The participants were excluded from analysis if they met criteria for current alcohol/substance abuse, a history of alcohol/substance dependence, or history of neurological disorder. In sum, 88 participants with an SSD and 66 control participants were included in the analyses.Prior to study participation, the participants completed informed verbal and written consent. The participants were administered the Structured Clinical Interview for DSM-IV Patient Version or the SCID-non-patient version to confirm diagnoses. People with an SSD were also administered the Brief Psychiatric Rating Scale and the Scale for the Assessment of Negative Symptoms to assess current symptoms; the Strauss Carpenter Outcome Scale to assess social functioning and work functioning ; and the Global Assessment of Functioning . All participants completed the TEPS , which is comprised of ten items assessing trait dispositions of anticipatory pleasure experiences and eight items assessing trait dispositions of consummatory pleasure experiences. An example of an anticipatory pleasure item is, “I get so excited the night before a major holiday I can hardly sleep.” An example of a consummatory pleasure item is, “The smell of freshly cut grass is enjoyable to me.” The participants rated each on a scale from one to six how true each item was for them “in general.” In the current study, we assessed whether deficits in the propensity to experience anticipatory pleasure are evident early in the course of schizophrenia spectrum disorders. We found that people in the early course of an SSD reported lower dispositional anticipatory pleasure but did not differ in reported dispositional consummatory pleasure compared to healthy controls. These findings are consistent with studies of more chronically ill people with schizophrenia .
However, our findings differ from two recent studies with people early in the course of an SSD . Identifying reasons why some studies find deficits in anticipatory pleasure and others do not is an important direction for future research. Likely explanations include the characteristics of the clinical and control groups. With respect to clinical characteristics, our sample did not include any participants with current substance use disorder,cannabis grow kit whereas most participants in the Cassidy et al. study did . Another explanation may be related to how anticipatory deficits are described. We considered “deficits” in anticipatory pleasure as a significantly lower score on the TEPS anticipatory pleasure measure in people with an SSD compared to the controls. However, this assumes that the control group is homogeneous in a variety of factors that may influence self-reported anticipatory pleasure. There are likely unstudied individual differences that influence TEPS scores within different groups that may partially account for why some studies fail to find anticipatory pleasure deficits in people with schizophrenia. For example, in Strauss et al. , the control group had a consummatory pleasure score of 4.96, while the control group in our study had a score of 4.39, a seemingly significant difference between the two groups. This may partially account for why Strauss et al. did not find the same pattern of differences in anticipatory and consummatory pleasure scores on the TEPS in people with and without schizophrenia as our study did. While Schlosser et al. did not find that people with recent onset schizophrenia differed from younger healthy controls in anticipatory pleasure, they found that people with recent onset schizophrenia reported significantly lower TEPS anticipatory pleasure than consummatory pleasure. Future studies may wish to adopt both within and between-group comparisons in defining “deficits” in self-reported pleasure. Furthermore, as studies continue to include the TEPS, meta analysis will prove useful in better understanding differences between people with and without schizophrenia on this measure. We found that both anticipatory and consummatory pleasure scores were related to negative symptoms, consistent with prior studies including more chronic samples . These results suggest that even in the early stages of the illness, people with an SSD who report lower dispositional anticipatory pleasure are also likely to exhibit negative symptoms.
Deficits in the propensity to experience anticipatory pleasure may be an indicator of early negative symptoms that may not be otherwise detectable. On the other hand, greater dispositional consummatory pleasure was related to lower negative symptom scores and depression, suggesting that while diminished experience of consummatory pleasure may also be an indicator of negative symptoms, it may additionally be more sensitive to state-dependent factors . It will be informative to assess the linkage between dispositional anticipatory and consummatory pleasure and symptom-level anticipatory and consummatory pleasure in future studies using measures that distinguish these types of pleasure, such as the Clinical Assessment Interview for Negative Symptoms . Contrary to our findings, studies of chronically ill people with schizophrenia have found that social functioning is related to TEPS anticipatory and consummatory pleasure . It is possible that people in our SSD group had other resources or support that help guide their functioning that chronically ill people with schizophrenia do not have, thus deficits in anticipatory pleasure may not be as tightly linked with their functioning. Another possibility is that the strength of the relationship between anticipatory pleasure deficits and functional outcome increases over time, even if both constructs remain independently stable. Herbener et al. found that over a 20-year period, neither physical anhedonia nor functional outcome became significantly more severe in a sample of people with schizophrenia; however, over time the strength of the correlation between physical anhedonia and functional outcome increased. They suggested that physical anhedonia may be one factor that contributes to the heterogeneity in functional outcome scores in schizophrenia samples and that the co-occurrence of both may reflect a common underlying deficit. The relationship between anticipatory pleasure and functional outcome may follow a similar trajectory over time, and future studies that examine the longitudinal nature of anticipatory pleasure and functioning in schizophrenia can help answer this open question. Although we administered the TEPS to a group of people who had experienced a psychotic episode, future studies should continue to examine other populations, including clinical high risk samples, to further pinpoint when anticipatory pleasure deficits may emerge during the development of an SSD.
Schlosser et al. found that CHR individuals reported less TEPS consummatory and anticipatory pleasure compared to demographically matched healthy controls, suggesting that such deficits may reflect a vulnerability towards a future psychotic episode. Future studies should continue to administer the TEPS during multiple time points as the illness progresses, both in between and within-group designs, to help understand the longitudinal course of anticipatory pleasure in schizophrenia. One limitation of our study is that our SSD group differed from our control group on demographic factors, including sex and ethnicity. While there were no significant sex differences in reports of either TEPS anticipatory or consummatory pleasure within our two groups, future studies will want to include more women with an SSD in their samples to replicate this finding and address the under-representation of women with schizophrenia in research more generally . A second limitation is that we only included one measure of anticipatory and consummatory pleasure. Augmenting the understanding of the temporal experience of emotion by including other measures, such as a behavioral measure of anticipatory and consummatory pleasure, is an important next step . This study extends our understanding of one aspect of the emotion deficits observed in schizophrenia — deficits in anticipatory pleasure — to those early in the course of the illness. A related emotion deficit that has been observed in samples of more chronically ill people with schizophrenia is the ability to maintain emotion experience . Ursu et al. found that emotion maintenance, specifically viewing an emotionally evocative picture and reporting emotion experience after a delay,cannabis grow supplies was associated with diminished dorsolateral prefrontal cortex activation among people with schizophrenia. This suggests that emotion maintenance relies upon neural processes that not only support emotion but also cognitive control processes. Anticipation likely recruits similar brain regions, as anticipation requires a host of similar cognitive operations, such as creating and maintaining visual images and accessing “mental time travel” processes. While we did not include any neuropsychological measures or fMRI in our study, future studies may wish to include these measures to help answer such questions as a) whether people early in the course of a schizophrenia spectrum disorder also experience difficulties in emotion maintenance and b) whether similar brain regions are involved in both emotion anticipation and maintenance. There has been some preliminary work showing that directly targeting anticipatory deficits in treatment is related to increases in self-reported anticipatory pleasure on the TEPS . Treating anticipatory deficits in newly diagnosed people with a schizophrenia spectrum disorder may be a particularly important time period for administering such interventions, as it is before deficits in anticipatory pleasure are related to functioning but after such deficits are correlated with negative symptoms.
An interesting yet unexplored question is whether an intervention targeting anticipatory deficits during the early stages of the illness would not only increase self-reported anticipatory pleasure, but whether the intervention would also be related to improved functional outcome or negative symptomatology over time. In summary, people with a recent-onset schizophrenia spectrum diagnosis reported lower levels of trait anticipatory pleasure but not consummatory pleasure on the TEPS when compared to a healthy control group. During the early stage of the illness, both anticipatory and consummatory pleasure scores appear to be related to negative symptom measures, but not to functional outcome measures. Future studies should continue to examine when anticipatory deficits emerge in schizophrenia, when such deficits relate to both symptoms and outcome measures, whether there are other individual differences that may account for such differences, and whether directly targeting anticipatory deficits in the early course of the illness would improve functional outcome or symptom severity as the illness progresses.Prenylated natural products are a large class of bio-active molecules with demonstrated medicinal properties. Examples include prenyl-flavanoids, prenyl-stilbenoids, and cannabinoids . Cannabinoids in particular show immense therapeutic potential with over 100 ongoing clinical trials as antiemetics, anticonvulsants, antidepressants, and analgesics. Nevertheless, despite the therapeutic potential of prenyl-natural products, their study and use is limited by the lack of cost-effective production methods. Plant-derived prenyl compounds are difficult to isolate due to the structural similarity of contaminating molecules, and the variable composition between crops. These challenges are further exacerbated when attempting to isolate low abundance compounds. Many chemical syntheses have been developed to address the challenges associated with making prenylated natural products, but they are generally impractical for drug manufacturing due to the degree of complexity and low yields. Microbial production is a useful alternative to natural extraction for prenylated natural products, but comes with many challenges such as the need to divert carbon flux from central metabolism and product toxicity to name a few. For example, prenyl-natural products like prenyl-naringenin, prenyl-resveratrol, and cannabidiol are derived from a combination of the metabolic pathways for fatty acid, isoprenoid, and polyketide biosynthesis. So, high-level production requires efficient rerouting of long, essential and highly regulated pathways. Despite the challenges, many groups have engineered microbes to produce unprenylated polyketides, like naringenin, resveratrol, and olivetolate, but at relatively low levels. Obtaining prenylated products is even more challenging because geranyl-pyrophosphate is an essential metabolite that is toxic to cells at moderate concentrations, creating a significant barrier for high-level microbial production. So, in spite of intense interest, to our knowledge there are no published reports of the complete biosynthesis of prenyl- flavonoids, prenyl-stilbenoids, or cannabinoids in recombinant microbes. Much recent effort has focused on alternative methods for cannabinoid production. Two groups have produced the polyketide cannabinoid intermediate, olivetolic acid at low levels in yeast or E. coli , but did not prenylate OA or produce a cannabinoid from the bio-synthesized OA. In other work, tetrahydrocannabinolic acid was produced in cell extracts from either exogenously added GPP and OA in a two enzyme pathway or from cannabigerolic acid using a single enzyme. However, it is unclear how GPP or CBGA could be obtained at sufficient levels for economical production due to the high cost of these molecules. Here, we propose an alternative biological approach to prenylated natural product biosynthesis using a cell-free enzymatic platform we call synthetic biochemistry, which has shown great promise for the production of bio-based molecules.