Rune Jonassen

Attentional functions in major depressive disorders with and without comorbid anxiety.

The aim of this study was to explore if the divergent results regarding attentional functions in patients with mood disorders are due to selective impairments in higher level or more basic and distinctive attentional subcomponents. We compared outpatients with current major depressive disorders (MDD; n = 37) and MDD with comorbid anxiety disorder (MDDA; n = 24) with healthy controls (n = 92) on Stroop and Attentional Network Test (ANT). The current data indicate that significant impairment in attentional functions corresponds to the presence of MDD and MDDA. MDDA displayed significantly lower performance on the Stroop variables, and MDD were significantly impaired in the alerting function in ANT. These results show impairments on different levels of attention in mood disorders. MDDA show impairments on higher level executive attention functions, whereas MDD display deficits at the basic attentional level. These findings suggest that including comorbid anxiety disorder in MDD is important for future research.

Serotonin transporter polymorphisms (5-HTTLPR) in emotion processing: Implications from current neurobiology

The candidate gene approach directly tests the effects of genetic variation within a potentially contributing gene in an association study. However, the candidate gene approach is limited by how much is known about the biology of the disease being investigated. The serotonin transporter gene SLC6A4 has been studied more than any other single candidate gene in the field of neurobiology. Transcription of the serotonin transporter gene is modulated by a polymorphic region, 5-HTTLPR, near the promoter. 5-HTTLPR genotype has been associated with individual variation in emotion processing, brain structure, and brain function. We present an updated review of the biological literature on the serotonin transporter polymorphism. Recent imaging and behavioral studies of the role of 5-HTTLPR genotype in emotion processing are discussed in light of new biological findings related to 5-HTTLPR variation. We also examine the clinical implications of discoveries about the role of serotonin and 5-HTTLPR genotype in neural plasticity and behavioral malleability.

Serotonin Transporter Polymorphism Modulates N-Back Task Performance and fMRI BOLD Signal Intensity in Healthy Women

Context Exploring intermediate phenotypes within the human brains functional and structural circuitry is a promising approach to explain the relative contributions of genetics, complex behaviors and neural mechanisms in the development of major depressive disorder (MDD). The polymorphic region 5-HTTLPR in the serotonin transporter gene (SLC6A4) has been shown to modulate MDD risk, but the neural underpinnings are incompletely understood. Objective 37 right handed healthy women between 21 and 61 years of age were invited to participate in an fMRI modified n-back study. The functional polymorphism 5-HTTLPR located in the promoter region of the SLC6A4 gene was genotyped using polymerase chain reaction (PCR). Results Short 5-HTTLPR allele carriers showed more blood-oxygen-level-dependent (BOLD) bilateral prefrontal cortex activation in the right [F(2, 30) = 4.8, η2 = .25, p = .026] and left [F(2, 30) = 4.1, η2 = .22, p = .015] inferior frontal gyrus pars triangularis with increasing n-back task difficulty relative to long 5-HTTLPR allele carriers. Short 5-HTTLPR allele carriers had inferior task performance on the most difficult n-back condition [F(2, 30) = 4.9, η2 = .26, p = .014]. Conclusions This activation pattern found in healthy at risk individuals resembles an activation pattern that is typically found in patients suffering from acute MDD. Altered function in these areas may reflect intermediate phenotypes and may help explain the increased risk of depression in short 5-HTTLPR allele carriers.

The effects of the serotonin transporter polymorphism and age on frontal white matter integrity in healthy adult women.

Studies of populations at genetic risk have the potential to explore the underlying structural and functional mechanisms in the development of psychological disorders. The polymorphic region (5-HTTLPR) in the serotonin transporter gene (SLC6A4) has been associated with major depression (MDD) (Caspi et al., 2003). In healthy women, variation in the human brain white matter microstructure integrity in the uncinate fascicule (UF) has been suggested as an endophenotypes in the development of MDD. Pacheco et al. (2009) found a unique effect of age and 5-HTTLPR within the left frontal UF. The present study examined whether these associations persist along the adult life span. Thirty-seven right-handed healthy women between 21 and 61 years of age were invited for a diffusion MRI study. The functional polymorphism 5-HTTLPR located in the promoter region of the SLC6A4 gene was genotyped using polymerase chain reaction (PCR). Fractional anisotropy (FA) was generated for the UF based on Tract-Based Spatial Statistics (TBSS). Models of emotion regulation circuitry suggest that working memory is important in conscious emotion regulation (Price and Drevets, 2010). To explore if 5-HTTLPR is related to this aspects of emotion processing, a working memory pathway, the superior longitudinal fascicule (SLF) was included. The results demonstrate that age may explain the hypothesized association between 5-HTTLPR and frontal UF white matter integrity in healthy adult women. Both white matter changes associated with the aging process and those associated with growth and development may explain why the earlier reported unique effects of genotype in frontal UF FA do not persist into adulthood.

Serotonin transporter polymorphisms predict response inhibition in healthy volunteers

Serotoninergic transmission is reliably implicated in inhibitory control processes. The aim of this study was to test the hypothesis if serotonin transporter polymorphisms mediate inhibitory control in healthy people. 141 healthy subjects, carefully screened for previous and current psychopathology, were genotyped for the 5-HTTLPR and rs25531 polymorphisms. Inhibitory control was ascertained with the Stop Signal Task (SST) from the Cambridge Neuropsychological Test Automated Battery (CANTAB). The triallelic gene model, reclassified and presented in a biallelic functional model, revealed a dose-dependent gene effect on SST performance with Individuals carrying the low expressive allele had inferior inhibitory control compared to high expressive carriers. This directly implicates serotonin transporter polymorphisms (5-HTTLPR plus rs25531) in response inhibition in healthy subjects.

Verbal Memory Functions in Unipolar Major Depression With and Without Co-Morbid Anxiety

The aim of this study was to examine both executive control of verbal working memory and verbal learning as well as long-term storage function in outpatients with major depressive disorder (n = 61) compared to healthy controls (n = 92). A total of 37 patients had no co-morbid anxiety disorder, whereas 24 had a co-morbid anxiety disorder. Both patient groups showed impaired working memory test performance compared to healthy controls. Patients with co-morbid depression and anxiety disorder performed significantly below the depression group. Only patients with depression and co-morbid anxiety displayed deficient long-term memory function compared to healthy controls. The present results show impairments in various memory functions in patients presenting depression and depression with co-morbid anxiety disorder.

Cognitive Control Functions in Unipolar Major Depression with and without Co-Morbid Anxiety Disorder.

Background: Impaired cognitive control functions have been demonstrated in both major depression (MDD) and anxiety disorder (A), but few studies have systematically examined the impact of MDD with co-morbid A (MDDA), which is the main aim of this study. Method: We compared patients with MDD with (MDDA; n = 24) and without co-morbid A (n = 37) to a group of healthy controls (HC; n = 92) on three subtests from the Cambridge Neuropsychological Test Automated Battery; intra–extra dimensional, stop signal task, and spatial working memory. These tasks correspond to a theoretical model consisting of three separable but interrelated executive control functions: Shifting, Inhibition, and Updating. A simple psychomotor speed measure was also included. Results: After controlling for age, gender, and education level, the results showed that the MDDA group displayed significantly impaired performance on the functions Shifting and Updating compared to HC. There emerged no significant differences between any of the patient groups and HC regarding Inhibition. The pure MDD group did not display dysfunctions relative to the HC group on the main executive control variables, but displayed slowed psychomotor speed. Contrary to expectation there were no significant differences between the MDDA and the MDD groups. Conclusion: Co-morbid anxiety should be taken into account when studying cognitive control functions in major depression.

Associations between serotonin transporter polymorphisms and cognitive processing applying the Emo 1-back task.

Down regulation of serotonin transporter (5-HTT) expression has been associated with brain function and major depression. The aim of this study was to explore the allelic variation (short and long) of the 5-HTTLPR polymorphism in attention bias associated with top-down processing of emotion. One hundred sixty-two healthy participants underwent genotyping (5-HTTLPR), background interviews, psychological screening, and a computerised test session (The Emo 1-back task). Carriers of the short 5-HTTLPR alleles in the serotonin transporter gene (SLC6A4) demonstrated less accuracy in The Emo 1-back task when presented with successive images of sad or fearful faces, but not for happy or neutral emotional faces. The study suggests an association between 5-HTTLPR variation in the serotonin transporter gene and altered emotion processing.

Dysfunctional Metacognitive Beliefs Are Associated with Decreased Executive Control

Dysfunctional metacognitive beliefs (“metacognitions”) and executive control are important factors in mental disorders such as depression and anxiety, but the relationship between these concepts has not been studied systematically. We examined whether there is an association between metacognitions and executive control and hypothesized that decreased executive control statistically predicts increased levels of metacognitions. Two hundred and ninety-nine individuals recruited from the general population and outpatient psychiatric clinics completed the Metacognitions Questionnaire-30 and three subtests from the Cambridge Neuropsychological Test Automated Battery corresponding to the three-component model of executive functions. Controlling for current depression and anxiety symptoms, decreased ability to shift between mental sets was associated with increased negative beliefs about the uncontrollability and danger of worry and beliefs about the need to control thoughts. The results suggest a basic association between metacognitions and executive control. Individual differences in executive control could prove important in the personalization of metacognitive therapy.

Effects of Attentional Bias Modification on Residual Symptoms in depression. A Randomized Controlled Trial.

Objective Following treatment, many depressed patients have significant residual symptoms. However, large randomised controlled trials (RCT) in this population are lacking. Attention bias modification training (ABM) can modify biases in emotion processing and may lead to symptom relief. We hypothesized that two weeks of ABM training would reduce clinician rated and self-reported residual symptoms and that change towards more positive attentional biases (AB) would be associated with symptom reduction. Method A total of 322 patients with a history of depression were included in a preregistered randomized controlled double-blinded trial. Patients were randomised to an emotional ABM paradigm over fourteen days or a closely matched control condition. Symptoms based on the Hamilton Rating Scale for Depression (HRSD) and Beck Depression Inventory II (BDI-II) were obtained at baseline and after ABM training. The primary outcome was change in HRSD and BDI-II. Participants were assessed for AB before and after the intervention. Results ABM training led to significantly greater decrease in clinician rated symptoms of depression as compared to the control condition. No differences between ABM and placebo were found for self-reported symptoms. ABM induced a change of AB towards more positive versus neutral stimuli with a more positive bias being associated with greater symptom reduction. Conclusion The current study demonstrates that ABM produces early changes in both AB and residual depressive symptoms. ABM may have practical potential in the treatment of residual depression. Trial Registration clinicaltrials.gov Identifier: NCT02658682.