| 1. |
- Aardal-Eriksson, Elisabeth, et al.
(author)
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Salivary cortisol and serum prolactin in relation to stress rating scales in a group of rescue workers
- 1999
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In: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 46:6, s. 850-855
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Journal article (peer-reviewed)abstract
- Background: Rescue service personnel are often exposed to traumatic events as part of their occupation, and higher prevalence rates of psychiatric illness have been found among this group.Methods: In 65 rescue workers, salivary cortisol at 8 am and 10 pm and serum prolactin at 8 am were related to the psychiatric self-rating scale General Health Questionnaire (GHQ-28) measuring psychiatric health, and the Impact of Events Scale (IES) and Post Traumatic Symptom Scale (PTSS) measuring posttraumatic symptoms.Results: Seventeen percent of the study population scored above the GHQ-28 cut-off limit but none scored beyond the cut-off limit in the IES and PTSS questionnaires. Salivary cortisol concentration at 10 pm correlated with statistical significance to anxiety (p < .005) and depressive symptoms (p < .01) measured with GHQ-28, as well as to posttraumatic symptoms, with avoidance behavior measured with IES (p < .01) and PTSS (p < .005). Two of the rescue workers were followed over time with the same sampling procedure after a major rescue commission.Conclusions: The correlation between evening salivary cortisol and anxiety, depressiveness, and posttraumatic avoidance symptoms indicates that these parameters can be used in screening and follow-up after traumatic stress events.
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| 2. |
- Aardal-Eriksson, Elisabeth, et al.
(author)
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Salivary cortisol, posttraumatic stress symptoms, and general health in the acute phase and during 9-month follow-up
- 2001
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In: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 50:12, s. 986-993
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Journal article (peer-reviewed)abstract
- Background: Because traumatic events are unpredictable, there are few studies of psychobiological states immediately following such events. Our study aimed to determine the relation of salivary cortisol to psychologic distress immediately after a traumatic event and then during follow-up.Methods: Measurement of morning and evening salivary cortisol and ratings of psychologic distress (using the Impact of Events Scale [IES], the Post Traumatic Symptom Scale, and the General Health Questionnaire) were performed with 31 United Nations soldiers at three time points—5 days and 2 and 9 months—following a mine accident in Lebanon.Results: Five days after the accident, 15 subjects reported substantial posttraumatic distress according to the IES, as well as significantly lower morning and higher evening cortisol levels compared with the low-impact group. Within 9 months, the posttraumatic distress of the high-impact group was reduced, accompanied by an increase in morning and a decrease in evening cortisol levels. There were significant relationships between evening cortisol and all rating scales at the first and third time points.Conclusions: Subclinical posttraumatic stress following an adverse event can be measured biologically via salivary cortisol levels soon after the event.
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| 3. |
- Abé, Christoph, et al.
(author)
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Longitudinal Cortical Thickness Changes in Bipolar Disorder and the Relationship to Genetic Risk, Mania, and Lithium Use.
- 2020
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In: Biological psychiatry. - : Elsevier BV. - 1873-2402 .- 0006-3223. ; 87:3, s. 271-281
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Journal article (peer-reviewed)abstract
- Bipolar disorder (BD) is a highly heritable psychiatric disorder characterized by episodes of manic and depressed mood states and associated with cortical brain abnormalities. Although the course of BD is often progressive, longitudinal brain imaging studies are scarce. It remains unknown whether brain abnormalities are static traits of BD or result from pathological changes over time. Moreover, the genetic effect on implicated brain regions remains unknown.Patients with BD and healthy control (HC) subjects underwent structural magnetic resonance imaging at baseline (123 patients, 83 HC subjects) and after 6 years (90 patients, 61 HC subjects). Cortical thickness maps were generated using FreeSurfer. Using linear mixed effects models, we compared longitudinal changes in cortical thickness between patients with BD and HC subjects across the whole brain. We related our findings to genetic risk for BD and tested for effects of demographic and clinical variables.Patients showed abnormal cortical thinning of temporal cortices and thickness increases in visual/somatosensory brain areas. Thickness increases were related to genetic risk and lithium use. Patients who experienced hypomanic or manic episodes between time points showed abnormal thinning in inferior frontal cortices. Cortical changes did not differ between diagnostic BD subtypes I and II.In the largest longitudinal BD study to date, we detected abnormal cortical changes with high anatomical resolution. We delineated regional effects of clinical symptoms, genetic factors, and medication that may explain progressive brain changes in BD. Our study yields important insights into disease mechanisms and suggests that neuroprogression plays a role in BD.
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| 4. |
- Abé, Christoph, et al.
(author)
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Longitudinal Structural Brain Changes in Bipolar Disorder: A Multicenter Neuroimaging Study of 1232 Individuals by the ENIGMA Bipolar Disorder Working Group.
- 2022
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In: Biological psychiatry. - : Elsevier BV. - 1873-2402 .- 0006-3223. ; 91:6, s. 582-592
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Journal article (peer-reviewed)abstract
- Bipolar disorder (BD) is associated with cortical and subcortical structural brain abnormalities. It is unclear whether such alterations progressively change over time, and how this is related to the number of mood episodes. To address this question, we analyzed a large and diverse international sample with longitudinal magnetic resonance imaging (MRI) and clinical data to examine structural brain changes over time in BD.Longitudinal structural MRI and clinical data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) BD Working Group, including 307 patients with BD and 925 healthy control subjects, were collected from 14 sites worldwide. Male and female participants, aged 40 ± 17 years, underwent MRI at 2 time points. Cortical thickness, surface area, and subcortical volumes were estimated using FreeSurfer. Annualized change rates for each imaging phenotype were compared between patients with BD and healthy control subjects. Within patients, we related brain change rates to the number of mood episodes between time points and tested for effects of demographic and clinical variables.Compared with healthy control subjects, patients with BD showed faster enlargement of ventricular volumes and slower thinning of the fusiform and parahippocampal cortex (0.18
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| 12. |
- Barbier, Estelle, et al.
(author)
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Downregulation of Synaptotagmin 1 in the Prelimbic Cortex Drives Alcohol-Associated Behaviors in Rats
- 2021
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In: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 89:4, s. 398-406
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Journal article (peer-reviewed)abstract
- Background: Alcohol addiction is characterized by persistent neuroadaptations in brain structures involved in motivation, emotion, and decision making, including the medial prefrontal cortex, the nucleus accumbens, and the amygdala. We previously reported that induction of alcohol dependence was associated with long-term changes in the expression of genes involved in neurotransmitter release. Specifically, Syt1, which plays a key role in neurotransmitter release and neuronal functions, was downregulated. Here, we therefore examined the role of Syt1 in alcohol-associated behaviors in rats. Methods: We evaluated the effect of Syt1 downregulation using an adeno-associated virus (AAV) containing a short hairpin RNA against Syt1. Cre-dependent Syt1 was also used in combination with an rAAV2 retro-Cre virus to assess circuit-specific effects of Syt1 knockdown (KD). Results: Alcohol-induced downregulation of Syt1 is specific to the prelimbic cortex (PL), and KD of Syt1 in the PL resulted in escalated alcohol consumption, increased motivation to consume alcohol, and increased alcohol drinking despite negative consequences (“compulsivity”). Syt1 KD in the PL altered the excitation/inhibition balance in the basolateral amygdala, while the nucleus accumbens core was unaffected. Accordingly, a projection-specific Syt1 KD in the PL–basolateral amygdala projection was sufficient to increase compulsive alcohol drinking, while a KD of Syt1 restricted to PL–nucleus accumbens core projecting neurons had no effect on tested alcohol-related behaviors. Conclusions: Together, these data suggest that dysregulation of Syt1 is an important mechanism in long-term neuroadaptations observed after a history of alcohol dependence, and that Syt1 regulates alcohol-related behaviors in part by affecting a PL–basolateral amygdala brain circuit. © 2020 Society of Biological Psychiatry
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| 14. |
- Berna, Chantal, et al.
(author)
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Induction of Depressed Mood Disrupts Emotion Regulation Neurocircuitry and Enhances Pain Unpleasantness
- 2010
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In: Biological Psychiatry. - : ELSEVIER SCIENCE INC. - 0006-3223 .- 1873-2402. ; 67:11, s. 1083-1090
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Journal article (peer-reviewed)abstract
- Background: Depressed mood alters the pain experience. Yet, despite its clear clinical relevance, little is known about the cognitive and neural mechanisms underlying this phenomenon. We tested an experimental manipulation to unravel the interaction between depressed mood and pain. We hypothesized that dysregulation of the neural circuitry underlying emotion regulation is the mechanism whereby pain processing is affected during depressed mood. Methods: Using functional magnetic resonance imaging, we compared the effects of sad and neutral cognitive mood inductions on affective pain ratings, pain-specific cognitions, and central pain processing of a tonic noxious heat stimulus in 20 healthy volunteers. Results: The increase in negative pain-specific cognitions during depressed mood predicted the perceived increase in pain unpleasantness. Following depressed mood induction, brain responses to noxious thermal stimuli were characterized by increased activity in a broad network including prefrontal areas, subgenual anterior cingulate cortex, and hippocampus, as well as significantly less deactivation when compared with pain responses in a neutral mood. The participants who reported the largest increase in pain unpleasantness after the sad mood induction showed greater inferior frontal gyrus and amygdala activation, linking changes in emotion regulation mechanisms with enhancement of pain affect. Conclusions: Our results inform how depressed mood and chronic pain co-occur clinically and may serve to develop and translate effective interventions using pharmacological or psychological treatment.
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| 15. |
- Bilbao, Ainhoa, et al.
(author)
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A Pharmacogenetic Determinant of Mu-Opioid Receptor Antagonist Effects on Alcohol Reward and Consumption : Evidence from Humanized Mice.
- 2015
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In: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 77:10, s. 850-858
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Journal article (peer-reviewed)abstract
- BACKGROUND: It has been proposed that therapeutic responses to naltrexone in alcoholism are moderated by variation at the mu-opioid receptor gene locus (OPRM1). This remains controversial because human results vary and no prospectively genotyped studies have been reported. We generated humanized mice carrying the respective human OPRM1 A118G alleles. Here, we used this model system to examine the role of OPRM1 A118G variation for opioid antagonist effects on alcohol responses.METHODS: Effects of naltrexone on alcohol reward were examined using intracranial self-stimulation. Effects of naltrexone or nalmefene on alcohol intake were examined in continuous access home cage two-bottle free-choice drinking and operant alcohol self-administration paradigms.RESULTS: Alcohol lowered brain stimulation reward thresholds in 118GG mice in a manner characteristic of rewarding drugs, and this effect was blocked by naltrexone. Brain stimulation reward thresholds were unchanged by alcohol or naltrexone in 118AA mice. In the home cage, increased alcohol intake emerged in 118GG mice with increasing alcohol concentrations and was 33% higher at 17% alcohol. At this concentration, naltrexone selectively suppressed alcohol intake in 118GG animals to a level virtually identical to that of 118AA mice. No effect of naltrexone was found in the latter group. Similarly, both naltrexone and nalmefene were more effective in suppressing operant alcohol self-administration in 118GG mice.CONCLUSIONS: In a model that allows close experimental control, OPRM1 A118G variation robustly moderates effects of opioid antagonism on alcohol reward and consumption. These findings strongly support a personalized medicine approach to alcoholism treatment that takes into account OPRM1 genotype.
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| 18. |
- Blokland, G. A. M., et al.
(author)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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In: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Journal article (peer-reviewed)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 20. |
- Boen, Rune, et al.
(author)
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Beyond the global brain differences : intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers
- 2024
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In: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 95:2, s. 147-160
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Journal article (peer-reviewed)abstract
- Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference.Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness.Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
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| 24. |
- Brazel, David M., et al.
(author)
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Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use
- 2019
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In: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 85:11, s. 946-955
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Journal article (peer-reviewed)abstract
- BACKGROUND: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk.METHODS: We analyzed ∼250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci.RESULTS: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals.CONCLUSIONS: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.
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| 25. |
- Brikell, Isabell, et al.
(author)
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Familial Liability to Epilepsy and Attention-Deficit/Hyperactivity Disorder : A Nationwide Cohort Study
- 2018
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In: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 83:2, s. 173-180
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Journal article (peer-reviewed)abstract
- BACKGROUND: Epilepsy and attention-deficit/hyperactivity disorder (ADHD) are strongly associated; however, the underlying factors contributing to their co-occurrence remain unclear. A shared genetic liability has been proposed as one possible mechanism. Therefore, our goal in this study was to investigate the familial coaggregation of epilepsy and ADHD and to estimate the contribution of genetic and environmental risk factors to their co-occurrence.METHODS: We identified 1,899,654 individuals born between 1987 and 2006 via national Swedish registers and linked each individual to his or her biological relatives. We used logistic regression to estimate the association between epilepsy and ADHD within individual and across relatives. Quantitative genetic modeling was used to decompose the cross-disorder covariance into genetic and environmental factors.RESULTS: Individuals with epilepsy had a statistically significant increased risk of ADHD (odds ratio [OR] = 3.47, 95% confidence interval [CI] = 3.33-3.62). This risk increase extended to children whose mothers had epilepsy (OR = 1.85, 95% CI = 1.75-1.96), children whose fathers had epilepsy (OR = 1.64, 95% CI = 1.54-1.74), full siblings (OR = 1.56, 95% CI = 1.46-1.67), maternal half siblings (OR = 1.28, 95% CI = 1.14-1.43), paternal half siblings (OR = 1.10, 95% CI = 0.96-1.25), and cousins (OR = 1.15, 95% CI = 1.10-1.20). The genetic correlation was 0.21 (95% CI = 0.02-0.40) and explained 40% of the phenotypic correlation between epilepsy and ADHD, with the remaining variance largely explained by nonshared environmental factors (49%, nonshared environmental correlation = 0.36, 95% CI = 0.23-0.49). The contribution of shared environmental factors to the cross-disorder overlap was not statistically significant (11%, shared environmental correlation = 0.32, 95% CI = 20.16-0.79).CONCLUSIONS: This study demonstrates a strong and etiologically complex association between epilepsy and ADHD, with shared familial factors and risk factors unique to the individual contributing to co-occurrence of the disorders. Our findings suggest that epilepsy and ADHD may share less genetic risk as compared with other neurodevelopmental disorders.
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