

Section: Outcome Prediction: Current Evidencementioning

confidence: 99%

Is It Possible to Predict the Future in First-Episode Psychosis?

et al. 2018

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The outcome of first-episode psychosis (FEP) is highly variable, ranging from early sustained recovery to antipsychotic treatment resistance from the onset of illness. For clinicians, a possibility to predict patient outcomes would be highly valuable for the selection of antipsychotic treatment and in tailoring psychosocial treatments and psychoeducation. This selective review summarizes current knowledge of prognostic markers in FEP. We sought potential outcome predictors from clinical and sociodemographic factors, cognition, brain imaging, genetics, and blood-based biomarkers, and we considered different outcomes, like remission, recovery, physical comorbidities, and suicide risk. Based on the review, it is currently possible to predict the future for FEP patients to some extent. Some clinical features—like the longer duration of untreated psychosis (DUP), poor premorbid adjustment, the insidious mode of onset, the greater severity of negative symptoms, comorbid substance use disorders (SUDs), a history of suicide attempts and suicidal ideation and having non-affective psychosis—are associated with a worse outcome. Of the social and demographic factors, male gender, social disadvantage, neighborhood deprivation, dysfunctional family environment, and ethnicity may be relevant. Treatment non-adherence is a substantial risk factor for relapse, but a small minority of patients with acute onset of FEP and early remission may benefit from antipsychotic discontinuation. Cognitive functioning is associated with functional outcomes. Brain imaging currently has limited utility as an outcome predictor, but this may change with methodological advancements. Polygenic risk scores (PRSs) might be useful as one component of a predictive tool, and pharmacogenetic testing is already available and valuable for patients who have problems in treatment response or with side effects. Most blood-based biomarkers need further validation. None of the currently available predictive markers has adequate sensitivity or specificity used alone. However, personalized treatment of FEP will need predictive tools. We discuss some methodologies, such as machine learning (ML), and tools that could lead to the improved prediction and clinical utility of different prognostic markers in FEP. Combination of different markers in ML models with a user friendly interface, or novel findings from e.g., molecular genetics or neuroimaging, may result in computer-assisted clinical applications in the near future.

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“…Such finding is in line with previous evidence showing structural and functional changes in this structure in early psychoses and in atrisk mental state/first-episode psychosis, in comparison to healthy controls 60 , 61 , 62 , 63 . Normal hippocampal function is required for a number of mental functions including memory and emotional behaviour 48 , 49 and it has been proposed that reduced volume in this structure may represent a marker of a negative clinical outcome in patients with a firstepisode psychosis 66 . However, in contrast to the results, hippocampal deficits have been also reported in young and adult cannabis users, who have been found to have thinner cortices and reduced volumes in this region 67 , 68 , 69 , 70 .…”

Section: Discussionmentioning

confidence: 99%

Brain Morphology of Cannabis Users With or Without Psychosis: A Pilot MRI Study

Delvecchio

Oldani

Mandolini

et al. 2020

JoVE

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Cannabis is the illicit drug most commonly used worldwide, and its consumption can both induce psychiatric symptoms in otherwise healthy subjects and unmask a florid psychotic picture in patients with a prior psychotic risk. Previous studies suggest that chronic and long-term cannabis exposure may exert significant negative effects in brain areas enriched with cannabinoid receptors. However, whether brain alterations determined by cannabis dependency will lead to a clinically significant phenotype or to a psychotic outbreak at some point of an abuser's life remains unclear. The aim of this study was to investigate morphological brain differences between chronic cannabis users with cannabis-induced psychosis (CIP) and non-psychotic cannabis users (NPCU) without any psychiatric conditions and correlate brain deficits with selective socio-demographic, clinical and psychosocial variables. 3T magnetic resonance imaging (MRI) scans of 10 CIP patients and 12 NPCU were acquired. The type of drug, the frequency, and the duration, as well socio-demographic, clinical and psychosocial parameters of dependency were measured. CIP patients had extensive grey matter (GM) decreases in right superior frontal gyrus, right precentral, right superior temporal gyrus, insula bilaterally, right precuneus, right medial occipital gyrus, right fusiform gyrus, and left hippocampus in comparison to chronic cannabis users without psychosis. Finally, in CIP patients, the results showed a negative correlation between a domain of the Brief Psychiatric Rating Scale (BPRS), BPRS-Activity, and selective GM volumes. Overall, the results suggest that cannabis-induced psychosis is characterized by selective brain reductions Copyright © 2020 JoVE jove.com August 2020 • 162 • e60881 • Page 2 of 20 that are not present in NPCU. Therefore, neuroimaging studies may provide a potential ground for identifying putative biomarkers associated with the risk of developing psychosis in cannabis users.

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Volumetric and morphological characteristics of the hippocampus are associated with progression to schizophrenia in patients with first-episode psychosis

Cited by 28 publications

References 43 publications

Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics

Evaluation of NDEL1 oligopeptidase activity in blood and brain in an animal model of schizophrenia: effects of psychostimulants and antipsychotics

Is It Possible to Predict the Future in First-Episode Psychosis?

Brain Morphology of Cannabis Users With or Without Psychosis: A Pilot MRI Study

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