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1.
J Neurosci ; 40(11): 2282-2295, 2020 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-32024781

RESUMEN

Oxytocin (OT) is critical for the expression of social behavior across a wide array of species; however, the role of this system in the encoding of socially relevant information is not well understood. In the present study, we show that chemogenetic activation of OT neurons within the paraventricular nucleus of the hypothalamus (PVH) of male mice (OT-Ires-Cre) enhanced social investigation during a social choice test, while chemogenetic inhibition of these neurons abolished typical social preferences. These data suggest that activation of the OT system is necessary to direct behavior preferentially toward social stimuli. To determine whether the presence of a social stimulus is sufficient to induce activation of PVH-OT neurons, we performed the first definitive recording of OT neurons in awake mice using two-photon calcium imaging. These recordings demonstrate that social stimuli activate PVH-OT neurons and that these neurons differentially encode social and nonsocial stimuli, suggesting that PVH-OT neurons may act to convey social salience of environmental stimuli. Finally, an attenuation of social salience is associated with social disorders, such as autism. We therefore also examined possible OT system dysfunction in a mouse model of autism, Shank3b knock-out (KO) mice. Male Shank3b KO mice showed a marked reduction in PVH-OT neuron number and administration of an OT receptor agonist improved social deficits. Overall, these data suggest that the presence of a social stimulus induces activation of the PVH-OT neurons to promote adaptive social behavior responses.SIGNIFICANCE STATEMENT Although the oxytocin (OT) system is well known to regulate a diverse array of social behaviors, the mechanism in which OT acts to promote the appropriate social response is poorly understood. One hypothesis is that the presence of social conspecifics activates the OT system to generate an adaptive social response. Here, we selectively recorded from OT neurons in the paraventricular hypothalamic nucleus (PVH) to show that social stimulus exposure indeed induces activation of the OT system. We also show that activation of the OT system is necessary to promote social behavior and that mice with abnormal social behavior have reduced numbers of PVH-OT neurons. Finally, aberrant social behavior in these mice was rescued by administration of an OT receptor agonist.


Asunto(s)
Neuronas/fisiología , Oxitocina/fisiología , Núcleo Hipotalámico Paraventricular/fisiología , Conducta Social , Potenciales de Acción/efectos de los fármacos , Animales , Conducta Apetitiva/efectos de los fármacos , Conducta Apetitiva/fisiología , Trastorno Autístico/fisiopatología , Benzodiazepinas/farmacología , Señalización del Calcio , Clozapina/farmacología , Modelos Animales de Enfermedad , Conducta Exploratoria/efectos de los fármacos , Conducta Exploratoria/fisiología , Genes Reporteros , Masculino , Ratones , Ratones Noqueados , Proteínas de Microfilamentos/genética , Proteínas del Tejido Nervioso/genética , Neuronas/efectos de los fármacos , Oxitocina/análisis , Núcleo Hipotalámico Paraventricular/fisiopatología , Técnicas de Placa-Clamp , Pirazoles/farmacología , Receptores de Oxitocina/agonistas , Receptores de Oxitocina/antagonistas & inhibidores , Receptores de Oxitocina/fisiología , Vigilia
2.
MMWR Morb Mortal Wkly Rep ; 70(17): 605-611, 2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33914722

RESUMEN

Persons identified in early childhood as having autism spectrum disorder (autism) often have co-occurring health problems that extend into adolescence (1-3). Although only limited data exist on their health and use of health care services as they transition to adolescence, emerging data suggest that a minority of these persons receive recommended guidance* from their primary care providers (PCPs) starting at age 12 years to ensure a planned transition from pediatric to adult health care (4,5). To address this gap in data, researchers analyzed preliminary data from a follow-up survey of parents and guardians of adolescents aged 12-16 years who previously participated in the Study to Explore Early Development (https://www.cdc.gov/ncbddd/autism/seed.html). The adolescents were originally studied at ages 2-5 years and identified at that age as having autism (autism group) or as general population controls (control group). Adjusted prevalence ratios (aPRs) that accounted for differences in demographic characteristics were used to compare outcomes between groups. Adolescents in the autism group were more likely than were those in the control group to have physical difficulties (21.2% versus 1.6%; aPR = 11.6; 95% confidence interval [CI] = 4.2-31.9), and to have additional mental health or other conditions† (one or more condition: 63.0% versus 28.9%; aPR = 1.9; 95% CI = 1.5-2.5). Adolescents in the autism group were more likely to receive mental health services (41.8% versus 22.1%; aPR = 1.8, 95% CI = 1.3-2.6) but were also more likely to have an unmet medical or mental health service need§ (11.0% versus 3.2%; aPR = 3.1; 95% CI = 1.1-8.8). In both groups, a small percentage of adolescents (autism, 7.5%; control, 14.1%) received recommended health care transition (transition) guidance. These findings are consistent with previous research (4,5) indicating that few adolescents receive the recommended transition guidance and suggest that adolescents identified with autism in early childhood are more likely than adolescents in the general population to have unmet health care service needs. Improved provider training on the heath care needs of adolescents with autism and coordination of comprehensive programs¶ to meet their needs can improve delivery of services and adherence to recommended guidance for transitioning from pediatric to adult health care.


Asunto(s)
Trastorno Autístico/epidemiología , Estado de Salud , Aceptación de la Atención de Salud/estadística & datos numéricos , Adolescente , Femenino , Humanos , Masculino , Estados Unidos/epidemiología
3.
J Clin Child Adolesc Psychol ; 43(5): 828-43, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25216048

RESUMEN

This article suggests future directions for research aimed at improving our understanding of the etiology and pathophysiology of autism spectrum disorder (ASD) as well as pharmacologic and psychosocial interventions for ASD across the lifespan. The past few years have witnessed unprecedented transformations in the understanding of ASD neurobiology, genetics, early identification, and early intervention. However, recent increases in ASD prevalence estimates highlight the urgent need for continued efforts to translate novel ASD discoveries into effective interventions for all individuals with ASD. In this article we highlight promising areas for ongoing and new research expected to quicken the pace of scientific discovery and ultimately the translation of research findings into accessible and empirically supported interventions for those with ASD. We highlight emerging research in the following domains as particularly promising and pressing: (a) preclinical models, (b) experimental therapeutics, (c) early identification and intervention, (d) psychiatric comorbidities and the Research Domain Criteria initiative, (e) ecological momentary assessment, (f) neurotechnologies, and (g) the needs of adults with ASD. Increased research emphasis in these areas has the potential to hasten the translation of knowledge on the etiological mechanisms of ASD to psychosocial and biological interventions to reduce the burden of ASD on affected individuals and their families.


Asunto(s)
Investigación Biomédica/tendencias , Trastornos Generalizados del Desarrollo Infantil , Predicción , Niño , Humanos
4.
J Affect Disord ; 361: 128-138, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38815760

RESUMEN

BACKGROUND: Anhedonia is a transdiagnostic symptom often resistant to treatment. The identification of biomarkers sensitive to anhedonia treatment will aid in the evaluation of novel anhedonia interventions. METHODS: This is an exploratory analysis of changes in subcortical brain volumes accompanying psychotherapy in a transdiagnostic anhedonic sample using ultra-high field (7-Tesla) MRI. Outpatients with clinically impairing anhedonia (n = 116) received Behavioral Activation Treatment for Anhedonia, a novel psychotherapy, or Mindfulness-Based Cognitive Therapy (ClinicalTrials.gov Identifiers NCT02874534 and NCT04036136). Subcortical brain volumes were estimated via the MultisegPipeline, and regions of interest were the amygdala, caudate nucleus, hippocampus, pallidum, putamen, and thalamus. Bivariate mixed effects models estimated pre-treatment relations between anhedonia severity and subcortical brain volumes, change over time in subcortical brain volumes, and associations between changes in subcortical brain volumes and changes in anhedonia symptoms. RESULTS: As reported previously (Cernasov et al., 2023), both forms of psychotherapy resulted in equivalent and significant reductions in anhedonia symptoms. Pre-treatment anhedonia severity and subcortical brain volumes were not related. No changes in subcortical brain volumes were observed over the course of treatment. Additionally, no relations were observed between changes in subcortical brain volumes and changes in anhedonia severity over the course of treatment. LIMITATIONS: This trial included a modest sample size and did not have a waitlist-control condition or a non-anhedonic comparison group. CONCLUSIONS: In this exploratory analysis, psychotherapy for anhedonia was not accompanied by changes in subcortical brain volumes, suggesting that subcortical brain volumes may not be a candidate biomarker sensitive to response to psychotherapy.


Asunto(s)
Anhedonia , Encéfalo , Imagen por Resonancia Magnética , Humanos , Anhedonia/fisiología , Masculino , Femenino , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Psicoterapia/métodos , Adulto Joven , Persona de Mediana Edad , Terapia Cognitivo-Conductual/métodos , Atención Plena , Resultado del Tratamiento , Tamaño de los Órganos
5.
Psychoneuroendocrinology ; 156: 106339, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37540905

RESUMEN

Depression is highly prevalent during the menopause transition (perimenopause), and often presents with anxious and anhedonic features. This increased vulnerability for mood symptoms is likely driven in part by the dramatic hormonal changes that are characteristic of the menopause transition, as prior research has linked fluctuations in estradiol (E2) to emergence of depressed mood in at risk perimenopausal women. Transdermal estradiol (TE2) has been shown to reduce the severity of depression in clinically symptomatic women, particularly in those with recent stressful life events. This research extends prior work by examining the relation between E2 and reward seeking behaviors, a precise behavioral indicator of depression. Specifically, the current study utilizes a randomized, double blind, placebo-controlled design to investigate whether mood sensitivity to E2 flux ("hormone sensitivity") predicts the beneficial effects of TE2 interventions on reward seeking behaviors in perimenopausal women, and whether recent stressful life events moderate any observed associations. METHOD: Participants were 66 women who met standardized criteria for being early or late perimenopausal based on bleeding patterns. Participants were recruited from a community sample; therefore, mood symptoms varied across the continuum and the majority of participants did not meet diagnostic criteria for a depressive or anxiety disorder at the time of enrollment. Hormone sensitivity was quantified over an 8-week baseline period, using within-subjects correlations between repeated weekly measures of E2 serum concentrations and weekly anxiety (State Trait Anxiety Inventory) and anhedonia ratings (Snaith-Hamilton Pleasure Scale). Women were then randomized to receive 8 weeks of TE2 (0.1 mg) or transdermal placebo, and reward-seeking behaviors were assessed using the Effort-Expenditure for Rewards Task (EEfRT). RESULTS: Participants who were randomized to receive transdermal estradiol and who demonstrated greater anxiety sensitivity to E2 fluctuations at baseline, demonstrated more reward seeking behaviors on the EEfRT task. Notably, the strength of the association between E2-anxiety sensitivity and post-randomization EEfRT for TE2 participants increased when women experienced more recent stressful life events and rated those events as more stressful. E2-anhedonia sensitivity was not associated with reward-seeking behaviors. CONCLUSION: Perimenopausal women who are more sensitive to E2 fluctuations and experienced more recent life stress may experience a greater benefit of TE2 as evidenced by an increase in reward seeking behaviors.


Asunto(s)
Estradiol , Perimenopausia , Femenino , Humanos , Anhedonia , Menopausia , Afecto
6.
Behav Res Ther ; 166: 104322, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37148652

RESUMEN

OBJECTIVE: Homework is a key theoretical component of cognitive-behavioral therapies, however, the effects of homework on clinical outcomes have largely been evaluated between-persons rather than within-persons. METHODS: The effects of homework completion on treatment response were examined in a randomized trial comparing Behavioral Activation Treatment for Anhedonia (BATA, n = 38), a novel psychotherapy, to Mindfulness-Based Cognitive Therapy (MBCT, n=35). The primary endpoint was consummatory reward sensitivity, measured weekly by the Snaith Hamilton Pleasure Scale (SHAPS), up to 15 weeks. Multilevel models evaluated change in SHAPS scores over time and the effects of clinician-reported and participant-reported homework. RESULTS: BATA and MBCT resulted in significant, equivalent reductions in SHAPS scores. Unexpectedly, participants who completed greater mean total amounts of homework did not improve at a faster rate (i.e., no between-person effect). However, sessions with greater than average participant-reported homework completion were associated with greater than average reductions in SHAPS scores (i.e., a within-person effect). For clinician-reported homework, this effect was only evident within the BATA condition. CONCLUSION: This study shows psychotherapy homework completion relates to symptomatic improvement in cognitive-behavioral treatments for anhedonia when session-to-session changes are examined within-person. On the contrary, we found no evidence that total homework completion predicted greater improvements between-person. When possible, psychotherapy researchers should evaluate their constructs of interest across multiple sessions (not just pre/post) to allow more direct tests of hypotheses predicted by theoretical models of individual change processes.


Asunto(s)
Terapia Cognitivo-Conductual , Atención Plena , Adulto , Humanos , Anhedonia/fisiología , Cognición , Terapia Cognitivo-Conductual/métodos , Placer/fisiología
7.
Trials ; 24(1): 150, 2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36855177

RESUMEN

BACKGROUND: The perimenopausal transition is accompanied by psychiatric symptoms in over 10% of women. Symptoms commonly include depressed mood and anhedonia and less commonly include psychosis. Psychiatric symptoms have been linked to the depletion and/or variability of circulating estradiol, and estradiol treatment reduces perimenopausal anhedonia and psychosis in some women. Estrogen fluctuations may disrupt function in the mesolimbic reward system in some women, leading to psychiatric symptoms like anhedonia or psychosis. The Perimenopausal Effects of Estradiol on Anhedonia and Psychosis Study (PEEPs) is a mechanistic clinical trial that aims to (1) identify relationships between perimenopausal-onset anhedonia and psychosis and neuromolecular markers of mesolimbic reward responses and (2) determine the extent to which estradiol treatment-induced changes in mesolimbic reward responses are associated with alleviation of perimenopausal onset anhedonia or psychosis. METHODS: This study will recruit 100 unmedicated women ages 44-55 in the late-stage perimenopausal transition, sampling across the range of mild-to-high anhedonia and absent-to-moderate psychosis symptoms. Patients will be randomized to receive either estradiol or placebo treatment for 3 weeks. Clinical outcome measures will include symptoms of anhedonia (measured with Snaith-Hamilton Pleasure Scale; SHAPS) and psychosis (measured with Brief Psychiatric Rating Scale; BPRS psychosis subscale) as well as neural markers of mesolimbic reward system functioning, including reward-related fMRI activation and PET-derived measure of striatal dopamine binding. Pre-treatment associations between (1) SHAPS/BPRS scores and (2) reward-related striatal dopamine binding/BOLD activation will be examined. Furthermore, longitudinal mixed models will be used to estimate (1) symptom and neuromolecular trajectories as a function of estradiol vs. placebo treatment and (2) how changes in reward-related striatal dopamine binding and BOLD activation predict variability in symptom trajectories in response to estradiol treatment. DISCUSSION: This clinical trial will be the first to characterize neural and molecular mechanisms by which estradiol treatment ameliorates anhedonia and psychosis symptoms during the perimenopausal transition, thus laying the groundwork for future biomarker research to predict susceptibility and prognosis and develop targeted treatments for perimenopausal psychiatric symptoms. Furthermore, in alignment with the National Institute for Mental Health Research Domain Criteria initiative, this trial will improve our understanding of a range of disorders characterized by anhedonia, psychosis, and reward system dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov NCT05282277.


Asunto(s)
Estradiol , Trastornos Psicóticos , Femenino , Humanos , Estradiol/uso terapéutico , Anhedonia , Dopamina , Perimenopausia , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto
8.
Soc Cogn Affect Neurosci ; 18(1)2023 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-36287067

RESUMEN

The motivation to socially connect with peers increases during adolescence in parallel with changes in neurodevelopment. These changes in social motivation create opportunities for experiences that can impact risk for psychopathology, but the specific motivational presentations that confer greater psychopathology risk are not fully understood. To address this issue, we used a latent profile analysis to identify the multidimensional presentations of self-reported social goals in a sample of 220 girls (9-15 years old, M = 11.81, SD = 1.81) that was enriched for internalizing symptoms, and tested the association between social goal profiles and psychopathology. Associations between social goals and brain network connectivity were also examined in a subsample of 138 youth. Preregistered analyses revealed four unique profiles of social goal presentations in these girls. Greater psychopathology was associated with heightened social goals such that higher clinical symptoms were related to a greater desire to attain social competence, avoid negative feedback and gain positive feedback from peers. The profiles endorsing these excessive social goals were characterized by denser connections among social-affective and cognitive control brain regions. These findings thus provide preliminary support for adolescent-onset changes in motivating factors supporting social engagement that may contribute to risk for psychopathology in vulnerable girls.


Asunto(s)
Objetivos , Trastornos Mentales , Femenino , Humanos , Adolescente , Niño , Psicopatología , Encéfalo , Motivación
9.
Psychiatry Res Neuroimaging ; 333: 111660, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37301129

RESUMEN

BACKGROUND: Anhedonia is hypothesized to be associated with blunted mesocorticolimbic dopamine (DA) functioning in samples with major depressive disorder. The purpose of this study was to examine linkages between striatal DA, reward circuitry functioning, anhedonia, and, in an exploratory fashion, self-reported stress, in a transdiagnostic anhedonic sample. METHODS: Participants with (n = 25) and without (n = 12) clinically impairing anhedonia completed a reward-processing task during simultaneous positron emission tomography and magnetic resonance (PET-MR) imaging with [11C]raclopride, a DA D2/D3 receptor antagonist that selectively binds to striatal DA receptors. RESULTS: Relative to controls, the anhedonia group exhibited decreased task-related DA release in the left putamen, caudate, and nucleus accumbens and right putamen and pallidum. There were no group differences in task-related brain activation (fMRI) during reward processing after correcting for multiple comparisons. General functional connectivity (GFC) findings revealed blunted fMRI connectivity between PET-derived striatal seeds and target regions in the anhedonia group. Associations were identified between anhedonia severity and the magnitude of task-related DA release to rewards in the left putamen, but not mesocorticolimbic GFC. CONCLUSIONS: Results provide evidence for reduced striatal DA functioning during reward processing and blunted mesocorticolimbic network functional connectivity in a transdiagnostic sample with clinically significant anhedonia.


Asunto(s)
Trastorno Depresivo Mayor , Dopamina , Humanos , Racloprida , Dopamina/metabolismo , Anhedonia , Tomografía de Emisión de Positrones , Imagen por Resonancia Magnética
10.
BMC Psychiatry ; 12: 152, 2012 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-22998631

RESUMEN

BACKGROUND: Studies of individuals who do not meet criteria for major depressive disorder (MDD) but with subclinical levels of depressive symptoms may aid in the identification of neurofunctional abnormalities that possibly precede and predict the development of MDD. The purpose of this study was to evaluate relations between subclinical levels of depressive symptoms and neural activation patterns during tasks previously shown to differentiate individuals with and without MDD. METHODS: Functional magnetic resonance imaging (fMRI) was used to assess neural activations during active emotion regulation, a resting state scan, and reward processing. Participants were twelve females with a range of depressive symptoms who did not meet criteria for MDD. RESULTS: Increased depressive symptom severity predicted (1) decreased left midfrontal gyrus activation during reappraisal of sad stimuli; (2) increased right midfrontal gyrus activation during distraction from sad stimuli; (3) increased functional connectivity between a precuneus seed region and left orbitofrontal cortex during a resting state scan; and (4) increased paracingulate activation during non-win outcomes during a reward-processing task. CONCLUSIONS: These pilot data shed light on relations between subclinical levels of depressive symptoms in the absence of a formal MDD diagnosis and neural activation patterns. Future studies will be needed to test the utility of these activation patterns for predicting MDD onset in at-risk samples.


Asunto(s)
Encéfalo/fisiopatología , Depresión/fisiopatología , Emociones/fisiología , Adulto , Mapeo Encefálico , Femenino , Neuroimagen Funcional , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Red Nerviosa/fisiopatología , Proyectos Piloto , Índice de Severidad de la Enfermedad
11.
Int J Neurosci ; 122(9): 483-93, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22471393

RESUMEN

Functional magnetic resonance imaging (fMRI) has helped to elucidate the neurobiological bases of psychiatric and neurodevelopmental disorders by localizing etiologically-relevant aberrations in brain function. Functional MRI also has shown great promise to help understand potential mechanisms of action of effective treatments for a range of psychiatric and neurodevelopmental disorders, including mood and anxiety disorders, schizophrenia, and autism. However, the use of fMRI to probe intervention effects in psychiatry is associated with unique methodological considerations, including the psychometric properties of repeated fMRI scans, how to assess potential relations between the effects of an intervention on symptoms and on specific brain activation patterns, and how to best make causal inferences about intervention effects on brain function. Additionally, the study of treatment effects in neurodevelopmental disorders presents additional unique challenges related to brain maturation, analysis methods, and the potential for motion artifacts. We review these methodological considerations and provide recommendations for best practices for each of these topics.


Asunto(s)
Encéfalo/irrigación sanguínea , Alucinógenos/uso terapéutico , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/patología , Encéfalo/efectos de los fármacos , Mapeo Encefálico , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Pruebas Neuropsicológicas , Oxígeno/sangre , Psicometría
12.
Curr Top Behav Neurosci ; 58: 237-254, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35397066

RESUMEN

Although autism spectrum disorder (ASD) is defined by impaired social communication and restricted and repetitive behaviors and interests, ASD is also characterized by impaired motivational processes. The "social motivation theory of autism" describes how social motivation disruptions in ASD in early childhood may impede the drive to engage in reciprocal social behaviors and ultimately interfere with the development of neural networks critical for social communication (Chevallier et al., Trends Cogn Sci 16:231-239, 2012b). Importantly, clinical studies and preclinical research using model organisms for ASD indicate that motivational impairments in ASD are not constrained to social rewards but are evident in response to a range of nonsocial rewards as well. Additionally, translational studies on certain genetically defined neurodevelopmental disorders associated with ASD indicate that these syndromic forms of ASD are also characterized by motivational deficits and mesolimbic dopamine impairments. In this chapter we summarize clinical and preclinical research relevant to reward processing impairments in ASD and related neurodevelopmental disorders. We also propose a nosology to describe reward processing impairments in these disorders that uses a three-axes model. In this triaxial nosology, the first axis defines the direction of the reward response (i.e., anhedonic, hyperhedonic); the second axis defines the construct of the reward process (e.g., reward liking, reward wanting); and the third axis defines the context of the reward response (e.g., social, nonsocial). A more precise nosology for describing reward processing impairments in ASD and related neurodevelopmental disorders will aid in the translation of preclinical research to clinical investigations which will ultimately help to speed up the development of interventions that target motivational systems for ASD and related neurodevelopmental disorders.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Anhedonia , Trastorno del Espectro Autista/complicaciones , Preescolar , Humanos , Recompensa , Conducta Social
13.
Psychiatry Res ; 194(3): 263-270, 2011 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-22079658

RESUMEN

Anhedonia, the loss of interest or pleasure in normally rewarding activities, is a hallmark feature of unipolar Major Depressive Disorder (MDD). A growing body of literature has identified frontostriatal dysfunction during reward anticipation and outcomes in MDD. However, no study to date has directly compared responses to different types of rewards such as pleasant images and monetary rewards in MDD. To investigate the neural responses to monetary and pleasant image rewards in MDD, a modified Monetary Incentive Delay task was used during functional magnetic resonance imaging to assess neural responses during anticipation and receipt of monetary and pleasant image rewards. Participants included nine adults with MDD and 13 affectively healthy controls. The MDD group showed lower activation than controls when anticipating monetary rewards in right orbitofrontal cortex and subcallosal cortex, and when anticipating pleasant image rewards in paracingulate and supplementary motor cortex. The MDD group had relatively greater activation in right putamen when anticipating monetary versus pleasant image rewards, relative to the control group. Results suggest reduced reward network activation in MDD when anticipating rewards, as well as relatively greater hypoactivation to pleasant image than monetary rewards.


Asunto(s)
Encéfalo/patología , Trastorno Depresivo Mayor , Emociones , Motivación/fisiología , Recompensa , Adolescente , Adulto , Encéfalo/irrigación sanguínea , Mapeo Encefálico , Conducta de Elección/fisiología , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/psicología , Femenino , Juegos Experimentales , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Red Nerviosa/irrigación sanguínea , Red Nerviosa/fisiopatología , Oxígeno/sangre , Tiempo de Reacción/fisiología , Adulto Joven
14.
J Affect Disord ; 292: 161-171, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34126308

RESUMEN

BACKGROUND: The neural mechanisms associated with anhedonia treatment response are poorly understood. Additionally, no study has investigated changes in resting-state functional connectivity (rsFC) accompanying psychosocial treatment for anhedonia. METHODS: We evaluated a novel psychotherapy, Behavioral Activation Therapy for Anhedonia (BATA, n = 38) relative to Mindfulness-Based Cognitive Therapy (MBCT, n = 35) in a medication-free, transdiagnostic, anhedonic sample in a parallel randomized controlled trial. Participants completed up to 15 sessions of therapy and up to four 7T MRI scans before, during, and after treatment (n = 185 scans). Growth curve models estimated change over time in anhedonia and in rsFC using average region-of-interest (ROI)-to-ROI connectivity within the default mode network (DMN), frontoparietal network (FPN), salience network, and reward network. Changes in rsFC from pre- to post-treatment were further evaluated using whole-network seed-to-voxel and ROI-to-ROI edgewise analyses. RESULTS: Growth curve models showed significant reductions in anhedonia symptoms and in average rsFC within the DMN and FPN over time, across BATA and MBCT. There were no differences in anhedonia reductions between treatments. Within-person, changes in average rsFC were unrelated to changes in anhedonia. Between-person, higher than average FPN rsFC was related to less anhedonia across timepoints. Seed-to-voxel and edgewise rsFC analyses corroborated reductions within the DMN and between the DMN and FPN over time, across the sample. CONCLUSIONS: Reductions in rsFC within the DMN, FPN, and between these networks co-occurred with anhedonia improvement across two psychosocial treatments for anhedonia. Future anhedonia clinical trials with a waitlist control group should disambiguate treatment versus time-related effects on rsFC.


Asunto(s)
Terapia Cognitivo-Conductual , Atención Plena , Anhedonia , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Humanos , Imagen por Resonancia Magnética
15.
J Autism Dev Disord ; 51(4): 1173-1187, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32656738

RESUMEN

To evaluate an eye tracking task as a predictor and outcome measure of treatment response for autism spectrum disorder (ASD) social skills interventions, adolescents and young adults with ASD completed the eye tracking task before, immediately after, and two months after completing Social Cognition and Interaction Training for Autism (SCIT-A). The study compared SCIT-A participants (n = 20) to participants with ASD who received treatment as usual (TAU; n = 21). Overall, increased visual attention to faces and background objects and decreased attention to hands playing with toys at baseline were associated with improved social functioning immediately following intervention, suggesting this eye tracking task may reliably predict ASD social intervention outcomes.


Asunto(s)
Trastorno del Espectro Autista/terapia , Tecnología de Seguimiento Ocular , Psicoterapia/métodos , Habilidades Sociales , Adolescente , Adulto , Trastorno del Espectro Autista/rehabilitación , Movimientos Oculares , Femenino , Humanos , Masculino , Evaluación de Resultado en la Atención de Salud
16.
Transl Psychiatry ; 11(1): 33, 2021 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-33431841

RESUMEN

The social motivation hypothesis of autism posits that autism spectrum disorder (ASD) is characterized by impaired motivation to seek out social experience early in life that interferes with the development of social functioning. This framework suggests that impaired mesolimbic dopamine function underlies compromised responses to social rewards in ASD. Although this hypothesis is supported by functional magnetic resonance imaging (fMRI) studies, no molecular imaging study has evaluated striatal dopamine functioning in response to rewards in ASD. Here, we examined striatal functioning during monetary incentive processing in ASD and controls using simultaneous positron emission tomography (PET) and fMRI. Using a bolus + infusion protocol with the D2/D3 dopamine receptor antagonist [11C]raclopride, voxel-wise binding potential (BPND) was compared between groups (controls = 12, ASD = 10) in the striatum. Striatal clusters showing significant between-group BPND differences were used as seeds in whole-brain fMRI general functional connectivity analyses. Relative to controls, the ASD group demonstrated decreased phasic dopamine release to incentives in the bilateral putamen and left caudate, as well as increased functional connectivity between a PET-derived right putamen seed and the precuneus and insula. Within the ASD group, decreased phasic dopamine release in the putamen was related to poorer theory-of-mind skills. Our findings that ASD is characterized by impaired striatal phasic dopamine release to incentives provide support for the social motivation hypothesis of autism. PET-fMRI may be a suitable tool to evaluate novel ASD therapeutics targeting the striatal dopamine system.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno Autístico/diagnóstico por imagen , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/metabolismo , Dopamina , Humanos , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Racloprida , Receptores de Dopamina D2/metabolismo
17.
Depress Anxiety ; 27(9): 859-63, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20336799

RESUMEN

BACKGROUND: The Sweet Taste Test (STT) measures hedonic responses to sweet tastes and has been linked to both alcoholism and to a family history of alcoholism. However, STT response profiles in unipolar major depressive disorder (MDD), a disorder characterized by anhedonia, have been minimally investigated. METHODS: Twelve adults with and 15 adults without MDD participated in two identical STT assessments separated by approximately 12 weeks. Between assessments, MDD outpatients received Behavioral Activation Therapy for Depression, a psychotherapy modality designed to increase engagement with rewarding stimuli and reduce avoidance behaviors. Primary-dependent measures included sensitivity to sucrose, hedonic response to sucrose, and designation as a Sweet-Liker or Sweet-Disliker. RESULTS: A total of 75% of adults with MDD were treatment responders. There were no significant differences in STT response profiles between groups overall or at either timepoint. Furthermore, STT profiles of MDD participants did not differ after psychotherapy, relative to baseline. CONCLUSIONS: Findings suggest that although anhedonia is a symptom of MDD, the disorder is not characterized by altered responses to sweet tastes. Implications and future directions are discussed.


Asunto(s)
Trastorno Bipolar/psicología , Trastorno Depresivo Mayor/psicología , Sacarosa/administración & dosificación , Gusto , Adulto , Trastorno Bipolar/epidemiología , Trastorno Bipolar/terapia , Estudios de Casos y Controles , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicoterapia , Adulto Joven
18.
Neurocase ; 16(4): 307-16, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20178033

RESUMEN

Autism is characterized by abnormal prefrontal brain activation during cognitive control, a potential biomarker of repetitive behaviors. In this proof-of-principle study, functional magnetic resonance imaging (fMRI) was used to examine brain activity during an oddball task in two high-functioning males with autism before and after 12 weeks of treatment with citalopram, a selective serotonin reuptake inhibitor. One participant showed marked reductions in repetitive behaviors whereas the other showed mild worsening. Brain activation in relevant prefrontal regions increased in only the participant whose repetitive behavior symptoms improved. These findings suggest that fMRI may elucidate potential mechanisms of action of targeted autism interventions.


Asunto(s)
Trastorno Autístico/fisiopatología , Conducta/fisiología , Imagen por Resonancia Magnética/métodos , Trastorno Autístico/tratamiento farmacológico , Citalopram/uso terapéutico , Humanos , Masculino , Pruebas Neuropsicológicas , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Adulto Joven
19.
Autism Res Treat ; 2020: 8014248, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32257439

RESUMEN

Previous studies examining the neural substrates of reward processing in ASD have explored responses to rewards for oneself but not rewards earned for others (i.e., vicarious reward). This omission is notable given that vicarious reward processing is a critical component of creating and maintaining social relationships. The current study examined the neural mechanisms of vicarious reward processing in 15 adults with ASD and 15 age- and gender-matched typically developing controls. Individuals with ASD demonstrated attenuated activation of reward-related regions during vicarious reward processing. Altered connectivity was also observed in individuals with ASD during reward receipt. These findings of altered neural sensitivity to vicarious reward processing may represent a mechanism that hinders the development of social abilities in ASD.

20.
Front Hum Neurosci ; 14: 212, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32581753

RESUMEN

Restricted interests (RIs) in autism spectrum disorder (ASD) are clinically impairing interests of unusual focus or intensity. They are a subtype of restricted and repetitive behaviors which are one of two diagnostic criteria for the disorder. Despite the near ubiquity of RIs in ASD, the neural basis for their development is not well understood. However, recent cognitive neuroscience findings from nonclinical samples and from individuals with ASD shed light on neural mechanisms that may explain the emergence of RIs. We propose the nexus model of RIs in ASD, a novel conceptualization of this symptom domain that suggests that RIs may reflect a co-opting of brain systems that typically serve to integrate complex attention, memory, semantic, and social communication functions during development. The nexus model of RIs hypothesizes that when social communicative development is compromised, brain functions typically located within the lateral surface of cortex may expand into social processing brain systems and alter cortical representations of various cognitive functions during development. These changes, in turn, promote the development of RIs as an alternative process mediated by these brain networks. The nexus model of RIs makes testable predictions about reciprocal relations between the impaired development of social communication and the emergence of RIs in ASD and suggests novel avenues for treatment development.

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