Functional disturbances within frontostriatal circuits across multiple childhood psychopathologies
Open accessAbstract
OBJECTIVE: Neuroimaging studies of healthy individuals inform us about the normative maturation of the frontostriatal circuits that subserve self-regulatory control processes. Findings from these studies can be used as a reference frame against which to compare the aberrant development of these processes in individuals across a wide range of childhood psychopathologies. METHOD: The authors reviewed extensive neuroimaging evidence for the presence of abnormalities in frontostriatal circuits in children and adults with Tourette's syndrome and obsessive-compulsive disorder (OCD) as well as a more limited number of imaging studies of adolescents and adults with anorexia nervosa or bulimia nervosa that, together, implicate dysregulation of frontostriatal control systems in the pathogenesis of these eating disorders. RESULTS: The presence of an impaired capacity for self-regulatory control that derives from abnormal development of frontostriatal circuits likely interacts in similar ways with normally occurring somatic sensations and motor urges, intrusive thoughts, sensations of hunger, and preoccupation with body shape and weight to contribute, respectively, to the development of the tics of Tourette's syndrome, the obsessions of OCD, the binge eating behaviors of bulimia, and the self-starvation of anorexia. CONCLUSIONS: Analogous brain mechanisms in parallel frontostriatal circuits, or even in differing portions of the same frontostriatal circuit, may underlie the differing behavioral disturbances in these multiple disorders, although further research is needed to confirm this hypothesis.
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- Findingcitation
Our fMRI findings among women with bulimia suggest that failure to engage frontostriatal circuits appropriately contributes to impairments in behavioral self-regulation.
“Our fMRI findings among women with bulimia suggest that their failure to engage frontostriatal circuits appropriately contributes to their impairments in behavioral self-regulation (87).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [87] source
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- Findingown data
Analyses of brain activity during errors indicated greater activation of dorsal anterior cingulate cortex in patients during incorrect responses relative to correct responses on conflict trials, suggesting heightened error detection or performance monitoring.
“Analyses of brain activity during the commission of errors indicated greater activation of the dorsal anterior cingulate cortex of patients during incorrect responses relative to correct responses on conflict trials, suggesting the presence of heightened error detection or performance monitoring activity.”
Quote in the paperSubstantial claim - Findingown data
Even when responding correctly on incongruent trials, patients with bulimia failed to generate the same activity as comparison subjects in frontostriatal pathways including inferolateral prefrontal and anterior cingulate cortices, inferior frontal gyrus, putamen, and caudate.
“Even when responding correctly on incongruent trials, patients failed to generate the same activity as comparison subjects in the frontostriatal pathways thought to subserve inhibitory control, including the in-ferolateral prefrontal and anterior cingulate cortices, inferior frontal gyrus, putamen, and caudate.”
Quote in the paperSubstantial claim - Premisereasoning
Difficulty controlling ego-dystonic thoughts, urges, or behaviors is a common characteristic of several psychiatric disorders that arise in childhood or adolescence.
“Difficulty controlling ego-dystonic thoughts, urges, or behaviors is a common characteristic of several psychiatric disorders that arise in childhood or adolescence.”
Quote in the paperSubstantial claim - Premisecitation
Frontostriatal circuits subserve the capacity for self-regulation in both health and illness.
“Substantial evidence suggests that frontostriatal circuits subserve the capacity for self-regulation in both health (5) and illness (6).”
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- cites [6] Peterson BS, 2000
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- Premisecitation
Sensitivity to these cues is usually experienced as a compulsory urge that is only relieved by the performance of a tic.
“Sensitivity to these cues is usually experienced as a compulsory urge that is only relieved by the performance of a tic (13).”
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- Premisecitation
Persons with anorexia and bulimia have higher rates of OCD and obsessive-compulsive personality features than the general population.
“Consistent with the phenomenological similarities of these eating disorders with OCD, persons with anorexia and bulimia also have higher rates of OCD and obsessive-compulsive personality features than what is present in the general population (23).”
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- Interpretationreasoning
Disturbances in the maturation of frontostriatal circuits may contribute to the shared difficulties controlling thoughts, urges, and behaviors across these disorders.
“Thus, disturbances in the maturation of frontostriatal circuits may contribute to the shared difficulties controlling thoughts, urges, and behaviors across these seemingly disparate disorders.”
Quote in the paperSubstantial claim - Premisecitation
Prefrontal cortices that mediate more advanced, higher-order control functions mature later than areas subserving more basic cognitive functions such as sensation and movement.
“Findings suggest that the prefrontal cortices that mediate more advanced, higher-order control functions mature later than do areas that subserve more basic cognitive functions, such as sensation and movement (38–40).”
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These urges and the preoccupation with them bear a phenomenological resemblance to the obsessional urges that typically precede compulsive behaviors.
“These urges and the preoccupation with them bear a phenomenological resemblance to the obsessional urges that typically precede compulsive behaviors.”
Quote in the paperSubstantial claim - Interpretationreasoning
Dysregulation of frontostriatal circuits may also be a core characteristic of anorexia and bulimia.
“Thus, the dysregulation of frontostriatal circuits may also be a core characteristic of anorexia and bulimia.”
Quote in the paperSubstantial claim - Premisecitation
Performance on Stroop, flanker, go/no-go, and stop-signal reaction time tasks continues to improve over childhood, not reaching adult levels until at least 12 years of age.
“Findings from developmental studies of self-regulatory processes show that performance on Stroop, flanker, go/no-go, and stop-signal reaction time tasks continues to improve over childhood, not reaching adult levels until at least 12 years of age (30, 31).”
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Patients with Tourette's syndrome are often affected with OCD.
“In fact, patients with Tourette’s syndrome are often affected with OCD (14).”
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- Premisecitation
The dorsal striatum responds to rewards only when an action is required, consistent with its involvement in stimulus-response learning.
“Although both the dorsal striatum and ventral striatum respond to rewards, the dorsal striatum appears to do so only when an action is required, consistent with its putative involvement in stimulus-response learning (11).”
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- Premisecitation
At least five parallel loops have been identified within frontostriatal circuits, originating from and projecting back to the supplementary motor area, frontal eye fields, dorsolateral prefrontal cortex, lateral orbitofrontal cortex, and anterior cingulate cortex.
“At least five parallel loops have been identified within frontostriatal circuits, initiating from and projecting back to the 1) supplementary motor area, 2) frontal eye fields, 3) dorsolateral prefrontal cortex, 4) lateral orbitofrontal cortex, and 5) anterior cingulate cortex (7, 8).”
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Repetitive, ritualistic, highly controlled behaviors in anorexia may represent attempts to compensate for inability to control obsessive thoughts and anxiety.
“As with OCD, the repetitive, ritualistic, and highly controlled behaviors in persons with anorexia may represent attempts to compensate for their inability to control obsessive thoughts and anxiety (21).”
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- Premisecitation
A developmental fMRI study of the Stroop task among healthy participants suggested that frontostriatal circuits mature as self-regulation improves with age.
“Findings from a developmental functional magnetic resonance imaging (fMRI) study of the Stroop task among healthy participants (27) suggested that frontostriatal circuits mature as the capacity for self-regulation improves with advancing age.”
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- Premisecitation
Extensive neuroimaging evidence suggests that the pathophysiology of both Tourette's syndrome and OCD involves disturbances in the frontostriatal circuits that subserve self-regulation.
“Extensive neuroimaging evidence suggests that the pathophysiology of both disorders involves disturbances in the frontostriatal circuits that subserve the capacity for self-regulation (15–19).”
Quote in the paperSubstantial claim0 of 5 sources checked - Interpretationnone given
Stringent control over food intake in anorexia suggests excessive self-regulatory control.
“In contrast, the stringent control over food intake in anorexia suggests the presence of excessive self-regulatory control.”
Quote in the paperSubstantial claim - Premisereasoning
Anorexia nervosa and bulimia nervosa share with Tourette's syndrome and OCD the phenomenological characteristic of disordered control over behaviors or urges to perform them.
“Anorexia nervosa and bulimia nervosa seem to share with Tourette’s syndrome and OCD this phenomenological characteristic of disordered control over behaviors or the urges to perform them.”
Quote in the paperSubstantial claim - Interpretationcitation
Increasing prefrontal activation during inhibitory tasks from childhood to adulthood likely reflects synaptic pruning and increasing myelination in the frontal lobe.
“Increasing prefrontal activation during inhibitory tasks from childhood to adulthood (2, 27, 31) likely reflects synaptic pruning and increasing myelination in the frontal lobe (37).”
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This inability could explain the failure of Tourette's to remit during adolescence in the minority of patients who continue to experience tics in adulthood.
“This inability could explain the failure of Tourette’s syndrome to remit during adolescence in the minority of patients who continue to experience tics in adulthood (46), which was true of the adults in these imaging studies.”
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- Premiseown data
The magnitude of activations (caudate) or deactivations (putamen, pallidum, thalamus) during tic suppression correlated with tic severity in the month preceding the scan.
“The magnitude of the activations (caudate) or deactivations (putamen, pallidum, and thalamus) during tic suppression correlated with tic severity in the month preceding the scan.”
Quote in the paperSubstantial claim - Premisecitation
Children with Tourette's syndrome are commonly affected with OCD.
“Children with Tourette’s syndrome are commonly affected with OCD (13).”
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- Premisenone given
Few studies have employed a developmental perspective to investigate the pathogenesis of these disorders.
“To date, however, few studies have employed a developmental perspective to investigate the pathogenesis of these disorders, which would be best captured by longitudinal studies beginning at or before illness onset.”
Quote in the paperSubstantial claim - Interpretationreasoning
When frontostriatal control systems fail, tics may be released from inhibitory control.
“Together, these anatomical and functional findings from individuals with Tourette’s syndrome suggest that when frontostriatal control systems fail, tics may be released from inhibitory control.”
Quote in the paperSubstantial claim - Premisecitation
PET and SPECT studies suggest that dopamine D2 receptors are excessively sensitive in Tourette's syndrome.
“Positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies suggest that dopamine D2 receptors are excessively sensitive in Tourette’s syndrome (48, 49).”
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- cites [49] Wong DF, 1997, J Nucl Med
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Activation of supplementary motor area, paralimbic regions (anterior cingulate and insular cortices), and parietal operculum accompanies the experience of sensory cues that precede tics.
“These interpretations are consistent with a report (52) that activation of supplementary motor area, paralimbic regions (including the anterior cingulate and insular cortices), and parietal operculum accompanies the experience of the sensory cues that precede tics.”
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- Premisecitation
fMRI studies have reported that adults, but not children, with Tourette's rely on exaggerated activation of frontostriatal circuits to achieve normal performance on the Stroop task.
“Consistent with this interpretation, fMRI studies have reported that adults, but not children, with Tourette’s syndrome rely on exaggerated activation of frontostriatal circuits in order to achieve normal performance on the Stroop task.”
Quote in the paperSubstantial claim - Premisecitation
An fMRI study of tic suppression demonstrated that suppression of tics in adults with Tourette's produced changes in activity of frontostriatal systems.
“Consistent with this interpretation of the anatomical hypertrophy of the frontal cortex, an fMRI study of tic suppression demonstrated that the suppression of tics in adults with Tourette’s syndrome produced changes in activity of frontostriatal systems.”
Quote in the paperSubstantial claim - Premisecitation
Neuroimaging evidence from children and adults with Tourette's syndrome suggests both anatomical and functional abnormalities in frontostriatal circuits that subserve self-regulatory capacities.
“Neuroimaging evidence from studies of children and adults with Tourette’s syndrome suggests the presence of both anatomical (15, 16) and functional (17, 45) abnormalities in the frontostriatal circuits that subserve self-regulatory capacities.”
Quote in the paperSubstantial claim0 of 4 sources checked - Premisecitation
Tourette's syndrome can be conceptualized as a disorder of impaired control of sensory urges and motor behaviors.
“It can be conceptualized as a disorder of impaired control of sensory urges and motor behaviors (44).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [44] Marsh R
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- Interpretationreasoning
A greater capacity of the cortex to modulate activity in the basal ganglia likely attenuates tic severity.
“Thus, a greater capacity of the cortex to modulate activity in the basal ganglia likely attenuates tic severity.”
Quote in the paperSubstantial claim - Interpretationreasoning
Abnormal maturation of specific pathways in cortico-striato-thalamo-cortical circuits, particularly sensorimotor pathways looping between cortex and basal ganglia, may contribute to the genesis of tic behaviors.
“Together, these findings suggest that abnormal maturation of specific pathways in portions of cortico-striato-thalamo-cortical circuits, particularly those involving sensorimotor pathways looping between the cortex and basal ganglia, may contribute to the genesis of tic behaviors.”
Quote in the paperSubstantial claim - Interpretationcitation
Smaller prefrontal volumes in adults with Tourette's may reflect an inability to produce this activity-dependent plastic response to repeated attempts to control tics.
“In contrast, the smaller prefrontal volumes in adults who have Tourette’s syndrome may reflect an inability to produce this activity-dependent plastic response to repeated attempts to control tics (15).”
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- Premisecitation
Family and twin studies indicate that Tourette's syndrome and OCD are genetically related.
“Family and twin studies indicate that these disorders are genetically related (53).”
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- Study design and conductcitation
Differences across diagnostic groups in age trajectories of imaging measures could be confounded by systematic differences across age groups in patient characteristics such as illness duration, comorbidities, and disease subtypes.
“However, differences across diagnostic groups in the age trajectories of imaging measures in these studies could be confounded by systematic differences across age groups in the characteristics of the patients who are recruited into the study. For example, children and adults with a given disorder may differ in their durations of illness, rates of comorbidities, and disease subtypes (42).”
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- Interpretationcitation
Inverse correlations of symptom severity with activity in right orbitofrontal and dorsal anterior cingulate cortices during response inhibition on a go/no-go task suggested that patients who activated these regions most were better at suppressing unwanted thoughts and compulsions.
“Furthermore, inverse correlations of symptom severity with activity in the right orbitofrontal and dorsal anterior cingulate cortices during response inhibition on a go/no-go task suggested that the patients who activated these regions most were better at suppressing their unwanted thoughts and compulsions (66).”
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- Interpretationcitation
OCD may also involve abnormalities of the action monitoring or error detection system mediated by the anterior cingulate.
“OCD may also involve abnormalities of the action monitoring or error detection system that is mediated by the anterior cingulate (69, 70).”
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Event-related potential and fMRI studies have shown increased anterior cingulate activation in adults with OCD relative to healthy comparison subjects following errors or high-conflict trials on inhibitory control tasks.
“Event-related potential and fMRI studies have shown increased anterior cingulate activation in adults with OCD relative to healthy comparison subjects following errors or high-conflict trials on inhibitory control tasks (69–71).”
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The degree of anterior cingulate hyperactivation is proportional to symptom severity in OCD.
“Furthermore, the degree of hyperactivation is proportional to symptom severity (69, 70).”
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The childhood-onset form of OCD most commonly occurs in the context of a personal or family history of tic disorder.
“The childhood-onset form most commonly occurs in the context of a personal or family history of tic disorder (tic-related OCD) (55).”
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- Premisecitation
Findings of increased anterior cingulate volumes in children with OCD contrast with normal volumes in adults with OCD.
“Findings of increased anterior cingulate volumes in children (18, 61) contrast with findings of normal volumes in adults with OCD (19, 59).”
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Findings from a wide range of studies suggest that disturbances in orbitofrontal cortex may play a causal role in producing OCD symptoms.
“Nevertheless, findings from a wide range of studies suggest that disturbances in orbitofrontal cortex may play a causal role in producing the symptoms of OCD (67).”
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- Interpretationcitation
Abnormalities in frontostriatal circuits involving orbitofrontal cortex, anterior cingulate cortex, and striatum may contribute to the development of OCD.
“Anatomical findings suggest that abnormalities in frontostriatal circuits involving the orbitofrontal cortex, anterior cingulate cortex, and striatum may contribute to the development of OCD (18, 19, 59).”
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An fMRI study reported less error-related anterior cingulate activation in adolescents with partially remitted OCD relative to healthy comparison subjects.
“In contrast, an fMRI study reported less error-related anterior cingulate activation in adolescents with partially remitted OCD relative to healthy comparison subjects (73).”
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- Premisecitation
Individuals with OCD perform poorly on tasks requiring inhibitory control of behaviors and cognitions.
“Findings from neuropsychological studies suggest that individuals with OCD perform poorly on tasks requiring inhibitory control of behaviors and cognitions (56, 57).”
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Disturbances of serotonin metabolism within frontal cortices may predispose to bulimia by reducing feelings of satiety.
“Disturbances of serotonin metabolism within frontal cortices (79, 80) may predispose to the development of bulimia by reducing feelings of satiety (79).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [79] Wolfe BE, 1997, Psychopharmacol Bull
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- cites [80] source
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- Interpretationcitation
Available evidence suggests that dysfunctional frontal control systems may contribute to binge eating and impulsivity in bulimia.
“Although fMRI studies of persons with bulimia are few, the available evidence suggests that dysfunctional frontal control systems may contribute to their binge eating and impulsivity (77).”
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- Interpretationreasoning
Dysfunction in regulatory systems may produce inability to control preoccupation with body shape and weight, inducing purging behaviors in bulimia.
“Dysfunction in regulatory systems may also produce an inability of persons with bulimia to control their preoccupation with body shape and weight, thereby inducing purging behaviors.”
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These circuit-level distinctions may contribute to phenotypic differences between Tourette's and OCD.
“These circuit-level distinctions of frontostriatal dysfunction may contribute to the phenotypic differences between these often co-occurring conditions.”
Quote in the paperSubstantial claim - Interpretationcitation
In bulimia, this vulnerability may stem from altered serotonergic functioning that can produce impulsivity and decreased satiety.
“In bulimia, this vulnerability may stem from altered functioning of serotonergic systems that can produce both impulsivity and decreased satiety (78).”
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Treatment with SSRIs tends to decrease frequency of binges.
“Consistent with this possibility, treatment with SSRIs tends to decrease the frequency of binges (81).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [81] Mayer LE, 1998, J Clin Psychiatry
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- Premisecitation
Episodes of binge eating are associated with a severe sense of loss of control.
“Episodes of binge eating are associated with a severe sense of loss of control (76).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [76] Kaye W, Strober M, Jimerson DC: The neurobiology of eating disorders, in The Neurobiology of Mental Illness. Edited by Charney D, Nestler EJ. New York,Oxford University Press, 2004, pp1112-1128
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- Interpretationreasoning
Binge eating in bulimia may arise from or be facilitated by dysfunctional control systems that release a preexisting vulnerability from inhibitory control.
“Binge eating behaviors in persons with bulimia, similar to the defining behaviors of Tourette’s syndrome and OCD, may arise from or may at least be facilitated by the presence of dysfunctional control systems that release from inhibitory control a preexisting vulnerability to developing this particular illness.”
Quote in the paperSubstantial claim - Interpretationreasoning
Dysfunctional self-regulation may contribute to binge eating by releasing feeding behaviors from regulatory control.
“Dysfunctional self-regulation may therefore contribute to binge eating by releasing feeding behaviors from regulatory control.”
Quote in the paperSubstantial claim - Interpretationcitation
Differentially segregated cortical inputs and outputs of cortico-striato-thalamo-cortical circuits may provide a neuroanatomical basis for differential release of tics or compulsions from regulatory control in Tourette's or OCD.
“In other words, the differentially segregated cortical inputs and outputs of cortico-striato-thalamo-cortical circuits may provide a neuroanatomical basis for the differential release of either tics or compulsions from regulatory control in persons with Tourette’s syndrome or OCD, respectively (75).”
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- Interpretationcitation
Binge eating could also be caused by disturbances in frontostriatal circuits subserving motivation and reward, including orbitofrontal cortex and ventral striatum involved in processing hedonic value of food.
“Binge eating could also be caused by disturbances in the frontostriatal circuits that subserve motivation and reward, including the orbitofrontal cortex and ventral striatum that are involved in processing the hedonic value of food (88).”
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- Interpretationcitation
Consistent with our model, binge eating may reflect inability to control temptation for immediate rewards (food) in favor of delayed reward (slimmer body).
“Consistent with our model of self-regulatory disturbances in bulimia, binge eating may reflect an inability to control the temptation for immediate rewards (food consumption) in favor of a more delayed reward (a slimmer body) (92).”
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- Interpretationreasoning
These findings suggest that inability of persons with bulimia to engage frontostriatal systems likely contributes to their binge eating and other impulsive behaviors.
“These findings suggest that the inability of persons with bulimia to engage frontostriatal systems likely contributes to their binge eating and other impulsive behaviors.”
Quote in the paperSubstantial claim - Interpretationcitation
That elevated D2/D3 binding may account for the atypical reward-related brain activity seen in anorexia.
“possibly explaining their abnormal brain activity during reward processing.”
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- Premisecitation
Individuals with anorexia have perfectionist and obsessive temperaments that persist following recovery.
“Individuals with anorexia have perfectionist and obsessive temperaments that persist following recovery (95).”
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- Premisecitation
PET studies report alterations in postsynaptic serotonin 5-HT1A and 5-HT2A receptors in anterior cingulate cortex in both ill and recovered patients with anorexia.
“Third, PET studies report alterations in postsynaptic serotonin 5-HT1A and 5-HT2A receptors in the anterior cingulate cortex in both ill (106) and recovered (107) patients.”
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SPECT studies suggest adults with anorexia have lower resting regional cerebral blood flow in anterior cingulate cortex relative to comparison subjects, both before and after weight restoration.
“Second, SPECT studies suggest that adults with anorexia have lower resting regional cerebral blood flow in the anterior cingulate cortex relative to comparison subjects, both before and after weight restoration (105).”
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- Interpretationcitation
Given the central role of anterior cingulate in self-regulatory control, these abnormalities seem likely to contribute to self-regulatory disturbances in patients with anorexia.
“Given the central role of this region in self-regulatory control (27), these abnormalities seem likely to contribute to self-regulatory disturbances in patients with anorexia (78).”
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Several lines of evidence point to abnormalities of anterior cingulate cortex in both ill and recovered persons with anorexia.
“Several lines of evidence point to abnormalities of the anterior cingulate cortex in both ill and recovered persons with anorexia.”
Quote in the paperSubstantial claim - Interpretationcitation
High rates of diagnostic crossover between anorexia and bulimia suggest they may be manifestations of the same or comparable underlying disease processes, similar to Tourette's and OCD.
“The high rates of diagnostic crossover between these disorders (22) suggest that anorexia and bulimia, similar to Tourette’s syndrome and OCD, may be manifestations of the same or comparable underlying disease processes.”
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- Premisecitation
Individuals with anorexia have difficulty controlling obsessive preoccupation with thinness and ritualistic behaviors pertaining to eating and exercising.
“However, individuals with anorexia have difficulty controlling their obsessive preoccupation with thinness and their ritualistic behaviors that pertain to eating and exercising (102).”
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In a guessing-game study, women with anorexia showed similar ventral striatal activation after positive and negative feedback.
“In one study that involved a guessing game (93), women with anorexia activated the ventral striatum similarly during their responses to both positive and negative feedback.”
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PET research has found higher D2/D3 receptor binding in the ventral striatum of anorexia patients both before and after recovery.
“PET studies have also reported increased D2/D3 receptor binding in the ventral striatum both before and after recovery in patients with anorexia (94)”
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Reward processing is impaired in people with anorexia, according to functional MRI evidence.
“Findings from fMRI studies suggest that reward processing is dysfunctional in persons with anorexia.”
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Similar to OCD, symptoms of anorexia may represent a failure to shift or regulate attentional resources away from intrusive thoughts that motivate calorie restriction and produce ritualistic behaviors.
“Thus, similar to OCD, symptoms of anorexia may represent a failure to shift or to regulate attentional resources away from the intrusive thoughts that motivate calorie restriction and produce ritualistic behaviors.”
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Decreased volumes of dorsal anterior cingulate cortex have been reported in ill and recovered adult patients with anorexia relative to comparison subjects.
“First, decreased volumes of the dorsal anterior cingulate cortex have been reported in ill (103) and recovered (104) adult patients relative to comparison subjects.”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationreasoning
Altered ventral striatal and related frontostriatal reward-circuit function may reduce the motivation to eat in anorexia.
“Dysfunction in the ventral striatum and related portions of frontostriatal circuits that subserve reward processing may contribute to a diminished motivation to eat in individuals with anorexia.”
Quote in the paperSubstantial claim - Interpretationreasoning
This excessive control may help explain why anorexia patients can deny themselves food pleasure in pursuit of a thinner body.
“Excessive control may thereby contribute to the remarkable capacity of individuals with anorexia to deny themselves the gratification of food ingestion in the service of attaining a thinner body.”
Quote in the paperSubstantial claim - Premisecitation
On inhibitory-control tasks, OCD patients showed greater anterior cingulate activation than healthy controls when making errors.
“persons with OCD activated the anterior cingulate cortex more during the commission of errors than healthy comparison subjects on tasks that required inhibitory control”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationcitation
Circuit dysfunction, including atypical ventral striatal response to negative feedback, may also lessen anorexia patients' motivation to avoid negative outcomes such as starvation and repeated hospitalization.
“Dysfunction in this circuit, including abnormal activation of the ventral striatum during negative feedback (93), may also contribute to the diminished motivation of these individuals to avoid negative consequences, such as starvation and repeated hospitalization.”
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- Premisecitation
Acutely ill anorexia patients, however, showed less anterior cingulate activation than controls when making errors on a flanker task.
“However, acutely ill patients with anorexia activated the anterior cingulate cortex less than comparison subjects during the commission of errors on a flanker task (121).”
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- Interpretationcitation
This error-related anterior cingulate hyperactivity in OCD suggests an overactive error-monitoring system.
“suggesting the presence of a hyperactive error monitoring system (69, 70, 120).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationreasoning
Individual differences in susceptibility to sensorimotor urges and food preoccupation probably interact with differences in self-regulatory capacity to determine which disorder develops and how severe it becomes.
“Finally, differing predispositions to experience sensorimotor urges and preoccupation with food likely interact with differing capacities for self-regulation to determine who develops Tourette’s syndrome, OCD, anorexia, or bulimia and to what degree of clinical severity.”
Quote in the paperSubstantial claim - Interpretationreasoning
In anorexia restricting subtype, starvation may instead result directly from an excessive self-regulatory capacity.
“Starvation in anorexia restricting subtype may alternatively arise directly from a heightened and excessive capacity for self-regulation (Figure 1).”
Quote in the paperNot a substantial claim - Interpretationreasoning
Tourette's syndrome and OCD may have stronger biological determinants than anorexia and bulimia.
“suggesting that they may have stronger biological determinants than anorexia and bulimia.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [122] source
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- cites [123] Sasson Y, 1997, J Clin Psychiatry
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- Interpretationreasoning
Tourette's syndrome and OCD probably involve disturbances in different parts of frontostriatal circuits.
“Tourette’s syndrome and OCD likely arise from disturbances in differing portions of frontostriatal circuits.”
Quote in the paperSubstantial claim - Interpretationreasoning
Shared phenotypic features produced by self-regulatory disturbances and shared frontostriatal involvement across these disorders provide some support for a dimensional view of these predispositions, capacities, and illnesses.
“The shared phenotypic characteristics that self-regulatory disturbances produce and the shared involvement of frontostriatal circuits across these varied disorders support, to some extent, a dimensional conceptualization of these predispositions, capacities, and manifest illnesses.”
Quote in the paperSubstantial claim - Interpretationreasoning
Converging evidence indicates that anatomical and functional frontostriatal disturbances are involved in the pathogenesis of each of these disorders.
“converging lines of evidence suggest that the pathogenesis of each of these disorders involves anatomical and functional disturbances in frontostriatal circuits.”
Quote in the paperSubstantial claim - Interpretationcitation
Food may be less rewarding for people with anorexia than for others.
“Food may not be as rewarding to them as it is to others (116).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [116] source
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- Premisecitation
Cultural ideals of thinness are at least partly causal in anorexia and bulimia.
“However, anorexia and bulimia are also at least partly caused by cultural ideals of thinness (122)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [122] source
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- Premisenone given
The maturation of frontostriatal circuits underlies the development of self-regulation capacity.
“Substantial evidence suggests that the development of a capacity for self-regulation relies on the maturation of frontostriatal circuits.”
Quote in the paperSubstantial claim
- May combine two claims. 54
- Classified as probably not a substantial claim. 22
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Findingown dataThose with most severe bulimia symptoms engaged these regions least and demonstrated poorest performance on the task.
“In addition, those with the most severe bulimia symptoms engaged these regions the least and demonstrated the poorest performance on the task.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataActivation of this region did not modulate impulsive performance on subsequent trials, since reaction times did not slow following errors.
“However, activation of this region did not modulate the impulsive performance of the patients on subsequent trials, since their reaction times did not slow following errors.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataPatients with bulimia responded impulsively and made more errors relative to comparison subjects on the Simon task.
“Patients with bulimia responded impulsively and made more errors relative to comparison subjects on the Simon task, a nonverbal analogue of the Stroop task.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S4 (based).
Interpretationnone givenAnalogous brain mechanisms in parallel frontostriatal circuits, or in differing portions of the same circuit, may underlie the differing behavioral disturbances in Tourette's syndrome, OCD, bulimia, and anorexia.
“Analogous brain mechanisms in parallel frontostriatal circuits, or even in differing portions of the same frontostriatal circuit, may underlie the differing behavioral disturbances in these multiple disorders, although further research is needed to confirm this hypothesis.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationThe development of self-regulation parallels and is thought to depend on the maturation of frontostriatal circuits.
“The development of this capacity parallels and is thought to depend on the maturation of frontostriatal circuits (27–29).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
PremisecitationAll of these illnesses typically begin during childhood or adolescence, periods during which self-regulation develops rapidly.
“All of these illnesses typically begin during childhood or adolescence (24, 25), periods during which the capacity for self-regulation develops rapidly (5, 26).”
Quote in the paperSubstantial claim0 of 4 sources checkedMay combine two claims.
PremisecitationIn that study, activation of inferolateral prefrontal cortex and lenticular nucleus increased with age as well as response speed and accuracy, suggesting that increasing activity of frontostriatal circuits improves behavioral control as children mature.
“The study found that activation of the inferolateral prefrontal cortex and lenticular nucleus increased with age as well as response speed and accuracy, suggesting that increasing activity of frontostriatal circuits improves behavioral control as children mature.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [27] source
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InterpretationcitationRecurrent binge eating episodes, frequent impulsive behaviors, and inability to inhibit preoccupation with weight and body shape suggest impaired self-regulation in bulimia.
“The recurrent binge eating episodes, the frequency of other accompanying impulsive behaviors (20), and the inability to inhibit the constant preoccupation with weight and body shape suggest the presence of an impaired capacity for self-regulation in bulimia.”
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PremisecitationThe tics of Tourette's syndrome are typically brief, nonpurposeful or semipurposeful behavioral fragments often enacted in response to internal or external sensory cues.
“The tics of Tourette’s syndrome are typically brief, nonpurposeful or semipurposeful behavioral fragments often enacted in response to internal or external sensory cues (13).”
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InterpretationcitationHigh rates of diagnostic crossover from anorexia to bulimia suggest these disorders may share a common neural substrate.
“The high rates of diagnostic crossover from anorexia to bulimia further suggest that these disorders may share a common neural substrate (22).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] source
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InterpretationreasoningAnorexia shares with bulimia the inability to inhibit weight- and body shape-related thoughts, which may suggest a reduced rather than enhanced capacity for self-regulation in anorexia.
“However, anorexia shares with bulimia the inability to inhibit weight- and body shape-related thoughts, which may alternatively suggest that a reduced rather than enhanced capacity for self-regulation is present in anorexia.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe first three frontostriatal loops pass through the dorsal striatum, and the last two pass through the ventromedial striatum, including the nucleus accumbens.
“The first three of these loops pass through the dorsal striatum, and the last two pass through the ventromedial striatum, including the nucleus accumbens (8).”
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PremisecitationInhibiting the prepotent reading response during incongruent Stroop trials requires mobilization of attentional resources and resolution of cognitive conflict, with down-modulation of automatic reading and up-modulation of color-naming.
“Inhibiting the prepotent reading response during incongruent trials requires the mobilization of attentional resources and the resolution of cognitive conflict, with down-modulation of the more automatic reading response and up-modulation of the less automatic but more task-relevant color-naming response (32).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [32] Cohen JD, 2004
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PremisecitationThe prefrontal components of frontostriatal pathways have long been assigned a central role in controlling thought and behavior in accord with the pursuit of future goals.
“The prefrontal components of these pathways have long been assigned a central role in controlling thought and behavior in accord with the pursuit of future goals (12).”
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PremisecitationBrain activity when naming colors of incongruent stimuli is greater than for congruent stimuli, particularly in anterior cingulate, prefrontal and parietal cortices, and striatum, in both adults and children.
“Brain activity when naming the colors of incongruent stimuli is greater than when naming the colors of congruent stimuli, particularly in the anterior cingulate, prefrontal and parietal cortices, and striatum, in both adults (33) and children (34).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationThe dorsal striatum mediates habit- or stimulus-response learning, while the ventral striatum mediates reward, drive, and motivation.
“Findings from both animal and human studies suggest that the dorsal striatum mediates habit-or stimulus-response learning (9), while the ventral striatum mediates reward, drive, and motivation (10).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationIn each circuit, information flows predominantly through either a direct or an indirect pathway, both modulated by dopamine.
“In each circuit, information flows predominantly through either a direct or an indirect pathway, both of which are modulated by dopamine (47).”
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PremisecitationIn that study, frontal cortices activated prominently, and magnitude of frontal activation correlated with increased caudate activity, which was associated with greater decreases in putamen, globus pallidus, and thalamus activity.
“Findings from the study revealed that frontal cortices activated prominently, and the magnitude of frontal activation correlated significantly with increased activity in the caudate, which, in turn, was associated with greater decreases in activity of the putamen, globus pallidus, and thalamus.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S4 (based).
Premisenone givenNormal maturational trajectories in frontostriatal systems provide a reference frame from which to identify deviant patterns of development in Tourette's syndrome, OCD, bulimia, and anorexia.
“Normal maturational trajectories in frontostriatal systems provide a reference frame from which we can identify deviant patterns of development in individuals with Tourette’s syndrome, OCD, bulimia, and anorexia.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationThe need to suppress tics in social settings likely activates prefrontal cortices frequently and powerfully, possibly stimulating activity-dependent neuroplastic hypertrophy.
“Therefore, the nearly ubiquitous need to suppress tics in school and other social settings likely activates prefrontal cortices frequently and powerfully (45), possibly stimulating in them an activity-dependent neuroplastic hypertrophy.”
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PremisecitationDiffusion tensor imaging studies have shown changes in prefrontal white matter during development that presumably reflect myelination of axons during childhood and adolescence.
“In addition, diffusion tensor imaging studies have shown changes in prefrontal white matter during development that presumably reflect the previously documented myelination of axons during childhood and adolescence.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningHyperinnervation of the striatum by dopaminergic neurons may excessively stimulate the direct pathway while inhibiting the indirect pathway in Tourette's, contributing to difficulty regulating tics.
“These findings, together with reports that the administration of dopamine antagonists reduces tic severity (50), suggest that hyperinnervation of the striatum by dopaminergic neurons may excessively stimulate the direct pathway while inhibiting the indirect pathway in individuals with Tourette’s syndrome, thereby contributing to their difficulty in regulating their tics (44).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [50] source
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- cites [44] Marsh R
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InterpretationreasoningPhenomenological similarities between tics and compulsions and their common genetic basis suggest that Tourette's syndrome and pediatric OCD may be manifestations of the same underlying disease process, likely sharing a common neurobiological substrate.
“These phenomenological similarities between tics and compulsions and their common genetic basis suggest that Tourette’s syndrome and pediatric OCD may be manifestations of the same underlying disease process, likely sharing a common neurobiological substrate.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationBoth tics and compulsions present as habit-like behaviors that have escaped regulatory control.
“Both tics and compulsions present as “habit-like” behaviors that have escaped regulatory control (13).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] source
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PremisecitationOCD age of onset is likely bimodal, with one mode at 10 to 12 years and another in early adulthood.
“Its age of onset is likely bimodal, with one mode at 10 to 12 years of age and the other occurring in early adulthood (54).”
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PremisecitationOngoing myelination increases the speed of neuronal communication, thus enhancing cognitive processing with increasing age.
“Ongoing myelination increases the speed of neuronal communication, thus enhancing cognitive processing with increasing age (41).”
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PremisecitationAbnormal thinning of sensorimotor, primary motor, and premotor cortices in children with Tourette's is proportional to tic severity, and hypoplasia of the caudate nucleus occurs in children and adults with the disorder.
“Other anatomical imaging studies have identified abnormal thinning of the sensorimotor, primary motor, and premotor cortices in children with Tourette’s syndrome, with the degree of thinning proportional to the severity of their tics (51), as well as hypoplasia of the caudate nucleus in children and adults with the disorder (16).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationAnatomical findings in Tourette's include decreased caudate volumes in children and adults and larger dorsolateral prefrontal cortices in children but not adults, relative to age-matched comparison subjects.
“Anatomical findings include decreased caudate volumes in children and adults (16) and larger dorsolateral prefrontal cortices in children but not in adults who have the disorder, relative to age-matched comparison subjects.”
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InterpretationcitationDifferent imaging findings across children and adults with Tourette's syndrome may be produced by compensatory behavioral, cognitive, or emotional processes more developed in adults with longer illness.
“Thus, different imaging findings across children and adults with Tourette’s syndrome, for instance, may be produced by compensatory behavioral, cognitive, or emotional processes that may be more developed in adults who have had the illness longer (15).”
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InterpretationcitationImpaired frontally mediated inhibitory reserve confers a need for increased functional recruitment of these cortices to overcome enduring difficulties with self-regulation during self-regulatory tasks.
“Presumably, impaired frontally mediated inhibitory reserve confers a need for increased functional recruitment of these cortices in order to overcome enduring difficulties with self-regulation during performance of self-regulator tasks (17).”
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PremisecitationThe prefrontal portions of cortico-striato-thalamo-cortical circuits project to specific striatal regions, which project to specific regions of the internal globus pallidus and substantia nigra pars reticulata; these nuclei project to thalamus, which projects back to cortex.
“The prefrontal portions of cortico-striato-thalamo-cortical circuits project to specific regions of the striatum, which, in turn, project directly or indirectly to specific regions of the internal segment of the globus pallidus and the substantia nigra pars reticulata. These nuclei then project to the thalamus, which closes the loop by projecting back to the cortex (7).”
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InterpretationcitationThe larger dorsolateral prefrontal volumes in children with Tourette's accompanied less severe tic symptoms and may represent a compensatory or adaptive process that attenuates tics.
“The larger dorsolateral prefrontal volumes in children have accompanied less severe tic symptoms (15) and therefore may have represented a compensatory or adaptive process that attenuates tics, consistent with the role of the prefrontal cortex in inhibiting inappropriate impulses or behaviors.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] source
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PremisecitationThese findings include anatomical abnormalities in orbitofrontal cortices of adults with OCD, development of OCD following naturalistic lesions of orbitofrontal cortex, and improvement after neurosurgical lesions of white matter tracts to/from orbitofrontal cortex.
“These findings include anatomical abnormalities in orbitofrontal cortices of adults with OCD, the development of OCD following various naturalistic lesions of the orbitofrontal cortex, and the improvement in symptoms following neurosurgical lesions of white matter tracts leading to and from the orbitofrontal cortex (68).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [68] source
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InterpretationcitationUndiagnosed comorbid tic disorders could account for striatal abnormalities in children with OCD and adults with childhood-onset OCD.
“However, the presence of undiagnosed comorbid tic disorders could also account for striatal abnormalities in children with OCD and in adults with childhood-onset OCD (18, 60).”
Quote in the paperNot a substantial claim0 of 2 sources checkedClassified as probably not a substantial claim. May combine two claims.
InterpretationreasoningMost adolescents in this small sample were taking SSRIs, which may have blunted their error-related activity.
“Most of the adolescents in this small sample were taking selective serotonin reuptake inhibitors (SSRIs), which may have blunted their error-related activity.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationSelf-regulatory impairments on Stroop, go/no-go, and oculomotor suppression tasks correlate with symptom severity in OCD, suggesting that increasing functional disturbances in self-regulatory circuits may produce more severe symptoms.
“Furthermore, self-regulatory impairments on Stroop, go/no-go (56), and oculomotor suppression tasks (58) correlate with the severity of symptoms, suggesting that increasing degrees of functional disturbances in self-regulatory circuits may produce increasingly more severe symptoms.”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
InterpretationreasoningChildren with OCD continued to show error-related hyperactivity of anterior cingulate after successful cognitive behavior therapy, suggesting higher activity following errors may be a trait-like disturbance in OCD.
“Children with OCD continued to show error-related hyperactivity of the anterior cingulate after successful treatment with cognitive behavior therapy, suggesting that higher activity in the anterior cingulate following errors may be a trait-like disturbance in OCD.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationOne event-related potential study reported increased error-related anterior cingulate activity in children with OCD relative to healthy children, although activation did not correlate with symptom severity.
“One event-related potential study reported increased error-related anterior cingulate activity in children with OCD relative to healthy children, although the degree of activation did not correlate with symptom severity (72).”
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InterpretationcitationGreater activation of orbitofrontal cortices during symptom provocation in adults with OCD was associated with a smaller increase in reported symptoms, suggesting activation may have inhibited rather than caused symptoms.
“Greater activation of orbitofrontal cortices during symptom provocation in adults with OCD was in fact associated with a smaller increase in reported symptoms (65), suggesting that activation of orbitofrontal cortices may have inhibited rather than caused symptoms.”
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InterpretationcitationOCD symptoms may represent an incapacity to shift or self-regulate attentional resources away from obsessions, and a failure to regulate compulsory behaviors.
“OCD symptoms may represent an individual’s incapacity to shift or self-regulate attentional resources away from his or her focus on obsessions (57), as well as a failure to regulate compulsory behaviors, similar to the failure to regulate tic behaviors in persons with Tourette’s syndrome.”
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InterpretationcitationAlternatively, hyperactivation could represent attempts to inhibit compulsions or suppress behavioral withdrawal during scanning.
“Alternatively, hyperactivation could represent attempts on the part of the person with OCD to inhibit the performance of compulsions or to suppress behavioral withdrawal when presented with the provoking stimulus during the scanning process (64).”
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InterpretationcitationIncreased activity within frontostriatal circuits during symptom provocation suggests that hyperactivity in these circuits generates OCD symptoms.
“Increased activity within frontostriatal circuits during symptom provocation suggests that hyperactivity in frontostriatal circuits generates the symptoms of OCD (63).”
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PremisecitationReports of increased gray matter in orbitofrontal cortex of children with OCD contrast with reduced orbitofrontal volume in adults.
“Reports of increased gray matter in the orbitofrontal cortex of children with OCD (60) also contrast with findings of reduced volume of the orbitofrontal cortex in adults (19, 62).”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
InterpretationcitationMood instability and impulsive, aggressive, and compulsory behaviors are common in bulimia, perhaps indicating more pervasive self-regulation difficulties.
“Mood instability and impulsive, aggressive, and compulsory behaviors are common in individuals with bulimia, perhaps indicating the presence of more pervasive difficulties in self-regulation (76).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [76] Kaye W, Strober M, Jimerson DC: The neurobiology of eating disorders, in The Neurobiology of Mental Illness. Edited by Charney D, Nestler EJ. New York,Oxford University Press, 2004, pp1112-1128
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PremisecitationThe functioning of these circuits has not been investigated longitudinally in OCD, and only two fMRI studies have assessed them in younger patients, precluding understanding of developmental origins.
“The functioning of these circuits has not been investigated longitudinally in patients with OCD, however, and only two fMRI studies to date have assessed the functioning of these circuits in younger patients (73, 74), thereby precluding our understanding of the developmental origins of frontostriatal disturbances in OCD.”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationAlthough fMRI studies suggest anorexia may involve dysfunction in reward circuits, reward processing has not been assessed systematically in bulimia.
“Although fMRI studies have suggested that anorexia may involve dysfunction in reward circuits (93, 94), reward processing has not yet been assessed systematically in individuals with bulimia.”
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InterpretationreasoningWhereas Tourette's pathogenesis involves frontostriatal circuits consisting of motor and premotor cortices and dorsal striatum, OCD seems to involve disturbances in orbitofrontal and anterior cingulate portions of frontostriatal circuits.
“Whereas the pathogenesis of Tourette’s syndrome involves frontostriatal circuits consisting of motor and premotor cortices and the dorsal striatum, OCD seems to involve disturbances in the orbitofrontal and anterior cingulate portions of frontostriatal circuits.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
InterpretationreasoningInteractions with aesthetic cultural ideals of thinness and physical fitness likely produce purging behaviors to counteract weight gain from binge eating.
“Interactions with the aesthetic cultural ideals of thinness and physical fitness then likely produce purging behaviors to counteract the weight gain that binge eating would otherwise produce.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationConsumption of food is associated with increased dopamine release in reward circuits, and increases in dopamine are associated with more motivated food-seeking behavior in rats and humans.
“The consumption of food is associated with increased dopamine release in these reward circuits (89), and increases in dopamine are associated with more motivated (food seeking) behavior in rats (90) and humans (91).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
InterpretationcitationSerotonergic disturbances have been documented in both ill and recovered individuals with bulimia, suggesting they may be trait-like.
“Moreover, serotonergic disturbances have been documented in both ill (82) and recovered (83) individuals with bulimia, suggesting that these may be trait-like disturbances in this population.”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationConflict-related activation of anterior cingulate following correct responses could represent exaggerated arousal or greater anxiety relative to comparison subjects during challenging tasks.
“Conflict-related activation of the anterior cingulate cortex following correct responses (71) could similarly represent exaggerated arousal or even greater anxiety relative to comparison subjects while performing challenging tasks in an experimental setting.”
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Interpretationnone givenEvidence suggests that frontostriatal circuits including orbitofrontal and anterior cingulate cortices are functionally abnormal in adults with OCD and likely contribute to their symptoms of impaired regulation.
“Evidence suggests that the frontostriatal circuits that include the orbitofrontal and anterior cingulate cortices are functionally abnormal in adults with OCD and likely contribute to their symptoms of impaired regulation.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationSerotonergic abnormalities may contribute to feeding disturbances and to high impulsivity in bulimia, consistent with literature linking serotonin abnormalities with impulsivity.
“Serotonergic abnormalities may contribute not only to feeding disturbances (84), but also to the high levels of impulsivity reported in persons with bulimia (85), consistent with a vast literature linking serotonin abnormalities with impulsivity in both humans and animals (86).”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
InterpretationreasoningFeelings of hunger produce urges to binge, which may be released inappropriately by dysfunctional control systems to produce binge eating episodes.
“Feelings of hunger in turn produce urges to binge, which may be released inappropriately by dysfunctional control systems to produce binge eating episodes.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationAnorexia nervosa and bulimia nervosa have similar phenotypes and clinical courses.
“Anorexia nervosa and bulimia nervosa have similar phenotypes and clinical courses (25).”
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InterpretationcitationAnorexia and bulimia appear to lie on a spectrum of self-regulatory control over feeding behaviors, with excessive control in anorexia restricting subtype, less control in anorexia binge/purge subtype, and paucity of control in bulimia.
“Anorexia and bulimia therefore appear to lie on a spectrum of self-regulatory control over feeding behaviors, with excessive control present in anorexia restricting subtype, less control present in anorexia binge/purge subtype, and a paucity of control in bulimia (101).”
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PremisecitationHealthy participants in that task instead showed stronger ventral striatal responses to positive feedback, matching earlier evidence that this region responds to reward rather than punishment in healthy people.
“Healthy participants, in contrast, activated the ventral striatum preferentially in response to positive feedback, consistent with prior findings of ventral striatal responses to reward but not punishment during this task in healthy participants (115).”
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InterpretationreasoningRigid control over feeding behaviors in anorexia seems to suggest pathological self-regulation.
“Their rigid control over feeding behaviors seems to suggest the presence of pathological self-regulation.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationThese receptors mediate inhibitory and excitatory actions of 5-HT on cortical neurons; thus these alterations may produce further functional abnormalities in anterior cingulate cortex.
“These receptors mediate, respectively, the inhibitory and excitatory actions of 5-HT on cortical neurons (108); thus these alterations may produce further functional abnormalities in the anterior cingulate cortex.”
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PremisecitationApproximately one-third of adults with bulimia describe past histories of anorexia, and a significant proportion of patients with anorexia regularly binge eat or purge.
“Approximately one-third of adults with bulimia describe past histories of anorexia (96), and a significant proportion of patients with anorexia regularly binge eat or purge (25).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Interpretationnone givenAlternatively, ritualistic behaviors in anorexia and OCD may represent a failure to regulate the behaviors themselves.
“Alternatively, the ritualistic behaviors in anorexia and OCD may represent a failure to regulate the behaviors themselves.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningPhenotypic similarities such as intense preoccupation with food and high prevalence of OCD and obsessive-compulsive personality traits that predict poor outcome suggest anorexia and bulimia share neural substrates.
“In addition, their phenotypic similarities, such as an intense preoccupation with food and a high prevalence of OCD and obsessive-compulsive personality traits (97–99) that predict poor outcome (100), suggest that these disorders share neural substrates.”
Quote in the paperNot a substantial claim0 of 4 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisenone givenBoth anorexia and bulimia primarily affect women and typically begin in adolescence.
“Both primarily affect women, and both typically begin in adolescence.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationcitationHigher D2 receptor numbers in anorexia may strengthen self-regulatory control and support food avoidance.
“increases in the numbers of D2 receptors in persons with anorexia may enhance self-regulatory control and promote abstention from eating.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [94] source
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PremisecitationTourette's syndrome and OCD have relatively consistent prevalence and presentation across cultures.
“whereas the clinical presentations of Tourette’s syndrome and OCD are relatively uniform in prevalence and presentation across cultures (123)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [123] Sasson Y, 1997, J Clin Psychiatry
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PremisecitationThere is current nosological controversy over whether mental disorders, especially developmental psychopathologies, are best classified categorically or dimensionally.
“A current controversy in nosology is whether mental disorders, particularly developmental psychopathologies, are best characterized using a categorical or dimensional approach (124).”
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PremisecitationLower striatal D2 receptor numbers in obese people may weaken self-regulatory control and increase overeating.
“Whereas decreases in the numbers of striatal D2 receptors in obese individuals (117) may reduce self-regulatory control and promote overeating”
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PremisecitationPatients with anorexia or OCD commonly show unrealistically high standards and excessive concern about mistakes.
“Unrealistically high personal standards and excessive concerns with making mistakes are common in patients with either anorexia or OCD (118, 119).”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S4 (based).
InterpretationreasoningIf different frontostriatal portions are responsible for one disorder rather than another, categorical distinctions among these disorders may remain most appropriate.
“However, if differing portions of frontostriatal circuits are indeed responsible for the development of one rather than another of these disorders, then categorical distinctions among them may still be most appropriate.”
Quote in the paperNot a substantial claimMay combine two claims.
InterpretationreasoningFrontostriatal anatomical and functional disturbances may release urges, thoughts, and drives from inhibitory control, producing tics in Tourette's syndrome, obsessions in OCD, body-shape preoccupation in anorexia, or binge eating in bulimia.
“anatomical and functional disturbances of frontostriatal systems may release them from inhibitory control to allow expression of the tics in Tourette’s syndrome, the obsessions in OCD, the preoccupation with body shape and weight in anorexia, or the binge eating in bulimia (Figure 1).”
Quote in the paperNot a substantial claim- Rests on an assumption: In healthy people, self-regulation normally keeps sensory and motor urges, intrusive thoughts, hunger, and body-shape concerns under control.
- Rests on an assumption: Sensory and motor urges, intrusive thoughts, hunger, and concern with body shape and weight occur in both healthy and ill people.
May combine two claims.
InterpretationreasoningThe clinical features of Tourette's syndrome, OCD, bulimia, and anorexia indicate impaired control processes in each condition.
“The clinical presentations of Tourette’s syndrome, OCD, bulimia, and anorexia suggest the presence of impaired control processes in each of these conditions”
Quote in the paperSubstantial claim
The paper relies on this without support.
In healthy people, self-regulation normally keeps sensory and motor urges, intrusive thoughts, hunger, and body-shape concerns under control.
“Although a capacity for self-regulation keeps these urges, thoughts, and drives under control in healthy individuals”
The paper relies on this without support.
Sensory and motor urges, intrusive thoughts, hunger, and concern with body shape and weight occur in both healthy and ill people.
“Sensory and motor urges, intrusive thoughts, hunger, and concern with body shape and weight are common in both healthy and ill individuals.”
The paper relies on this without support.
Obsessions in OCD, body-shape preoccupation in anorexia, and fear of weight gain from binge eating in bulimia are predominantly ego dystonic and therefore elicit compensatory behaviors that produce compulsions, starvation, or purging.
“The obsessions in OCD, the obsessive preoccupation with body shape and weight in anorexia, and the fear of gaining weight from binge eating in bulimia are predominantly ego dystonic and therefore elicit compensatory behaviors that aim to alleviate the associated anxiety or discomfort, producing compulsions, starvation, or purging, respectively.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Greater frontostriatal activation has been demonstrated in unmedicated OCD patients during engagement of control and conflict resolution on the Simon task.
“greater frontostriatal activation has been demonstrated in unmedicated OCD patients during engagement of control and conflict resolution on the Simon task 68.”
From DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS: Review: Dissecting OCD Circuits: Animals to Treatments (2015) · cites this paper as [68]
Alterations of anterior cingulate cortex-based frontal-striatal-thalamic circuitry for cognitive control and ventral medial frontal cortex-based circuitry for emotion processing during development may increase vulnerability for obsessive-compulsive disorder and other psychopathologies including Tourette's syndrome, eating disorders, and attention deficit hyperactivity disorder.
“Alterations of ACC-based FSTC for cognitive control and vMFC-based FSTC for emotion processing during development may increase vulnerability for OCD, but also other forms of psychopathology, including Tourette's syndrome, eating disorders, and attention deficit hyperactivity disorder35.”
From Developmental alterations of frontal-striatal-thalamic connectivity in obsessive-compulsive disorder (2011) · cites this paper as [35]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Reported 5-HT2A alteration conflicts with the cited study title
MinorThe text says PET studies found altered 5-HT2A receptors in ill patients with anorexia, citing reference 106. That reference's title instead describes normal 5-HT2A receptor activity in ill patients.
“Third, PET studies report alterations in postsynaptic serotonin 5-HT1A and 5-HT2A receptors in the anterior cingulate cortex in both ill (106) and recovered (107) patients.”
“Exaggerated 5-HT1A but normal 5-HT2A receptor activity in individuals ill with anorexia nervosa”
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- Authors
- Marsh, R., Maia, T. V., & Peterson, B. S.
- Affiliations
- New York State Psychiatric Institute (US)
- Venue
- American Journal of Psychiatry
- Published
- 2009-06
- Volume
- 166
- Issue
- 6
- Pages
- 664-674
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC2734479
- OpenAlex
- W2107177274
- Semantic Scholar
- 66f2974e72c91c15a37f3fa0677d27020c42fce7
- Cited by
- 187
- References
- 129
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 2 · 2022: 12 · 2021: 4 · 2020: 10 · 2019: 7 · 2018: 9 · 2017: 7 · 2016: 14 · 2015: 19 · 2014: 15 · 2013: 21 · 2012: 17
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- U.S. Public Health Service (K-02-74677)
- National Institute of Mental Health (K01MH077652, R01MH068318, MH 068318, R01MH090062)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Clinical Psychology › Eating Disorders and Behaviors
- Keywords
- frontostriatal circuits, childhood psychopathology, Tourette syndrome, obsessive-compulsive disorder, anorexia nervosa, bulimia nervosa, developmental neuroimaging, tics, obsession, binge eating, eating disorders, intrusive thoughts, body image
- MeSH terms
- Adolescent, Anorexia, Bulimia, Child, Corpus Striatum, Frontal Lobe, Tourette Syndrome, Humans, Magnetic Resonance Imaging, Nerve Net, Obsessive-Compulsive Disorder, Self Efficacy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-04.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-04.
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