Tryptophan and its catabolites (TRYCATs) have been suggested to link peripheral immune system activation and central neurotransmitter abnormalities with relevance to the etio-pathophysiology of schizophrenia (SZ) and major depressive disorder (MDD). The relationship to different psychopathological dimensions within these disorders however remains to be elucidated. We thus investigated potential group differences of tryptophan, kynurenine, kynurenic acid, 3-hydroxy kynurenine and quinolinic acid in the plasma of 19 healthy controls (HC), 45 patients with SZ and 43 patients with MDD and correlated plasma proteins with the “motivation and pleasure” dimension and cognition. After correcting for the covariates age, sex, body mass index, smoking and medication, patients with MDD showed lower kynurenine and 3-hydroxy kynurenine levels compared to HC. Quinolinic acid correlated negatively with composite cognitive score in patients with SZ, indicating that more severe cognitive impairments were associated with increased plasma levels of quinolinic acid. No correlations were found in patients with MDD. These results indicate that MDD and SZ are associated with dysregulation of the kynurenine pathway. Quinolinic acid might be specifically implicated in the pathophysiology of cognitive deficits in patients with SZ. Further studies are needed to determine whether TRYCATs are causally involved in the etiology of these neuropsychiatric disorders.

One aspect of goal-directed behavior, which is known to be impaired in patients with schizophrenia (SZ), is balancing between exploiting a familiar choice with known reward value and exploring a lesser known but potentially more rewarding option. Despite its relevance to several symptom domains of SZ, this has received little attention in SZ research. In addition, while there is increasing evidence that SZ is associated with chronic low-grade inflammation, few studies have investigated how this relates to specific behaviors, such as balancing exploration and exploitation. We therefore assessed behaviors underlying the exploration-exploitation trade-off using a threearmed bandit task in 45 patients with SZ and 19 healthy controls (HC). This task allowed us to dissociate goal-unrelated (random) from goal-related (directed) exploration and correlate them with psychopathological symptoms. Moreover, we assessed a broad range of inflammatory proteins in the blood and related them to bandit task behavior. We found that, compared to HC, patients with SZ showed reduced task performance. This impairment was due to a shift from exploitation to random exploration, which was associated with symptoms of disorganization. Relative to HC, patients with SZ showed a pro-inflammatory blood profile. Furthermore, high sensitivity C-reactive protein (CRP) positively correlated with random exploration, but not with directed exploration or exploitation. In conclusion, we show that low-grade inflammation in patients with SZ is associated with random exploration, which can be considered a behavioral marker for disorganization. CRP may constitute a marker for severity of, and a potential treatment target for maladaptive exploratory behaviors.

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One aspect of goal-directed behavior, which is known to be impaired in patients with schizophrenia (SZ), is balancing between exploiting a familiar choice with known reward value and exploring a lesser known, but potentially more rewarding option. Despite its relevance to several symptom domains of SZ, this has received little attention in SZ research. In addition, while there is increasing evidence that SZ is associated with chronic low-grade inflammation, few studies have investigated how this relates to specific behaviors, such as balancing exploration and exploitation. We therefore assessed behaviors underlying the exploration–exploitation trade-off using a three-armed bandit task in 45 patients with SZ and 19 healthy controls (HC). This task allowed us to dissociate goal-unrelated (random) from goal-related (directed) exploration and correlate them with psychopathological symptoms. Moreover, we assessed a broad range of inflammatory proteins in the blood and related them to bandit task behavior. We found that, compared to HC, patients with SZ showed reduced task performance. This impairment was due to a shift from exploitation to random exploration, which was associated with symptoms of disorganization. Relative to HC, patients with SZ showed a pro-inflammatory blood profile. Furthermore, high-sensitivity C-reactive protein (hsCRP) positively correlated with random exploration, but not with directed exploration or exploitation. In conclusion, we show that low-grade inflammation in patients with SZ is associated with random exploration, which can be considered a behavioral marker for disorganization. hsCRP may constitute a marker for severity of, and a potential treatment target for maladaptive exploratory behaviors.

Deficits in goal-directed decision making and motivation are hallmark characteristics of several neuropsychiatric disorders, including schizophrenia (SZ) and major depressive disorder (MDD). Studies using effort based decision making tasks have shown that both patients with SZ and MDD invest less physical effort in order to obtain rewards. However, how these motivational deficits relate to clinically assessed symptom dimensions such as apathy remains controversial. Using a grip-strength based effort discounting task we assessed effort based decision making behaviour in healthy controls (HC) (N = 18), patients with SZ (N = 42) and MDD (N = 44). We then investigated how effort discounting relates to different symptom dimensions. There were no differences in effort discounting between HC participants and patients with SZ or MDD. In addition, we did not observe a correlation between effort discounting and negative symptoms in patients with SZ or MDD. In conclusion, the current study does not support an association between effort discounting and negative symptoms in SZ or MDD. Further studies are needed to investigate effort discounting and its relation to psychopathological dimensions across different neuropsychiatric disorders.

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Background: A growing body of neuroimaging research has revealed a relationship between blunted activation of the ventral striatum (VS) and apathy in schizophrenia. In contrast, the association between reduced striatal volume and apathy is less well established, while the relationship between VS function and structure in patients with schizophrenia remains an open question. Here, we aimed to replicate previous structural findings in a larger independent sample and to investigate the relationship between VS hypoactivation and VS volume. Methods: We included brain structural magnetic resonance imaging (MRI) data from 60 patients with schizophrenia (SZ) that had shown an association of VS hypoactivation with apathy during reward anticipation and 58 healthy controls (HC). To improve replicability, we applied analytical methods developed in two previously published studies: Voxel-based morphometry and the Multiple Automatically Generated Templates (MAGeT) algorithm. VS and dorsal striatum (DS) volume were correlated with apathy correcting for age, gender and total brain volume. Additionally, left VS activity was correlated with left VS volume. Results: We failed to replicate the association between apathy and reduced VS volume and did not find a correlation with DS volume. Functional and structural left VS measures exhibited a trend-level correlation (rs=0.248, p=0.067, r2=0.06). Conclusions: Our present data suggests that functional and structural striatal neuroimaging correlates of apathy can occur independently. Replication of previous findings may have been limited by other factors (medication, illness duration, age) potentially related to striatal volume changes in SZ. Finally, associations between reward-related VS function and structure should be further explored.