From neurological soft signs to functional outcome in young individuals in treatment with secondary services for non-psychotic disorders: a path analysis

Minichino, Amedeo; Francesconi, Marta; Carrión, Ricardo; Chiaie, R. Delle; Bevilacqua, Arturo; Parisi, Maurizio; Rullo, S.; Bersani, Francesco Saverio; Biondi, Massimo; Cadenhead, Kristin S.

doi:10.1017/s0033291716003056

Cited by 6 publications

(7 citation statements)

References 71 publications

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“…The authors also showed that NSS predicted a longitudinal decrease in the white matter integrity of the cerebello-thalamic tract that was associated with higher levels of negative symptoms. Consistent with the trans-diagnostic approach used in the current study, high levels of NSS have been associated with specific neural network abnormalities, cognitive dysfunction, negative symptoms and low functioning in both psychotic and non-psychotic individuals (Minichino et al, 2016a;Dazzan and Murray, 2002).…”

Section: Discussionsupporting

confidence: 76%

“…Third, a genetic marker improved the predictive model, suggesting that genetic markers may also have a relevant impact on functional outcome. Fourth, LF was not entirely dependent on the development of psychosis, further promoting the need for a broader trans-diagnostic approach in the field of functional recovery (Minichino et al, 2016a;Minichino et al, 2016b;Lee et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Negative symptoms have traditionally been associated with schizophrenia spectrum disorders (Norman et al, 2015). However, a growing body of evidence suggests that they are expressed in association with LF across different psychiatric diagnoses (Minichino et al, 2016a). Thus, it is not surprising that Avolition may represent a predictor of functional outcome independent of the ARMS status and DSM-IV diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“…Specifically: negative and disorganized symptoms, neurological soft signs, theory of mind, neurocognition, and baseline functioning abnormalities have been consistently detected in young psychiatric outpatients and related to future outcomes independent of DSM diagnosis and psychosis-risk status (Lee et al, 2015;Plaisier et al, 2010;Iosifescu, 2012;Francesconi et al, 2016;Minichino et al, 2016a). These domains may represent optimal trans-categorical predictors of functioning and thus new promising therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

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Prediction of functional outcome in young patients with a recent-onset psychiatric disorder: Beyond the traditional diagnostic classification system

Minichino

Francesconi

Carrión

et al. 2017

Schizophrenia Research

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A critical research goal is to identify modifiable risk factors leading to functional disabilities in young psychiatric patients. The authors developed a multidimensional trans-diagnostic predictive model of functional outcome in patients with the recent-onset of a psychiatric illness. Baseline clinical, psychosis-risk status, cognitive, neurological-soft-signs measures, and dopamine-related-gene polymorphisms (DRD1-rs4532, COMT-rs165599, and DRD4-rs1800955) were collected in 138 young non-psychotic outpatients. 116 individuals underwent follow-up (mean=2.2years, SD=0.9) examination. A binary logistic model was used to predict low-functioning status at follow-up as defined by a score lower than 65 in the social occupational functioning assessment scale. A total of 54% of patients experiences low functioning at follow-up. Attention, Avolition, and Motor-Coordination subscale were significant predictors of low-functioning with an accuracy of 79.7%. A non-significant trend was found for a dopamine-related-gene polymorphism (DRD1-rs4532). The model was independent of psychotic-risk status, DSM-diagnosis, and psychotic conversion. A trans-diagnostic approach taking into account specific neurocognitive, clinical, and neurological information has the potential to identify those individuals with low-functioning independent of DSM diagnosis or the level of psychosis-risk. Specific early interventions targeting modifiable risk factors and emphasize functional recovery in young psychiatric samples, independent of DSM-diagnosis and psychosis-risk, are essential.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Prediction of functional outcome in young patients with a recent-onset psychiatric disorder: Beyond the traditional diagnostic classification system

Minichino

Francesconi

Carrión

et al. 2017

Schizophrenia Research

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“…Similar to other dimensional constructs (e.g., psychotic-like experiences – PLEs), anhedonia and amotivation in otherwise “healthy” subjects might also have a clinical relevance per se as these symptoms are believed to predate the onset of a wide range of debilitating clinical conditions (psychosis, depression, substance misuse, chronic fatigue, and dementia) [ 5 , 6 ]. Shedding light on new treatment targets for anhedonia and amotivation is a clinical and research priority, as these symptoms still represent an unmet therapeutic need across diagnostic boundaries [ 3 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Endocannabinoid system mediates the association between gut-microbial diversity and anhedonia/amotivation in a general population cohort

et al. 2021

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Anhedonia and amotivation are debilitating symptoms and represent unmet therapeutic needs in a range of clinical conditions. The gut-microbiome-endocannabinoid axis might represent a potential modifiable target for interventions. Based on results obtained from animal models, we tested the hypothesis that the endocannabinoid system mediates the association between gut-microbiome diversity and anhedonia/amotivation in a general population cohort. We used longitudinal data collected from 786 volunteer twins recruited as part the TwinsUK register. Our hypothesis was tested with a multilevel mediation model using family structure as random intercept. The model was set using alpha diversity (within-individual gut-microbial diversity) as predictor, serum and faecal levels of the endocannabinoid palmitoylethanolamide (PEA) as mediator, and anhedonia/amotivation as outcome. PEA is considered the endogenous equivalent of cannabidiol, with increased serum levels believed to have anti-depressive effects, while increased stool PEA levels, reflecting increased excretion, are believed to have opposite, detrimental, effects on mental health. We therefore expected that either reduced serum PEA or increased stool PEA would mediate the association between microbial diversity and anhedonia amotivation. Analyses were adjusted for obesity, diet, antidepressant use, sociodemographic and technical covariates. Data were imputed using multiple imputation by chained equations. Mean age was 65.2 ± 7.6; 93% of the sample were females. We found a direct, significant, association between alpha diversity and anhedonia/amotivation (β = −0.37; 95%CI: −0.71 to −0.03; P = 0.03). Faecal, but not serum, levels of the endocannabinoid palmitoylethanolamide (PEA) mediated this association: the indirect effect was significant (β = −0.13; 95%CI: −0.24 to −0.01; P = 0.03), as was the total effect (β = −0.38; 95%CI: −0.72 to −0.04; P = 0.03), whereas the direct effect of alpha diversity on anhedonia/amotivation was attenuated fully (β = −0.25; 95%CI: −0.60 to 0.09; P = 0.16). Our results suggest that gut-microbial diversity might contribute to anhedonia/amotivation via the endocannabinoid system. These findings shed light on the biological underpinnings of anhedonia/amotivation and suggest the gut microbiota-endocannabinoid axis as a promising therapeutic target in an area of unmet clinical need.

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Unmet Therapeutic Needs in Psychotic Illness: The Gut Microbiome-Endocannabinoid Axis as a Target for the Development of New Preventative Strategies

Minichino

2022

Prevention in Mental Health

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From neurological soft signs to functional outcome in young individuals in treatment with secondary services for non-psychotic disorders: a path analysis

Cited by 6 publications

References 71 publications

Prediction of functional outcome in young patients with a recent-onset psychiatric disorder: Beyond the traditional diagnostic classification system

Prediction of functional outcome in young patients with a recent-onset psychiatric disorder: Beyond the traditional diagnostic classification system

Endocannabinoid system mediates the association between gut-microbial diversity and anhedonia/amotivation in a general population cohort

Unmet Therapeutic Needs in Psychotic Illness: The Gut Microbiome-Endocannabinoid Axis as a Target for the Development of New Preventative Strategies

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