Cold executive function processes and their hot analogs in schizotypy.

OBJECTIVE: To examine cold (based on logical reasoning) versus hot (having emotional components) executive function processes in groups with high individual schizotypal traits. METHOD: Two-hundred and forty-seven participants were administered the Schizotypal Personality Questionnaire and were allocated into schizotypal (cognitive-perceptual, paranoid, negative, disorganized) or control groups according to pre-specified criteria. Participants were also administered a battery of tasks examining working memory, complex selective attention, response inhibition, decision-making and fluid intelligence and their affective counterparts. The outcome measures of each task were reduced to one composite variable thus formulating five cold and five hot cognitive domains. Between-group differences in the cognitive domains were examined with repeated measures analyses of covariance. RESULTS: For working memory, the control and the cognitive-perceptual groups outperformed negative schizotypes, while for affective working memory controls outperformed the disorganized group. Controls also scored higher compared with the disorganized group in complex selective attention, while both the control and the cognitive-perceptual groups outperformed negative schizotypes in complex affective selective attention. Negative schizotypes also had striking difficulties in response inhibition, as they scored lower compared with all other groups. Despite the lack of differences in fluid intelligence, controls scored higher compared with all schizotypal groups (except from cognitive-perceptual schizotypes) in emotional intelligence; the latter group reported higher emotional intelligence compared with negative schizotypes. CONCLUSION: Results indicate that there is no categorical association between the different schizotypal dimensions with solely cold or hot executive function processes and support impoverished emotional intelligence as a core feature of schizotypy.

The moderating role of early traumatic experiences on the association of schizotypal traits with visual perception.

The findings on the association of schizotypal traits with the perception of visual illusions are scarce and inconsistent and have not taken into consideration potential effects of childhood traumatic experiences, a risk factor for schizophrenia-spectrum conditions. Thus, the present study addressed the question of potential moderating effects of early traumatic experiences on the association between different aspects of schizotypal traits with the perception of the Müller-Lyer and Navon's Hierarchical Letters (NHL) illusions. The study revealed that (a) increased suspiciousness was associated with increased liability to the Müller-Lyer illusion, when the exposure to traumatic events was high, whereas the opposite pattern was true when the exposure to traumatic events was low; (b) negative schizotypy was associated with more accurate global perception, and high disorganized schizotypy was associated with superior accuracy when target letters were present during the NHL illusion, when early traumatic experiences were at lower levels; and (c) high negative, disorganized, and total schizotypy were associated with lower accuracy when target letters were present in the NHL paradigm, when early traumatic experiences were at higher levels. The findings of the study suggest that early traumatic events differentially moderate the relationship between various aspects of schizotypal traits and visual perceptual processing.

Pleiotropic Meta-Analysis of Cognition, Education, and Schizophrenia Differentiates Roles of Early Neurodevelopmental and Adult Synaptic Pathways.

Susceptibility to schizophrenia is inversely correlated with general cognitive ability at both the phenotypic and the genetic level. Paradoxically, a modest but consistent positive genetic correlation has been reported between schizophrenia and educational attainment, despite the strong positive genetic correlation between cognitive ability and educational attainment. Here we leverage published genome-wide association studies (GWASs) in cognitive ability, education, and schizophrenia to parse biological mechanisms underlying these results. Association analysis based on subsets (ASSET), a pleiotropic meta-analytic technique, allowed jointly associated loci to be identified and characterized. Specifically, we identified subsets of variants associated in the expected ("concordant") direction across all three phenotypes (i.e., greater risk for schizophrenia, lower cognitive ability, and lower educational attainment); these were contrasted with variants that demonstrated the counterintuitive ("discordant") relationship between education and schizophrenia (i.e., greater risk for schizophrenia and higher educational attainment). ASSET analysis revealed 235 independent loci associated with cognitive ability, education, and/or schizophrenia at p < 5 × 10-8. Pleiotropic analysis successfully identified more than 100 loci that were not significant in the input GWASs. Many of these have been validated by larger, more recent single-phenotype GWASs. Leveraging the joint genetic correlations of cognitive ability, education, and schizophrenia, we were able to dissociate two distinct biological mechanisms-early neurodevelopmental pathways that characterize concordant allelic variation and adulthood synaptic pruning pathways-that were linked to the paradoxical positive genetic association between education and schizophrenia. Furthermore, genetic correlation analyses revealed that these mechanisms contribute not only to the etiopathogenesis of schizophrenia but also to the broader biological dimensions implicated in both general health outcomes and psychiatric illness.

Self-perceived cognitive lapses and psychological well-being in schizotypy: Generalized and domain-specific associations.

A critical link between schizotypy and schizophrenia is impoverished cognitive functioning. In the majority of studies, though: (1) cognition is examined with standard neuropsychological tasks; and (2) high-schizotypal individuals are defined according to criteria applied in the respective study sample. Taking these considerations into account, the aims of the present study were to examine: (1) differences between four pre-defined, according to normative criteria, schizotypal (paranoid, negative, disorganized and cognitive-perceptual) and one control groups in self-perceived cognitive lapses; and (2) associations between schizotypal dimensions, self-perceived cognitive lapses and psychological well-being. Two hundred and sixty-one participants were administered the Schizotypal Personality Questionnaire, the Cognitive Failures Questionnaire (CFQ) and the Flourishing Scale, which assesses psychological well-being. Negative schizotypals reported higher scores in almost all CFQ measures compared with the control group (all p values < 0.01) along with poorer psychological well-being compared with the control and the cognitive-perceptual groups (both p values < 0.001). The disorganized group had higher scores in distractibility, blunders and total CFQ scores compared with the control group (all p values < 0.001). High psychological well-being was significantly associated with low negative schizotypy and CFQ blunders along with high cognitive-perceptual schizotypy (all p values < 0.05). To summarize, negative schizotypy is associated with a profile of "generalized" self-perceived cognitive lapses while disorganized schizotypy is characterized by self-perceived cognitive slips that have previously been shown to be mediated by a fronto-parietal network. Although psychological well-being is negatively associated with social-context specific cognitive failures and negative schizotypy, it is positively associated with cognitive-perceptual schizotypy.

The association of schizotypal traits with Prepulse Inhibition: a double approach exploration.

Introduction: According to the fully-dimensional approach, schizotypy is a personality trait present in the population in a continuous manner while the quasi-dimensional approach emphasises its extreme presentations. In this study we examined the relationship between sensorimotor gating, a core risk-index of the schizophrenia-spectrum, and four schizotypal factors in a dimensional-wise and a dichotomising-wise approach. Methods: Two-hundred and eighty-three participants were assessed with the Schizotypal Personality Questionnaire and were tested for Prepulse Inhibition (PPI). Associations between the schizotypal factors and startle measures were examined with stepwise regressions (dimensional-wise approach). Individuals in the lower 20% or the upper 20% for each schizotypal factor were identified and between-group comparisons were conducted (dichotomising-wise approach). Results: We found that with both approaches, only high paranoid or negative schizotypy were associated with reduced PPI. The low negative schizotypy group had prolonged onset and peak latencies, indicating that prolonged stimulus detection accompanies superior sensorimotor gating in this group. Conclusions: The findings suggest that although differentiating the effects of the various schizotypal factors is primary, the approach employed is secondary. The study also adds evidence in the literature supporting PPI as a useful endophenotypic marker of the schizophrenia-spectrum and highlights the contribution of specific aspects of schizotypy.

Multi-Trait Analysis of GWAS and Biological Insights Into Cognition: A Response to Hill (2018).

Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88) presented a critique of our recently published paper in Cell Reports entitled 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' (Lam et al., Cell Reports, Vol. 21, 2017, 2597-2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229-237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from 'inflation in the FDR [false discovery rate]', as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84-88), and are not 'more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence'.

Associations of differential schizotypal dimensions with executive working memory: A moderated-mediation analysis.

BACKGROUND: Increased schizotypal traits are observed in a percentage of the general population and in the schizophrenia-spectrum and have been associated with impairments in working memory. In this study we examined the effects of four schizotypal dimensions [Negative (NegS), Paranoid (ParS), Cognitive-Perceptual (CPS), Disorganized (DiS)] on executive working memory (EWM), as mediated by set-shifting, planning and control inhibition. We also examined whether these associations are moderated by family-history of psychosis. METHODS: Our sample consisted of 110 unaffected first-degree relatives of schizophrenia-spectrum patients and 120 control individuals. Schizotypy was assessed with the Schizotypal Personality Questionnaire. Participants were also tested with the Letter-Number Sequencing, Wisconsin Card Sorting, Stroop Color-Word and Stockings of Cambridge tasks. The effects of set-shifting, control inhibition and planning on the relationship between schizotypy and EWM were examined with mediation analyses. Moderated-mediation analyses examined potential moderating effects of group membership (unaffected relative/community participant). RESULTS: All mediators were significant in the relationship between NegS and EWM. The effects of ParS were mediated only by set-shifting and planning. Planning and control inhibition were the only significant mediators on the effects of CPS and DiS on EWM, respectively. The moderated-mediation analyses revealed that these findings apply only in the community group. CONCLUSIONS: We found that the effects of different schizotypal dimensions on EWM are mediated by other cognitive processes in individuals without personal/family history of psychosis. This is probably due to either more severe impairments in the cognitive processes of the relatives or restrictions in our sample and study-design.

Emotion processing deficits in the different dimensions of psychometric schizotypy.

Schizotypy refers to a personality structure indicating "proneness" to schizophrenia. Around 10% of the general population has increased schizotypal traits, they also share other core features with schizophrenia and are thus at heightened risk for developing schizophrenia and spectrum disorders. A key aspect in schizophrenia-spectrum pathology is the impairment observed in emotion-related processes. This review summarizes findings on impairments related to central aspects of emotional processes, such as emotional disposition, alexithymia, facial affect recognition and speech prosody, in high schizotypal individuals in the general population. Although the studies in the field are not numerous, the current findings indicate that all these aspects of emotional processing are deficient in psychometric schizotypy, in accordance to the schizophrenia-spectrum literature. A disturbed frontotemporal neural network seems to be the critical link between these impairments, schizotypy and schizophrenia. The limitations of the current studies and suggestions for future research are discussed.

The validity of the Schizotypal Personality Questionnaire in a Greek sample: Tests of measurement invariance and latent mean differences.

BACKGROUND: The Schizotypal Personality Questionnaire (SPQ) is a widely used scale for measuring schizotypal characteristics modeled on DSM-III-R criteria for schizotypal personality disorder (SPD). The aim of this study was to examine the factorial structure of the Greek SPQ, its factorial invariance across gender and different age groups and possible gender and age group differences at latent mean level. METHODS: Eight hundred sixty-five community participants completed the Greek version of the SPQ. RESULTS: With regard to the factorial structure of the original first-order model, the results showed that a seven-factor model (sub-scales "no close friends" with "constricted affect" and "ideas of reference" with "unusual perceptual experiences" were combined) was replicated adequately. Furthermore, the second-order "paranoid" model provided also adequate fit. With regard to the factorial invariance of the SPQ across gender and age, the analysis revealed that both, the first- and second-order models showed measurement invariance (configural, metric and structural) across gender and age groups (17-35 vs. 36-70). Latent mean differences across gender and age groups were also found. CONCLUSIONS: Based on these findings, we can conclude that the Greek version of the SPQ is a psychometrically sound instrument for measuring schizotypal characteristics and a useful screening tool for SPD across gender and age.

Independent evidence for an association between general cognitive ability and a genetic locus for educational attainment.

Cognitive deficits and reduced educational achievement are common in psychiatric illness; understanding the genetic basis of cognitive and educational deficits may be informative about the etiology of psychiatric disorders. A recent, large genome-wide association study (GWAS) reported a genome-wide significant locus for years of education, which subsequently demonstrated association to general cognitive ability ("g") in overlapping cohorts. The current study was designed to test whether GWAS hits for educational attainment are involved in general cognitive ability in an independent, large-scale collection of cohorts. Using cohorts in the Cognitive Genomics Consortium (COGENT; up to 20,495 healthy individuals), we examined the relationship between g and variants associated with educational attainment. We next conducted meta-analyses with 24,189 individuals with neurocognitive data from the educational attainment studies, and then with 53,188 largely independent individuals from a recent GWAS of cognition. A SNP (rs1906252) located at chromosome 6q16.1, previously associated with years of schooling, was significantly associated with g (P = 1.47 × 10(-4) ) in COGENT. The first joint analysis of 43,381 non-overlapping individuals for this a priori-designated locus was strongly significant (P = 4.94 × 10(-7) ), and the second joint analysis of 68,159 non-overlapping individuals was even more robust (P = 1.65 × 10(-9) ). These results provide independent replication, in a large-scale dataset, of a genetic locus associated with cognitive function and education. As sample sizes grow, cognitive GWAS will identify increasing numbers of associated loci, as has been accomplished in other polygenic quantitative traits, which may be relevant to psychiatric illness.

Facial emotion recognition and schizotypal traits: A systematic review of behavioural studies.

AIM: Previous research has indicated that individuals expressing high schizotypal traits and patients with Schizotypal Personality Disorder (SPD), show deficits in facial emotion recognition, compared to low schizotypal or control groups. On the other hand, non-significant findings also exist and the association of facial emotion recognition deficits with the different schizotypal dimensions is not well defined, thus limiting any conclusive outcomes. Therefore, the aim of this systematic review was to further clarify this relationship. METHODS: PsychInfo, Web of Science, Scopus and PubMed were systematically searched, and 23 papers with a cross-sectional design were selected. Nineteen studies examined individuals with high schizotypal traits and four studies evaluated SPD individuals with behavioural facial emotion recognition paradigms and self-report measures or clinical interviews for schizotypal traits. All selected studies were published between 1994 and August 2020. RESULTS: According to the evidence of studies, high schizotypal individuals and SPD patients have poorer performance in facial emotion recognition tasks. Negative schizotypy was related to lower accuracy for positive and negative emotions and faster emotion labeling while positive schizotypy was associated with worse accuracy for positive, negative and neutral emotions and more biases. Disorganized schizotypy was associated with poorer accuracy for negative emotions and suspiciousness with higher accuracy for disgust faces but lower total accuracy. CONCLUSIONS: These findings are consistent with the vulnerability for schizophrenia spectrum disorders and support the idea that emotion recognition deficits are trait markers for these conditions. Thus, the effectiveness of early-intervention programmes could increase by also targeting this class of deficits.

Cognitive Processes and Resting-State Functional Neuroimaging Findings in High Schizotypal Individuals and Schizotypal Personality Disorder Patients: A Systematic Review.

Ample research findings indicate that there is altered brain functioning in the schizophrenia spectrum. Nevertheless, functional neuroimaging findings remain ambiguous for healthy individuals expressing high schizotypal traits and patients with schizotypal personality disorder (SPD). The purpose of this systematic review was to identify patterns of task-related and resting-state neural abnormalities across these conditions. MEDLINE-PubMed and PsycINFO were systematically searched and forty-eight studies were selected. Forty studies assessed healthy individuals with high schizotypal traits and eight studies examined SPD patients with functional neuroimaging techniques (fNIRS; fMRI; Resting-state fMRI). Functional alterations in striatal, frontal and temporal regions were found in healthy individuals with high schizotypal traits. Schizotypal personality disorder was associated with default mode network abnormalities but further research is required in order to better conceive its neural correlates. There was also evidence for functional compensatory mechanisms associated with both conditions. To conclude, the findings suggest that brain dysfunctions are evident in individuals who lie along the subclinical part of the spectrum, further supporting the continuum model for schizophrenia susceptibility. Additional research is required in order to delineate the counterbalancing processes implicated in the schizophrenia spectrum, as this approach will provide promising insights for both conversion and protection from conversion into schizophrenia.

Cognitive and prepulse inhibition deficits in psychometrically high schizotypal subjects in the general population: relevance to schizophrenia research.

Schizophrenia and schizotypal personality disorder share common clinical profiles, neurobiological and genetic substrates along with Prepulse Inhibition and cognitive deficits; among those, executive, attention, and memory dysfunctions are more consistent. Schizotypy is considered to be a non-specific "psychosis-proneness," and understanding the relationship between schizotypal traits and cognitive function in the general population is a promising approach for endophenotypic research in schizophrenia spectrum disorders. In this review, findings for executive function, attention, memory, and Prepulse Inhibition impairments in psychometrically defined schizotypal subjects have been summarized and compared to schizophrenia patients and their unaffected first-degree relatives. Cognitive flexibility, sustained attention, working memory, and Prepulse Inhibition impairments were consistently reported in high schizotypal subjects in accordance to schizophrenia patients. Genetic studies assessing the effects of various candidate gene polymorphisms in schizotypal traits and cognitive function are promising, further supporting a polygenic mode of inheritance. The implications of the findings, methodological issues, and suggestions for future research are discussed.

The CACNA1C and ANK3 risk alleles impact on affective personality traits and startle reactivity but not on cognition or gating in healthy males.

OBJECTIVES: The rs10994336 ANK3 and rs1006737 CACNA1C genetic variants have recently been identified as the most consistent, genome-wide significant risk factors for bipolar disorder, while the CACNA1C variant has also been associated with schizophrenia and major depression. The aim of this study was to examine the phenotypic consequences of the risk CACNA1C and ANK3 alleles in a large homogeneous cohort of healthy young males. METHODS: We recruited 703 randomly selected, healthy army conscripts (mean age 22.1 ± 3.0 years) from the first wave of the Learning on Genetics of Schizophrenia project in Heraklion, Crete. Of those recruited, 530 subjects entered and completed the study. Subjects were assessed for prepulse inhibition (PPI), startle reactivity, neuropsychology, and personality. RESULTS: UNPHASED analysis revealed that the rs1006737 A-allele was associated with lower extraversion and higher harm avoidance, trait anxiety, and paranoid ideation, while the rs10994336 T-allele was associated with lower novelty seeking and behavioral activation scores (p < 0.01). Both alleles were associated with high startle reactivity (p < 0.05). There were no significant associations with any cognitive task performance or PPI. CONCLUSIONS: The CACNA1C genotype was associated with proneness to anxiety and negative mood, while the ANK3 genotype was associated with proneness to anhedonia. Both risk genotypes were associated with high startle reactivity, suggesting a role of these polymorphisms in threat/stress signal processing, probably in the hippocampus and/or amygdala. None of the risk genotypes affected sensorimotor gating or behavioral performance in an extensive battery of executive function tests in this cohort of healthy males.

Working memory training effects across the lifespan: Evidence from human and experimental animal studies.

Working memory refers to a cognitive function that provides temporary storage and manipulation of the information necessary for complex cognitive tasks. Due to its central role in general cognition, several studies have investigated the possibility that training on working memory tasks could improve not only working memory function but also increase other cognitive abilities or modulate other behaviors. This possibility is still highly controversial, with prior studies providing contradictory findings. The lack of systematic approaches and methodological shortcomings complicates this debate even more. This review highlights the impact of working memory training at different ages on humans. Finally, it demonstrates several findings about the neural substrate of training in both humans and experimental animals, including non-human primates and rodents.

Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics.

Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify "druggable" targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing.

Cognitive Functioning and Schizotypy: A Four-Years Study.

Although there is ample evidence from cross-sectional studies indicating cognitive deficits in high schizotypal individuals that resemble the cognitive profile of schizophrenia-spectrum patients, there is still lack of evidence by longitudinal/follow-up studies. The present study included assessments of schizotypal traits and a wide range of cognitive functions at two time points (baseline and 4-years assessments) in order to examine (a) their stability over time, (b) the predictive value of baseline schizotypy on cognition at follow-up and (c) differences in cognition between the two time points in high negative schizotypal and control individuals. Only high negative schizotypal individuals were compared with controls due to the limited number of participants falling in the other schizotypal groups at follow-up. Seventy participants (mean age: 36.17; 70% females) were assessed at baseline and follow-up. Schizotypal traits were evaluated with the Schizotypal Personality Questionnaire. We found that schizotypal traits decreased over time, except in a sub-group of participants ("schizotypy congruent") that includes individuals who consistently meet normative criteria of inclusion in either a schizotypal or control group. In these individuals, negative schizotypy and aspects of cognitive-perceptual and disorganized schizotypy remained stable. The stability of cognitive functioning also varied over time: response inhibition, aspects of cued attention switching, set-shifting and phonemic/semantic verbal fluency improved at follow-up. High negative schizotypy at baseline predicted poorer response inhibition and semantic switching at follow-up while high disorganized schizotypy predicted poorer semantic processing and complex processing speed/set-shifting. The between-group analyses revealed that response inhibition, set-shifting and complex processing speed/set-shifting were poorer in negative schizotypals compared with controls at both time points, while maintaining set and semantic switching were poorer only at follow-up. Taken together, the findings show differential stability of the schizotypal traits over time and indicate that different aspects of schizotypy predict a different pattern of neuropsychological task performance during a 4-years time window. These results are of significant use in the formulation of targeted early-intervention strategies for high-risk populations.

Schizotypal traits, neurocognition, and paternal age in unaffected first degree relatives of patients with familial or sporadic schizophrenia.

Studies comparing cognitive processes between familial and sporadic schizophrenia have yielded inconsistent findings. In this study we examined differences in neurocognition and schizotypal traits in unaffected relatives of schizophrenia-spectrum patients with either the familial (multiplex) or the sporadic (simplex) subtype of the disorder, taking paternal age at birth into consideration. Simplex (n = 65; SR), multiplex (n = 35; MR) relatives and controls (n = 114) were compared on several cognitive functions and schizotypal traits; between-group differences were evaluated with and without including paternal age in the analyses. SR and MR had higher negative and paranoid traits compared with controls, but paternal age abolished the differences between the SR and control groups. When taking into account schizotypal traits and participants' age, controls outperformed MR in strategy formation and set-shifting and SR in psychomotor speed, set-shifting and executive working memory. After including paternal age in the analyses, controls outperformed MR in strategy formation, working memory and executive working memory and both groups in psychomotor speed and set-shifting. These findings suggest that multiplex relatives present with a "riskier" personality and cognitive profile when considering the effects of paternal age. Nevertheless, simplex relatives are impaired in fundamental cognitive processes, thus highlighting the detrimental effects of paternal age on neurocognition.

Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

Planning, decision-making and the COMT rs4818 polymorphism in healthy males.

Recent evidence suggests that a synonymous polymorphism within the COMT gene (rs4818 C/G) accounts for a greater variation of COMT activity compared to the functional Val158Met polymorphism. This is the first study on the effects of the rs4818 C/G polymorphism on cognition. One hundred and seven healthy males were tested with the Stockings of Cambridge (SoC) and the Iowa Gambling Task (IGT) and then grouped according to their COMT rs4818 C/G status into three groups (G/G, C/G, C/C). ANOVAs showed that C/C individuals had the best performance in the SoC, G/G the worse, while C/G were intermediate. G/G individuals had strikingly better performance in the IGT compared to the other two groups and their performances in the two tasks were inversely related. These results show that the rs4818 C/G polymorphism imparts strong and differential effects on PFC functions. Low prefrontal dopamine levels are disadvantageous for planning in non-emotional problem solving but lead to optimal effects in emotionally informed decision-making. While high prefrontal dopamine levels may be advantageous for non-emotional problem solving, they lead to disadvantageous choices when decision-making depends on processing of emotional feedback.