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| 2. |
- Castensson, Anja, et al.
(författare)
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Decrease of serotonin receptor 2C in schizophrenia brains identified by high-resolution mRNA expression analysis
- 2003
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 54:11, s. 1212-1221
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Tidskriftsartikel (refereegranskat)abstract
- Background: RNA expression profiling can provide hints for the selection of candidate susceptibility genes, for formulation of hypotheses about the development of a disease, and/or for selection of candidate gene targets for novel drug development. We measured messenger RNA expression levels of 16 candidate genes in brain samples from 55 schizophrenia patients and 55 controls. This is the largest sample so far used to identify genes differentially expressed in schizophrenia brains.Methods: We used a sensitive real-time polymerase chain reaction methodology and a novel statistical approach, including the development of a linear model of analysis of covariance type.Results: We found two genes differentially expressed: monoamine oxidase B was significantly increased in schizophrenia brain (p = .001), whereas one of the serotonin receptor genes, serotonin receptor 2C, was significantly decreased (p = .001). Other genes, previously proposed to be differentially expressed in schizophrenia brain, were invariant in our analysis.Conclusions: The differential expression of serotonin receptor 2C is particularly relevant for the development of new atypical antipsychotic drugs. The strategy presented here is useful to evaluate hypothesizes for the development of the disease proposed by other investigators.
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| 3. |
- Falck-Ytter, Terje, Professor, 1979-, et al.
(författare)
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Social attention : Developmental foundations and relevance for autism spectrum disorder
- 2023
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 94:1, s. 8-17
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Tidskriftsartikel (refereegranskat)abstract
- The use of the term Social Attention (SA) in the cognitive neuroscience and developmental psychopathology literature has increased exponentially in recent years, in part motivated by the aim to understand the early development of autism spectrum disorder (ASD). Unfortunately, theoretical discussions around the term have lagged behind its various uses. Here, we evaluate SA through a review of key candidate SA phenotypes emerging early in life, from newborn gaze cueing and preference for face-like configurations to later emerging skills such as joint attention. We argue that most of the considered SA phenotypes are unlikely to represent unique socio-attentional processes but have to be understood in the broader context of bottom-up and emerging top-down (domain-general) attention. Some types of SA behaviors (e.g., initiation of joint attention) are linked to the early development of ASD, but this may reflect differences in social motivation rather than attention per se. Several SA candidates are not linked to ASD early in life, including the ones that may represent uniquely socio-attentional processes (e.g., orienting to faces, predicting others’ manual action goals). Although SA may be a useful super-ordinate category under which one can organize certain research questions, the widespread use of the term without proper definition is problematic. Characterizing gaze patterns and visual attention in infants at elevated likelihood for ASD in social contexts may facilitate early detection, but conceptual clarity regarding the underlying processes at play are needed to sharpen research questions and identify potential targets for early intervention.
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| 4. |
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| 5. |
- Frick, Andreas, et al.
(författare)
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Classifying social anxiety disorder using multivoxel pattern analyses of brain function and structure
- 2014
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 75:9, s. 358S-358S
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Tidskriftsartikel (refereegranskat)abstract
- Functional neuroimaging of social anxiety disorder (SAD) support altered neural activation to threat-provoking stimuli focally in the fear network, while structural differences are distributed over the temporal and frontal cortices as well as limbic structures. Previous neuroimaging studies have investigated the brain at the voxel level using mass-univariate methods which do not enable detection of more complex patterns of activity and structural alterations that may separate SAD from healthy individuals. Support vector machine (SVM) is a supervised machine learning method that capitalizes on brain activation and structural patterns to classify individuals. The aim of this study was to investigate if it is possible to discriminate SAD patients (n = 14) from healthy controls (n = 12) using SVM based on (1) functional magnetic resonance imaging during fearful face processing and (2) regional gray matter volume. Whole brain and region of interest (fear network) SVM analyses were performed for both modalities. For functional scans, significant classifications were obtained both at whole brain level and when restricting the analysis to the fear network while gray matter SVM analyses correctly classified participants only when using the whole brain search volume. These results support that SAD is characterized by aberrant neural activation to affective stimuli in the fear network, while disorder-related alterations in regional gray matter volume are more diffusely distributed over the whole brain. SVM may thus be useful for identifying imaging biomarkers of SAD.
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| 7. |
- Leitman, David I., et al.
(författare)
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Not pitch perfect : Sensory contributions to affective communication impairment in schizophrenia
- 2011
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Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 70:7, s. 611-618
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Tidskriftsartikel (refereegranskat)abstract
- Background: Schizophrenia patients have vocal affect (prosody) deficits that are treatment resistant and associated with negativesymptoms and poor outcome. The neural correlates of this dysfunction are unclear. Prior study has suggested that schizophrenia vocal affectperception deficits stem from an inability to use acoustic cues, notably pitch, in decoding emotion. Methods: Functional magnetic resonance imaging was performed in 24 schizophrenia patients and 28 healthy control subjects, during theperformance of a four-choice (happiness, fear, anger, neutral) vocal affect identification task in which items for each emotion variedparametrically in affective salient acoustic cue levels. Results: We observed that parametric increases in cue levels in schizophrenia failed to produce the same identification rate increases as incontrol subjects. These deficits correlated with diminished reciprocal activation changes in superior temporal and inferior frontal gyri andreduced temporo-frontal connectivity. Task activation also correlated with independent measures of pitch perception and negativesymptom severity. Conclusions: These findings illustrate the interplay between sensory and higher-order cognitive dysfunction in schizophrenia. Sensorycontributions to vocal affect deficits also suggest that this neurobehavioral marker could be targeted by pharmacological or behavioralremediation of acoustic feature discrimination.
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| 8. |
- Månsson, Kristoffer, et al.
(författare)
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Affective Brain Signal Variability Separates Social Anxiety Disorder Patients From Healthy Individuals
- 2018
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 83:9, s. S249-S250
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Amygdala hyper-responsiveness to negative socio-affective stimuli have typically been demonstrated in patients with social anxiety disorder (SAD). Relative to conventional methods, there is emerging evidence that brain signal variability could be a better predictor of behavior than mean neural response.Methods: We recruited 46 patients with SAD (mean age 31, 63% females) and 40 matched healthy controls (HC) to undergo 3 Tesla functional magnetic resonance imaging (fMRI) at 2 time-points, totaling 172 MRIsessions. Blood-oxygen level-dependent (BOLD-fMRI) was performed while viewing happy and fearful faces in blocks of 80 seconds. BOLD-fMRI data was reviewed by manually classifying signal from noise. Variability was calculated as each voxel’s standard deviation on signal across scanning-time. Multivariate partial least squares (PLS) estimated patterns of variability that separates patient from controls.Results: PLS found one significant latent variable with cross-block covariance on 64%, permutated (x 1000) P<0.001, bootstrapped 95% confidence intervals on each condition, demonstrating less signal variability to happy faces in patients, relative to controls. This pattern of response was spatially located in several regions across the whole-brain, with large clusters appearing in bilateral amygdala, medial prefrontal cortex and posterior cingulate cortex/precuneus.Conclusions: We found that neural response variability to positive socio-affective stimuli accurately separated patients from controls. It is likely that less signal variability highlights a deficit in effective emotion processing. We add to the growing literature on healthy individuals suggesting that task-specific brain signal variability contains useful information. The brain signal variability approach opens new avenues to evaluate and better understand brain function in common psychopathology.
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| 9. |
- Månsson, Kristoffer, et al.
(författare)
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Brain Before Behavior : Temporal Dynamics in the Treatment of Social Anxiety - Neural Changes Occur Early and Precede Clinical Improvement
- 2018
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 83:9, s. S130-S131
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: The brain rapidly responds to affective processing and neural responsivity can separate anxiety disorder patients from healthy individuals. Psychiatric treatment also alters brain responsiveness however, the brain’s temporal dynamics during treatment remain unknown. Here, patients with social anxiety disorder (SAD) were treated with cognitive-behavioral therapy (CBT) and functional magnetic resonance imaging (fMRI) assessments were performed before, during and after intervention.Methods: Forty-six SAD patients received a 9-week Internet-delivered CBTand symptoms were assessed weekly using the Liebowitz social anxiety scale (LSAS-SR). MRI was acquired at 4 time-points (2 baselines, mid- and post-treatment). Blood-oxygen level-dependent(BOLD-fMRI) was performed while patients viewed negative facial expressions. BOLD-fMRI data was reviewed manually by classifying signal from noise, all subjects contributing with complete data.Results: Patients improved slightly from baseline to mid-treatment (P<.001, Cohen’s d=0.34) on the LSAS-SR, but more so from mid- to post-treatment (P<.001, d=1.46). Whole-brain neural responsivity decreased from baseline to post-treatment (False Discovery Rate, FDR P<.005) in the medial prefrontal cortex, precuneus and amygdala/parahippocampus. However, no changes (FDR P>.05) from mid- to post-treatment were found, suggesting that the early alterations accounted for the effect. Furthermore, early response reductions were positively associated with symptom improvement from pre-post treatment (Pearson’s r=.50, P<.001).Conclusions: This is, to our knowledge, the first study assessing early and late psychiatric treatment changes in the brain. Interestingly, altered neural responsivity in limbic and default-mode network regions preceded self-reported alleviation of social anxiety. Understanding the brain’s temporal dynamics and subsequent modification of behavior may be highly important for future clinical neuroimaging research.
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| 10. |
- Månsson, Kristoffer, et al.
(författare)
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Can Psychological Treatment Slow Down Cellular Aging in Social Anxiety Disorder? : An Intervention Study Evaluating Changes in Telomere Length and Telomerase Activity
- 2018
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 83:9, s. S351-S352
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Mental illness, including anxiety disorders, is linked to accelerated cell aging. This is evidenced by shorter leukocyte telomere length. Cells with critically short telomeres may undergo apoptosis. In dividing cells, telomere shortening is counteracted by the telomeraseenzyme. Telomerase is reportedly low following chronic psychological stress. We hypothesized that a psychological treatment may increase telomerase activity, less telomere attritionand greater symptom improvement.Methods: Forty-six patients (91% SSRI naïve) with social anxiety disorder(SAD; mean age 31, 63% females) underwent a 9-week waiting period, and 9 weeks of Internet-delivered cognitive behavior therapy(CBT). During treatment, symptoms were assessed weekly using the Liebowitz Social Anxiety Scale (LSAS-SR). Fasting blood samples were collected twice before treatment, and at post-treatment. Genomic DNA was extracted using DNeasy® Blood & Tissue Kit (Qiagene) to assess leukocyte telomere length. Telomerase activity was detected by real-time telomeric repeat amplification protocol (RT-TRAP).Results: Patients improved significantly on the LSAS-SR (p<.001; Cohen’s d=1.5). Pre-post changes in telomerase and telomere length correlated positively (Pearson’s r=.31, p=.05). Reduced telomerase activity (<33th percentile) was associated with less improvement and increased activity (>66th percentile) with more improvement on the LSAS-SR (Z=-2.4, p=.02).Conclusions: We demonstrate, to our knowledge for the first time, that altered telomerase activity is associated with clinical response to a psychological treatment in a psychiatric population. The observed CBT effect on telomerase in patients with SAD is consistent with results from animal trials and a small previous study of antidepressants in humans. Thus, telomerase activation may play an important role in clinical recovery.
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