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Antipsychotics and amotivation.

ABSTRACT: Antipsychotic drugs are thought to produce secondary negative symptoms, which can also exacerbate primary negative symptoms. In the present study, we examined whether motivational deficits in particular were related to antipsychotic treatment in patients with schizophrenia in a dose-dependent manner. Five hundred and twenty individuals with schizophrenia who were receiving antipsychotic monotherapy for at least 6 months and followed prospectively were included in the present study. Participants were receiving one of five antipsychotic medications (olanzapine, perphenazine, quetiapine, risperidone, or ziprasidone), and analyses were conducted for patients receiving each drug separately. Analysis of covariance models were constructed to examine the effect of antipsychotic dose on level of motivational impairment, controlling for selected demographic and clinical variables (eg, positive symptoms). Level of motivation, or deficits therein, were evaluated using a derived measure from the Quality of Life Scale, and in addition with scores derived from the Positive and Negative Syndrome Scale. Antipsychotic dose was not related to the level of amotivation for any of the medications examined. Moreover, severity of sedation was not significantly related to the degree of amotivation. One hundred and twenty-one individuals were identified as antipsychotic-free at baseline, and after 6 months of antipsychotic treatment, no change in motivation was found. Chronic treatment with antipsychotics does not necessarily impede or enhance goal-directed motivation in patients with schizophrenia. It is possible that the negative impact of antipsychotics in this regard is overstated; conversely, the present results also indicate that we must look beyond antipsychotics in our efforts to improve motivation.

SUBMITTER: Fervaha G

PROVIDER: S-EPMC4397414 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Antipsychotics and amotivation.

Fervaha Gagan G Takeuchi Hiroyoshi H Lee Jimmy J Foussias George G Fletcher Paul J PJ Agid Ofer O Remington Gary G

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20150108 6

Antipsychotic drugs are thought to produce secondary negative symptoms, which can also exacerbate primary negative symptoms. In the present study, we examined whether motivational deficits in particular were related to antipsychotic treatment in patients with schizophrenia in a dose-dependent manner. Five hundred and twenty individuals with schizophrenia who were receiving antipsychotic monotherapy for at least 6 months and followed prospectively were included in the present study. Participants ...[more]

PMID: 25567425

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Project description:IntroductionSuboptimal effort-based decision-making with reduced willingness to expend effort for high-probability/high-value reward is observed in schizophrenia patients and is related to diminished motivation, but is understudied in schizotypy. This study aimed to examine effort-allocation in schizotypy individuals and its association with amotivation and psychosocial functioning.MethodsWe recruited 40 schizotypy individuals and 40 demographically-matched healthy controls, based on Schizotypal Personality Questionnaire-Brief (SPQ-B) score (top and bottom 10% SPQ-B scores, respectively), from 2400 young people aged 15-24 years participating a population-based mental health survey in Hong Kong and examined effort-allocation using the Effort Expenditure for Reward Task (EEfRT). Negative / amotivation symptoms and psychosocial functioning were assessed by the Brief Negative Symptom Scale (BNSS) and the Social Functioning and Occupational Assessment Scale (SOFAS), respectively. Schizotypy individuals were categorized into high-amotivation and low-amotivation groups based on a median-split of BNSS amotivation domain score.ResultsOur results showed no main group effect (in either two or three-group comparison) on effort task performance. Three-group comparison analyses on selected EEfRT performance indices revealed that high-amotivation schizotypy individuals displayed significantly less increase in effortful options from low-value to high-value reward (reward-difference score) and from low-probability/low-value to high-probability/high-value reward (probability/reward-difference score) than low-amotivation individuals and controls. Correlation analyses demonstrated trend-wise significance between BNSS amotivation domain score and several EEfRT performance indices in schizotypy group. Schizotypy individuals with poorer psychosocial functioning tended to exhibit smaller probability/reward-difference score relative to other two groups.DiscussionOur findings indicate subtle effort-allocation abnormalities in schizotypy individuals with high levels of diminished motivation, and suggest the link between laboratory-based effort-cost measures and real-world functional outcome.

Project description: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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Antipsychotics and amotivation.

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Antipsychotics and amotivation.

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