Masennuslääkkeiden vaikutukset tunteiden käsittelyyn

Vertaisarvioitu. English summaryPeer reviewe

Masennuslääkkeiden vaikutukset tunteiden käsittelyyn

Masennukseen liittyy emotionaalisen tiedon käsittelyn vääristymiä. Masennuspotilaat esimerkiksi muistavat ja tulkitsevat ympäristön tapahtumia negatiivisesti vääristyneellä tavalla. Masennuksen eri hoitomuodot pyrkivät muovaamaan näitä vääristymiä. Myös masennuslääkkeet vaikuttavat emotionaalisen tiedon käsittelyyn jo ennen kuin masennusoireet väistyvät. Masennuslääkkeet heikentävät aivojen tunneverkoston keskeisten alueiden reaktiivisuutta negatiivisiin ärsykkeisiin ja voimistavat reaktiivisuutta positiivisiin ärsykkeisiin. Dorsolateraalisen etuaivokuoren aktiivisuus voimistuu, mikä viittaa parantuneeseen tunteiden säätelyyn. Masennuslääkkeet vaikuttavat myös laaja-alaisten aivoverkostojen toiminnallisiin yhteyksiin. Nämä varhaiset emotionaalisen prosessoinnin muutokset vaikuttavat ennustavan viikkoja myöhemmin saavutettavaa hoitovastetta. Emotionaalisen tiedonkäsittelyn muutokset saattaisivat siis toimia hoidon valintaa ohjaavina ennustetekijöinä, joita ei nykyisin ole kliinisessä käytössä. Masennuslääkkeiden vaikutusmekanismien tunteminen systeemitasolla on tärkeää myös uusien hoitomuotojen kehittämisen kannalta.</p

Bipolar disorder predicted shorter and borderline personality disorder symptoms longer time to remission-A prospective cohort study of major depressive patients

Background: Major depressive episodes (MDEs) of major depressive (MDD) or bipolar disorders (BD) are frequently complicated by features of borderline personality disorder (BPD). Mixed features are a hallmark of BD and affective lability of BPD, and both may markedly influence illness course. However, direct comparisons of outcome of depression in MDD, BD, and BPD are scarce.Methods: In a cohort study based on stratified sampling, we diagnosed psychiatric MDE patients with SCID-I/P and SCID-II interviews and examined mixed symptoms using the Mix-MDE scale and borderline symptoms using the Borderline Personality Disorder Severity Index. During a six-month prospective follow-up, the MDE patients with MDD (n = 39), BD (n = 33), or BPD (n = 23) completed biweekly online assessments. Using life chart methodology, we divided the follow-up period into qualitatively different mood state periods. We investigated durations of mood episodes, times to first full symptomatic remission, and their predictors.Results: Remission rates were similar in MDD, MDE/BD, and MDE/BPD patients. MDE/BD patients experienced more numerous and shorter distinct mood state periods during follow-up than the others. MDE/BD was associated with shorter (HR = 2.44, 95 % CI = 1.27-4.67) and dimensionally assessed BPD severity with longer time to first remission (HR = 0.95, 95 % CI = 0.91-1.00). Limitations: Moderate sample size and follow-up duration.Conclusions: Course of illness over six months differs between the three depressive groups. Bipolar depressive patients have the most alternating course and the shortest time to first period of remission. Dimensionally assessed severity of BPD may predict longer time to remission from depression.Peer reviewe

Borderline Personality Disorder With Depression Confers Significant Risk of Suicidal Behavior in Mood Disorder Patients—A Comparative Study

ObjectiveWe investigated risk factors for suicidal ideation and behavior among currently depressed patients with major depressive disorder (MDD), major depressive episode (MDE) in bipolar disorder (BD), or MDE with comorbid borderline personality disorder (MDE/BPD). We compared current and lifetime prevalence of suicidal ideation and behavior, and investigated dimensional measures of BPD or mixed affective features of the MDE as indicators of risk.MethodsBased on screening of 1,655 referrals, we recruited 124 psychiatric secondary care outpatients with MDE and stratified them into three subcohorts (MDD, BD, and MDE/BPD) using the Structured Clinical Interview for DSM-IV I and II. We examined suicidal ideation and behavior with the Columbia Suicide Severity Rating Scale (CSSRS). In addition, we quantified the severity of BPD symptoms and BD mixed features both categorically/diagnostically and dimensionally (using instruments such as the Borderline Personality Disorder Severity Index) in two time frames.ResultsThere were highly significant differences between the lifetime prevalences of suicide attempts between the subcohorts, with attempts reported by 16% of the MDD, 30% of the BD, and 60% of the BPD subcohort. Remarkably, the lifetime prevalence of suicide attempts in patients with comorbid BD and BPD exceeded 90%. The severity of BPD features was independently associated with risk of suicide attempts both lifetime and during the current MDE. It also associated in a dose-dependent manner with recent severity of ideation in both BPD and non-BPD patients. In multinominal logistic regression models, hopelessness was the most consistent independent risk factor for severe suicidal ideation in both time frames, whereas younger age and more severe BPD features were most consistently associated with suicide attempts.ConclusionsAmong patients with major depressive episodes, diagnosis of bipolar disorder, or presence of comorbid borderline personality features both imply remarkably high risk of suicide attempts. Risk factors for suicidal ideation and suicidal acts overlap, but may not be identical. The estimated severity of borderline personality features seems to associate with history of suicidal behavior and current severity of suicidal ideation in dose-dependent fashion among all mood disorder patients. Therefore, reliable assessment of borderline features may advance the evaluation of suicide risk.Peer reviewe

Reduced visual contrast suppression during major depressive episodes

Background: Previous studies have suggested that processing of visual contrast information could be altered in major depressive disorder. To clarify the changes at different levels of the visual hierarchy, we behaviourally measured contrast perception in 2 centre-surround conditions, assessing retinal and cortical processing. Methods: As part of a prospective cohort study, our sample consisted of controls (n = 29; 21 female) and patients with unipolar depression, bipolar disorder and borderline personality disorder who had baseline major depressive episodes (n = 111; 74 female). In a brightness induction test that assessed retinal processing, participants compared the perceived luminance of uniform patches (presented on a computer screen) as the luminance of the backgrounds was varied. In a contrast suppression test that assessed cortical processing, participants compared the perceived contrast of gratings, which were presented with collinearly or orthogonally oriented backgrounds. Results: Brightness induction was similar for patients with major depressive episodes and controls (p = 0.60, d = 0.115, Bayes factor = 3.9), but contrast suppression was significantly lower for patients than for controls (p < 0.006, d = 0.663, Bayes factor = 35.2). We observed no statistically significant associations between contrast suppression and age, sex, or medication or diagnostic subgroup. At follow-up (n = 74), we observed some normalization of contrast perception. Limitations: We assessed contrast perception using behavioural tests instead of electrophysiology. Conclusion: The reduced contrast suppression we observed may have been caused by decreased retinal feedforward or cortical feedback signals. Because we observed intact brightness induction, our results suggest normal retinal but altered cortical processing of visual contrast during a major depressive episode. This alteration is likely to be present in multiple types of depression and to partially normalize upon remission.Peer reviewe

Escitalopram enhances synchrony of brain responses during emotional narratives in patients with major depressive disorder

One-week treatment with escitalopram decreases amygdala responses to fearful facial expressions in depressed patients, but it remains unknown whether it also modulates processing of complex and freely processed emotional stimuli resembling daily life emotional situations. Inter-subject correlation (ISC) offers a means to track brain activity during complex, dynamic stimuli in a model-free manner. Twenty-nine treatment-seeking patients with major depressive disorder were randomized in a double-blind study design to receive either escitalopram or placebo for one week, after which functional magnetic resonance imaging (fMRI) was performed. During fMRI the participants listened to spoken emotional narratives. Level of ISC between the escitalopram and the placebo group was compared across all the narratives and separately for the episodes with positive and negative valence. Across all the narratives, the escitalopram group had higher ISC in the default mode network of the brain as well as in the fronto-temporal narrative processing regions, whereas lower ISC was seen in the middle temporal cortex, hippocampus and occipital cortex. Escitalopram increased ISC during positive parts of the narratives in the precuneus, medial prefrontal cortex, anterior cingulate and fronto-insular cortex, whereas there was no significant synchronization in brain responses to positive vs negative events in the placebo group. Increased ISC may imply improved emotional synchronization with others, particularly during observation of positive events. Further studies are needed to test whether this contributes to the later therapeutic effect of escitalopram.Peer reviewe

Short-term escitalopram treatment normalizes aberrant self-referential processing in major depressive disorder

Background: Increased self-focus and negative self-concept play an important role in depression. Antidepressants influence self-referential processing in healthy volunteers, but their function in self-processing of depressed patients remains unknown. Methods: Thirty-two depressed patients were randomly allocated to receive either escitalopram 10 mg or placebo for one week. After one week, neural responses to positive and negative self-referential adjectives and neutral control stimuli were assessed with functional magnetic resonance imaging. A group of matched healthy volunteers served as a control group. Results: Escitalopram decreased responses of medial fronto-parietal regions to self-referential words relative to non-emotional control stimuli, driven by increased responses to the control condition. Escitalopram also increased responses in the pre-defined region of the medial prefrontal cortex (MPFC) and the anterior cingulate cortex (ACC) to positive relative to negative words. Importantly, the changes in neural responses occurred before any effect on depressive symptoms, implying a direct effect of escitalopram. Furthermore, the placebo group had decreased responses of the MPFC and the ACC to positive self-referential processing relative to the matched healthy controls. However, neural responses of the escitalopram group and the healthy unmedicated controls were similar. Limitations: Differences between the groups in self-reported depression symptoms and personality traits may have influenced the results. Conclusion: One-week treatment with escitalopram normalized aberrant self-referential processing in depressed patients, shifting the focus from the self to the external environment and potentiating positive self-referential processing. This may be an important factor in mechanism of action of antidepressants.Peer reviewe