D2/D3 dopamine supports the precision of mental state inferences and self-relevance of joint social outcomes.

Striatal dopamine is important in paranoid attributions, although its computational role in social inference remains elusive. We employed a simple game-theoretic paradigm and computational model of intentional attributions to investigate the effects of dopamine D2/D3 antagonism on ongoing mental state inference following social outcomes. Haloperidol, compared with the placebo, enhanced the impact of partner behaviour on beliefs about the harmful intent of partners, and increased learning from recent encounters. These alterations caused substantial changes to model covariation and negative correlations between self-interest and harmful intent attributions. Our findings suggest that haloperidol improves belief flexibility about others and simultaneously reduces the self-relevance of social observations. Our results may reflect the role of D2/D3 dopamine in supporting self-relevant mentalising. Our data and model bridge theory between general and social accounts of value representation. We demonstrate initial evidence for the sensitivity of our model and short social paradigm to drug intervention and clinical dimensions, allowing distinctions between mechanisms that operate across traits and states.

Dopamine manipulations modulate paranoid social inferences in healthy people.

Altered dopamine transmission is thought to influence the formation of persecutory delusions. However, despite extensive evidence from clinical studies there is little experimental evidence on how modulating the dopamine system changes social attributions related to paranoia, and the salience of beliefs more generally. Twenty seven healthy male participants received 150mg L-DOPA, 3 mg haloperidol, or placebo in a double-blind, randomised, placebo-controlled study, over three within-subject sessions. Participants completed a multi-round Dictator Game modified to measure social attributions, and a measure of belief salience spanning themes of politics, religion, science, morality, and the paranormal. We preregistered predictions that altering dopamine function would affect (i) attributions of harmful intent and (ii) salience of paranormal beliefs. As predicted, haloperidol reduced attributions of harmful intent across all conditions compared to placebo. L-DOPA reduced attributions of harmful intent in fair conditions compared to placebo. Unexpectedly, haloperidol increased attributions of self-interest about opponents' decisions. There was no change in belief salience within any theme. These results could not be explained by scepticism or subjective mood. Our findings demonstrate the selective involvement of dopamine in social inferences related to paranoia in healthy individuals.

Paranoia, sensitization and social inference: findings from two large-scale, multi-round behavioural experiments.

The sensitization model suggests that paranoia is explained by over-sensitivity to social threat. However, this has been difficult to test experimentally. We report two preregistered social interaction studies that tested (i) whether paranoia predicted overall attribution and peak attribution of harmful intent and (ii) whether anxiety, interpersonal sensitivity and worry predicted the attribution of harmful intent. In Study 1, we recruited a large general population sample (N = 987) who serially interacted with other participants in multi-round dictator games and matched to fair, partially fair or unfair partners. Participants rated attributions of harmful intent and self-interest after each interaction. In Study 2 (N = 1011), a new sample of participants completed the same procedure and additionally completed measures of anxiety, worry and interpersonal sensitivity. As predicted, prior paranoid ideation was associated with higher and faster overall harmful intent attributions, whereas attributions of self-interest were unaffected, supporting the sensitization model. Contrary to predictions, neither worry, interpersonal sensitivity nor anxiety was associated with harmful intent attributions. In a third exploratory internal meta-analysis, we combined datasets to examine the effect of paranoia on trial-by-trial attributional changes when playing fair and unfair dictators. Paranoia was associated with a greater reduction in harmful intent attributions when playing a fair but not unfair dictator, suggesting that paranoia may also exaggerate the volatility of beliefs about the harmful intent of others.

Hypnosis as therapy for functional neurologic disorders.

Suggestion in hypnosis has been applied to the treatment of functional neurologic symptoms since the earliest descriptions of hypnosis in the 19th century. Suggestion in this sense refers to an intentional communication of beliefs or ideas, whether verbally or nonverbally, to produce subjectively convincing changes in experience and behavior. The recognition of suggestion as a psychologic process with therapeutic applications was closely linked to the derivation of hypnosis from earlier healing practices. Animal magnetism, the immediate precursor of hypnosis, arrived at a psychologic concept of suggestion along with other ideas and practices which were then incorporated into hypnosis. Before then, other forms of magnetism and ritual healing practices such as exorcism involved unintentionally suggestive verbal and nonverbal stimuli. We consider the derivation of hypnosis from these practices not only to illustrate the range of suggestive processes, but also the consistency with which suggestion has been applied to the production and removal of dissociative and functional neurologic symptoms over many centuries. Nineteenth-century practitioners treated functional symptoms with induction of hypnosis per se; imperative suggestions, or commands for specific effects; "medical clairvoyance" in hypnotic trance, in which patients diagnosed their own condition and predicted the time and manner of their recovery; and suggestion without prior hypnosis, known as "fascination" or "psychotherapeutics." Modern treatments largely involve different types of imperative suggestion with or without hypnosis. However, the therapeutic application of suggestion in hypnosis to functional and other symptoms waned in the first half of the 20th century under the separate pressures of behaviorism and psychoanalysis. In recent decades suggestion in hypnosis has been more widely applied to treating functional neurologic symptoms. Suggestion is typically applied within the context of other treatment approaches, such as cognitive-behavioral, rehabilitative, or psychodynamic therapy. Suggestions are generally symptom-focused (designed to resolve a symptom) or exploratory (using methods such as revivification or age regression to explore experiences associated with symptom onset). The evidence base is dominated by case studies and series, with a paucity of randomized controlled trials. Future evaluation studies should allow for the fact that suggestion with or without hypnosis is a component of broader treatment interventions adapted to a wide range of symptoms and presentations. An important role of the concept of suggestion in the management of functional neurologic symptoms is to raise awareness of how interactions with clinicians and wider clinical contexts can alter expectancies and beliefs of patients in ways that influence the onset, course, and remission of symptoms.

Hypnosis as a model of functional neurologic disorders.

In the 19th century it was recognized that neurologic symptoms could be caused by "morbid ideation" as well as organic lesions. The subsequent observation that hysteric (now called "functional") symptoms could be produced and removed by hypnotic suggestion led Charcot to hypothesize that suggestion mediated the effects of ideas on hysteric symptoms through as yet unknown effects on brain activity. The advent of neuroimaging 100 years later revealed strikingly similar neural correlates in experiments matching functional symptoms with clinical analogs created by suggestion. Integrative models of suggested and functional symptoms regard these alterations in brain function as the endpoint of a broader set of changes in information processing due to suggestion. These accounts consider that suggestions alter experience by mobilizing representations from memory systems, and altering causal attributions, during preconscious processing which alters the content of what is provided to our highly edited subjective version of the world. Hypnosis as a model for functional symptoms draws attention to how radical alterations in experience and behavior can conform to the content of mental representations through effects on cognition and brain function. Experimental study of functional symptoms and their suggested counterparts in hypnosis reveals the distinct and shared processes through which this can occur.

Are You Suggesting That's My Hand? The Relation Between Hypnotic Suggestibility and the Rubber Hand Illusion.

Hypnotic suggestibility (HS) is the ability to respond automatically to suggestions and to experience alterations in perception and behavior. Hypnotically suggestible participants are also better able to focus and sustain their attention on an experimental stimulus. The present study explores the relation between HS and susceptibility to the rubber hand illusion (RHI). Based on previous research with visual illusions, it was predicted that higher HS would lead to a stronger RHI. Two behavioral output measures of the RHI, an implicit (proprioceptive drift) and an explicit (RHI questionnaire) measure, were correlated against HS scores. Hypnotic suggestibility correlated positively with the implicit RHI measure contributing to 30% of the variation. However, there was no relation between HS and the explicit RHI questionnaire measure, or with compliance control items. High hypnotic suggestibility may facilitate, via attentional mechanisms, the multisensory integration of visuoproprioceptive inputs that leads to greater perceptual mislocalization of a participant's hand. These results may provide insight into the multisensory brain mechanisms involved in our sense of embodiment.

Using suggestion to model different types of automatic writing.

Our sense of self includes awareness of our thoughts and movements, and our control over them. This feeling can be altered or lost in neuropsychiatric disorders as well as in phenomena such as "automatic writing" whereby writing is attributed to an external source. Here, we employed suggestion in highly hypnotically suggestible participants to model various experiences of automatic writing during a sentence completion task. Results showed that the induction of hypnosis, without additional suggestion, was associated with a small but significant reduction of control, ownership, and awareness for writing. Targeted suggestions produced a double dissociation between thought and movement components of writing, for both feelings of control and ownership, and additionally, reduced awareness of writing. Overall, suggestion produced selective alterations in the control, ownership, and awareness of thought and motor components of writing, thus enabling key aspects of automatic writing, observed across different clinical and cultural settings, to be modelled.

Frontotemporal white-matter microstructural abnormalities in adolescents with conduct disorder: a diffusion tensor imaging study.

BACKGROUND: Children with conduct disorder (CD) are at increased risk of developing antisocial personality disorder (ASPD) and psychopathy in adulthood. The biological basis for this is poorly understood. A preliminary diffusion tensor magnetic resonance imaging (DT-MRI) study of psychopathic antisocial adults reported significant differences from controls in the fractional anisotropy (FA) of the uncinate fasciculus (UF), a white-matter tract that connects the amygdala to the frontal lobe. However, it is unknown whether developmental abnormalities are present in the UF of younger individuals with CD. METHOD: We used DT-MRI tractography to investigate, for the first time, the microstructural integrity of the UF in adolescents with CD, and age-related differences in this tract. We compared FA and perpendicular diffusivity of the UF in 27 adolescents with CD and 16 healthy controls (12 to 19 years old) who did not differ significantly in age, IQ or substance use history. To confirm that these findings were specific to the UF, the same measurements were extracted from two non-limbic control tracts. Participants in the CD group had a history of serious aggressive and violent behaviour, including robbery, burglary, grievous bodily harm and sexual assault. RESULTS: Individuals with CD had a significantly increased FA (p = 0.006), and reduced perpendicular diffusivity (p = 0.002), in the left UF. Furthermore, there were significant age-related between-group differences in perpendicular diffusivity of the same tract (Z obs = 2.40, p = 0.01). Controls, but not those with CD, showed significant age-related maturation. There were no significant between-group differences in any measure within the control tracts. CONCLUSIONS: Adolescents with CD have significant differences in the 'connectivity' and maturation of UF.

Anatomy and aging of the amygdala and hippocampus in autism spectrum disorder: an in vivo magnetic resonance imaging study of Asperger syndrome.

It has been proposed that people with autism spectrum disorder (ASD) have abnormal morphometry and development of the amygdala and hippocampus (AH). However, previous reports are inconsistent, perhaps because they included people of different ASD diagnoses, ages, and health. We compared, using magnetic resonance imaging, the in vivo anatomy of the AH in 32 healthy individuals with Asperger syndrome (12-47 years) and 32 healthy controls who did not differ significantly in age or IQ. We measured bulk (gray + white matter) volume of the AH using manual tracing (MEASURE). We first compared the volume of AH between individuals with Asperger syndrome and controls and then investigated age-related differences. We compared differences in anatomy before, and after, correcting for whole brain size. There was no significant between group differences in whole brain volume. However, individuals with Asperger syndrome had a significantly larger raw bulk volume of total (P<0.01), right (P<0.01), and left amygdala (P<0.05); and when corrected for overall brain size, total (P<0.05), and right amygdala (P<0.01). There was a significant group difference in aging of left amygdala; controls, but not individuals with Asperger syndrome, had a significant age-related increase in volume (r = 0.486, P<0.01, and r = 0.007, P = 0.97, z = 1.995). There were no significant group differences in volume or age-related effects in hippocampus. Individuals with Asperger syndrome have significant differences from controls in bulk volume and aging of the amygdala.

Clinical and anatomical heterogeneity in autistic spectrum disorder: a structural MRI study.

BACKGROUND: Autistic spectrum disorder (ASD) is characterized by stereotyped/obsessional behaviours and social and communicative deficits. However, there is significant variability in the clinical phenotype; for example, people with autism exhibit language delay whereas those with Asperger syndrome do not. It remains unclear whether localized differences in brain anatomy are associated with variation in the clinical phenotype. METHOD: We used voxel-based morphometry (VBM) to investigate brain anatomy in adults with ASD. We included 65 adults diagnosed with ASD (39 with Asperger syndrome and 26 with autism) and 33 controls who did not differ significantly in age or gender. RESULTS: VBM revealed that subjects with ASD had a significant reduction in grey-matter volume of medial temporal, fusiform and cerebellar regions, and in white matter of the brainstem and cerebellar regions. Furthermore, within the subjects with ASD, brain anatomy varied with clinical phenotype. Those with autism demonstrated an increase in grey matter in frontal and temporal lobe regions that was not present in those with Asperger syndrome. CONCLUSIONS: Adults with ASD have significant differences from controls in the anatomy of brain regions implicated in behaviours characterizing the disorder, and this differs according to clinical subtype.

Altered connections on the road to psychopathy.

Psychopathy is strongly associated with serious criminal behaviour (for example, rape and murder) and recidivism. However, the biological basis of psychopathy remains poorly understood. Earlier studies suggested that dysfunction of the amygdala and/or orbitofrontal cortex (OFC) may underpin psychopathy. Nobody, however, has ever studied the white matter connections (such as the uncinate fasciculus (UF)) linking these structures in psychopaths. Therefore, we used in vivo diffusion tensor magnetic resonance imaging (DT-MRI) tractography to analyse the microstructural integrity of the UF in psychopaths (defined by a Psychopathy Checklist Revised (PCL-R) score of > or = 25) with convictions that included attempted murder, manslaughter, multiple rape with strangulation and false imprisonment. We report significantly reduced fractional anisotropy (FA) (P<0.003), an indirect measure of microstructural integrity, in the UF of psychopaths compared with age- and IQ-matched controls. We also found, within psychopaths, a correlation between measures of antisocial behaviour and anatomical differences in the UF. To confirm that these findings were specific to the limbic amygdala-OFC network, we also studied two 'non-limbic' control tracts connecting the posterior visual and auditory areas to the amygdala and the OFC, and found no significant between-group differences. Lastly, to determine that our findings in UF could not be totally explained by non-specific confounds, we carried out a post hoc comparison with a psychiatric control group with a past history of drug abuse and institutionalization. Our findings remained significant. Taken together, these results suggest that abnormalities in a specific amygdala-OFC limbic network underpin the neurobiological basis of psychopathy.

A study of psychiatrists' concepts of mental illness.

BACKGROUND: There are multiple models of mental illness that inform professional and lay understanding. Few studies have formally investigated psychiatrists' attitudes. We aimed to measure how a group of trainee psychiatrists understand familiar mental illnesses in terms of propositions drawn from different models. METHOD: We used a questionnaire study of a sample of trainees from South London and Maudsley National Health Service (NHS) Foundation Trust designed to assess attitudes across eight models of mental illness (e.g. biological, psychodynamic) and four psychiatric disorders. Methods for analysing repeated measures and a principal components analysis (PCA) were used. RESULTS: No one model was endorsed by all respondents. Model endorsement varied with disorder. Attitudes to schizophrenia were expressed with the greatest conviction across models. Overall, the 'biological' model was the most strongly endorsed. The first three components of the PCA (interpreted as dimensions around which psychiatrists, as a group, understand mental illness) accounted for 56% of the variance. Each main component was classified in terms of its distinctive combination of statements from different models: PC1 33% biological versus non-biological; PC2 12% 'eclectic' (combining biological, behavioural, cognitive and spiritual models); and PC3 10% psychodynamic versus sociological. CONCLUSIONS: Trainee psychiatrists are most committed to the biological model for schizophrenia, but in general are not exclusively committed to any one model. As a group, they organize their attitudes towards mental illness in terms of a biological/non-biological contrast, an 'eclectic' view and a psychodynamic/sociological contrast. Better understanding of how professional group membership influences attitudes may facilitate better multidisciplinary working.

Genetic variation in the serotonin transporter modulates neural system-wide response to fearful faces.

A distributed, serotonergically innervated neural system comprising extrastriate cortex, amygdala and ventral prefrontal cortex is critical for identification of socially relevant emotive stimuli. The extent to which a genetic variation of serotonin transporter gene 5-HTTLPR impacts functional connectivity between the amygdala and the other components of this neural system remains little examined. In our study, neural activity was measured using event-related functional magnetic resonance imaging in 29 right-handed, white Caucasian healthy subjects as they viewed mild or prototypical fearful and neutral facial expressions. 5-HTTLPR genotype was classified as homozygous for the short allele (S/S), homozygous for the long allele (L/L) or heterozygous (S/L). S/S showed greater activity than L/L within right fusiform gyrus (FG) to prototypically fearful faces. To these fearful faces, S/S more than other genotype subgroups showed significantly greater positive functional connectivity between right amygdala and FG and between right FG and right ventrolateral prefrontal cortex (VLPFC). There was a positive association between measure of psychoticism and degree of functional connectivity between right FG and right VLPFC in response to prototypically fearful faces. Our data are the first to show that genotypic variation in 5-HTTLPR modulates both the amplitude within and the functional connectivity between different components of the visual object-processing neural system to emotionally salient stimuli. These effects may underlie the vulnerability to mood and anxiety disorders potentially triggered by socially salient, emotional cues in individuals with the S allele of 5-HTTLPR.