Neuropsychological assessment of aggressive offenders: a Delphi consensus study.

Objective: This study explores the intricate relationship between cognitive functioning and aggression, with a specific focus on individuals prone to reactive or proactive aggression. The purpose of the study was to identify important neuropsychological constructs and suitable tests for comprehending and addressing aggression. Methods: An international panel of 32 forensic neuropsychology experts participated in this three-round Delphi study consisting of iterative online questionnaires. The experts rated the importance of constructs based on the Research Domain Criteria (RDoC) framework. Subsequently, they suggested tests that can be used to assess these constructs and rated their suitability. Results: The panel identified the RDoC domains Negative Valence Systems, Social Processes, Cognitive Systems and Positive Valence Systems as most important in understanding aggression. Notably, the results underscore the significance of Positive Valence Systems in proactive aggression and Negative Valence Systems in reactive aggression. The panel suggested a diverse array of 223 different tests, although they noted that not every RDoC construct can be effectively measured through a neuropsychological test. The added value of a multimodal assessment strategy is discussed. Conclusions: This research advances our understanding of the RDoC constructs related to aggression and provides valuable insights for assessment strategies. Rather than suggesting a fixed set of tests, our study takes a flexible approach by presenting a top-3 list for each construct. This approach allows for tailored assessment to meet specific clinical or research needs. An important limitation is the predominantly Dutch composition of the expert panel, despite extensive efforts to diversify.

Comparing psychotic experiences in low-and-middle-income-countries and high-income-countries with a focus on measurement invariance.

BACKGROUND: The prevalence of psychotic experiences (PEs) is higher in low-and-middle-income-countries (LAMIC) than in high-income countries (HIC). Here, we examine whether this effect is explicable by measurement bias. METHODS: A community sample from 13 countries (N = 7141) was used to examine the measurement invariance (MI) of a frequently used self-report measure of PEs, the Community Assessment of Psychic Experiences (CAPE), in LAMIC (n = 2472) and HIC (n = 4669). The CAPE measures positive (e.g. hallucinations), negative (e.g. avolition) and depressive symptoms. MI analyses were conducted with multiple-group confirmatory factor analyses. RESULTS: MI analyses showed similarities in the structure and understanding of the CAPE factors between LAMIC and HIC. Partial scalar invariance was found, allowing for latent score comparisons. Residual invariance was not found, indicating that sum score comparisons are biased. A comparison of latent scores before and after MI adjustment showed both overestimation (e.g. avolition, d = 0.03 into d = -0.42) and underestimation (e.g. magical thinking, d = -0.03 into d = 0.33) of PE in LAMIC relative to HIC. After adjusting the CAPE for MI, participants from LAMIC reported significantly higher levels on most CAPE factors but a significantly lower level of avolition. CONCLUSION: Previous studies using sum scores to compare differences across countries are likely to be biased. The direction of the bias involves both over- and underestimation of PEs in LAMIC compared to HIC. Nevertheless, the study confirms the basic finding that PEs are more frequent in LAMIC than in HIC.

Autistic traits in psychotic disorders: prevalence, familial risk, and impact on social functioning.

BACKGROUND: Prevalence estimates of autistic traits in individuals with psychotic disorders (PD) vary greatly and it is unclear whether individuals with a familial risk (FR) for psychosis have an increased propensity to display autistic traits. Furthermore, it is unknown whether the presence of comorbid autism traits disproportionally affects the cognitive and behavioral aspects of social functioning in PD. METHODS: In total, 504 individuals with PD, 587 unaffected siblings with FR, and 337 typical comparison (TC) individuals (16-50 years) were included. Autistic and psychotic traits were measured with the Autism Spectrum Quotient (AQ) and the Community Assessment of Psychic Experiences (CAPE). Social cognition was assessed with the Picture Sequencing Task (PST) and social behavior with the Social Functioning Scale (SFS). RESULTS: For PD 6.5% scored above AQ clinical cut-off (⩾32), 1.0% for FR, and 1.2% for TC. After accounting for age, sex, and IQ, the PD group showed significantly more autistic traits and alterations in social behavior and cognition, while FR and TC only displayed marginal differences. Within the PD group autistic traits were a robust predictor of social behavior and there were no interactions with positive psychotic symptoms. CONCLUSIONS: Levels of autistic traits are substantially elevated in PD and have a profoundly negative association with social functioning. In contrast, autistic traits above the clinical cut-off are not elevated in those with FR, and only marginally on a dimensional level. These findings warrant specific clinical guidelines for psychotic patients who present themselves with autistic comorbidity to help address their social needs.

Educating parents to improve parent-child interactions: Fostering the development of attentional control and executive functioning.

BACKGROUND: Parent-child interaction is essential in the development of attentional control (AC) and executive functioning (EF). Educating parents in AC and EF development may help them to respond more adaptively to their child's developmental needs. AIM: This study aimed to investigate whether parents can be educated to improve interactions with their child through a compact psycho-educational programme that focuses on fostering the development of AC and EF. SAMPLE: Parents and their children in a low-risk sample of four- to eight-year-olds were randomly assigned to either the educational programme condition (N = 34) or the control condition (N = 36). METHODS: Parental supportive presence and intrusiveness were observed during home visits, and children's performance-based AC and EF were assessed before and after the four-session programme. RESULT: Parents in the educational programme improved significantly in support ( η p 2  = .19) and intrusiveness ( η p 2  = .09) compared to controls. There was no short-term programme mediation effect on child AC and EF through parental support and intrusiveness. This study showed, however, that parents who improved after the educational programme had children who improved on AC and EF. CONCLUSION: Parent-child interaction can be enhanced in a low-risk sample of four- to eight-year-olds using a compact educational group programme within the school community. Future studies should aim at examining variations in programme responsiveness and assessing associations between parent-child interaction and AC and EF over time.

Longitudinal trajectories of brain age in young individuals at familial risk of mood disorder from the Scottish Bipolar Family Study.

Background: Within young individuals, mood disorder onset may be related to changes in trajectory of brain structure development. To date, however, longitudinal prospective studies remain scarce and show partly contradictory findings, with a lack of emphasis on changes at the level of global brain patterns. Cross-sectional adult studies have applied such methods and show that mood disorders are associated with accelerated brain aging. Currently, it remains unclear whether young individuals show differential brain structure aging trajectories associated with onset of mood disorder and/or presence of familial risk. Methods: Participants included young individuals (15-30 years, 53%F) from the prospective longitudinal Scottish Bipolar Family Study with and without close family history of mood disorder. All were well at time of recruitment. Implementing a structural MRI-based brain age prediction model, we globally assessed individual trajectories of age-related structural change using the difference between predicted brain age and chronological age (brain-predicted age difference (brain-PAD)) at baseline and at 2-year follow-up. Based on follow-up clinical assessment, individuals were categorised into three groups: (i) controls who remained well (C-well, n = 93), (ii) high familial risk who remained well (HR-well, n = 74) and (iii) high familial risk who developed a mood disorder (HR-MD, n = 35). Results: At baseline, brain-PAD was comparable between groups. Results showed statistically significant negative trajectories of brain-PAD between baseline and follow-up for HR-MD versus C-well ( ß = -0.60, p corrected < 0.001) and HR-well ( ß = -0.36, p corrected = 0.02), with a potential intermediate trajectory for HR-well ( ß = -0.24 years, p corrected = 0.06).   Conclusions: These preliminary findings suggest that within young individuals, onset of mood disorder and familial risk may be associated with a deceleration in brain structure aging trajectories. Extended longitudinal research will need to corroborate findings of emerging maturational lags in relation to mood disorder risk and onset.

Psychotic Experiences and Related Distress: A Cross-national Comparison and Network Analysis Based on 7141 Participants From 13 Countries.

Psychotic experiences (PEs) are common in the general population but do not necessarily reflect a risk status if they occur in relative isolation or are not distressing. Emerging evidence suggests that PEs might be experienced as more benign for individuals from collectivistic low- and middle-income countries (LAMIC) compared with individualistic high-income countries (HIC). The aim of this study was to determine whether: (1) self-reported PEs are less distressing in community samples from LAMIC than from HIC; (2) the network of PEs is significantly less connected in a sample from LAMIC than from HIC. Adults from 8 HIC (n = 4669) and 5 LAMIC (n = 2472) were compared. The lifetime frequency of PEs and related distress were assessed with the Community Assessment of Psychic Experiences. We analyzed the associations of PEs with distress and country type. The interconnection of PEs was visualized by a network analysis and tested for differences in global connection strengths. The average endorsement rates of PEs were significantly higher in LAMIC than in HIC (χ2 = 1772.87, P < .01, Φcramer = 0.50). There was a universal positive correlation between higher frequency of PEs and more distress, but the distress levels controlled for frequency were significantly higher in HIC (R2 = 0.11; b = 0.26; SE = 0.01; T = 17.68; P < .001). Moreover, the network of PEs was significantly less connected in LAMIC (S = 0.40, P < .05). The findings indicate that PEs are of less clinical relevance in LAMIC compared with HIC. The universal use of current high-risk criteria might thus not be adequate without consideration of associated distress and cultural values.

Attentional control and executive functioning in school-aged children: Linking self-regulation and parenting strategies.

Good parenting strategies can shape children's neurocognitive development, yet little is known about the nature of this relation in school-aged children and whether this association shifts with age. We aimed to investigate the relation between parenting strategies observed during a home visit and children's performance-based attentional control and executive functioning (N=98, aged 4-8years). Linear and curvilinear regression analyses showed that children of parents who were more supportive, were less intrusive, and asked more open-ended questions displayed better inhibitory control. In addition, children of parents who asked relatively more open-ended than closed-ended questions showed better performance on inhibition, working memory, and cognitive flexibility tasks. Curvilinear relations indicated the presence of an optimal amount of closed-ended and elaborative questions by parents-that is, not too few and not too many-which is linked to increased performance on attentional and inhibitory control in children. Higher parental intrusiveness and more frequent elaborative questioning were associated with decreased inhibitory control in younger children, whereas no such negative associations were present in older children. These results suggest that susceptibility to certain parenting strategies may shift with age. Our findings underscore the importance of adaptive parenting strategies to both the age and needs of school-aged children, which may positively affect their self-regulation skills.

Linking Parenting and Social Competence in School-Aged Boys and Girls: Differential Socialization, Diathesis-Stress, or Differential Susceptibility?

Girls generally demonstrate superior skill levels in social competence compared to boys. The exact relations of parenting with these gender differences are currently unclear. Gender differences may occur due to exposure to different parenting strategies (differential socialization model) or due to a different impact of similar parenting strategies for boys and girls (differential susceptibility and diathesis-stress model). Objective: In this study we assessed both hypotheses using a multi-method multi-informant approach. We investigated (1) to what extent different parenting strategies mediate the relation between gender and social competence and (2) whether gender and age moderate the relation between parenting strategies and social competence. Design: Parenting strategies were observed during home visits and social competence was assessed using parent and teacher questionnaires and performance-based neurocognitive tasks (N = 98, aged 4 to 8). Results: (1) Parenting strategies did not mediate the relation between gender and social competence. (2) Gender moderated the association between parental questioning style and children's level of social competence: parents asking fewer questions was associated with poorer social cognitive skills in boys only. Parental supportive presence and intrusiveness were related to aspects of social competence irrespective of gender. Age moderated the relation between parenting and aspects of social competence, though in various (unexpected) directions. Conclusion: Our findings do not support the differential socialization hypothesis and provide partial evidence for a diathesis-stress model as an explanation for parental influence on gender differences in social competence.

Cognitive, Parent and Teacher Rating Measures of Executive Functioning: Shared and Unique Influences on School Achievement.

Very little is known about the relative influence of cognitive performance-based executive functioning (EF) measures and behavioral EF ratings in explaining differences in children's school achievement. This study examined the shared and unique influence of these different EF measures on math and spelling outcome for a sample of 84 first and second graders. Parents and teachers completed the Behavior Rating Inventory of Executive Function (BRIEF), and children were tested with computer-based performance tests from the Amsterdam Neuropsychological Tasks (ANT). Mixed-model hierarchical regression analyses, including intelligence level and age, showed that cognitive performance and teacher's ratings of working memory and shifting concurrently explained differences in spelling. However, teacher's behavioral EF ratings did not explain any additional variance in math outcome above cognitive EF performance. Parent's behavioral EF ratings did not add any unique information for either outcome measure. This study provides support for the ecological validity of performance- and teacher rating-based EF measures, and shows that both measures could have a complementary role in identifying EF processes underlying spelling achievement problems. The early identification of strengths and weaknesses of a child's working memory and shifting capabilities, might help teachers to broaden their range of remedial intervention options to optimize school achievement.

Self-regulation and quality of life in high-functioning young adults with autism.

BACKGROUND: Autism is generally associated with poor functional outcome but little is known about predictors of quality of life, especially during early adulthood. This study was conducted to assess subjective quality of life during early adulthood in high-functioning autism spectrum disorder and its relation with self-regulating abilities. Individuals with high-functioning autism spectrum disorder who progressed into post-secondary higher education ( N = 75) were compared to a typical peer control group ( N = 28) based on behavioral self-report questionnaires. The results indicated that individuals with high-functioning autism spectrum disorder reported significantly lower subjective quality of life than typical controls ( p < 0.001, effect size ( d) = 1.84). In addition, individuals with high-functioning autism spectrum disorder reported more problems with emotion processing ( p < 0.05, effect size ( d) = 0.79) and daily executive functioning ( p < 0.001, effect size ( d) = 1.29) than controls. A higher level of executive functioning problems was related to lower quality of life in the high-functioning autism spectrum disorder group, but no significant relation between level of emotion processing and subjective quality of life became apparent in the regression analysis. Our findings show that even in high-functioning young adults with autism, executive functioning, emotion processing, and subjective quality of life are low compared to typically developing peers. Furthermore, these results emphasize the importance of targeting executive functioning problems in individuals with autism to improve subjective quality of life.

Individual prediction of long-term outcome in adolescents at ultra-high risk for psychosis: Applying machine learning techniques to brain imaging data.

An important focus of studies of individuals at ultra-high risk (UHR) for psychosis has been to identify biomarkers to predict which individuals will transition to psychosis. However, the majority of individuals will prove to be resilient and go on to experience remission of their symptoms and function well. The aim of this study was to investigate the possibility of using structural MRI measures collected in UHR adolescents at baseline to quantitatively predict their long-term clinical outcome and level of functioning. We included 64 UHR individuals and 62 typically developing adolescents (12-18 years old at recruitment). At six-year follow-up, we determined resilience for 43 UHR individuals. Support Vector Regression analyses were performed to predict long-term functional and clinical outcome from baseline MRI measures on a continuous scale, instead of the more typical binary classification. This led to predictive correlations of baseline MR measures with level of functioning, and negative and disorganization symptoms. The highest correlation (r = 0.42) was found between baseline subcortical volumes and long-term level of functioning. In conclusion, our results show that structural MRI data can be used to quantitatively predict long-term functional and clinical outcome in UHR individuals with medium effect size, suggesting that there may be scope for predicting outcome at the individual level. Moreover, we recommend classifying individual outcome on a continuous scale, enabling the assessment of different functional and clinical scales separately without the need to set a threshold. Hum Brain Mapp 38:704-714, 2017. © 2016 Wiley Periodicals, Inc.

Brain development in adolescents at ultra-high risk for psychosis: Longitudinal changes related to resilience.

BACKGROUND: The main focus of studies of individuals at ultra-high risk for psychosis (UHR) has been on identifying brain changes in those individuals who will develop psychosis. However, longitudinal studies have shown that up to half of UHR individuals are resilient, with symptomatic remission and good functioning at follow-up. Yet little is known about brain development in resilient individuals. Therefore, the aim of this study was to investigate differences in brain development between resilient and non-resilient individuals. METHODS: A six-year longitudinal structural MRI study was performed with up to three scans per individual. The final sample consisted of 48 UHR individuals and 48 typically developing controls with a total of 225 MRI-scans, aged 12-20 years at the time of the first MRI-scan and matched for age, gender and number of follow-up scans. At six-year follow-up, 35 UHR individuals were divided in resilient (good functional outcome) and non-resilient (poor functional outcome) subgroups, defined by the modified Global Assessment of Functioning. The main outcome measures were developmental changes in MR-based measures of cortical and subcortical anatomy. RESULTS: We found widespread differences in volume of frontal, temporal and parietal cortex between resilient and non-resilient individuals. These were already present at baseline and remained stable over development (12-24 years). Furthermore, there were differences in the development of cortical surface area in frontal regions including cingulate gyrus. CONCLUSIONS: Developmental differences may reflect compensatory neural mechanisms, where better functioning in resilient individuals leads to less tissue loss over development.

Confirmatory factor analysis of psychotic-like experiences in a general population sample.

Psychotic-like experiences (PLEs) are sub-psychotic expressions of the psychosis continuum. Several studies have suggested multifactorial models, including a bifactor model, of the putative PLEs assessed with the popular Community Assessment of Psychic Experiences (CAPE) questionnaire. Our confirmatory results in a gender-balanced population of adolescents and young adults support a three-factor Paranoia-Delusions-Hallucinations structure of PLEs, which excludes Grandiosity and Common Paranormal Beliefs. The best latent models achieved excellent fit when taking the categorical nature of the responses into consideration.

Working memory capacity and psychotic-like experiences in a general population sample of adolescents and young adults.

Working memory (WM) impairment is a common feature in individuals with schizophrenia and high-risk for psychosis and a promising target for early intervention strategies. However, it is unclear to what extent WM impairment parallels specific behavioral symptoms along the psychosis continuum. To address this issue, the current study investigated the relation of WM capacity with psychotic-like experiences (PLEs) in a large Swedish population sample (N = 1012) of adolescents and young adults (M = 24.4 years, range 12-35). WM was assessed with two online computer tasks: a task where participants had to identify and remember the location of an odd shape and a task of remembering and following instructions. PLE scores were derived from a translated symptom questionnaire (Community Assessment of Psychic Experiences), which includes positive, negative, and depressive symptom scales. Positive and negative symptom scales were further subdivided into symptom clusters based on factor analyses. The results showed that low WM capacity was modestly associated with increased reports of bizarre experiences (BE) and depressive symptoms, after controlling for age, gender, and global symptom scores. Interestingly, when analyses were repeated for separate age groups, low WM was exclusively associated with a higher frequency of BE for young adults (20-27 years) and with depressive symptoms for older adults (28-35 years). These findings suggest that specific PLEs can be indicative of reduced WM capacity in early adulthood, which in turn may reflect an increased risk for psychosis and a greater need for targeted intervention. In contrast, during adolescence individual differences in cognitive development may influence the strength of the relationships and thereby mask potential vulnerabilities for psychopathology.

Progressive structural brain changes during development of psychosis.

BACKGROUND: Ultra-high risk (UHR) for psychosis has been associated with widespread structural brain changes in young adults. The onset of these changes and their subsequent progression over time are not well understood. METHODS: Rate of brain change over time was investigated in 43 adolescents at UHR for psychosis compared with 30 healthy controls. Brain volumes (total brain, gray matter, white matter [WM], cerebellum, and ventricles), cortical thickness, and voxel-based morphometry were measured at baseline and at follow-up (2 y after baseline) and compared between UHR individuals and controls. Post hoc analyses were done for UHR individuals who became psychotic (N = 8) and those who did not (N = 35). RESULTS: UHR individuals showed a smaller increase in cerebral WM over time than controls and more cortical thinning in the left middle temporal gyrus. Post hoc, a more pronounced decrease over time in total brain and WM volume was found for UHR individuals who became psychotic relative to controls and a greater decrease in total brain volume than individuals who were not psychotic. Furthermore, UHR individuals with subsequent psychosis displayed more thinning than controls in widespread areas in the left anterior cingulate, precuneus, and temporo-parieto-occipital area. Volume loss in the individuals who developed psychosis could not be attributed to medication use. CONCLUSION: The development of psychosis during adolescence is associated with progressive structural brain changes around the time of onset. These changes cannot be attributed to (antipsychotic) medication use and are therefore likely to reflect a pathophysiological process related to clinical manifestation of psychosis.

Reduced prepulse inhibition as an early vulnerability marker of the psychosis prodrome in adolescence.

BACKGROUND: The onset of psychosis is thought to be preceded by neurodevelopmental changes in the brain. However, the timing and nature of these changes have not been established. The aim of the present study was to determine whether three "classic" neurophysiological markers of schizophrenia are also characteristic of young adolescents (12-18 years) at ultra-high risk for psychosis (UHR). METHODS: 63 young UHR individuals and 68 typically developing, age-, sex- and IQ-matched controls were recruited for neurophysiological assessment. Data for P50 suppression, prepulse inhibition (PPI) and smooth pursuit eye movements (SPEM) were gathered and compared. RESULTS: UHR individuals showed reduced PPI compared to controls, which became more pronounced when controls were directly compared to medication-naive UHR individuals (N=39). There were no group differences in P50 or SPEM measures. CONCLUSIONS: These results suggest that PPI is a relatively early vulnerability marker, while changes in other neurophysiological measures may only be detected or affected later during the illness course. Antipsychotic and antidepressant medication may aid in elevating PPI levels and potentially have a neuroprotective effect.

Transition and remission in adolescents at ultra-high risk for psychosis.

BACKGROUND: Future success of early intervention initiatives to prevent the onset of psychosis will rely on the validity of methods to predict clinical outcome. Proper identification is particularly essential for young adolescents, as psychotic-like symptoms are often transitory during this period and mislabeling can lead to early stigmatization and unnecessary treatment. This article presents results from a prospective, naturalistic 2-year follow-up study of a cohort of young adolescents putatively at ultra-high risk (UHR) for psychosis. METHODS: Seventy-two adolescents between 12 and 18years were recruited, fulfilling either UHR criteria or the basic symptom-based criterion cognitive disturbances (COGDIS). Incidence of transition as well as the remission rate from UHR status was calculated. Individuals who made a transition (UHR-P) were compared to those who did not (UHR-NP) and to those who remitted (UHR-R) on socio-demographic and clinical characteristics. RESULTS: Fifty-seven UHR individuals completed the 2-year follow-up assessment. The confirmed transition rate was 15.6% and 35.3% still met UHR criteria. The remaining 49.1% had remitted from an initial UHR status. The UHR subgroups did not differ on socio-demographic or clinical variables at baseline. CONCLUSIONS: Half of young adolescents meeting UHR criteria continue to experience prodromal or psychotic symptoms after 2 years. However, they are at least three times more likely to have remitted from their UHR status than to have made a transition to psychosis. In addition, baseline characteristics are not indicative of clinical outcome at follow-up. Our results emphasize the need for further improvement and stratification of relative risk factors for psychosis.

No evidence for structural brain changes in young adolescents at ultra high risk for psychosis.

OBJECTIVE: The onset of psychosis is thought to be preceded by neurodevelopmental changes in the brain. However, the timing of these changes has not been established. We investigated structural brain changes in a sample of young adolescents (12-18 years) at ultra high-risk for psychosis (UHR). METHODS: Structural MRI data from young UHR subjects (n=54) and typically developing, matched controls (n=54) were acquired with a 1.5 Tesla scanner and compared. RESULTS: None of the measures differed between UHR subjects and controls. CONCLUSIONS: Our results do not support the presence of gross neuroanatomical changes in young UHR subjects. This suggests that early changes are too subtle to detect with conventional imaging techniques. Therefore, changes observed in older cohorts may only onset later developmentally or occur secondary to prodromal symptoms.

Dopamine transporter genotype conveys familial risk of attention-deficit/hyperactivity disorder through striatal activation.

OBJECTIVE: The dopamine transporter (DAT1) gene has been implicated in attention-deficit/hyperactivity disorder (ADHD), although the mechanism by which it exerts its effects remains unknown. The polymorphism associated with ADHD has been shown to affect expression of the transporter in vitro and in vivo. Dopamine transporters are predominantly expressed in the striatum, but also in the cerebellar vermis. Stimulant medication is often effective in ADHD and is believed to exert its effects by blocking dopamine transporters in the striatum. We set out to investigate the effect of the DAT1 genotype in ADHD in a small, preliminary study. We hypothesized that the DAT1 genotype would affect brain activation patterns in a manner similar to that of stimulant medication, with the lesser expressing allele mirroring its effects. METHOD: We investigated DAT1 gene effects on brain activation patterns in an all-male sample of sibling pairs discordant for ADHD (n = 20) and controls (n = 9). All of the subjects participated in a functional magnetic resonance imaging session using a go/no-go paradigm and provided a DNA sample for analysis. RESULTS: DAT1 genotype affected activation in the striatum and cerebellar vermis. The genotype interacted with familial risk of ADHD in the striatum but not the vermis. CONCLUSIONS: These preliminary results suggest that the DAT1 gene effects in the striatum are involved in translating the genetic risk of ADHD into a neurobiological substrate. As such, this study represents a first step in elucidating the neurobiological mechanisms underlying genetic influences in ADHD. Furthermore, these results may contribute to long-term possibilities for the development of new treatments: If the DAT1 genotype has differential effects on striatal activation, then it may be useful as a surrogate endpoint in individualized treatments targeting genotype/functional magnetic resonance imaging activation profiles.