Neuroticism-related personality traits are related to symptom severity in patients with premenstrual dysphoric disorder and to the serotonin transporter gene-linked polymorphism 5-HTTPLPR

Neuroticism has been linked to a functional polymorphism in the serotonin transporter gene (5-HTTLPR), with short-allele carriers being overrepresented among high-scorers on neuroticism. Studies evaluating neuroticism-related personality traits in relation to the 5-HTTLPR polymorphism among patients with premenstrual dysphoric disorder (PMDD) and are lacking. The primary aim of this study was to evaluate the relationship between PMDD and neuroticism-related personality traits, and secondly, to relate the personality trait scores of PMDD patients to experienced symptom severity and to the 5-HTTLPR short allele. Thirty PMDD patients and 55 asymptomatic healthy controls were included in the study. The Swedish Universities Scale of Personality was used to evaluate personality traits. Genotype analyses were available in 27 PMDD patients and 18 healthy controls. Women with PMDD displayed higher levels of neuroticism-related personality traits (psychic trait anxiety, somatic trait anxiety, embitterment, stress susceptibility and mistrust) than healthy controls, and these effects were most prominent in women with more severe luteal phase symptoms. Furthermore, PMDD patients with at least one copy of the short allele of the 5-HTTLPR polymorphism scored higher on psychic trait anxiety and lack of assertiveness than PMDD patients who were homozygous for the long allele. PMDD patients who suffer from more severe luteal phase symptoms also display increased scores of neuroticism-related personality traits in comparison with healthy controls. Within the group of PMDD patients, differences in certain personality trait scores are associated with the short allele of the 5-HTTLPR polymorphism

Ovarian Steroid Hormones, Emotion Processing and Mood

It is known that some psychiatric disorders may deteriorate in relation to the menstrual cycle. However, in some conditions, such as premenstrual dysphoric disorder (PMDD), symptomatology is triggered mainly by the variations in ovarian steroid hormones. Although symptoms induced by fluctuations in ovarian steroids often are affective, little is known about how emotion processing in women is influenced by variations, or actual levels, of ovarian steroid hormones. The general aim of this thesis was to evaluate menstrual cycle effects on reactivity in emotion generating and controlling areas in the corticolimbic system to emotional stimulation and anticipation, in healthy controls and women with PMDD. A second aim was to evaluate corticolimbic reactivity during long-term administration of exogenous ovarian steroids. In study I, III and IV effects of the menstrual cycle on emotional reactivity in women with PMDD was studied. In study I, women with PMDD in displayed higher amygdala reactivity than healthy controls to emotional faces, not in the luteal phase as was hypothesised, but in the follicular phase. No difference between menstrual cycle phases was obtained in women with PMDD, while healthy controls had an increased reactivity in the luteal phase. The results of study I was further elaborated in study III, where women with PMDD were observed to have an increased anticipatory reactivity to negative emotional stimuli. However, no differences in amygdala reactivity to emotional stimuli were obtained across the menstrual cycle. Finally, in study IV the hypothesis that amygdala reactivity increase in the luteal phase in women with PMDD is linked to social stimuli rather than generally arousing stimuli was suggested, tested and supported. In study II, re-exposure to COC induced mood symptoms de novo in women with a previous history of COC-induced adverse mood. Women treated with COC reported increased levels of mood symptoms both as compared to before treatment, and as compared to the placebo group. There was a relatively strong correlation between depressive scores before and during treatment. The effects of repeated COC administration on subjective measures and brain function were however dissociated with increased aversive experiences accompanied by reduced reactivity in the insular cortex

Ovarian Steroid Hormones, Emotion Processing and Mood

It is known that some psychiatric disorders may deteriorate in relation to the menstrual cycle. However, in some conditions, such as premenstrual dysphoric disorder (PMDD), symptomatology is triggered mainly by the variations in ovarian steroid hormones. Although symptoms induced by fluctuations in ovarian steroids often are affective, little is known about how emotion processing in women is influenced by variations, or actual levels, of ovarian steroid hormones. The general aim of this thesis was to evaluate menstrual cycle effects on reactivity in emotion generating and controlling areas in the corticolimbic system to emotional stimulation and anticipation, in healthy controls and women with PMDD. A second aim was to evaluate corticolimbic reactivity during long-term administration of exogenous ovarian steroids. In study I, III and IV effects of the menstrual cycle on emotional reactivity in women with PMDD was studied. In study I, women with PMDD in displayed higher amygdala reactivity than healthy controls to emotional faces, not in the luteal phase as was hypothesised, but in the follicular phase. No difference between menstrual cycle phases was obtained in women with PMDD, while healthy controls had an increased reactivity in the luteal phase. The results of study I was further elaborated in study III, where women with PMDD were observed to have an increased anticipatory reactivity to negative emotional stimuli. However, no differences in amygdala reactivity to emotional stimuli were obtained across the menstrual cycle. Finally, in study IV the hypothesis that amygdala reactivity increase in the luteal phase in women with PMDD is linked to social stimuli rather than generally arousing stimuli was suggested, tested and supported. In study II, re-exposure to COC induced mood symptoms de novo in women with a previous history of COC-induced adverse mood. Women treated with COC reported increased levels of mood symptoms both as compared to before treatment, and as compared to the placebo group. There was a relatively strong correlation between depressive scores before and during treatment. The effects of repeated COC administration on subjective measures and brain function were however dissociated with increased aversive experiences accompanied by reduced reactivity in the insular cortex

Ovarian Steroid Hormones, Emotion Processing and Mood

It is known that some psychiatric disorders may deteriorate in relation to the menstrual cycle. However, in some conditions, such as premenstrual dysphoric disorder (PMDD), symptomatology is triggered mainly by the variations in ovarian steroid hormones. Although symptoms induced by fluctuations in ovarian steroids often are affective, little is known about how emotion processing in women is influenced by variations, or actual levels, of ovarian steroid hormones. The general aim of this thesis was to evaluate menstrual cycle effects on reactivity in emotion generating and controlling areas in the corticolimbic system to emotional stimulation and anticipation, in healthy controls and women with PMDD. A second aim was to evaluate corticolimbic reactivity during long-term administration of exogenous ovarian steroids. In study I, III and IV effects of the menstrual cycle on emotional reactivity in women with PMDD was studied. In study I, women with PMDD in displayed higher amygdala reactivity than healthy controls to emotional faces, not in the luteal phase as was hypothesised, but in the follicular phase. No difference between menstrual cycle phases was obtained in women with PMDD, while healthy controls had an increased reactivity in the luteal phase. The results of study I was further elaborated in study III, where women with PMDD were observed to have an increased anticipatory reactivity to negative emotional stimuli. However, no differences in amygdala reactivity to emotional stimuli were obtained across the menstrual cycle. Finally, in study IV the hypothesis that amygdala reactivity increase in the luteal phase in women with PMDD is linked to social stimuli rather than generally arousing stimuli was suggested, tested and supported. In study II, re-exposure to COC induced mood symptoms de novo in women with a previous history of COC-induced adverse mood. Women treated with COC reported increased levels of mood symptoms both as compared to before treatment, and as compared to the placebo group. There was a relatively strong correlation between depressive scores before and during treatment. The effects of repeated COC administration on subjective measures and brain function were however dissociated with increased aversive experiences accompanied by reduced reactivity in the insular cortex

Unchanged cognitive performance and concurrent prefrontal blood oxygenation after accelerated intermittent theta-burst stimulation in depression : a sham-controlled study

Aim: Intermittent theta-burst stimulation (iTBS) delivered over the dorsomedial prefrontal cortex (DMPFC) has shown promise as a treatment for anhedonia and amotivation in patients with depression. Here, we investigated whether this protocol modulates cognitive performance and concurrent prefrontal blood oxygenation. We also examined whether depressed patients exhibit cognitive dysfunction and prefrontal hypoactivity at baseline compared to healthy controls. Methods: This sham-controlled study comprises 52 patients randomized to either active or sham accelerated iTBS over the DMPFC (applied twice daily) for 10 consecutive treatment days, and 55 healthy controls. Cognitive performance was assessed at baseline and once again 4 weeks later using a cognitive test battery targeting attention, inhibitory control, and numerical, verbal, and visual working memory. Concurrent prefrontal oxygenated hemoglobin (oxy-Hb) was captured with functional near-infrared spectroscopy. Results: Active iTBS over DMPFC did not affect cognitive performance or concurrent oxy-Hb change compared to sham iTBS in patients with depression. Compared to controls, patients at baseline showed impaired performance in the Trail Making Test,the Rey Auditory Verbal Learning Test, the Animal Naming Test, and the Digit Symbol Substitution Test, however no difference in prefrontal oxy-Hb was observed. Conclusion: Patients with treatment-resistant depression displayed cognitive deficits, however without prefrontal hypoactivity, compared to healthy controls at baseline. iTBS treatment did not alter cognitive performance, nor concurrent prefrontal blood oxygenation, in patients. Taken together, iTBS can likely be considered a cognitively safe treatment option in this sample of patients

Blinding integrity of dorsomedial prefrontal intermittent theta burst stimulation in depression

Background: The antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) is partly placebo, making blinding integrity important. Blinding of high-frequency rTMS and intermittent theta burst stimulation (iTBS) has been reported as successful at study end. However, blinding integrity at study start is rarely reported. The aim of this study was to investigate blinding integrity during a treatment course of iTBS over the dorsomedial prefrontal cortex (DMPFC) in depression. Methods: Forty-nine patients with depression from a double-blind-designed randomized controlled trial (NCT02905604) were included. Patients received either active or sham iTBS over the DMPFC with a placebo coil. The sham group received iTBS-synchronized transcutaneous electrical nerve stimulation. Results: After one session, 74% of participants were able to correctly guess their treatment allocation. This was above chance level (p = 0.001). The percentage dropped to 64% and 56% after the fifth and last sessions. Belong-ing to the active group influenced the choice to guess "active" (odds ratio: 11.7, 95% CI 2.5-53.7). A higher treat-ment intensity of the sham treatment increased the probability to guess "active", but pain did not influence the choice. Conclusions: Blinding integrity in iTBS trials must be investigated at study start to avoid uncontrolled confounding. Better sham methods are needed

An fMRI-study of leading and following using rhythmic tapping

Leading and following is about synchronizing and joining actions in accordance with the differ- ences that the leader and follower roles provide. The neural reactivity representing these roles was measured in an explorative fMRI-study, where two persons lead and followed each other in finger tapping using simple, individual, pre-learnt rhythms. All participants acted both as leader and follower. Neural reactivity for both lead and follow related to social awareness and adaptation distributed over the lateral STG, STS and TPJ. Reactivity for follow contrasted with lead mostly reflected sensorimotor and rhythmic processing in cerebellum IV, V, somatosensory cortex and SMA. During leading, as opposed to following, neural reactivity was observed in the insula and bilaterally in the superior temporal gyrus, pointing toward empathy, sharing of feelings, temporal coding and social engagement. Areas for continuous adaptation, in the posterior cerebellum and Rolandic operculum, were activated during both leading and following. This study indicated mutual adaptation of leader and follower during tapping and that the roles gave rise to largely similar neuronal reactivity. The differences between the roles indicated that leading was more socially focused and following had more motoric- and temporally related neural reactivity

Internet-delivered approach-avoidance conflict task shows temporal stability and relation to trait anxiety

Excessive avoidance causes functional impairment and maintains anxiety disorders. In the laboratory, approach-avoidance conflict tasks (AACT) can be used to study approach-avoidance behavior in mixed outcome situations (i.e., the same behavior entails both aversive and rewarding consequences). We tested the feasibility of a novel, internet-delivered AACT (iAACT) by conceptually replicating results from laboratory AACTs, including the temporal stability of results and the relation between trait anxiety and approach-avoidance behavior. Individuals from the general population (n = 186) completed a measure of trait anxiety and the iAACT, which entailed choosing either to approach aversive stimuli (image-sound) and receive a reward (points), or to avoid them and not receive a reward (i.e., costly avoidance). The temporal stability of approach-avoidance behavior was assessed by inviting participants to repeat the iAACT six weeks later (n = 91). Consistent with previous findings in laboratory AACTs, results showed that approach behavior to aversive stimuli increased with higher reward levels. These findings were replicated in the follow-up session. Also consistent with previous studies, higher trait anxiety was associated with elevated costly avoidance. In conclusion, the consistency of our results with laboratory studies indicates that the iAACT is feasible and may provide a cost-effective and scalable method to study anxiety-related approach-avoidance behavior remotely

Intermittent theta burst stimulation over the dorsomedial prefrontal cortex modulates resting-state connectivity in depressive patients : A sham-controlled study

The mechanisms underlying repetitive transcranial magnetic stimulation (rTMS) treatment are largely unknown. Although there is a general lack of sham controlled studies, findings show altered functional connectivity to the stimulated region following treatment. When targeting the dorsolateral prefrontal cortex (dlPFC), connectivity with the subgenual anterior cingulate cortex (sgACC) is predictive of response, but less is known about the effects on functional connectivity of targeting the dorsomedial PFC (dmPFC). Here, 30 patients with an ongoing depressive episode were recruited and randomized to 20 sessions at target intensity of either active or sham intermittent theta burst stimulation (iTBS) over dmPFC. Those receiving sham were offered active treatment in a subsequent open phase. A seven minute resting-state scan and depressive symptom assessment was performed before and after treatment. After exclusions due to attrition and excessive head movements 23 patients remained for analysis. Seed-based resting-state connectivity was calculated using two seeds for the dmPFC target as well as the sgACC. A symptom related increase in dmPFC connectivity after active treatment, compared to sham treatment, was found. The effect was observed in a region overlapping the precuneus and the posterior cingulate cortex (PCC), suggesting an increase in the connectivity between the targeted salience network and the default mode network mediating improvement in depressive symptoms. Connectivity between the precuneus and both the sgACC and the treatment target was predictive of symptom improvement following active treatment. The findings have implications for understanding the mechanisms behind iTBS and may inform future efforts to individualize the treatment