Psychometric Properties of the Verbal Affective Memory Test-26 and Evaluation of Affective Biases in Major Depressive Disorder.

We developed the Verbal Affective Memory Test-26 (VAMT-26), a computerized test to assess verbal memory, as an improvement of the Verbal Affective Memory Test-24 (VAMT-24). Here, we psychometrically evaluate the VAMT-26 in 182 healthy controls, examine 1-month test-retest stability in 48 healthy controls, and examine whether 87 antidepressant-free patients diagnosed with Major Depressive Disorder (MDD) tested with VAMT-26 differed in affective memory biases from 335 healthy controls tested with VAMT24/26. We also examine whether affective memory biases are associated with depressive symptoms across the patients and healthy controls. VAMT-26 showed good psychometric properties. Age, sex, and IQ, but not education, influenced VAMT-26 scores. VAMT-26 scores converged satisfactorily with scores on a test associated with non-affective verbal memory. Test-retest analyses showed a learning effect and a r ≥ 0.0.8, corresponding to a typical variation of 10% in recalled words from first to second test. Patients tended to remember more negative words relative to positive words compared to healthy controls at borderline significance (p = 0.06), and affective memory biases were negatively associated with depressive symptoms across the two groups at borderline significance (p = 0.07), however, the effect sizes were small. Future studies are needed to address whether VAMT-26 can be used to distinguish between depression subtypes in patients with MDD. As a verbal memory test, VAMT-26 is a well validated neuropsychological test and we recommend it to be used in Danish and international studies on affective memory.

Serotonin transporter gene (SLC6A4) variation and sensory processing sensitivity-Comparison with other anxiety-related temperamental dimensions.

BACKGROUND: The short (s) allele of the 5-HTTLPR polymorphism in the promoter region of the human serotonin transporter (5-HTT) gene SLC6A4 has previously been associated with anxiety-related personality dimensions. However, this relationship has not been confirmed in all studies and may be modified by environmental circumstances and/or psychiatric illness. This study examined whether the temperamental trait sensory processing sensitivity (SPS), characterized by increased responsivity to environmental stimuli, is related to 5-HTTLPR/rs25531 genotype. METHODS: 5-HTTLPR and rs25531 genotypes, level of SPS, self-reported Revised NEO Personality Inventory (NEO-PI-R) and Temperament and Character Inventory (TCI) personality profiles, and symptoms of psychological distress (SCL-90R Global Severity Index) were determined for 405 healthy volunteers. RESULTS: Sensory processing sensitivity was highly correlated with the anxiety-related dimensions of the NEO-PI-R and the TCI models of personality, Neuroticism, and Harm Avoidance, respectively. However, the level of SPS was not associated with the combined 5-HTTLPR and rs25531 s'/s' genotype. Neuroticism and Harm Avoidance were also not associated with 5-HTTLPR/rs25531 s'/s' genotype. Correcting for symptoms of psychological distress had no effect on the relationships between personality and genotype. CONCLUSION: The level of SPS was not associated with serotonin transporter gene variation. Further, combined 5-HTTLPR and rs25531 genotype was not associated with other anxiety-related dimensions.

Sensory processing sensitivity and its association with seasonal affective disorder.

It has been hypothesized that an increased sensitivity to the surroundings, can leave some individuals vulnerable to experience the environmental stress of winter more overwhelming, thus leading to a greater risk of Seasonal Affective Disorder (SAD). However, the association between trait Sensory Processing Sensitivity (SPS) and SAD is not known. We therefore aimed to investigate: 1)cross-seasonal group differences in trait SPS, in 31 individuals with SAD compared to 30 age-, gender- and education-matched healthy controls, and 2)the association between trait SPS in remitted phase (summer) and depression severity in symptomatic phase (winter) in individuals with SAD. All participants completed the Highly Sensitive Person Scale, as a measure of SPS, and the Major Depression Inventory in summer and in winter, using a longitudinal and seasonally counterbalanced design. In both remitted and symptomatic phase, individuals with SAD exhibited higher trait SPS compared to healthy controls, which for individuals with SAD was heightened during depression in winter. Notably, when averaged across season, about 25% of the individuals with SAD display high-sensitivity whereas this is only the case for 5% of the healthy controls. In addition, higher trait SPS in summer was associated with more severe SAD symptoms in winter. Our findings suggest that those with SAD are more likely to score high on SPS and that high SPS may be a vulnerability marker related to more severe SAD symptomatology.

Amygdala reactivity to fearful faces correlates positively with impulsive aggression.

Facial expressions robustly activate the amygdala, a brain structure playing a critical role in aggression. Whereas previous studies suggest that amygdala reactivity is related to various measures of impulsive aggression, we here estimate a composite measure of impulsive aggression and evaluate whether it is associated with amygdala reactivity to angry and fearful faces. We estimated amygdala reactivity with functional magnetic resonance imaging in 47 men with varying degree of aggressive traits (19 incarcerated violent offenders and 28 healthy controls). We modeled a composite "impulsive aggression" trait construct (LVagg) using a linear structural equation model, with a single latent variable capturing the shared correlation between five self-report measures of trait aggression, anger and impulsivity. We tested for associations between amygdala reactivity and the LVagg, adjusting for age and group. The LVagg was significantly positively associated with amygdala reactivity to fearful (p = 0.001), but not angry faces (p = 0.9). We found no group difference in amygdala reactivity to fearful or angry faces. The findings suggest that that amygdala reactivity to fearful faces is represented by a composite index of impulsive aggression and provide evidence that impulsive aggression is associated with amygdala reactivity in response to submissive cues, i.e., fearful faces.

Amygdala response to emotional faces in seasonal affective disorder.

BACKGROUND: Seasonal affective disorder (SAD) is characterized by seasonally recurring depression. Heightened amygdala activation to aversive stimuli is associated with major depressive disorder but its relation to SAD is unclear. We evaluated seasonal variation in amygdala activation in SAD and healthy controls (HC) using a longitudinal design targeting the asymptomatic/symptomatic phases of SAD. We hypothesized increased amygdala activation to aversive stimuli in the winter in SAD individuals (season-by-group interaction). METHODS: Seventeen SAD individuals and 15 HCs completed an implicit emotional faces BOLD-fMRI paradigm during summer and winter. We computed amygdala activation (SPM5) to an aversive contrast (angry & fearful minus neutral) and angry, fearful and neutral faces, separately. Season-by-group and main effects were evaluated using Generalized Least Squares. In SAD individuals, we correlated change in symptom severity, assessed with The Hamilton Rating Scale for Depression - Seasonal Affective Disorder version (SIGH-SAD), with change in amygdala activation. RESULTS: We found no season-by-group, season or group effect on our aversive contrast. Independent of season, SAD individuals showed significantly lower amygdala activation to all faces compared to healthy controls, with no evidence for a season-by-group interaction. Seasonal change in amygdala activation was unrelated to change in SIGH-SAD. LIMITATIONS: Small sample size, lack of positive valence stimuli. CONCLUSIONS: Amygdala activation to aversive faces is not increased in symptomatic SAD individuals. Instead, we observed decreased amygdala activation across faces, independent of season. Our findings suggest that amygdala activation to angry, fearful and neutral faces is altered in SAD individuals, independent of the presence of depressive symptoms.

Men with high serotonin 1B receptor binding respond to provocations with heightened amygdala reactivity.

Serotonin signalling influences amygdala reactivity to threat-related emotional facial expressions in healthy adults, but in vivo serotonin signalling has never been investigated in the context of provocative stimuli in aggressive individuals. The aim of this study was to evaluate associations between serotonin 1B receptor (5-HT1BR) levels and brain reactivity to provocations. We quantified regional 5-HT1BR binding using [11C]AZ10419369 positron emission tomography (PET) and measured brain activation following provocations with functional magnetic resonance imaging (fMRI) in eighteen violent offenders and 25 healthy control subjects. The point-subtraction aggression paradigm (PSAP) was used in fMRI to elicit provocations in terms of monetary subtractions from a fictive opponent. We estimated global 5-HT1BR binding using a linear structural equation model, with a single latent response variable (LV1B) modelling shared correlation between 5-HT1BR binding across multiple brain regions (neocortex, anterior and posterior cingulate cortex, raphe, amygdala, hippocampus and striatum). We tested whether the LV1B was associated with amygdala, striatal and prefrontal reactivity to provocations, adjusting for age, injected mass and group. Across participants, LV1B was statistically significantly positively associated with amygdala (p = 0.01) but not with striatal (p = 0.2) or prefrontal reactivity to provocations (p = 0.3). These findings provide novel evidence that 5-HT1BR levels are linked to amygdala reactivity to provocations in a cohort of men displaying a wide range of aggressive behavior. The data suggest that 5-HT1BR represents an intriguing target for reducing excessive neural reactivity to provocations and thereby putatively violent behavior.

Brain serotonin 4 receptor binding is inversely associated with verbal memory recall.

BACKGROUND: We have previously identified an inverse relationship between cerebral serotonin 4 receptor (5-HT 4R) binding and nonaffective episodic memory in healthy individuals. Here, we investigate in a novel sample if the association is related to affective components of memory, by examining the association between cerebral 5-HT 4R binding and affective verbal memory recall. METHODS: Twenty-four healthy volunteers were scanned with the 5-HT 4R radioligand [11C]SB207145 and positron emission tomography, and were tested with the Verbal Affective Memory Test-24. The association between 5-HT 4R binding and affective verbal memory was evaluated using a linear latent variable structural equation model. RESULTS: We observed a significant inverse association across all regions between 5-HT 4R binding and affective verbal memory performances for positive (p = 5.5 × 10-4) and neutral (p = .004) word recall, and an inverse but nonsignificant association for negative (p = .07) word recall. Differences in the associations with 5-HT 4R binding between word categories (i.e., positive, negative, and neutral) did not reach statistical significance. CONCLUSION: Our findings replicate our previous observation of a negative association between 5-HT 4R binding and memory performance in an independent cohort and provide novel evidence linking 5-HT 4R binding, as a biomarker for synaptic 5-HT levels, to the mnestic processing of positive and neutral word stimuli in healthy humans.

State-dependent alterations in inhibitory control and emotional face identification in seasonal affective disorder.

BACKGROUND: Depressed individuals often exhibit impaired inhibition to negative input and identification of positive stimuli, but it is unclear whether this is a state or trait feature. We here exploited a naturalistic model, namely individuals with seasonal affective disorder (SAD), to study this feature longitudinally. AIM: The goal of this study was to examine seasonal changes in inhibitory control and identification of emotional faces in individuals with SAD. METHOD: Twenty-nine individuals diagnosed with winter-SAD and 30 demographically matched controls with no seasonality symptoms completed an emotional Go/NoGo task, requiring inhibition of prepotent responses to emotional facial expressions and an emotional face identification task twice, in winter and summer. RESULTS: In winter, individuals with SAD showed impaired ability to inhibit responses to angry (p = .0006) and sad faces (p = .011), and decreased identification of happy faces (p = .032) compared with controls. In summer, individuals with SAD and controls performed similarly on these tasks (ps > .24). CONCLUSION: We provide novel evidence that inhibition of angry and sad faces and identification of happy faces are impaired in SAD in the symptomatic phase, but not in the remitted phase. The affective biases in cognitive processing constitute state-dependent features of SAD. Our data show that reinstatement of a normal affective cognition should be possible and would constitute a major goal in psychiatric treatment to improve the quality of life for these patients. (PsycINFO Database Record

Seasonal difference in brain serotonin transporter binding predicts symptom severity in patients with seasonal affective disorder.

Cross-sectional neuroimaging studies in non-depressed individuals have demonstrated an inverse relationship between daylight minutes and cerebral serotonin transporter; this relationship is modified by serotonin-transporter-linked polymorphic region short allele carrier status. We here present data from the first longitudinal investigation of seasonal serotonin transporter fluctuations in both patients with seasonal affective disorder and in healthy individuals. Eighty (11)C-DASB positron emission tomography scans were conducted to quantify cerebral serotonin transporter binding; 23 healthy controls with low seasonality scores and 17 patients diagnosed with seasonal affective disorder were scanned in both summer and winter to investigate differences in cerebral serotonin transporter binding across groups and across seasons. The two groups had similar cerebral serotonin transporter binding in the summer but in their symptomatic phase during winter, patients with seasonal affective disorder had higher serotonin transporter than the healthy control subjects (P = 0.01). Compared to the healthy controls, patients with seasonal affective disorder changed their serotonin transporter significantly less between summer and winter (P < 0.001). Further, the change in serotonin transporter was sex- (P = 0.02) and genotype- (P = 0.04) dependent. In the patients with seasonal affective disorder, the seasonal change in serotonin transporter binding was positively associated with change in depressive symptom severity, as indexed by Hamilton Rating Scale for Depression - Seasonal Affective Disorder version scores (P = 0.01). Our findings suggest that the development of depressive symptoms in winter is associated with a failure to downregulate serotonin transporter levels appropriately during exposure to the environmental stress of winter, especially in individuals with high predisposition to affective disorders.media-1vid110.1093/brain/aww043_video_abstractaww043_video_abstract.

Development and psychometric validation of the verbal affective memory test.

We here present the development and validation of the Verbal Affective Memory Test-24 (VAMT-24). First, we ensured face validity by selecting 24 words reliably perceived as positive, negative or neutral, respectively, according to healthy Danish adults' valence ratings of 210 common and non-taboo words. Second, we studied the test's psychometric properties in healthy adults. Finally, we investigated whether individuals diagnosed with Seasonal Affective Disorder (SAD) differed from healthy controls on seasonal changes in affective recall. Recall rates were internally consistent and reliable and converged satisfactorily with established non-affective verbal tests. Immediate recall (IMR) for positive words exceeded IMR for negative words in the healthy sample. Relatedly, individuals with SAD showed a significantly larger decrease in positive recall from summer to winter than healthy controls. Furthermore, larger seasonal decreases in positive recall significantly predicted larger increases in depressive symptoms. Retest reliability was satisfactory, rs ≥ .77. In conclusion, VAMT-24 is more thoroughly developed and validated than existing verbal affective memory tests and showed satisfactory psychometric properties. VAMT-24 seems especially sensitive to measuring positive verbal recall bias, perhaps due to the application of common, non-taboo words. Based on the psychometric and clinical results, we recommend VAMT-24 for international translations and studies of affective memory.

Personality characteristics in surgery seeking and non-surgery seeking obese individuals compared to non-obese controls.

It is currently unknown what makes some obese individuals opt for bariatric surgery whereas others choose not to. The aim of this study was to examine whether personality characteristics differed between obese individuals signed up for Roux-en-Y gastric bypass (RYGB) (N=30) and obese individuals not seeking RYGB (N=30) compared to non-obese controls (N=30). All participants completed the NEO Personality Inventory-Revised. The obese RYGB group displayed higher levels of Neuroticism and borderline lower levels of Extraversion compared to the obese non-RYGB and the non-obese group, while the two latter groups did not differ in terms of personality. The Neuroticism domain and possibly the Extraversion domain may therefore be worthwhile to consider in future studies investigating the outcome of bariatric surgery.