The prevalence of chronic pain rises with increasing age. It has been suggested that the mechanis... more The prevalence of chronic pain rises with increasing age. It has been suggested that the mechanisms responsible for the development of chronic pain overlap with mechanisms involved in aging, potentially implicating age-related changes in descending modulatory pathways. This observation raises the question whether other forms of endogenous pain modulation, in particular placebo analgesia, become compromised with age. Because of the known contribution of placebo effects to analgesic treatment outcomes this question is of important clinical relevance. In this study, we compared the response to thermal painful stimuli and the capacity for endogenous pain modulation between younger and older adults using a well established placebo analgesia paradigm involving expectancy and conditioning components. We recruited 30 younger (age 23-40 years, mean = 27.04, standard error of the mean ± .61) and 24 older adults (60-80 years, mean = 69.3, standard error of the mean ± .89). We observed increased heat pain thresholds and higher pain intensity ratings (in response to physically identical heat stimulation) in the older compared with the younger group. However, the placebo analgesic response was comparable between both age groups of healthy participants. The preserved capacity for placebo analgesia in our sample of older participants highlights the potential to use nonpharmacological analgesic treatment strategies in this age group and to exploit placebo mechanisms as an add-on to existing analgesic (pharmacological) treatment strategies. PERSPECTIVE In contrast to the commonly shared view that endogenous pain modulation declines with age we found a comparable capacity for placebo analgesia in a group of healthy older and younger adults.
There is little information regarding changes in placebo responsiveness with age, although first ... more There is little information regarding changes in placebo responsiveness with age, although first predictors of placebo responders such as psychological and physiological processes have been identified. Reviews and meta-analyses indicate that placebo response rates in randomized controlled trials (RCTs) are higher in children and adolescents compared with adults. As these studies cannot control for age-dependent differences in the natural course of the disease, biases might contribute to different placebo rates in RCTs. To avoid these biases, this study investigated age-related differences in placebo responsiveness between children and adults in a well-established experimental model of placebo analgesia combining classic conditioning and expectation. Our data confirm placebo analgesic responses in children, which did not differ in magnitude from those of adults. The influence of previous experience on subsequent treatment outcome was stronger in children than in adults, indicating an increased relevance of learning processes for treatment outcomes in children. Further studies are needed to understand the influence of treatment-related learning processes in children and adolescents, which might critically determine treatment responsiveness during adulthood. This study is the first to experimentally explore placebo analgesia and influences of previous experience on placebo responses in children compared with adults. We found comparable placebo responses in both groups and an increased relevance of learning processes for treatment outcomes in children.
Background Antidepressants are established as an evidence-based, guideline-recommended treatment ... more Background Antidepressants are established as an evidence-based, guideline-recommended treatment for Major Depressive Disorder. Prescriptions have markedly increased in past decades, with a specific surge in maintenance prescribing. Patients often remain on antidepressants longer than clinically necessary. When attempting to stop, many patients experience adverse discontinuation symptoms. Discontinuation symptoms can be debilitating and hinder successful discontinuation. While discontinuation symptoms can result from pharmacological effects, evidence on nocebo-induced side effects of antidepressant use suggests that patients' expectations may also influence occurrence. Methods To disentangle pharmacological and expectation effects in antidepressant discontinuation, patients with fully remitted Major Depressive Disorder who fulfill German guideline recommendations to discontinue will either remain on or discontinue their antidepressant. Participants' expectations will be mani...
The prevalence of chronic pain rises with increasing age. It has been suggested that the mechanis... more The prevalence of chronic pain rises with increasing age. It has been suggested that the mechanisms responsible for the development of chronic pain overlap with mechanisms involved in aging, potentially implicating age-related changes in descending modulatory pathways. This observation raises the question whether other forms of endogenous pain modulation, in particular placebo analgesia, become compromised with age. Because of the known contribution of placebo effects to analgesic treatment outcomes this question is of important clinical relevance. In this study, we compared the response to thermal painful stimuli and the capacity for endogenous pain modulation between younger and older adults using a well established placebo analgesia paradigm involving expectancy and conditioning components. We recruited 30 younger (age 23-40 years, mean = 27.04, standard error of the mean ± .61) and 24 older adults (60-80 years, mean = 69.3, standard error of the mean ± .89). We observed increased heat pain thresholds and higher pain intensity ratings (in response to physically identical heat stimulation) in the older compared with the younger group. However, the placebo analgesic response was comparable between both age groups of healthy participants. The preserved capacity for placebo analgesia in our sample of older participants highlights the potential to use nonpharmacological analgesic treatment strategies in this age group and to exploit placebo mechanisms as an add-on to existing analgesic (pharmacological) treatment strategies. PERSPECTIVE In contrast to the commonly shared view that endogenous pain modulation declines with age we found a comparable capacity for placebo analgesia in a group of healthy older and younger adults.
There is little information regarding changes in placebo responsiveness with age, although first ... more There is little information regarding changes in placebo responsiveness with age, although first predictors of placebo responders such as psychological and physiological processes have been identified. Reviews and meta-analyses indicate that placebo response rates in randomized controlled trials (RCTs) are higher in children and adolescents compared with adults. As these studies cannot control for age-dependent differences in the natural course of the disease, biases might contribute to different placebo rates in RCTs. To avoid these biases, this study investigated age-related differences in placebo responsiveness between children and adults in a well-established experimental model of placebo analgesia combining classic conditioning and expectation. Our data confirm placebo analgesic responses in children, which did not differ in magnitude from those of adults. The influence of previous experience on subsequent treatment outcome was stronger in children than in adults, indicating an increased relevance of learning processes for treatment outcomes in children. Further studies are needed to understand the influence of treatment-related learning processes in children and adolescents, which might critically determine treatment responsiveness during adulthood. This study is the first to experimentally explore placebo analgesia and influences of previous experience on placebo responses in children compared with adults. We found comparable placebo responses in both groups and an increased relevance of learning processes for treatment outcomes in children.
While treatment side effects may adversely impact patients, they could also potentially function ... more While treatment side effects may adversely impact patients, they could also potentially function as indicators for effective treatment. In this study, we investigated whether and how side effects can trigger positive treatment expectations and enhance treatment outcomes.In this preregistered trial (DRKS00026648), 77 healthy participants were made to believe that they will receive fentanyl nasal sprays before receiving thermal pain in a controlled experimental setting. However, nasal sprays did not contain fentanyl, rather they either contained capsaicin to induce a side effect (mild burning sensation) or saline (control). Following the initial phase, participants were randomized to two groups and underwent functional magnetic resonance imaging (fMRI). One group continued to believe that the nasal sprays could contain fentanyl while the other group was explicitly informed that no fentanyl was included. This allowed for the independent manipulation of the side effects and the expectat...
Resting-state connectivity has become an increasingly important measure in characterizing the fun... more Resting-state connectivity has become an increasingly important measure in characterizing the functional integrity of brain circuits in neuro-psychiatric conditions. One approach that has recently gained prominence in this regard-and which we use in this study-is to investigate how resting-state connectivity depends on the integrity of certain neuromodulator systems. Here, we use a pharmacological challenge in combination with functional magnetic resonance imaging to investigate the impact of dopaminergic receptor blockade on whole brain functional connectivity in twenty healthy human subjects. Administration of the D2-receptor antagonist haloperidol led to a profound change in functional integration in network nodes linked to the amygdala. Compared to placebo and baseline measurements, network-based statistics and pairwise connectivity analyses revealed reduced connectivity and decreased link strength between the amygdala and the bilateral posterior cingulate cortex and other cortical areas. This was complemented by less extensive but very circumscribed enhanced connectivity between the amygdala and the right putamen during D2-receptor blockade. It will be interesting to investigate whether these pharmacologically induced shifts in resting-state connectivity will similarly be evident in clinical conditions that involve a dysfunction of the dopaminergic system. Our findings might also aid in interpreting alterations in more complex states, such as those seen psychiatric conditions and their treatment.
One promising approach in the current ambition to maximise treatment benefit for anxiety disorder... more One promising approach in the current ambition to maximise treatment benefit for anxiety disorders is the pharmacological enhancement of cognitive-behavioural treatment efficacy, which can be experimentally modelled by pharmacological enhancement of extinction learning/consolidation. Noradrenaline (NA) is involved in memory consolidation, and NAergic innervations are found in brain areas implicated in fear conditioning and extinction. Thus, to enhance extinction memory consolidation through boosted NAergic signalling, we administered 4 mg reboxetine (RBX) immediately after extinction learning (day 2, 24 h after conditioning on day 1) in a randomised, placebo (PLC)-controlled design. At a delayed memory test (day 8), we probed cued and contextual fear and extinction memories before and after a reinstatement manipulation. After reinstatement, we find significantly enhanced amygdala and posterior hippocampus activation in the RBX group, areas implicated in fear memory expression, while the PLC group exhibited enhanced activation in areas associated with extinction memory expression (vmPFC, anterior hippocampus). No group differences were found in skin conductance responses. Thus, our data do not support our hypothesis that enhancement of NA signalling may facilitate extinction memory consolidation and provide preliminary evidence that this might rather enhance fear memories on a neural but not physiological (skin conductance responses) level.
ABSTRACTNicotine intake by cigarettes is linked to the maintenance and development of anxiety dis... more ABSTRACTNicotine intake by cigarettes is linked to the maintenance and development of anxiety disorders and impairs adaptive discrimination of threat and safety in humans. Yet, it is unclear if nicotine exerts a causal pharmacological effect on the affective and neural mechanisms that underlie aversive learning. We conducted a pre-registered, pseudo-randomly and double-blinded pharmacological fMRI study to investigate the effect of acute nicotine on Fear Acquisition and Extinction in non-smokers (n=88). Our results show that nicotine administration led to decreased discrimination between threat and safety in subjective fear. Nicotine furthermore decreased differential (threat vs. safety) activation in the hippocampus, which was functionally coupled with Nucleus Accumbens and amygdala, compared to placebo controls. Additionally, nicotine led to overactivation of the ventral tegmental area. This study provides mechanistic evidence that single doses of nicotine impair neural substrates...
Supplemental material, IMAGEN_DIS_Supplemental_Material_final for Extending the Construct Network... more Supplemental material, IMAGEN_DIS_Supplemental_Material_final for Extending the Construct Network of Trait Disinhibition to the Neuroimaging Domain: Validation of a Bridging Scale for Use in the European IMAGEN Project by Sarah J. Brislin, Christopher J. Patrick, Herta Flor, Frauke Nees, Angela Heinrich, Laura E. Drislane, James R. Yancey, Tobias Banaschewski, Arun L. W. Bokde, Uli Bromberg, Christian Büchel, Erin Burke Quinlan, Sylvane Desrivières, Vincent Frouin, Hugh Garavan, Penny Gowland, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Dimitri Papadopoulos Orfanos, Luise Poustka, Juliane H. Fröhner, Michael N. Smolka, Henrik Walter, Robert Whelan, Patricia Conrod, Argyris Stringaris, Maren Struve, Betteke van Noort, Yvonne Grimmer, Tahmine Fadai, Gunter Schumann, and Jens Foell in Assessment
Traditional models of future alcohol use in adolescents have used variable-centered approaches, p... more Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the I...
Journal of the American Academy of Child & Adolescent Psychiatry, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Journal of the American Academy of Child & Adolescent Psychiatry, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Imaging genetics offers the possibility of detecting associations between genotype and brain stru... more Imaging genetics offers the possibility of detecting associations between genotype and brain structure as well as function, with effect sizes potentially exceeding correlations between genotype and behavior. However, study results are often limited due to small sample sizes and methodological differences, thus reducing the reliability of findings. The IMAGEN cohort with 2000 young adolescents assessed from the age of 14 onwards tries to eliminate some of these limitations by offering a longitudinal approach and sufficient sample size for analyzing gene-environment interactions on brain structure and function. Here, we give a systematic review of IMAGEN publications since the start of the consortium. We then focus on the specific phenotype ‘drug use’ to illustrate the potential of the IMAGEN approach. We describe findings with respect to frontocortical, limbic and striatal brain volume, functional activation elicited by reward anticipation, behavioral inhibition, and affective faces,...
The cortical‐cerebellar circuit is vulnerable to heavy drinking (HD) in adults. We hypothesized e... more The cortical‐cerebellar circuit is vulnerable to heavy drinking (HD) in adults. We hypothesized early microstructural modifications of the pons/midbrain region, containing core structures of the reward system, in HD adolescents. Thirty‐two otherwise symptom‐free HDs at age 14 (HD14) and 24 abstainers becoming HDs at age 16 (HD16) were identified in the community with the Alcohol Use Disorders Identification Test (AUDIT) and compared with abstainers. The monetary incentive delay (MID) task assessed reward‐sensitive performance. Voxelwise statistics of diffusion tensor imaging (DTI) values in the thalamo‐ponto‐mesencephalic region were obtained using tract‐based spatial statistics. Projections between the ventral tegmental area (VTA) and the nucleus accumbens (NAcc) were identified by probabilistic tractography. Lower fraction of anisotropy and higher radial diffusivity (RD) values were detected in the upper dorsal pons of HD14 adolescents, and a trend for higher RD in HD16, compared ...
The prevalence of chronic pain rises with increasing age. It has been suggested that the mechanis... more The prevalence of chronic pain rises with increasing age. It has been suggested that the mechanisms responsible for the development of chronic pain overlap with mechanisms involved in aging, potentially implicating age-related changes in descending modulatory pathways. This observation raises the question whether other forms of endogenous pain modulation, in particular placebo analgesia, become compromised with age. Because of the known contribution of placebo effects to analgesic treatment outcomes this question is of important clinical relevance. In this study, we compared the response to thermal painful stimuli and the capacity for endogenous pain modulation between younger and older adults using a well established placebo analgesia paradigm involving expectancy and conditioning components. We recruited 30 younger (age 23-40 years, mean = 27.04, standard error of the mean ± .61) and 24 older adults (60-80 years, mean = 69.3, standard error of the mean ± .89). We observed increased heat pain thresholds and higher pain intensity ratings (in response to physically identical heat stimulation) in the older compared with the younger group. However, the placebo analgesic response was comparable between both age groups of healthy participants. The preserved capacity for placebo analgesia in our sample of older participants highlights the potential to use nonpharmacological analgesic treatment strategies in this age group and to exploit placebo mechanisms as an add-on to existing analgesic (pharmacological) treatment strategies. PERSPECTIVE In contrast to the commonly shared view that endogenous pain modulation declines with age we found a comparable capacity for placebo analgesia in a group of healthy older and younger adults.
There is little information regarding changes in placebo responsiveness with age, although first ... more There is little information regarding changes in placebo responsiveness with age, although first predictors of placebo responders such as psychological and physiological processes have been identified. Reviews and meta-analyses indicate that placebo response rates in randomized controlled trials (RCTs) are higher in children and adolescents compared with adults. As these studies cannot control for age-dependent differences in the natural course of the disease, biases might contribute to different placebo rates in RCTs. To avoid these biases, this study investigated age-related differences in placebo responsiveness between children and adults in a well-established experimental model of placebo analgesia combining classic conditioning and expectation. Our data confirm placebo analgesic responses in children, which did not differ in magnitude from those of adults. The influence of previous experience on subsequent treatment outcome was stronger in children than in adults, indicating an increased relevance of learning processes for treatment outcomes in children. Further studies are needed to understand the influence of treatment-related learning processes in children and adolescents, which might critically determine treatment responsiveness during adulthood. This study is the first to experimentally explore placebo analgesia and influences of previous experience on placebo responses in children compared with adults. We found comparable placebo responses in both groups and an increased relevance of learning processes for treatment outcomes in children.
Background Antidepressants are established as an evidence-based, guideline-recommended treatment ... more Background Antidepressants are established as an evidence-based, guideline-recommended treatment for Major Depressive Disorder. Prescriptions have markedly increased in past decades, with a specific surge in maintenance prescribing. Patients often remain on antidepressants longer than clinically necessary. When attempting to stop, many patients experience adverse discontinuation symptoms. Discontinuation symptoms can be debilitating and hinder successful discontinuation. While discontinuation symptoms can result from pharmacological effects, evidence on nocebo-induced side effects of antidepressant use suggests that patients' expectations may also influence occurrence. Methods To disentangle pharmacological and expectation effects in antidepressant discontinuation, patients with fully remitted Major Depressive Disorder who fulfill German guideline recommendations to discontinue will either remain on or discontinue their antidepressant. Participants' expectations will be mani...
The prevalence of chronic pain rises with increasing age. It has been suggested that the mechanis... more The prevalence of chronic pain rises with increasing age. It has been suggested that the mechanisms responsible for the development of chronic pain overlap with mechanisms involved in aging, potentially implicating age-related changes in descending modulatory pathways. This observation raises the question whether other forms of endogenous pain modulation, in particular placebo analgesia, become compromised with age. Because of the known contribution of placebo effects to analgesic treatment outcomes this question is of important clinical relevance. In this study, we compared the response to thermal painful stimuli and the capacity for endogenous pain modulation between younger and older adults using a well established placebo analgesia paradigm involving expectancy and conditioning components. We recruited 30 younger (age 23-40 years, mean = 27.04, standard error of the mean ± .61) and 24 older adults (60-80 years, mean = 69.3, standard error of the mean ± .89). We observed increased heat pain thresholds and higher pain intensity ratings (in response to physically identical heat stimulation) in the older compared with the younger group. However, the placebo analgesic response was comparable between both age groups of healthy participants. The preserved capacity for placebo analgesia in our sample of older participants highlights the potential to use nonpharmacological analgesic treatment strategies in this age group and to exploit placebo mechanisms as an add-on to existing analgesic (pharmacological) treatment strategies. PERSPECTIVE In contrast to the commonly shared view that endogenous pain modulation declines with age we found a comparable capacity for placebo analgesia in a group of healthy older and younger adults.
There is little information regarding changes in placebo responsiveness with age, although first ... more There is little information regarding changes in placebo responsiveness with age, although first predictors of placebo responders such as psychological and physiological processes have been identified. Reviews and meta-analyses indicate that placebo response rates in randomized controlled trials (RCTs) are higher in children and adolescents compared with adults. As these studies cannot control for age-dependent differences in the natural course of the disease, biases might contribute to different placebo rates in RCTs. To avoid these biases, this study investigated age-related differences in placebo responsiveness between children and adults in a well-established experimental model of placebo analgesia combining classic conditioning and expectation. Our data confirm placebo analgesic responses in children, which did not differ in magnitude from those of adults. The influence of previous experience on subsequent treatment outcome was stronger in children than in adults, indicating an increased relevance of learning processes for treatment outcomes in children. Further studies are needed to understand the influence of treatment-related learning processes in children and adolescents, which might critically determine treatment responsiveness during adulthood. This study is the first to experimentally explore placebo analgesia and influences of previous experience on placebo responses in children compared with adults. We found comparable placebo responses in both groups and an increased relevance of learning processes for treatment outcomes in children.
While treatment side effects may adversely impact patients, they could also potentially function ... more While treatment side effects may adversely impact patients, they could also potentially function as indicators for effective treatment. In this study, we investigated whether and how side effects can trigger positive treatment expectations and enhance treatment outcomes.In this preregistered trial (DRKS00026648), 77 healthy participants were made to believe that they will receive fentanyl nasal sprays before receiving thermal pain in a controlled experimental setting. However, nasal sprays did not contain fentanyl, rather they either contained capsaicin to induce a side effect (mild burning sensation) or saline (control). Following the initial phase, participants were randomized to two groups and underwent functional magnetic resonance imaging (fMRI). One group continued to believe that the nasal sprays could contain fentanyl while the other group was explicitly informed that no fentanyl was included. This allowed for the independent manipulation of the side effects and the expectat...
Resting-state connectivity has become an increasingly important measure in characterizing the fun... more Resting-state connectivity has become an increasingly important measure in characterizing the functional integrity of brain circuits in neuro-psychiatric conditions. One approach that has recently gained prominence in this regard-and which we use in this study-is to investigate how resting-state connectivity depends on the integrity of certain neuromodulator systems. Here, we use a pharmacological challenge in combination with functional magnetic resonance imaging to investigate the impact of dopaminergic receptor blockade on whole brain functional connectivity in twenty healthy human subjects. Administration of the D2-receptor antagonist haloperidol led to a profound change in functional integration in network nodes linked to the amygdala. Compared to placebo and baseline measurements, network-based statistics and pairwise connectivity analyses revealed reduced connectivity and decreased link strength between the amygdala and the bilateral posterior cingulate cortex and other cortical areas. This was complemented by less extensive but very circumscribed enhanced connectivity between the amygdala and the right putamen during D2-receptor blockade. It will be interesting to investigate whether these pharmacologically induced shifts in resting-state connectivity will similarly be evident in clinical conditions that involve a dysfunction of the dopaminergic system. Our findings might also aid in interpreting alterations in more complex states, such as those seen psychiatric conditions and their treatment.
One promising approach in the current ambition to maximise treatment benefit for anxiety disorder... more One promising approach in the current ambition to maximise treatment benefit for anxiety disorders is the pharmacological enhancement of cognitive-behavioural treatment efficacy, which can be experimentally modelled by pharmacological enhancement of extinction learning/consolidation. Noradrenaline (NA) is involved in memory consolidation, and NAergic innervations are found in brain areas implicated in fear conditioning and extinction. Thus, to enhance extinction memory consolidation through boosted NAergic signalling, we administered 4 mg reboxetine (RBX) immediately after extinction learning (day 2, 24 h after conditioning on day 1) in a randomised, placebo (PLC)-controlled design. At a delayed memory test (day 8), we probed cued and contextual fear and extinction memories before and after a reinstatement manipulation. After reinstatement, we find significantly enhanced amygdala and posterior hippocampus activation in the RBX group, areas implicated in fear memory expression, while the PLC group exhibited enhanced activation in areas associated with extinction memory expression (vmPFC, anterior hippocampus). No group differences were found in skin conductance responses. Thus, our data do not support our hypothesis that enhancement of NA signalling may facilitate extinction memory consolidation and provide preliminary evidence that this might rather enhance fear memories on a neural but not physiological (skin conductance responses) level.
ABSTRACTNicotine intake by cigarettes is linked to the maintenance and development of anxiety dis... more ABSTRACTNicotine intake by cigarettes is linked to the maintenance and development of anxiety disorders and impairs adaptive discrimination of threat and safety in humans. Yet, it is unclear if nicotine exerts a causal pharmacological effect on the affective and neural mechanisms that underlie aversive learning. We conducted a pre-registered, pseudo-randomly and double-blinded pharmacological fMRI study to investigate the effect of acute nicotine on Fear Acquisition and Extinction in non-smokers (n=88). Our results show that nicotine administration led to decreased discrimination between threat and safety in subjective fear. Nicotine furthermore decreased differential (threat vs. safety) activation in the hippocampus, which was functionally coupled with Nucleus Accumbens and amygdala, compared to placebo controls. Additionally, nicotine led to overactivation of the ventral tegmental area. This study provides mechanistic evidence that single doses of nicotine impair neural substrates...
Supplemental material, IMAGEN_DIS_Supplemental_Material_final for Extending the Construct Network... more Supplemental material, IMAGEN_DIS_Supplemental_Material_final for Extending the Construct Network of Trait Disinhibition to the Neuroimaging Domain: Validation of a Bridging Scale for Use in the European IMAGEN Project by Sarah J. Brislin, Christopher J. Patrick, Herta Flor, Frauke Nees, Angela Heinrich, Laura E. Drislane, James R. Yancey, Tobias Banaschewski, Arun L. W. Bokde, Uli Bromberg, Christian Büchel, Erin Burke Quinlan, Sylvane Desrivières, Vincent Frouin, Hugh Garavan, Penny Gowland, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Dimitri Papadopoulos Orfanos, Luise Poustka, Juliane H. Fröhner, Michael N. Smolka, Henrik Walter, Robert Whelan, Patricia Conrod, Argyris Stringaris, Maren Struve, Betteke van Noort, Yvonne Grimmer, Tahmine Fadai, Gunter Schumann, and Jens Foell in Assessment
Traditional models of future alcohol use in adolescents have used variable-centered approaches, p... more Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the I...
Journal of the American Academy of Child & Adolescent Psychiatry, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Journal of the American Academy of Child & Adolescent Psychiatry, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Imaging genetics offers the possibility of detecting associations between genotype and brain stru... more Imaging genetics offers the possibility of detecting associations between genotype and brain structure as well as function, with effect sizes potentially exceeding correlations between genotype and behavior. However, study results are often limited due to small sample sizes and methodological differences, thus reducing the reliability of findings. The IMAGEN cohort with 2000 young adolescents assessed from the age of 14 onwards tries to eliminate some of these limitations by offering a longitudinal approach and sufficient sample size for analyzing gene-environment interactions on brain structure and function. Here, we give a systematic review of IMAGEN publications since the start of the consortium. We then focus on the specific phenotype ‘drug use’ to illustrate the potential of the IMAGEN approach. We describe findings with respect to frontocortical, limbic and striatal brain volume, functional activation elicited by reward anticipation, behavioral inhibition, and affective faces,...
The cortical‐cerebellar circuit is vulnerable to heavy drinking (HD) in adults. We hypothesized e... more The cortical‐cerebellar circuit is vulnerable to heavy drinking (HD) in adults. We hypothesized early microstructural modifications of the pons/midbrain region, containing core structures of the reward system, in HD adolescents. Thirty‐two otherwise symptom‐free HDs at age 14 (HD14) and 24 abstainers becoming HDs at age 16 (HD16) were identified in the community with the Alcohol Use Disorders Identification Test (AUDIT) and compared with abstainers. The monetary incentive delay (MID) task assessed reward‐sensitive performance. Voxelwise statistics of diffusion tensor imaging (DTI) values in the thalamo‐ponto‐mesencephalic region were obtained using tract‐based spatial statistics. Projections between the ventral tegmental area (VTA) and the nucleus accumbens (NAcc) were identified by probabilistic tractography. Lower fraction of anisotropy and higher radial diffusivity (RD) values were detected in the upper dorsal pons of HD14 adolescents, and a trend for higher RD in HD16, compared ...
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