Performance on a contour integration task as a function of contour shape in schizophrenia and controls.

Contour Integration (CI) is the ability to integrate elemental features into objects and is a basic visual process essential for object perception and recognition, and for functioning in visual environments. It is now well documented that people with schizophrenia (SZ), in addition to having cognitive impairments, also have several visual perceptual deficits, including in CI. Here, we retrospectively characterize the performance of both SZ and neurotypical individuals (NT) on a series of contour shapes, made up of Gabor elements, that varied in terms of closure and curvature. Participants in both groups performed a CI training task that included 7 different families of shapes (Lines, Ellipse, Blobs, Squiggles, Spiral, Circle and Letters) for up to 40 sessions. Two parameters were manipulated in the training task: Orientation Jitter (OJ, i.e., orientation deviations of individual Gabor elements from ideal for each shape) and Inducer Number (IN, i.e., number of Gabor elements defining the shape). Results show that both OJ and IN thresholds significantly differed between the groups, with higher (OJ) and lower (IN) thresholds observed in the controls. Furthermore, we found significant effects as a function of the contour shapes, with differences between groups emerging with contours that were considered more complex, e.g., due to having a higher degree of curvature (Blobs, Spiral, Letters). These data can inform future work that aims to characterize visual integration impairments in schizophrenia.

Retinal Neurodegeneration as a Potential Biomarker of Accelerated Aging in Schizophrenia Spectrum Disorders.

BACKGROUND AND HYPOTHESES: Several biological markers are believed to reflect accelerated aging in schizophrenia spectrum disorders; however, retinal neural changes have not yet been explored as potential CNS biomarkers of accelerated aging in this population. The aim of this study was to determine whether retinal neural layer thinning is more strongly related to age in schizophrenia and schizoaffective disorder patients (SZ) than in a psychiatrically healthy control group (CON). STUDY DESIGN: Schizophrenia (n = 60) and CON participants (n = 69) underwent spectral domain optical coherence tomography (OCT) scans to examine the following variables in both eyes: retinal nerve fiber layer (RNFL) thickness, macula central subfield (CSF) thickness, macula volume, ganglion cell layer-inner plexiform layer (GCL-IPL) thickness, optic cup volume, and cup-to-disc ratio. Eleven participants in each group had diabetes or hypertension. STUDY RESULTS: Significant negative relationships between age and RNFL thickness, macula volume, and GCL-IPL thickness were observed in the SZ group, while no significant relationships were observed in the CON group. However, many of the findings in the SZ group lost significance when participants with diabetes/hypertension were removed from analyses. A notable exception to this was that the age × SZ interaction accounted for a unique proportion of variance in GCL-IPL thinning over and above the effect of diabetes/hypertension. CONCLUSIONS: The results suggest that retinal atrophy occurs at an increased rate in schizophrenia spectrum disorders, potentially reflecting accelerated aging inherent to these conditions, with considerable contributions from systemic medical diseases closely linked to this population.

Dorsal attention network activity during perceptual organization is distinct in schizophrenia and predictive of cognitive disorganization.

Visual shape completion is a canonical perceptual organization process that integrates spatially distributed edge information into unified representations of objects. People with schizophrenia show difficulty in discriminating completed shapes, but the brain networks and functional connections underlying this perceptual difference remain poorly understood. Also unclear is whether brain network differences in schizophrenia occur in related illnesses or vary with illness features transdiagnostically. To address these topics, we scanned (functional magnetic resonance imaging, fMRI) people with schizophrenia, bipolar disorder, or no psychiatric illness during rest and during a task in which they discriminated configurations that formed or failed to form completed shapes (illusory and fragmented condition, respectively). Multivariate pattern differences were identified on the cortical surface using 360 predefined parcels and 12 functional networks composed of such parcels. Brain activity flow mapping was used to evaluate the likely involvement of resting-state connections for shape completion. Illusory/fragmented task activation differences ('modulations') in the dorsal attention network (DAN) could distinguish people with schizophrenia from the other groups (AUCs > .85) and could transdiagnostically predict cognitive disorganization severity. Activity flow over functional connections from the DAN could predict secondary visual network modulations in each group, except in schizophrenia. The secondary visual network was strongly and similarly modulated in each group. Task modulations were dispersed over more networks in patients compared to controls. In summary, DAN activity during visual perceptual organization is distinct in schizophrenia, symptomatically relevant, and potentially related to improper attention-related feedback into secondary visual areas.

Evaluating Educational and Employment Services for Young People With Psychiatric Conditions: A Systematic Review.

OBJECTIVE: The authors conducted a systematic review of studies evaluating vocational interventions for young people with psychiatric conditions to determine the extent to which services were adapted for young people and whether services promoted gains in postsecondary education and employment. METHODS: Five databases (PubMed, PsycINFO, Web of Science, Academic Search Premier, and ERIC) were searched. Sources eligible for inclusion were controlled studies published between 2000 and mid-2020 that evaluated a vocational intervention and examined postsecondary educational or employment outcomes for youths or young adults (ages 14-35 years) with psychiatric conditions. RESULTS: Ten studies met the inclusion criteria. Several of the studies evaluated services that were adapted for young people, including through the incorporation of educational supports. The most consistent finding was that services based on the individual placement and support (IPS) model improved employment outcomes more effectively than did comparison approaches and treatment as usual. Fewer studies assessed educational outcomes, and they yielded mixed results; however, recent findings from a controlled trial indicate that an enhanced IPS intervention that included well-specified supported education and skills training led to significantly superior outcomes in both education and employment. CONCLUSIONS: These results provide support for the efficacy of IPS-based services to improve employment outcomes among young people with psychiatric conditions and suggest that adapting IPS to include comprehensive educational supports and skills training may be important for efforts to improve postsecondary educational outcomes. Additional well-controlled intervention studies that examine educational and longer-term outcomes should further inform the development and delivery of vocational services for this population.

Increased face detection responses on the mooney faces test in people at clinical high risk for psychosis.

Identifying state-sensitive measures of perceptual and cognitive processes implicated in psychosis may allow for objective, earlier, and better monitoring of changes in mental status that are predictive of an impending psychotic episode, relative to traditional self-report-based clinical measures. To determine whether a measure of visual perception that has demonstrated sensitivity to the clinical state of schizophrenia in multiple prior studies is sensitive to features of the at-risk mental state, we examined differences between young people identified as being at clinical high risk for psychosis (CHR; n = 37) and non-psychiatric matched controls (n = 29) on the Mooney Faces Test (MFT). On each trial of the MFT, participants report whether they perceive a face in a degraded face image. The CHR group reported perceiving a greater number of faces in both upright and inverted MFT stimuli. Consistent with prior work, males reported more faces on the MFT than females in both conditions. However, the finding of greater reported face perception among CHR subjects was robustly observed in the female CHR group relative to the female control group. Among male CHR participants, greater reported face perception was related to increased perceptual abnormalities. These preliminary results are consistent with a small but growing literature suggesting that heightened perceptual sensitivity may characterize individuals at increased clinical risk for psychosis. Further studies are needed to determine the contributions of specific perceptual, cognitive, and motivational mechanisms to the findings.

Predicting Attention-Shaping Response in People With Schizophrenia.

ABSTRACT: People with schizophrenia often experience attentional impairments that hinder learning during psychological interventions. Attention shaping is a behavioral technique that improves attentiveness in this population. Because reinforcement learning (RL) is thought to be the mechanism by which attention shaping operates, we investigated if preshaping RL performance predicted level of response to attention shaping in people with schizophrenia. Contrary to hypotheses, a steeper attentiveness growth curve was predicted by less intact pretreatment RL ability and lower baseline attentiveness, accounting for 59% of the variance. Moreover, baseline attentiveness accounted for over 13 times more variance in response to attention shaping than did RL ability. Results suggest attention shaping is most effective for lower-functioning patients, and those high in RL ability may already be close to ceiling in terms of their response to reinforcers. Attention shaping may not be a primarily RL-driven intervention, and other mechanisms of its effects should be considered.

Development and Evaluation of a Visual Remediation Intervention for People with Schizophrenia.

It is now well documented that schizophrenia is associated with impairments in visual processing at all levels of vision, and that these disturbances are related to deficits in multiple higher-level cognitive and social cognitive functions. Visual remediation methods have been slow to appear in the literature as a potential treatment strategy to target these impairments, however, in contrast to interventions that aim to improve auditory and higher cognitive functions in schizophrenia. In this report, we describe a National Institute of Mental Health (NIMH)-funded R61/R33 grant that uses a phased approach to optimize and evaluate a novel visual remediation intervention for people with schizophrenia. The goals of this project are: (1) in the R61 phase, to establish the optimal components and dose (number of sessions) of a visual remediation intervention from among two specific visual training strategies (and their combination) for improving low and mid-level visual functions in schizophrenia; and (2) in the R33 phase, to determine the extent to which the optimal intervention improves not only visual processing but also higher-level cognitive and role functions. Here we present the scientific background for and innovation of the study, along with our methods, hypotheses, and preliminary data. The results of this study will help determine the utility of this novel intervention approach for targeting visual perceptual, cognitive, and functional impairments in schizophrenia.

Amphetamine-induced striatal dopamine release in schizotypal personality disorder.

RATIONALE: Previous research has suggested that schizotypal personality disorder (SPD), a condition that shares clinical and cognitive features with schizophrenia, may be associated with elevated striatal dopamine functioning; however, there are no published studies of dopamine release within subregions of the striatum in SPD. OBJECTIVES: To characterize dopamine release capacity in striatal subregions and its relation to clinical and cognitive features in SPD. METHODS: We used positron emission tomography with [11C]raclopride and an amphetamine challenge to measure dopamine D2-receptor availability (binding potential, BPND), and its percent change post-amphetamine (∆BPND) to index amphetamine-induced dopamine release, in subregions of the striatum in 16 SPD and 16 healthy control participants. SPD participants were evaluated with measures of schizotypal symptom severity and working memory. RESULTS: There were no significant group differences in BPND or ∆BPND in any striatal subregion or whole striatum. Among SPD participants, cognitive-perceptual symptoms were associated at trend level with ∆BPND in the ventral striatum, and disorganized symptoms were significantly negatively related to ∆BPND in several striatal subregions. CONCLUSIONS: In contrast to previous findings, SPD was not associated with elevated striatal dopamine release. However, in SPD, there was a moderate positive association between ventral striatal dopamine release and severity of cognitive-perceptual symptoms, and negative associations between striatal dopamine release and severity of disorganized symptoms. Future larger scale investigations that allow for the separate examination of subgroups of participants based on clinical presentation will be valuable in further elucidating striatal DA functioning in SPD.

Retinal functioning and reward processing in schizophrenia.

Retinal responses to light, as measured by electroretinography (ERG), have been shown to be reduced in schizophrenia. Data from a prior ERG study in healthy humans indicated that activity of a retinal cell type affected in schizophrenia can be modified by the presence of a food reward. Therefore, we aimed to determine whether ERG amplitudes would be sensitive to the well-documented reward processing impairment in schizophrenia. Flash ERG data from 15 clinically stable people with schizophrenia or schizoaffective disorder and 15 healthy controls were collected under three conditions: baseline, anticipation of a food reward, and immediately after consuming the food reward. At the group level, data indicated that controls' ERG responses varied as a function of salience of the food reward (baseline vs. anticipation vs. consumption) whereas patients' ERG responses did not vary significantly across conditions. Correlations between ERG amplitudes and scores on measures of hedonic capacity (including motivation and pleasure negative symptom ratings for patients) indicated consistent relationships. These data suggest that flash ERG amplitudes may be a sensitive indicator of the integrity of reward processing mechanisms. However, several differences in the direction of findings between this and a prior study in controls point to the need for further investigation of the contributions of a number of key variables to the observed effects.

People with current major depression resemble healthy controls on flash Electroretinogram indices associated with impairment in people with stabilized schizophrenia.

Flash electroretinography (fERG) has been used to identify anomalies in retinal functioning in several psychiatric disorders. In schizophrenia (SCZ), fERG abnormalities are reliably observed, but findings from studies of major depressive disorder (MDD) have been less consistent. In this study, fERG data were recorded from MDD patients in a current major depressive episode (n = 25), and compared to data from SCZ patients (n = 25) and healthy controls (HC; n = 25), to determine the degree to which fERG anomalies in acute MDD overlap or contrast with those observed in stabilized (though not symptom free) SCZ. The primary variables of interest were a-wave (photoreceptor activity), b-wave (bipolar-Müller cell activity), and photopic negative response (PhNR; ganglion cell activity) amplitudes and implicit times. Across most conditions, there were no significant differences between the MDD and HC groups in a- or b-wave response, but the SCZ group consistently demonstrated reduced amplitudes. Interestingly, MDD patients demonstrated an increase in photopic a-wave implicit time relative to SCZ patients, and a decrease in PhNR implicit time relative to controls. Correlations between BDI-II scores and fERG metrics were not significant for either patient group. Overall, these data indicate that, using an fERG protocol that distinguishes SCZ patients from controls, MDD patients experiencing a current depressive episode closely resemble healthy controls in their fERG responses. Therefore, MDD-related fERG changes may be more subtle than those observed in SCZ and detectable only with larger sample sizes than we employed and/or using a different set of fERG test parameters.

Evaluation of a cognitive remediation intervention for college students with psychiatric conditions.

OBJECTIVE: Given the poor educational outcomes associated with psychiatric conditions, we developed Focused Academic Strength Training (FAST), a 12-week strategy-focused cognitive remediation intervention designed to improve academic functioning among college students with psychiatric conditions. Here we report initial results from a randomized controlled trial of FAST. METHOD: Seventy-two college students with mood, anxiety, and/or psychotic disorders were randomized to receive FAST or services as usual and were assessed at baseline and 4 months (posttreatment). RESULTS: Repeated-measures analyses of variance indicated FAST-associated improvements in self-reported cognitive strategy use (p < .001), self-efficacy (p = .001), and academic difficulties (p = .025). There were no significant treatment-related improvements in neuropsychological performance. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: FAST may lead to an increase in self-efficacy and cognitive strategy use, as well as a reduction in academic difficulties among students with psychiatric conditions. Future analyses with follow-up data through 12 months will address the potential of FAST to improve academic functioning among this population. (PsycINFO Database Record

Visual perceptual remediation for individuals with schizophrenia: Rationale, method, and three case studies.

OBJECTIVE: Few studies have evaluated the effects of visual remediation strategies in schizophrenia despite abundant evidence of visual-processing alterations in this condition. We report preliminary, case-study-based evidence regarding the effects of visual remediation in this population. METHOD: We describe implementation of a visual-perceptual training program called ULTIMEYES (UE) and initial results through 3 brief case studies of individuals with schizophrenia. UE targets broad-based visual function, including low-level processes (e.g., acuity, contrast sensitivity) as well as higher level visual functions. Three inpatients, recruited from a research unit, participated in at least 38 sessions 3 to 4 times per week for approximately 25 min per session. Contrast sensitivity (a trained task), as well as acuity and perceptual organization (untrained tasks), were assessed before and after the intervention. Levels of progression through the task are also reported. RESULTS: UE was well tolerated by the participants and led to improvements in contrast sensitivity, as well as more generalized gains in visual acuity in all 3 participants and perceptual organization in 2 participants. Symptom profiles were somewhat different for each participant, but all were symptomatic during the intervention. Despite this, they were able to focus on and benefit from training. The adaptive nature of the training was well suited to the slower progression of 2 participants. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: These case studies set the stage for further research, such as larger, randomized controlled trials of the intervention that include additional assessments of perceptual function and measures of cognition, social cognition, and functional outcomes. (PsycINFO Database Record

A proof-of-concept, randomized controlled trial of DAR-0100A, a dopamine-1 receptor agonist, for cognitive enhancement in schizophrenia.

BACKGROUND: Evidence from preclinical and human studies indicates the presence of reduced dopamine-1 receptor (D1R) signaling in the cortex, where D1Rs predominate, in patients with schizophrenia (SCZ), which may contribute to their cognitive deficits. Furthermore, studies in nonhuman primates (NHP) have suggested that intermittent administration of low doses of D1R agonists produce long-lasting reversals in cognitive deficits. The purpose of this trial was to test whether a similar design, involving subacute intermittent administration of low doses of a full, selective agonist at D1Rs, DAR-0100A, would improve cognitive deficits in SCZ. METHODS: We randomized 49 clinically stable individuals with SCZ to three weeks of intermittent treatment with 0.5 mg or 15 mg of DAR-0100A, or placebo (normal saline). Functional magnetic resonance imaging (fMRI) BOLD was used to evaluate the effects of drug administration on brain activity during a working memory (WM) task. Effects on cognition were also assessed using the MATRICS and the N-back task as primary endpoints. The CogState battery was used as a secondary endpoint. RESULTS: There were no observed treatment effects on either the BOLD fMRI signal during WM tasks or the WM domains of the MATRICS. Moderate improvement was detected on the CogState battery and on the attention domain of the MATRICS. CONCLUSION: These results suggest that low doses of D1 agonists that do not result in measureable occupancy of the D1R do not reliably improve cognition in SCZ, unlike the observations in NHP. As this drug is limited by its pharmacokinetic profile, better D1R agonists that can achieve adequate levels of D1R occupancy are needed to test the efficacy of this mechanism for cognitive enhancement in SCZ.

Deficits in prefrontal cortical and extrastriatal dopamine release in schizophrenia: a positron emission tomographic functional magnetic resonance imaging study.

IMPORTANCE: Multiple lines of evidence suggest a deficit in dopamine release in the prefrontal cortex (PFC) in schizophrenia. Despite the prevalence of the concept of prefrontal cortical hypodopaminergia in schizophrenia, in vivo imaging of dopamine release in the PFC has not been possible until now, when the validity of using the positron emission tomographic D2/3 radiotracer carbon 11-labeled FLB457 in combination with the amphetamine paradigm was clearly established. OBJECTIVES: To (1) test amphetamine-induced dopamine release in the dorsolateral PFC (DLPFC) in drug-free or drug-naive patients with schizophrenia (SCZ) and healthy control (HC) individuals matched for age, sex, race/ethnicity, and familial socioeconomic status;(2) test blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging activation during a working memory task in the same participants; and (3) examine the relationship between positron emission tomographic and functional magnetic resonance imaging outcome measures. DESIGN, SETTING AND PARTICIPANTS: Positron emission tomographic imaging with carbon 11-labeled FLB457 before and following 0.5 mg/kg of amphetamine by mouth. Blood oxygenation level-dependent functional magnetic resonance imaging during the self-ordered working memory task. Twenty patients with schizophrenia recruited from the inpatient and outpatient research facilities at New York State Psychiatric Institute and 21 healthy control individuals participated, and data were acquired between June 16, 2011, and February 25, 2014. MAIN OUTCOMES AND MEASURE: The percentage change in binding potential (∆BPND) in the DLPFC following amphetamine, BOLD activation during the self-ordered working memory task compared with the control task, and the correlation between these 2 outcome measures. RESULTS: We observed significant differences in the effect of amphetamine on DLPFC BPND (mean [SD], ∆BPND in HC: -7.5% [11%]; SCZ: +1.8% [11%]; P = .01); a generalized blunting in dopamine release in SCZ involving most extrastriatal regions and the midbrain; and a significant association between ∆BPND and BOLD activation in the DLPFC in the overall sample including patients with SCZ and HC individuals. CONCLUSIONS AND RELEVANCE: To our knowledge, these results provide the first in vivo evidence for a deficit in the capacity for dopamine release in the DLPFC in SCZ and suggest a more widespread deficit extending to many cortical and extrastriatal regions including the midbrain. This contrasts with the well-replicated excess in dopamine release in the associative striatum in SCZ and suggests a differential regulation of striatal dopamine release in associative striatum vs extrastriatal regions. Furthermore, dopamine release in the DLPFC relates to working memory-related activation of this region, suggesting that blunted release may affect frontal cortical function.

Anhedonia in the psychosis risk syndrome: associations with social impairment and basal orbitofrontal cortical activity.

BACKGROUND/OBJECTIVES: Anhedonia is associated with poor social function in schizophrenia. Here, we examined this association in individuals at clinical high risk (CHR) for schizophrenia and related psychotic disorders, taking into account social anxiety. We then explored correlations between anhedonia and basal metabolic activity in selected forebrain regions implicated in reward processing. METHODS: In 62 CHR individuals and 37 healthy controls, we measured social adjustment (Social Adjustment Self-Report Scale), social and physical anhedonia (Chapman Revised Anhedonia Scales), and social anxiety (Social Anxiety Scale for Adolescents) in cross-section. In a subgroup of 25 CHR individuals for whom high-spatial-resolution basal-state functional magnetic resonance imaging data were available, we also assessed correlations of these socio-affective constructs with basal cerebral blood volume in orbitofrontal cortex and related regions involved in reward processing. RESULTS: Relative to controls, CHR individuals reported social impairment, greater social and physical anhedonia, and more social anxiety, exhibiting impairments comparable to schizophrenia. Regression analyses showed that anhedonia predicted social impairment and correlated negatively with basal cerebral blood volume within the orbitofrontal cortex (all P's<0.05). CONCLUSIONS: Anhedonia and social anxiety are prominent in CHR individuals. Trait-like anhedonia may be a core phenotype related to orbitofrontal cortical function that, independent of symptoms, predicts social impairment. These data provide a rationale for interventions that target anhedonia and related activity in orbitofrontal cortical circuits in CHR individuals.

Dynamic shifts in brain network activation during supracapacity working memory task performance.

Despite significant advances in understanding how brain networks support working memory (WM) and cognitive control, relatively little is known about how these networks respond when cognitive capabilities are overtaxed. We used a fine-grained manipulation of memory load within a single trial to exceed WM capacity during functional magnetic resonance imaging to investigate how these networks respond to support task performance when WM capacity is exceeded. Analyzing correct trials only, we observed a nonmonotonic (inverted-U) response to WM load throughout the classic WM network (including bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and presupplementary motor areas) that peaked later in individuals with greater WM capacity. We also observed a relative increase in activity in medial anterior prefrontal cortex, posterior cingulate/precuneus, and lateral temporal and parietal regions at the highest WM loads, and a set of predominantly subcortical and prefrontal regions whose activation was greatest at the lowest WM loads. At the individual subject level, the inverted-U pattern was associated with poorer performance while expression of the early and late activating patterns was predictive of better performance. In addition, greater activation in bilateral fusiform gyrus and right occipital lobe at the highest WM loads predicted better performance. These results demonstrate dynamic and behaviorally relevant changes in the level of activation of multiple brain networks in response to increasing WM load that are not well accounted for by present models of how the brain subserves the cognitive ability to hold and manipulate information on-line.

Serotonin transporter availability in impulsive aggressive personality disordered patients: a PET study with [11C]DASB.

Serotonin (5-HT) has consistently been implicated in the pathophysiology of impulsive aggression. In the current study, we tested the hypothesis that 5-HT transporter (5-HTT) binding is reduced in the anterior cingulate cortex (ACC) in impulsive aggressive patients. Additionally, we characterized pathological personality dimensions, with a specific focus on callousness (i.e. emotional indifference, a facet of psychopathy). Callousness is putatively positively correlated with presynaptic 5-HT, and thus could potentially confound the hypothesized negative relation between 5-HTT levels and trait aggression. We determined 5-HTT binding with positron emission tomography and [(11)C]DASB in 29 patients with intermittent explosive disorder (IED-IR) and 30 controls. We assessed group differences in 5-HTT binding in the pregenual ACC, amygdala and subcortical regions and examined correlations between 5-HTT binding and clinical measures. There were no significant differences in 5-HTT binding between IED-IR patients and controls. Trait callousness exhibited a significant, positive correlation with ACC 5-HTT availability. Among IED-IR patients, a trend-level negative partial correlation was observed between trait aggression and ACC 5-HTT availability, while covarying for callousness and age. Exploratory analyses revealed a significant negative correlation between state aggression levels and 5-HTT availability in subcortical regions, namely striatum and thalamus. We did not confirm our hypothesis of lower ACC 5-HTT availability in impulsive aggressive patients, however, the positive correlation between callousness and ACC 5-HTT availability likely played a confounding role. Subtypes of aggression (e.g., reactive vs. proactive aggression), which are differentially associated with pathological personality dimensions such as callousness, may contribute to variability between 5-HT functioning and aggression.

Prefrontal dopamine D1 receptors and working memory in schizotypal personality disorder: a PET study with [¹¹C]NNC112.

RATIONALE: Schizotypal personality disorder (SPD) is associated with working memory (WM) impairments that are similar to those observed in schizophrenia. Imaging studies have suggested that schizophrenia is associated with alterations in dopamine D1 receptor availability in the prefrontal cortex (PFC) that may be related to the WM impairments that characterize this disorder. OBJECTIVES: The aim of this study was to characterize prefrontal D1 receptor availability and its relation to WM performance in SPD. METHODS: We used positron emission tomography (PET) and the radiotracer [(11)C]NNC112 with 18 unmedicated SPD and 21 healthy control participants; as an index of D1 receptor availability, binding potential (BP) measures (BPF, BPND, and BPP) were calculated for prefrontal and striatal subregions. To assess WM, SPD participants completed the 2-back and Paced Auditory Serial Addition Test (PASAT). RESULTS: There were no significant group differences in PFC BP. BPF and BPP in the medial PFC were significantly negatively related to PASAT performance (r s = -0.551, p = .022 and r s = -0.488, p = .047, respectively), but BP was not related to 2-back performance. CONCLUSIONS: In contrast to what has been found in schizophrenia, SPD was not associated with significant alterations in prefrontal D1 receptor availability. Similar to previous schizophrenia findings, however, higher prefrontal D1 receptor availability was associated with poorer WM performance (as measured by the PASAT) in SPD. These findings suggest that schizophrenia and SPD may share a common pathophysiological feature related to prefrontal dopamine functioning that contributes to WM dysfunction, but that in SPD, alterations in D1 may occur only in a subset of individuals and/or to an extent that is minor relative to what occurs in schizophrenia.