Background Notwithstanding the firmly established cross-sectional association of happiness with psychiatric disorders and their symptom severity, little is known about their temporal relationships.... Show moreBackground Notwithstanding the firmly established cross-sectional association of happiness with psychiatric disorders and their symptom severity, little is known about their temporal relationships. The goal of the present study was to investigate whether happiness is predictive of subsequent psychiatric disorders and symptom severity (and vice versa). Moreover, it was examined whether changes in happiness co-occur with changes in psychiatric disorder status and symptom severity. Methods In the Netherlands Study of Depression and Anxiety (NESDA), happiness (SRH: Self-Rated Happiness scale), depressive and social anxiety disorder (CIDI: Composite Interview Diagnostic Instrument) and depressive and anxiety symptom severity (IDS: Inventory of Depressive Symptomatology; BAI: Beck Anxiety Inventory; and FQ: Fear Questionnaire) were measured in 1816 adults over a three-year period. Moreover, we focused on occurrence and remittance of 6-month recency Major Depressive Disorder (MDD) and Social Anxiety Disorders (SAD) as the two disorders most intertwined with subjective happiness. Results Interindividual differences in happiness were quite stable (ICC of .64). Higher levels of happiness predicted recovery from depression (OR = 1.41; 95% CI = 1.10-1.80), but not social anxiety disorder (OR = 1.31; 95%CI = .94-1.81), as well as non-occurrence of depression (OR = 2.41; 95%CI = 1.98-2.94) and SAD (OR = 2.93; 95%CI = 2.29-3.77) in participants without MDD, respectively SAD at baseline. Higher levels of happiness also predicted a reduction of IDS depression (sr = - 0.08; 95%CI = -0.10 - -0.04), and BAI (sr = - 0.09; 95%CI = -0.12 - -0.05) and FQ (sr = - 0.06; 95%CI = -0.09 - -0.04) anxiety symptom scores. Conversely, presence of affective disorders, as well as higher depression and anxiety symptom severity at baseline predicted a subsequent reduction of self-reported happiness (with marginal to small sr values varying between -.04 (presence of SAD) to -.17 (depression severity on the IDS)). Moreover, changes in happiness were associated with changes in psychiatric disorders and their symptom severity, in particular with depression severity on the IDS (sr = - 0.46; 95%CI = -.50 - -.42). Conclusions Results support the view of rather stable interindividual differences in subjective happiness, although level of happiness is inversely associated with changes in psychiatric disorders and their symptom severity, in particular depressive disorder and depression severity. Show less
The current study investigated the role of social skills and its interaction with social anxiety as predictors of treatment outcome in children with an anxiety disorder either with or without a... Show moreThe current study investigated the role of social skills and its interaction with social anxiety as predictors of treatment outcome in children with an anxiety disorder either with or without a social anxiety disorder (SoAD). In total, 133 children (aged 8 to 13) with an anxiety disorder received a 10-session cognitive behavioral treatment (FRIENDS program). Pre- to post treatment Reliable Change (RC) and Treatment-Recovery (TR) were assessed from a multi-informant perspective, by including diagnostic information (ADIS C/P), child-reported anxiety symptoms (MASC) and parent-reported internalizing symptoms (CBCL-Int). Social skills were assessed with the parent-rated Social Skills Rating System (assertion, self-control, responsibility). Results showed that 1) parents of children with a SoAD reported significantly less favorable use of assertive and responsible social behavior in their children pre-treatment than parents of children without SoAD, 2) children with higher social skills had a better treatment recovery, and 3) children with anxiety and higher responsible behavior pre-treatment and without a SoAD had a better treatment recovery, but this effect did not show for children with SoAD. In conclusion, better use of social behavior increased the likelihood of treatment recovery but not of reliable change. Further studies on the role of social skills in the treatment of childhood (social) anxiety are needed to investigate the mechanisms by which social skills impact treatment outcome. Show less
Background: Affective disorders involve dysregulation of major biological stress systems (hypothalamic-pituitary adrenal (HPA)-axis, immune system, autonomic nervous system (ANS)).... Show moreBackground: Affective disorders involve dysregulation of major biological stress systems (hypothalamic-pituitary adrenal (HPA)-axis, immune system, autonomic nervous system (ANS)). Suchdysregulationshave rarely beensimultaneously examined across different stress systems.Methods: In the Netherlands Study of Depression and Anxiety (n=2789), we investigated whether current or remitted depressive and/or anxiety disorders (based on the CIDI semi-structured interview), including specific symptom profiles, were associated with separate markers and cumulative indexes of the HPA-axis (cortisol awakening response, evening cortisol, dexamethasone suppression test cortisol), immune system (C-reactive protein, interleukin-6, tumor necrosis factor-alpha), and ANS (heart rate, respiratory sinus arrhythmia, pre-ejection period).Results: Depressive andanxiety disorderswere significantlyassociated with changes in three biological stress systemsincluding HPA-axis hyperactivity, increased inflammatory activity, and a higher ANS tone, particularly for integrative and cumulative indexes of these stress systems (pFDR <.05) vs. controls. The strongest associations were seen with current disorders andcumulative indexes of the HPA-axis (13=.124, pFDR=.001), the immune system (13 =.057, pFDR=.032), and total cumulative index across stress systems (13=.102, pFDR=.004). Atypical, energy-related depression severity was linked to immune system markers (pFDR<0.001), melancholic depression severity to HPA-axis markers (pFDR=.032), and anxiety arousal severity to both HPA-axis and immune system markers (pFDR<0.05). Findings were partially explained by poorer lifestyle, more chronic diseases, or (especially for ANS-function) antidepressant use. Limitations: Cross-sectional analyses limit examination of temporal associations.Conclusion: Patients withdepressive and anxiety disorders showed consistent dysregulation across biological stress systems, particularly for current episodes.To understand stress system functionality in affective disorders, an integrated approach capturing cumulative stress indices within and across biological stress systems is important. Show less
Roelofs, E.F.; Bas-Hoogendam, J.M.; Ewijk, H. van; Ganjgahi, H.; Werff, S.J.A. van der; Barendse, M.E.A.; ... ; Wee, N.J.A. van der 2020
Background: Social anxiety disorder (SAD) is a mental illness with a complex, partially genetic background. Differences in characteristics of white matter (WM) microstructure have been reported in... Show moreBackground: Social anxiety disorder (SAD) is a mental illness with a complex, partially genetic background. Differences in characteristics of white matter (WM) microstructure have been reported in patients with SAD compared to healthy controls. Also, WM characteristics are moderately to highly heritable. Endophenotypes are measurable characteristics on the road from genotype to phenotype, putatively reflective of genetically based disease mechanisms. In search of candidate endophenotypes of SAD we used a unique sample of SAD patients and their family members of two generations to explore microstructure of WM tracts as candidate endophenotypes. We focused on two endophenotype criteria: co-segregation with social anxiety within the families, and heritability.Methods: Participants (n = 94 from 8 families genetically vulnerable for SAD) took part in the Leiden Family Lab Study on Social Anxiety Disorder (LFLSAD). We employed tract-based spatial statistics to examine structural WM characteristics, being fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD) and radial diffusivity (RD), in three a-priori defined tracts of interest: uncinate fasciculus (UF), superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF). Associations with social anxiety symptoms and heritability were estimated.Results: Increased FA in the left and right SLF co-segregated with symptoms of social anxiety. These findings were coupled with decreased RD and MD. All characteristics of WM microstructure were estimated to be at least moderately heritable.Conclusion: These findings suggest that alterations in WM microstructure in the SLF could be candidate endophenotypes of SAD, as they co-segregated within families genetically vulnerable for SAD and are heritable. These findings further elucidate the genetic susceptibility to SAD and improve our understanding of the overall etiology. Show less
Bas-Hoogendam, J.M.; Steenbergen, H. van; Wee, N.J.A. van der; Westenberg, P.M. 2020
Social anxiety disorder (SAD) runs in families, but the neurobiological pathways underlying the genetic susceptibility towards SAD are largely unknown. Here, we employed an endophenotype approach,... Show moreSocial anxiety disorder (SAD) runs in families, but the neurobiological pathways underlying the genetic susceptibility towards SAD are largely unknown. Here, we employed an endophenotype approach, and tested the hypothesis that amygdala hyperreactivity to faces conditioned with a social-evaluative meaning is a candidate SAD endophenotype. We used data from the multiplex, multigenerational Leiden Family Lab study on Social Anxiety Disorder (eight families, n = 105) and investigated amygdala activation during a social-evaluative conditioning paradigm with high ecological validity in the context of SAD. Three neutral faces were repeatedly presented in combination with socially negative, positive or neutral sentences. We focused on two endophenotype criteria: co-segregation of the candidate endophenotype with the disorder within families, and heritability. Analyses of the fMRI data were restricted to the amygdala as a region of interest, and association analyses revealed that bilateral amygdala hyperreactivity in response to the conditioned faces co-segregated with social anxiety (SA; continuous measure) within the families; we found, however, no relationship between SA and brain activation in response to more specific fMRI contrasts. Furthermore, brain activation in a small subset of voxels within these amygdala clusters was at least moderately heritable. Taken together, these findings show that amygdala engagement in response to conditioned faces with a social-evaluative meaning qualifies as a neurobiological candidate endophenotype of social anxiety. Thereby, these data shed light on the genetic vulnerability to develop SAD. Show less
The goal of this dissertation was to delineate psychophysiological endophenotypes of social anxiety disorder. We conducted a unique two-generation family study, including patients with social... Show moreThe goal of this dissertation was to delineate psychophysiological endophenotypes of social anxiety disorder. We conducted a unique two-generation family study, including patients with social anxiety disorder, their partner and children, and their siblings with partner and children. This dissertation focused on EEG and heart rate measures during resting state, a social performance task and a social judgment paradigm. In the social performance task, participants watched and evaluated a speech of a female peer and then gave a speech in front of a video camera themselves. In the social judgment paradigm, participants received social acceptance or rejection feedback, after indicating their expectations about the upcoming feedback. This dissertation focused on three criteria for endophenotypes: association with SAD, co-segregation with SAD within families, and heritability. Delta-beta correlation during anticipation of a stressful social situation, and N1 and P3 amplitude in the social judgment paradigm are candidate endophenotypes of SAD. Show less
Harrewijn, A.; Van der Molen, M.J.W.; Van Vliet, I.M.; Houwing-Duistermaat, J.J.; Westenberg, P.M. 2018
BackgroundSocial anxiety disorder (SAD) is characterized by an extreme and intense fear and avoidance of social situations. In this two-generation family study we examined delta-beta correlation... Show moreBackgroundSocial anxiety disorder (SAD) is characterized by an extreme and intense fear and avoidance of social situations. In this two-generation family study we examined delta-beta correlation during a social performance task as candidate endophenotype of SAD.MethodsNine families with a target participant (diagnosed with SAD), their spouse and children, as well as target's siblings with spouse and children performed a social performance task in which they gave a speech in front of a camera. EEG was measured during resting state, anticipation, and recovery. Our analyses focused on two criteria for endophenotypes: co-segregation within families and heritability.ResultsCo-segregation analyses revealed increased negative delta-low beta correlation during anticipation in participants with (sub)clinical SAD compared to participants without (sub)clinical SAD. Heritability analyses revealed that delta-low beta and delta-high beta correlation during anticipation were heritable. Delta-beta correlation did not differ between participants with and without (sub)clinical SAD during resting state or recovery, nor between participants with and without SAD during all phases of the task.LimitationsIt should be noted that participants were seen only once, they all performed the EEG tasks in the same order, and some participants were too anxious to give a speech.ConclusionsDelta-low beta correlation during anticipation of giving a speech might be a candidate endophenotype of SAD, possibly reflecting increased crosstalk between cortical and subcortical regions. If validated as endophenotype, delta-beta correlation during anticipation could be useful in studying the genetic basis, as well as improving treatment and early detection of persons at risk for developing SAD. Show less
Bas, J.M.; Steenbergen, H. van; Pannekoek, J.N.; Fouche, J.P.; Lochner, C.; Hattingh, C.J.; ... ; Wee, N.J.A. van der 2017
