A.J. Willem Van der Does

Heartbeat perception in panic disorder: a reanalysis

This article describes a reanalysis of seven studies on heart beat perception (HBP) in panic disorder. The pooled sample had 709 participants from eight diagnostic categories. Accurate HBP was uncommon, but more prevalent among panic disorder patients than among healthy controls, depressed patients, patients with palpitations and individuals with infrequent panic attacks. No differences were found between panic disorder patients and patients with other anxiety disorders. Accurate perceivers had higher anxiety sensitivity scores than inaccurate perceivers. The data remain inconclusive as to whether perceived heart rate is correlated with anxiety in inaccurate perceivers. Physical exercise, distraction, variations in instructions and treatment each influenced HBP. However, the influence was different than previously thought. Finally, it is suggested that HBP may be understood in terms of schema-guided information processing.

BDNF Val66Met polymorphism is associated with higher anticipatory cortisol stress response, anxiety, and alcohol consumption in healthy adults

BACKGROUND The brain-derived neurotrophic factor (BDNF) is a key protein in maintaining neuronal integrity. The BDNF gene is thought to play an important role in the pathophysiology of mood and anxiety disorders. The aim of this study was to investigate, for the first time in a single study, the association between BDNF Val(66)Met polymorphism, anxiety, alcohol consumption, and cortisol stress response. METHOD 98 healthy university students (54 females and 44 males), genotyped for the Val(66)Met polymorphism, participated in a physical-stress procedure (cold pressure test, CPT) after having been informed that they would undergo a painful experience. Indices of anxiety and of stress were collected from repeated measurement of salivary cortisol, blood pressure, and heart rate. RESULTS BDNF Met carriers, were more anxious during the CPT (p<0.001), drank more alcohol per week, (p<0.05), and showed significantly higher anticipatory cortisol response (p<0.05), but not in response to the CPT, than Val/Val homozygotes. The association of BDNF Val(66)Met polymorphism with HPA axis reactivity to stress was not modulated by gender. These results suggest that Met carriers are particularly sensitive in anticipating stressful events, which extends previous findings on the moderating role of the BDNF Val(66)Met polymorphism in the face of stressful life events.

Psychiatric history and subthreshold symptoms as predictors of the occurrence of depressive or anxiety disorder within 2 years

BACKGROUND Past episodes of depressive or anxiety disorders and subthreshold symptoms have both been reported to predict the occurrence of depressive or anxiety disorders. It is unclear to what extent the two factors interact or predict these disorders independently. AIMS To examine the extent to which history, subthreshold symptoms and their combination predict the occurrence of depressive (major depressive disorder, dysthymia) or anxiety disorders (social phobia, panic disorder, agoraphobia, generalised anxiety disorder) over a 2-year period. METHOD This was a prospective cohort study with 1167 participants: the Netherlands Study of Depression and Anxiety. Anxiety and depressive disorders were determined with the Composite International Diagnostic Interview, subthreshold symptoms were determined with the Inventory of Depressive Symptomatology-Self Report and the Beck Anxiety Inventory. RESULTS Occurrence of depressive disorder was best predicted by a combination of a history of depression and subthreshold symptoms, followed by either one alone. Occurrence of anxiety disorder was best predicted by both a combination of a history of anxiety disorder and subthreshold symptoms and a combination of a history of depression and subthreshold symptoms, followed by any subthreshold symptoms or a history of any disorder alone. CONCLUSIONS A history and subthreshold symptoms independently predicted the subsequent occurrence of depressive or anxiety disorder. Together these two characteristics provide reasonable discriminative value. Whereas anxiety predicted the occurrence of an anxiety disorder only, depression predicted the occurrence of both depressive and anxiety disorders.

Tryptophan Depletion Affects Heart Rate Variability and Impulsivity in Remitted Depressed Patients with a History of Suicidal Ideation

BACKGROUND Depression is a major risk factor for cardiovascular disease. An important risk factor for cardiovascular disease, low heart rate variability, often has been found in depressed patients and has been associated with impulsivity. The present study investigated whether experimental lowering of serotonin would decrease heart rate variability and increase impulsivity in remitted depressed patients, in particular in those patients with disturbed impulse control. METHODS Nineteen patients in remission from depression received high-dose and low-dose acute tryptophan depletion in a randomized, counterbalanced, double-blind crossover design. Heart rate variability and impulsivity were assessed during each acute tryptophan depletion session and during a baseline session. Suicidal ideation during past depression was used as an index for individual differences in impulse control. RESULTS High-dose acute tryptophan depletion led to a larger increase in depressive symptoms than did low-dose acute tryptophan depletion. High-dose acute tryptophan depletion decreased heart rate variability and increased impulsivity and anxiety, but only in patients with a history of suicidal ideation. Symptom effects of high-dose acute tryptophan depletion correlated with low heart rate variability at baseline. CONCLUSIONS Depressed patients who have problems with controlling impulsivity might be more at risk for developing cardiovascular disease, possibly related to increased vulnerability to impaired 5-hydroxytryptamine function.

Psychological traits and the cortisol awakening response : Results from the Netherlands Study of Depression and Anxiety

BACKGROUND Hypothalamus-Pituitary-Adrenal (HPA) axis dysregulation is often seen in major depression, and is thought to represent a trait vulnerability - rather than merely an illness marker - for depressive disorder and possibly anxiety disorder. Vulnerability traits associated with stress-related disorders might reflect increased sensitivity for the development of psychopathology through an association with HPA axis activity. Few studies have examined the association between psychological trait factors and the cortisol awakening response, with inconsistent results. The present study examined the relationship between multiple psychological trait factors and the cortisol awakening curve, including both the dynamic of the CAR and overall cortisol awakening levels, in a sample of persons without psychopathology, hypothesizing that persons scoring high on vulnerability traits demonstrate an elevated cortisol awakening curve. METHODS From 2981 participants of the Netherlands Study of Depression and Anxiety (NESDA), baseline data from 381 controls (aged 18-65) without previous, current and parental depression and anxiety disorders were analyzed. Psychological measures included the Big Five personality traits (neuroticism, extraversion, openness to experience, conscientiousness, and agreeableness) measured using the NEO-FFI, anxiety sensitivity assessed by the Anxiety Sensitivity Index, cognitive reactivity to sadness (hopelessness, acceptance/coping, aggression, control/perfectionism, risk aversion, and rumination) as measured by the LEIDS-R questionnaire, and mastery, assessed using the Pearlin and Schooler Mastery scale. Salivary cortisol levels were measured at awakening, and 30, 45, and 60 min afterwards. RESULTS In adjusted analyses, high scores of hopelessness reactivity (β=.13, p=.02) were consistently associated with a higher cortisol awakening response. In addition, although inconsistent across analyses, persons scoring higher on extraversion, control/perfectionism reactivity, and mastery tended to show a slightly flatter CAR. No significant associations were found for neuroticism, openness to experience, agreeableness, conscientiousness, anxiety sensitivity, and acceptance/coping, aggression, or risk aversion reactivity. CONCLUSION Of various psychological traits, only hopelessness reactivity, a trait that has been associated with depression and suicidality, is consistently associated with HPA axis dysregulation. Hopelessness reactivity may represent a predisposing vulnerability for the development of a depressive or anxiety disorder, possibly in part mediated by HPA axis activity.

Association of smoking and nicotine dependence with severity and course of symptoms in patients with depressive or anxiety disorder

BACKGROUND Previous research has indicated a strong association of smoking with depression and anxiety disorders, but the direction of the relationship is uncertain. Most research has been done in general population samples. We investigated the effect of smoking and nicotine dependence on the severity and course of depressive and anxiety symptoms in psychiatric patients. METHODS Data came from the Netherlands Study of Depression and Anxiety (NESDA) including participants with a current diagnosis of depression and/or an anxiety disorder (N=1725). The course of smoking status and symptoms of depression, general anxiety, social anxiety, and agoraphobia were measured at baseline and after one and two years. Age, gender, education, alcohol use, physical activity, and negative life events were treated as covariates. RESULTS At baseline, the symptoms of depression, general anxiety, and agoraphobia were more severe in nicotine-dependent smokers than in never-smokers, former smokers, and non-dependent smokers. These differences remained after adjusting for covariates. Smaller differences were observed for severity of social anxiety which were no longer significant after controlling for covariates. Over a two-year follow-up, the improvement of depressive and anxiety symptoms was slower in nicotine-dependent smokers than in the other groups even after controlling for covariates. There were no differences between the groups in the course of symptoms of social anxiety and agoraphobia over time. CONCLUSIONS In psychiatric patients, smoking is associated with higher severity of depressive and anxiety symptoms, and with slower recovery, but only when smokers are nicotine-dependent.

Psychological Characteristics of Chronic Depression: A Longitudinal Cohort Study

BACKGROUND Few studies have investigated the importance of psychological characteristics for chronicity of depression. Knowledge about psychological differences between chronically depressed persons and nonchronically depressed persons may help to improve treatment of chronic depression. This is the first study to simultaneously compare in large samples various psychological characteristics between chronically depressed and nonchronically depressed adults. METHOD Baseline data were drawn from the Netherlands Study of Depression and Anxiety (NESDA), an ongoing longitudinal cohort study aimed at examining the long-term course of depressive and anxiety disorders in different health care settings and phases of illness. Participants were aged 18 to 65 years at the baseline assessment in 2004-2007 and had a current diagnosis of DSM-IV major depressive disorder (N = 1,002). Chronicity of depression was defined as being depressed for 24 months or more in the past 4 to 5 years. The chronicity criterion was fulfilled by 31% (n = 312). The NEO Five-Factor Inventory measured the 5 personality domains, the Leiden Index of Depression Sensitivity-Revised was used to measure cognitive reactivity (eg, hopelessness, rumination), and the Mastery Scale measured external locus of control. RESULTS Compared to the nonchronically depressed persons, the chronically depressed persons reported significantly higher levels of neuroticism (OR = 1.81; 95% CI, 1.55-2.12; P < .001), external locus of control (OR = 1.94; 95% CI, 1.66-2.28; P < .001), and the following dimensions of cognitive reactivity: hopelessness (OR = 1.64; 95% CI, 1.43-1.88; P < .001), aggression (OR = 1.29; 95% CI, 1.13-1.48; P < .001), risk aversion (OR = 1.43; 95% CI, 1.24-1.63; P < .001), and rumination (OR = 1.55; 95% CI, 1.34-1.78; P < .001). They had significantly lower levels of extraversion (OR = 0.57; 95% CI, 0.49-0.67; P < .001), agreeableness (OR = 0.85; 95% CI, 0.74-0.97; P = .02), and conscientiousness (OR = 0.77; 95% CI, 0.67-0.88; P < .001). When testing these variables multivariably, the odds of chronic depression were significantly increased among those with low extraversion (OR = 0.73; 95% CI, 0.61-0.88; P = .001), high rumination (OR = 1.24; 95% CI, 1.01-1.53; P = .04), and high external locus of control (OR = 1.48; 95% CI, 1.21-1.80; P < .001). Controlling for severity of depressive symptoms, age at onset, comorbidity with anxiety disorders, medical illnesses, and treatment status did not change these results. CONCLUSIONS Our findings suggest that extraversion, rumination, and external locus of control, but not neuroticism, are differentiating psychological characteristics for chronicity of depression. These findings provide suggestions for more specific interventions, focused on extraversion, rumination, and external locus of control, in the treatment of chronic depression.

Cognitive reactivity: Investigation of a potentially treatable marker of suicide risk in depression

BACKGROUND Suicidal ideation is the most stable symptom of depression across episodes. This relative stability may be brought about by increased cognitive reactivity to sad mood (CR) during periods of remission. The idea is that a network of depressive cognitions, which include suicidal ideation, becomes strengthened with each episode of depression. Consequently, the whole network may be more easily re-activated, for instance by an episode of low mood. We examined the association between reactivity of suicidal cognitions during recovery and the presence of suicidal ideation and behavior during the previous depressive episode. METHODS In a case-control design, the CR profiles of recovered depressed participants with (N=355) and without (N=250) a history of suicidal ideation were compared. Structured clinical interviews were used to determine diagnoses and prior symptoms. Cognitive reactivity profile was measured with the Leiden Index of Depression Sensitivity-Revised (LEIDS-R). RESULTS Suicidal ideation during a depressive episode was associated with a distinct CR profile during remission: elevated hopelessness reactivity scores. This relationship between prior suicidality and current CR was independent of anxiety disorder comorbidity. Moreover, a history of suicide attempt(s) was also associated with a distinct CR profile. These individuals had both higher hopelessness reactivity and higher aggression reactivity than the non-suicidal and suicidal ideation groups. LIMITATIONS Symptoms during the previous depressive episode were assessed retrospectively. CONCLUSIONS This is the first study to show that CR may underlie the relative stability of suicidal symptoms independent of anxiety comorbidity and that suicidal ideation and suicidal behavior are associated with distinct patterns of CR. Since CR is a potentially treatable vulnerability marker of depression recurrence, this has important clinical implications.

Diet rich in α-lactalbumin improves memory in unmedicated recovered depressed patients and matched controls

Depression is associated with reduced brain serotonin (5-hydroxytryptamine; 5-HT) function and with cognitive dysfunctions. A diet rich in α-lactalbumin protein has been found to increase the ratio tryptophan /large neutral amino acids (Trp/σLNAA), and to improve cognitive functioning in individuals with high neuroticism scores. Since cognitive dysfunctions sometimes persist after remission of depression, the present study investigated the effects of α-lactalbumin-enriched diet on cognition in recovered depressed patients. Twenty-three recovered depressed patients and 20 healthy matched controls without a history of depression consumed meals rich in α-lactalbumin or casein protein in a double-blind crossover design. Mood, cognitive function and plasma amino acids were assessed at both sessions before and after dietary intake. Alpha-lactalbumin protein had no effect on mood, but improved abstract visual memory and impaired simple motor performance. These effects were independent of history of depression. Supplements of lactalbumin may be useful for nutrition research in relation to age- or disease-related memory decline. The present findings should be further examined in different (e.g. medicated) samples. The long-term effects of α-lactalbumin should also be investigated.

Cognitive and Serotonergic Vulnerability to Depression: Convergent Findings

Cognitive reactivity (CR) is a psychological vulnerability marker of depression, whereas response to acute tryptophan depletion (ATD; a serotonergic challenge procedure) is a biological vulnerability marker. The aim of this study was to investigate the relationship between these markers. Thirty-nine remitted depressed patients participated in 2 ATD sessions in a double-blind crossover design. CR, assessed prior to the ATD sessions, predicted depressive response to high-dose ATD. CR also diminished the effects of 2 known predictors of ATD response: gender and residual symptoms. Neuroticism and behavioral inhibition were unrelated to ATD response. CR is associated with an increased sensitivity to reductions of serotonin concentrations. These findings present a small step toward unifying cognitive and neurobiological theories of depression.