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1.
Neuroimage ; 297: 120724, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38971486

ABSTRACT

Psychopathy is characterized by antisocial behavior, poor behavioral control and lacking empathy, and structural alterations in the corresponding neural circuits. Molecular brain basis of psychopathy remains poorly characterized. Here we studied type 2 dopamine receptor (D2R) and mu-opioid receptor (MOR) availability in convicted violent offenders with high psychopathic traits (n = 11) and healthy matched controls (n = 17) using positron emission tomography (PET). D2R were measured with radioligand [11C]raclopride and MORs with radioligand [11C]carfentanil. Psychopathic subjects had lowered D2R availability in caudate and putamen, and striatal D2R availability was also associated with degree of psychopathic traits in this prisoner sample. No group differences were found in MOR availability, although in the prisoner sample, psychopathic traits were negatively correlated with MOR availability in the amygdala and nucleus accumbens. We conclude that D2R signaling could be the putative neuromolecular pathway for psychopathy, whereas evidence for alterations in the MOR system is more limited.


Subject(s)
Antisocial Personality Disorder , Criminals , Positron-Emission Tomography , Receptors, Dopamine D2 , Violence , Humans , Receptors, Dopamine D2/metabolism , Male , Antisocial Personality Disorder/diagnostic imaging , Antisocial Personality Disorder/metabolism , Adult , Positron-Emission Tomography/methods , Receptors, Opioid, mu/metabolism , Raclopride/pharmacokinetics , Young Adult , Brain/metabolism , Brain/diagnostic imaging , Fentanyl/analogs & derivatives
2.
Neuroimage ; 273: 120082, 2023 06.
Article in English | MEDLINE | ID: mdl-37030414

ABSTRACT

Laughter and crying are universal signals of prosociality and distress, respectively. Here we investigated the functional brain basis of perceiving laughter and crying using naturalistic functional magnetic resonance imaging (fMRI) approach. We measured haemodynamic brain activity evoked by laughter and crying in three experiments with 100 subjects in each. The subjects i) viewed a 20-minute medley of short video clips, and ii) 30 min of a full-length feature film, and iii) listened to 13.5 min of a radio play that all contained bursts of laughter and crying. Intensity of laughing and crying in the videos and radio play was annotated by independent observes, and the resulting time series were used to predict hemodynamic activity to laughter and crying episodes. Multivariate pattern analysis (MVPA) was used to test for regional selectivity in laughter and crying evoked activations. Laughter induced widespread activity in ventral visual cortex and superior and middle temporal and motor cortices. Crying activated thalamus, cingulate cortex along the anterior-posterior axis, insula and orbitofrontal cortex. Both laughter and crying could be decoded accurately (66-77% depending on the experiment) from the BOLD signal, and the voxels contributing most significantly to classification were in superior temporal cortex. These results suggest that perceiving laughter and crying engage distinct neural networks, whose activity suppresses each other to manage appropriate behavioral responses to others' bonding and distress signals.


Subject(s)
Crying , Laughter , Humans , Crying/physiology , Brain/physiology , Brain Mapping , Gyrus Cinguli/physiology
3.
Neuroimage ; 272: 120025, 2023 05 15.
Article in English | MEDLINE | ID: mdl-36958619

ABSTRACT

Humans rapidly extract diverse and complex information from ongoing social interactions, but the perceptual and neural organization of the different aspects of social perception remains unresolved. We showed short movie clips with rich social content to 97 healthy participants while their haemodynamic brain activity was measured with fMRI. The clips were annotated moment-to-moment for a large set of social features and 45 of the features were evaluated reliably between annotators. Cluster analysis of the social features revealed that 13 dimensions were sufficient for describing the social perceptual space. Three different analysis methods were used to map the social perceptual processes in the human brain. Regression analysis mapped regional neural response profiles for different social dimensions. Multivariate pattern analysis then established the spatial specificity of the responses and intersubject correlation analysis connected social perceptual processing with neural synchronization. The results revealed a gradient in the processing of social information in the brain. Posterior temporal and occipital regions were broadly tuned to most social dimensions and the classifier revealed that these responses showed spatial specificity for social dimensions; in contrast Heschl gyri and parietal areas were also broadly associated with different social signals, yet the spatial patterns of responses did not differentiate social dimensions. Frontal and subcortical regions responded only to a limited number of social dimensions and the spatial response patterns did not differentiate social dimension. Altogether these results highlight the distributed nature of social processing in the brain.


Subject(s)
Brain Mapping , Brain , Humans , Brain Mapping/methods , Brain/diagnostic imaging , Brain/physiology , Occipital Lobe/physiology , Magnetic Resonance Imaging , Social Perception
4.
Soc Cogn Affect Neurosci ; 18(1)2023 03 22.
Article in English | MEDLINE | ID: mdl-36847146

ABSTRACT

Difficulties in social interactions characterize both autism and schizophrenia and are correlated in the neurotypical population. It is unknown whether this represents a shared etiology or superficial phenotypic overlap. Both conditions exhibit atypical neural activity in response to the perception of social stimuli and decreased neural synchronization between individuals. This study investigated if neural activity and neural synchronization associated with biological motion perception are differentially associated with autistic and schizotypal traits in the neurotypical population. Participants viewed naturalistic social interactions while hemodynamic brain activity was measured with fMRI, which was modeled against a continuous measure of the extent of biological motion. General linear model analysis revealed that biological motion perception was associated with neural activity across the action observation network. However, intersubject phase synchronization analysis revealed neural activity to be synchronized between individuals in occipital and parietal areas but desynchronized in temporal and frontal regions. Autistic traits were associated with decreased neural activity (precuneus and middle cingulate gyrus), and schizotypal traits were associated with decreased neural synchronization (middle and inferior frontal gyri). Biological motion perception elicits divergent patterns of neural activity and synchronization, which dissociate autistic and schizotypal traits in the general population, suggesting that they originate from different neural mechanisms.


Subject(s)
Autistic Disorder , Brain , Schizophrenia , Schizophrenic Psychology , Social Interaction , Social Perception , Adult , Female , Humans , Male , Young Adult , Autistic Disorder/diagnostic imaging , Autistic Disorder/psychology , Brain/blood supply , Brain/diagnostic imaging , Brain/physiopathology , Hemodynamics , Magnetic Resonance Imaging , Schizophrenia/diagnostic imaging , Schizophrenia/physiopathology , Finland
5.
Hum Brain Mapp ; 44(6): 2543-2556, 2023 04 15.
Article in English | MEDLINE | ID: mdl-36773282

ABSTRACT

Sex differences in brain activity evoked by sexual stimuli remain elusive despite robust evidence for stronger enjoyment of and interest toward sexual stimuli in men than in women. To test whether visual sexual stimuli evoke different brain activity patterns in men and women, we measured hemodynamic brain activity induced by visual sexual stimuli in two experiments with 91 subjects (46 males). In one experiment, the subjects viewed sexual and nonsexual film clips, and dynamic annotations for nudity in the clips were used to predict hemodynamic activity. In the second experiment, the subjects viewed sexual and nonsexual pictures in an event-related design. Men showed stronger activation than women in the visual and prefrontal cortices and dorsal attention network in both experiments. Furthermore, using multivariate pattern classification we could accurately predict the sex of the subject on the basis of the brain activity elicited by the sexual stimuli. The classification generalized across the experiments indicating that the sex differences were task-independent. Eye tracking data obtained from an independent sample of subjects (N = 110) showed that men looked longer than women at the chest area of the nude female actors in the film clips. These results indicate that visual sexual stimuli evoke discernible brain activity patterns in men and women which may reflect stronger attentional engagement with sexual stimuli in men.


Subject(s)
Arousal , Sexual Behavior , Humans , Female , Male , Arousal/physiology , Sexual Behavior/physiology , Sex Characteristics , Pleasure , Perception
6.
Philos Trans R Soc Lond B Biol Sci ; 377(1863): 20210181, 2022 11 07.
Article in English | MEDLINE | ID: mdl-36126675

ABSTRACT

Laughter is a contagious prosocial signal that conveys bonding motivation; adult crying conversely communicates desire for social proximity by signalling distress. Endogenous mu-opioid receptors (MORs) modulate sociability in humans and non-human primates. In this combined PET-fMRI study (n = 17), we tested whether central MOR tone is associated with regional brain responses to social signals of laughter and crying. MOR availability was measured with positron emission tomography (PET) using the high-affinity agonist radioligand [11C]carfentanil. Haemodynamic responses to social laughter and crying vocalizations were measured using functional magnetic resonance imaging (fMRI). Social laughter evoked activation in the auditory cortex, insula, cingulate cortex, amygdala, primary and secondary somatosensory cortex, and primary and secondary motor cortex; crying sounds led to more restricted activation in the auditory cortex and nearby areas. MOR availability was negatively correlated with the haemodynamic responses to social laughter in the primary and secondary somatosensory cortex, primary and secondary motor cortex, posterior insula, posterior cingulate cortex, precuneus, cuneus, temporal gyri and lingual gyrus. For crying-evoked activations, MOR availability was negatively correlated with medial and lateral prefrontal haemodynamic responses. Altogether our findings highlight the role of the MOR system in modulating acute brain responses to both positive and negative social signals. This article is part of the theme issue 'Cracking the laugh code: laughter through the lens of biology, psychology and neuroscience'.


Subject(s)
Brain Mapping , Laughter , Adult , Brain/physiology , Humans , Laughter/physiology , Magnetic Resonance Imaging/methods , Positron-Emission Tomography
7.
Cereb Cortex ; 33(2): 374-384, 2022 12 20.
Article in English | MEDLINE | ID: mdl-35332920

ABSTRACT

Psychopathy and autism are both associated with aberrant social skills and empathy, yet only psychopaths are markedly antisocial and violent. Here, we compared the functional neural alterations underlying these two groups that both have aberrant empathetic abilities but distinct behavioral phenotypes. We studied 19 incarcerated male offenders with high psychopathic traits, 20 males with high-functioning autism, and 19 age-matched healthy controls. All groups underwent functional magnetic resonance imaging while they viewed dynamic happy, angry, and disgusted faces or listened to laughter and crying sounds. Psychopathy was associated with reduced somatomotor responses to almost all expressions, while participants with autism demonstrated less marked and emotion-specific alterations in the somatomotor area. These data suggest that psychopathy and autism involve both common and distinct functional alterations in the brain networks involved in the socioemotional processing. The alterations are more profound in psychopathy, possibly reflecting the more severely disturbed socioemotional brain networks in this population.


Subject(s)
Autistic Disorder , Humans , Male , Autistic Disorder/diagnostic imaging , Emotions/physiology , Brain/diagnostic imaging , Empathy , Brain Mapping , Magnetic Resonance Imaging
8.
CNS Spectr ; 27(6): 716-723, 2022 12.
Article in English | MEDLINE | ID: mdl-34369340

ABSTRACT

BACKGROUND: The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia. METHODS: Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects. RESULTS: There was a 3-year later age at onset for females (P < .001) and lower rates of negative symptoms (P < .01) and higher depression/anxiety measures (P < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness. DISCUSSION: Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.


Subject(s)
Schizophrenia , Humans , Female , Male , Schizophrenia/diagnosis , Schizophrenia/epidemiology , Age of Onset , Diagnostic and Statistical Manual of Mental Disorders
9.
Transl Psychiatry ; 11(1): 259, 2021 05 01.
Article in English | MEDLINE | ID: mdl-33934103

ABSTRACT

Obesity is a growing burden to health and the economy worldwide. Obesity is associated with central µ-opioid receptor (MOR) downregulation and disruption of the interaction between MOR and dopamine D2 receptor (D2R) system in the ventral striatum. Weight loss recovers MOR function, but it remains unknown whether it also recovers aberrant opioid-dopamine interaction. Here we addressed this issue by studying 20 healthy non-obese and 25 morbidly obese women (mean BMI 41) eligible for bariatric surgery. Brain MOR and D2R availability were measured using positron emission tomography (PET) with [11C]carfentanil and [11C]raclopride, respectively. Either Roux-en-Y gastric bypass or sleeve gastrectomy was performed on obese subjects according to standard clinical treatment. 21 obese subjects participated in the postoperative PET scanning six months after bariatric surgery. In the control subjects, MOR and D2R availabilities were associated in the ventral striatum (r = .62) and dorsal caudate (r = .61). Preoperatively, the obese subjects had disrupted association in the ventral striatum (r = .12) but the unaltered association in dorsal caudate (r = .43). The association between MOR and D2R availabilities in the ventral striatum was recovered (r = .62) among obese subjects following the surgery-induced weight loss. Bariatric surgery and concomitant weight loss recover the interaction between MOR and D2R in the ventral striatum in the morbidly obese. Consequently, the dysfunctional opioid-dopamine interaction in the ventral striatum is likely associated with an obese phenotype and may mediate excessive energy uptake. Striatal opioid-dopamine interaction provides a feasible target for pharmacological and behavioral interventions for treating obesity.


Subject(s)
Bariatric Surgery , Obesity, Morbid , Analgesics, Opioid , Dopamine , Female , Humans , Obesity, Morbid/surgery , Positron-Emission Tomography , Receptors, Dopamine D2 , Weight Loss
10.
Cereb Cortex ; 31(9): 4104-4114, 2021 07 29.
Article in English | MEDLINE | ID: mdl-33834203

ABSTRACT

Psychopathy is characterized by persistent antisocial behavior, impaired empathy, and egotistical traits. These traits vary also in normally functioning individuals. Here, we tested whether such antisocial personalities are associated with similar structural and neural alterations as those observed in criminal psychopathy. Subjects were 100 non-convicted well-functioning individuals, 19 violent male offenders, and 19 matched controls. Subjects underwent T1-weighted magnetic resonance imaging and viewed movie clips with varying violent content during functional magnetic resonance imaging. Psychopathic traits were evaluated with Levenson Self-Report Psychopathy Scale (controls) and Psychopathy Checklist-Revised (offenders). Psychopathic offenders had lower gray matter density (GMD) in orbitofrontal cortex and anterior insula. In the community sample, affective psychopathy traits were associated with lower GMD in the same areas. Viewing violence increased brain activity in periaqueductal grey matter, thalamus, somatosensory, premotor, and temporal cortices. Psychopathic offenders had increased responses to violence in thalamus and orbitofrontal, insular, and cingulate cortices. In the community sample, impulsivity-related psychopathy traits were positively associated with violence-elicited responses in similar areas. We conclude that brain characteristics underlying psychopathic spectrum in violent psychopathy are related to those observed in well-functioning individuals with asocial personality features.


Subject(s)
Antisocial Personality Disorder/diagnostic imaging , Antisocial Personality Disorder/psychology , Brain/diagnostic imaging , Criminals/psychology , Adult , Affect , Brain Mapping , Female , Gray Matter/diagnostic imaging , Healthy Volunteers , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Photic Stimulation , Self Report , Violence , Young Adult
11.
JCI Insight ; 6(10)2021 05 24.
Article in English | MEDLINE | ID: mdl-33848266

ABSTRACT

Bariatric surgery is the most effective method for weight loss in morbid obesity. There is significant individual variability in the weight loss outcomes, yet factors leading to postoperative weight loss or weight regain remain elusive. Alterations in the µ-opioid receptor (MOR) and dopamine D2 receptor (D2R) systems are associated with obesity and appetite control, and the magnitude of initial brain receptor system perturbation may predict long-term surgical weight loss outcomes. We tested this hypothesis by studying 19 morbidly obese women (mean BMI 40) scheduled to undergo bariatric surgery. We measured their preoperative MOR and D2R availabilities using positron emission tomography with [11C]carfentanil and [11C]raclopride, respectively, and then assessed their weight development association with regional MOR and D2R availabilities at 24-month follow-up. MOR availability in the amygdala consistently predicted weight development throughout the follow-up period, but no associations were found for D2R. This is the first study to our knowledge to demonstrate that neuroreceptor markers prior to bariatric surgery are associated with postoperative weight development. Postoperative weight regain may derive from dysfunction in the opioid system, and weight loss outcomes after bariatric surgery may be partially predicted based on preoperative brain receptor availability, opening up new potential for treatment possibilities.


Subject(s)
Brain , Obesity, Morbid , Receptors, Opioid, mu , Weight Gain/physiology , Adult , Bariatric Surgery , Brain/diagnostic imaging , Brain/metabolism , Female , Humans , Middle Aged , Neuroimaging , Obesity, Morbid/diagnostic imaging , Obesity, Morbid/metabolism , Obesity, Morbid/surgery , Positron-Emission Tomography , Preoperative Period , Receptors, Dopamine D2/analysis , Receptors, Dopamine D2/metabolism , Receptors, Opioid, mu/analysis , Receptors, Opioid, mu/metabolism , Weight Loss/physiology
12.
CNS Spectr ; 26(3): 290-298, 2021 06.
Article in English | MEDLINE | ID: mdl-32290897

ABSTRACT

BACKGROUND: The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model. METHODS: Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed. RESULTS: The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage. CONCLUSIONS: The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct "cores" of schizophrenia, the "Positive" and the "Negative," while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.


Subject(s)
Schizophrenia/diagnosis , Schizophrenic Psychology , Adolescent , Adult , Aged , Aged, 80 and over , Disease Progression , Female , Humans , Male , Middle Aged
13.
Cereb Cortex ; 31(5): 2549-2560, 2021 03 31.
Article in English | MEDLINE | ID: mdl-33367590

ABSTRACT

Music can induce strong subjective experience of emotions, but it is debated whether these responses engage the same neural circuits as emotions elicited by biologically significant events. We examined the functional neural basis of music-induced emotions in a large sample (n = 102) of subjects who listened to emotionally engaging (happy, sad, fearful, and tender) pieces of instrumental music while their hemodynamic brain activity was measured with functional magnetic resonance imaging (fMRI). Ratings of the four categorical emotions and liking were used to predict hemodynamic responses in general linear model (GLM) analysis of the fMRI data. Multivariate pattern analysis (MVPA) was used to reveal discrete neural signatures of the four categories of music-induced emotions. To map neural circuits governing non-musical emotions, the subjects were scanned while viewing short emotionally evocative film clips. The GLM revealed that most emotions were associated with activity in the auditory, somatosensory, and motor cortices, cingulate gyrus, insula, and precuneus. Fear and liking also engaged the amygdala. In contrast, the film clips strongly activated limbic and cortical regions implicated in emotional processing. MVPA revealed that activity in the auditory cortex and primary motor cortices reliably discriminated the emotion categories. Our results indicate that different music-induced basic emotions have distinct representations in regions supporting auditory processing, motor control, and interoception but do not strongly rely on limbic and medial prefrontal regions critical for emotions with survival value.


Subject(s)
Auditory Cortex/diagnostic imaging , Emotions/physiology , Motor Cortex/diagnostic imaging , Music/psychology , Adult , Amygdala/diagnostic imaging , Amygdala/physiology , Auditory Cortex/physiology , Brain/diagnostic imaging , Brain/physiology , Female , Functional Neuroimaging , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/physiology , Humans , Insular Cortex/diagnostic imaging , Insular Cortex/physiology , Magnetic Resonance Imaging , Male , Middle Aged , Motor Cortex/physiology , Parietal Lobe/diagnostic imaging , Parietal Lobe/physiology , Somatosensory Cortex/diagnostic imaging , Somatosensory Cortex/physiology , Young Adult
14.
Neuroimage ; 216: 116522, 2020 08 01.
Article in English | MEDLINE | ID: mdl-31926280

ABSTRACT

Fear protects organisms by increasing vigilance and preparedness, and by coordinating survival responses during life-threatening encounters. The fear circuit must thus operate on multiple timescales ranging from preparatory sustained alertness to acute fight-or-flight responses. Here we studied the brain basis of sustained and acute fear using naturalistic functional magnetic resonance imaging (fMRI) enabling analysis of different time-scales of fear responses. Subjects (N â€‹= â€‹37) watched feature-length horror movies while their hemodynamic brain activity was measured with fMRI. Time-variable intersubject correlation (ISC) was used to quantify the reliability of brain activity across participants, and seed-based phase synchronization was used for characterizing dynamic connectivity. Subjective ratings of fear were used to assess how synchronization and functional connectivity varied with emotional intensity. These data suggest that acute and sustained fear are supported by distinct neural pathways, with sustained fear amplifying mainly sensory responses, and acute fear increasing activity in brainstem, thalamus, amygdala and cingulate cortices. Sustained fear increased ISC in regions associated with acute fear, and also amplified functional connectivity within this network. The results were replicated in an independent experiment with a different subject sample and stimulus movie. The functional interplay between cortical networks involved in sustained anticipation of, and acute response to, threat involves a complex and dynamic interaction that depends on the proximity of threat, and the need to employ threat appraisals and vigilance for decision making and response selection.


Subject(s)
Anticipation, Psychological/physiology , Brain/physiology , Fear/physiology , Fear/psychology , Motion Pictures , Nerve Net/physiology , Adult , Brain/diagnostic imaging , Female , Humans , Magnetic Resonance Imaging/methods , Male , Nerve Net/diagnostic imaging , Photic Stimulation/methods , Young Adult
15.
Int J Neuropsychopharmacol ; 22(11): 681-697, 2019 11 01.
Article in English | MEDLINE | ID: mdl-31563956

ABSTRACT

INTRODUCTION: A specific clinically relevant staging model for schizophrenia has not yet been developed. The aim of the current study was to evaluate the factor structure of the PANSS and develop such a staging method. METHODS: Twenty-nine centers from 25 countries contributed 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Analysis of covariance, Exploratory Factor Analysis, Discriminant Function Analysis, and inspection of resultant plots were performed. RESULTS: Exploratory Factor Analysis returned 5 factors explaining 59% of the variance (positive, negative, excitement/hostility, depression/anxiety, and neurocognition). The staging model included 4 main stages with substages that were predominantly characterized by a single domain of symptoms (stage 1: positive; stages 2a and 2b: excitement/hostility; stage 3a and 3b: depression/anxiety; stage 4a and 4b: neurocognition). There were no differences between sexes. The Discriminant Function Analysis developed an algorithm that correctly classified >85% of patients. DISCUSSION: This study elaborates a 5-factor solution and a clinical staging method for patients with schizophrenia. It is the largest study to address these issues among patients who are more likely to remain affiliated with mental health services for prolonged periods of time.


Subject(s)
Disease Progression , Psychiatric Status Rating Scales/statistics & numerical data , Schizophrenia/diagnosis , Adult , Europe , Factor Analysis, Statistical , Female , Humans , Male , Middle Aged , Nigeria , Schizophrenia/classification , Schizophrenia/physiopathology , Sotos Syndrome , Young Adult
16.
Cereb Cortex ; 29(9): 4006-4016, 2019 08 14.
Article in English | MEDLINE | ID: mdl-30475982

ABSTRACT

Emotions can be characterized by dimensions of arousal and valence (pleasantness). While the functional brain bases of emotional arousal and valence have been actively investigated, the neuromolecular underpinnings remain poorly understood. We tested whether the opioid and dopamine systems involved in reward and motivational processes would be associated with emotional arousal and valence. We used in vivo positron emission tomography to quantify µ-opioid receptor and type 2 dopamine receptor (MOR and D2R, respectively) availability in brains of 35 healthy adult females. During subsequent functional magnetic resonance imaging carried out to monitor hemodynamic activity, the subjects viewed movie scenes of varying emotional content. Arousal and valence were associated with hemodynamic activity in brain regions involved in emotional processing, including amygdala, thalamus, and superior temporal sulcus. Cerebral MOR availability correlated negatively with the hemodynamic responses to arousing scenes in amygdala, hippocampus, thalamus, and hypothalamus, whereas no positive correlations were observed in any brain region. D2R availability-here reliably quantified only in striatum-was not associated with either arousal or valence. These results suggest that emotional arousal is regulated by the MOR system, and that cerebral MOR availability influences brain activity elicited by arousing stimuli.


Subject(s)
Arousal , Brain/physiology , Emotions/physiology , Receptors, Dopamine D2/metabolism , Receptors, Opioid, mu/metabolism , Adult , Brain/metabolism , Brain Mapping , Female , Humans , Magnetic Resonance Imaging , Middle Aged , Positron-Emission Tomography , Young Adult
17.
Int J Obes (Lond) ; 43(9): 1675-1680, 2019 09.
Article in English | MEDLINE | ID: mdl-30518825

ABSTRACT

STUDY AIM: Retinal microvasculature changes reflect systemic small vessel damage from obesity. The impact of bariatric surgery induced weight loss on the microvasculature is relatively unknown. We hypothesized that weight loss following bariatric surgery would be associated with improved structural changes in the retinal microvasculature, reflecting an overall improvement in microvascular health. METHODS: The study included 22 obese subjects scheduled for bariatric surgery (laparoscopic Roux-en-Y gastric bypass or a sleeve gastrectomy) and 15 lean, age-matched controls. Ophthalmic examination, including fundus photography, was performed at baseline and 6-months. Retinal microvasculature caliber was analysed quantitatively using a semi-automated computer program and summarized as central retinal artery equivalent (CRAE) and venular equivalent (CRVE). RESULTS: Mean weight loss at 6 months was 26.1 kg ± 8 kg in the bariatric surgery group. Retinal artery caliber increased (136.0 ± 1.4 to 141.4 ± 1.4 µm, p = 0.013) and venular caliber decreased (202.9 ± 1.9 to 197.3 ± 1.9 µm, p = 0.046) in the bariatric surgery group by 6 months, with no change in arteriolar (136.6 ± 1.1 to 134.5 ± 1.2, p = 0.222) or venular (195.1 ± 2.1 to 193.3 ± 2.2, p = 0.550) caliber in the control group. The arteriolar to venular ratio increased in the bariatric surgery group, with no change in the control group at 6 months. CONCLUSIONS: The findings suggest obesity-related microvascular changes are reversible after bariatric surgery-induced weight loss. The capacity for the retinal microvasculature to improve following bariatric surgery suggests plasticity of the human microvasculature early in the disease course.


Subject(s)
Bariatric Surgery/statistics & numerical data , Microvessels/pathology , Obesity, Morbid , Retinal Vessels/pathology , Adult , Female , Humans , Middle Aged , Obesity, Morbid/epidemiology , Obesity, Morbid/pathology , Obesity, Morbid/surgery , Prospective Studies , Treatment Outcome , Weight Loss/physiology
18.
Acta Ophthalmol ; 96(8): 849-852, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30238690

ABSTRACT

PURPOSE: Study purpose was to investigate the effects of bariatric surgery on intraocular pressure (IOP) and other ophthalmic parameters in a prospective observational follow-up study. METHODS: Ophthalmic examination was performed on 22 obese women before and 6 months after bariatric surgery. A control group of 15 non-obese age-matched women were studied twice 6 months apart. IOP was measured with the Goldmann applanation tonometer (GAT) and the Pascal dynamic contour tonometer (PDCT). None of the subjects had glaucoma. RESULTS: Average weight loss 6 months after bariatric surgery was 25 ±8 kg, (p < 0.05). Visual acuity (VA), pachymetry and systolic as well as diastolic blood pressures did not differ between the obese and control groups and no change between the visits was detected. At baseline, IOP was significantly higher in the obese group than in the controls (16.6 ± 3.0 mmHg GAT and 18.1 ± 2.2 mmHg PDCT compared with 14.3 ± 1.5 mmHg GAT and 16.5 ± 1.9 mmHg PDCT respectively). After bariatric surgery, IOP was significantly lower (15.2 ± 2.7 mmHg GAT and 16.5 ± 2.0 mmHg PDCT, p < 0.05) and no significant difference was detected between the operated and control groups. In the whole data at baseline, IOP correlated with weight, body mass index, waist circumference, body fat per cent and systolic blood pressure values. CONCLUSION: Intraocular pressure (IOP) is significantly higher in obese women than in non-obese age-matched controls. Obese subjects had a decrease in IOP after bariatric surgery with no change in IOP in the control group. This change in obese group may be related to weight loss. Different measures of obesity correlated with IOP at baseline.


Subject(s)
Bariatric Surgery , Intraocular Pressure/physiology , Obesity/surgery , Adolescent , Adult , Body Weight , Female , Follow-Up Studies , Humans , Male , Middle Aged , Obesity/physiopathology , Postoperative Period , Prospective Studies , Tonometry, Ocular , Young Adult
19.
Psychiatry Res Neuroimaging ; 276: 41-45, 2018 06 30.
Article in English | MEDLINE | ID: mdl-29655552

ABSTRACT

Both morbid obesity and binge eating disorder (BED) have previously been linked with aberrant brain opioid function. Behaviorally these two conditions are however different suggesting also differences in neurotransmitter function. Here we directly compared mu-opioid receptor (MOR) availability between morbidly obese and BED subjects. Seven BED and nineteen morbidly obese (non-BED) patients, and thirty matched control subjects underwent positron emission tomography (PET) with MOR-specific ligand [11C]carfentanil. Both subjects with morbid obesity and BED had widespread reduction in [11C]carfentanil binding compared to control subjects. However, there was no significant difference in brain MOR binding between subjects with morbid obesity and BED. Thus, our results indicate that there is common brain opioid abnormality in behaviorally different eating disorders involving obesity.


Subject(s)
Binge-Eating Disorder/metabolism , Brain/metabolism , Obesity, Morbid/metabolism , Receptors, Opioid, mu/metabolism , Adult , Analgesics, Opioid , Binge-Eating Disorder/diagnostic imaging , Brain/diagnostic imaging , Female , Fentanyl/analogs & derivatives , Humans , Male , Middle Aged , Obesity, Morbid/diagnostic imaging , Positron-Emission Tomography
20.
Diabetes Obes Metab ; 20(6): 1384-1390, 2018 06.
Article in English | MEDLINE | ID: mdl-29352513

ABSTRACT

AIMS: Bariatric surgery is the most effective treatment to tackle morbid obesity and type 2 diabetes, but the mechanisms of action are still unclear. The objective of this study was to investigate the effects of bariatric surgery on intestinal fatty acid (FA) uptake and blood flow. MATERIALS AND METHODS: We recruited 27 morbidly obese subjects, of whom 10 had type 2 diabetes and 15 were healthy age-matched controls. Intestinal blood flow and fatty acid uptake from circulation were measured during fasting state using positron emission tomography (PET). Obese subjects were re-studied 6 months after bariatric surgery. The mucosal location of intestinal FA retention was verified in insulin resistant mice with autoradiography. RESULTS: Compared to lean subjects, morbidly obese subjects had higher duodenal and jejunal FA uptake (P < .001) but similar intestinal blood flow (NS). Within 6 months after bariatric surgery, obese subjects had lost 24% of their weight and 7/10 diabetic subjects were in remission. Jejunal FA uptake was further increased (P < .03). Conversely, bariatric surgery provoked a decrease in jejunal blood flow (P < .05) while duodenal blood flow was preserved. Animal studies showed that FAs were taken up into enterocytes, for the most part, but were also transferred, in part, into the lumen. CONCLUSIONS: In the obese, the small intestine actively takes up FAs from circulation and FA uptake remains higher than in controls post-operatively. Intestinal blood flow was not enhanced before or after bariatric surgery, suggesting that enhanced intestinal FA metabolism is not driven by intestinal perfusion.


Subject(s)
Absorption, Physiological , Diabetes Mellitus, Type 2/metabolism , Fatty Acids, Nonesterified/metabolism , Intestinal Absorption , Intestinal Mucosa/metabolism , Intestine, Small/metabolism , Obesity, Morbid/metabolism , Adult , Animals , Bariatric Surgery , Body Mass Index , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/therapy , Dietary Fats/metabolism , Fatty Acids, Nonesterified/blood , Female , Fluorine Radioisotopes , Glucose Intolerance/blood , Glucose Intolerance/complications , Glucose Intolerance/metabolism , Glucose Intolerance/therapy , Humans , Insulin Resistance , Intestinal Mucosa/blood supply , Intestinal Mucosa/diagnostic imaging , Intestine, Small/blood supply , Intestine, Small/diagnostic imaging , Mice , Mice, Knockout , Middle Aged , Obesity, Morbid/complications , Obesity, Morbid/surgery , Obesity, Morbid/therapy , Positron-Emission Tomography , Regional Blood Flow , Weight Loss , Weight Reduction Programs
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