Suicidal ideation across depressive episodes: 9-year longitudinal cohort study.

BACKGROUND: Depression is a highly recurrent disorder, with more than 50% of those affected experiencing a subsequent episode. Although there is relatively little stability in symptoms across episodes, some evidence indicates that suicidal ideation may be an exception. However, these findings warrant replication, especially over longer periods and across multiple episodes. AIMS: To assess the relative stability of suicidal ideation in comparison with other non-core depressive symptoms across episodes. METHOD: We examined 490 individuals with current major depressive disorder (MDD) at baseline and at least one subsequent episode during 9-year follow-up within the Netherlands Study of Depression and Anxiety (NESDA). The Inventory of Depressive Symptomatology (IDS) was used to assess DSM-5 non-core MDD symptoms (fatigue, appetite/weight change, sleep disturbance, psychomotor disturbance, concentration difficulties, worthlessness/guilt, suicidal ideation) at baseline and 2-, 4-, 6- and 9-year follow-up. We examined consistency in symptom presentation (i.e. whether the symptom met the diagnostic threshold, based on a binary categorisation of the IDS) using kappa (κ) and percentage agreement, and stability in symptom severity using Spearman correlation, based on the continuous IDS scores. RESULTS: Out of all non-core depressive symptoms, insomnia appeared the most stable across episodes (r = 0.55-0.69, κ = 0.31-0.47) and weight decrease the least stable (r = 0.03-0.33, κ = 0.06-0.19). For suicidal ideation, correlations across episodes ranged from r = 0.36 to r = 0.55 and consistency ranged from κ = 0.28 to κ = 0.49. CONCLUSIONS: Suicidal ideation is moderately stable in recurrent depression over 9 years. Contrary to prior reports, however, it does not exhibit substantially more stability than most other non-core symptoms of depression.

Anger and cluster B personality traits and the conversion from unipolar depression to bipolar disorder.

INTRODUCTION: Feelings of anger and irritability are prominent symptoms of bipolar disorder (BD) that may occur during hypomanic, depressive and, especially, during mixed mood states. We aimed to determine whether such constructs are associated with the conversion to BD in subjects with a history of unipolar depression. METHODS: Data were derived from the depressed participants of Netherlands Study of Depression and Anxiety with 9 years of follow-up. Hypomania was ascertained using the Composite International Diagnostic Interview at 2, 4, 6, and 9 years follow-up. Cross-sectionally, we studied the association between prevalent hypomania and anger related constructs with the "Spielberger Trait Anger subscale," the "Anger Attacks" questionnaire, the cluster B personality traits part of the "Personality Disorder Questionnaire," and "aggression reactivity." Prospectively, we studied whether aggression reactivity predicted incident hypomania using Cox regression analyses. RESULTS: Cross-sectionally, the bipolar conversion group (n = 77) had significantly higher scores of trait anger and aggression reactivity, as well as a higher prevalence on "anger attacks," "antisocial traits," and "borderline traits" compared to current (n = 349) as well as remitted (n = 1159) depressive patients. In prospective analyses in 1744 participants, aggression reactivity predicted incident hypomania (n = 28), with a multivariate-adjusted hazard ratio of 1.4 (95% confidence interval: 1.02-1.93; p = .037). CONCLUSION: Anger is a risk factor for conversion from unipolar depression to BD. In addition, patients who converted to BD showed on average more anger, agitation and irritability than people with a history of unipolar depression who had not converted.

Trait anger and anger attacks in relation to depressive and anxiety disorders.

BACKGROUND: Patients with various psychiatric disorders may suffer from feelings of anger, sometimes leading to maladaptive (e.g., aggressive) behaviors. We examined to what extent depressive and anxiety disorders, relevant clinical correlates, and sociodemographics determined the level of trait anger and the prevalence of recent anger attacks. METHODS: In the Netherlands Study of Depression and Anxiety (NESDA), the Spielberger Trait Anger Subscale and the Anger Attacks Questionnaire were analyzed in patients with depressive (n = 204), anxiety (n = 288), comorbid (n = 222), and remitted disorders (n = 1,107), as well as in healthy controls (n = 470) based on DSM-IV criteria. RESULTS: On average, participants were 46.2 years old (SD = 13.1) and 66.3% were female. Trait anger and anger attacks were most prevalent in the comorbid group (M = 18.5, SD = 5.9, and prevalence 22.1%), followed by anxiety disorder, depressive disorder, remitted disorder, and controls (M = 12.7; SD = 2.9, and prevalence 1.3%). Major depressive disorder, social phobia, panic disorder, and generalized anxiety disorder were most strongly associated to trait anger and anger attacks. LIMITATIONS: Due to a cross-sectional design, it was not possible to provide evidence for temporal or causal relationships between anger and depressive and anxiety disorders. CONCLUSIONS: Trait anger and anger attacks are linked to depressive and anxiety disorders, although the strength of the relationship differed among both anger constructs.

Attentional bias and attentional control in Posttraumatic Stress Disorder.

Extensive evidence exists for an association between attentional bias (AB; attentional vigilance or avoidance) and anxiety. Recent studies in healthy participants suggest that attentional control (AC) may facilitate inhibition of automatic attentional processes associated with anxiety. To investigate relationships among AC, trauma-related AB, symptom severity and trait anxiety in patients with Posttraumatic Stress Disorder (PTSD), participants (N = 91) completed self-report measures of AC, posttraumatic stress symptoms (PTSS) and trait anxiety. AB was measured with a pictorial version of the Dot Probe Test. AC moderated the relationship between PTSS and AB (threat avoidance). Patients high in PTSS and low in AC showed attentional avoidance. No association between PTSS and AB in patients with medium or high levels of AC was found. A similar pattern of results was observed for the relationship between trait anxiety, AC and AB. These results suggest that a low ability to control attention is a risk factor for AB in PTSD. This first clinical study corroborates the accumulating evidence from analog studies that individual differences in top-down attentional control are of considerable importance in the expression of AB in anxious psychopathology.

Reference values for major depression questionnaires: the Leiden Routine Outcome Monitoring Study.

BACKGROUND: The Beck Depression Inventory-II (BDI-II), the Inventory of Depressive Symptoms (self-report) (IDS-SR) and the Montgomery-Äsberg Depression Rating Scale (MADRS) are questionnaires that assess symptom severity in patients with a depressive disorder, often part of Routine Outcome Monitoring (ROM). We aimed to generate reference values for both "healthy" and "clinically depressed" populations. METHODS: We included 1295 subjects from the general population (ROM reference-group) recruited through general practitioners, and 4627 psychiatric outpatients diagnosed with Major Depressive Disorder (MDD) or dysthymia (ROM patient-group). The outermost 5% of observations were used to define limits for one-sided reference intervals (95th percentiles; P95). Receiver Operating Characteristics (ROC) analyses were used to yield alternative cut-off values. Internal consistency was assessed. RESULTS: The mean age was 40.3yr (SD=12.6) and 39.3 (SD=12.3) for the ROM reference and patient-groups, respectively, and 62.8% versus 61.0% were female. Cut-off (P95) values differed for women and men, being respectively 15 and 12 for the BDI-II, 23 and 18 for the IDS-SR, and 12.5 and 9 for the MADRS. ROC analyses yielded almost equal reference values. The discriminative power of the BDI-II, IDS-SR and MADRS scores was very high. Internal consistency was excellent for total scores and satisfactory for all subscales, except for the IDS-SR subscale Atypical Characteristics. LIMITATIONS: Substantial non-response and limited generalizability. CONCLUSIONS: For the BDI-II, IDS-SR and MADRS a comprehensive set of reference values were provided. Reference values were higher in women than in men, implying the use of sex-specific cut-off values. Either instrument can be offered to every patient with MAS disorders to make responsible decisions about continuing, changing or terminating therapy.

Affective regulation of cognitive-control adjustments in remitted depressive patients after acute tryptophan depletion.

Negative affect in healthy populations regulates the appraisal of demanding situations, which tunes subsequent effort mobilization and adjustments in cognitive control. In the present study, we hypothesized that dysphoria in depressed individuals similarly modulates this adaptation, possibly through a neural mechanism involving serotonergic regulation. We tested the effect of dysphoria induced by acute tryptophan depletion (ATD) in remitted depressed patients on conflict adaptation in a Simon task. ATD temporarily lowers the availability of the serotonin precursor L-Tryptophan and is known to increase depressive symptoms in approximately half of remitted depressed participants. We found that depressive symptoms induced by ATD were associated with increased conflict adaptation. Our finding extends recent observations implying an important role of affect in regulating conflict-driven cognitive control.

Effects of omega-3 fatty acid supplementation on mood and emotional information processing in recovered depressed individuals.

Beneficial effects of omega-3 fatty acids have been reported for several psychiatric disorders, particularly for depression. Association studies show a relationship between omega-3 intake and depression risk. Meta-analyses of clinical trials have shown a moderate effect of supplementation on depressive symptoms, but not on normal mood states. Few studies have investigated effects on cognition. The purpose of this study was to examine effects of omega-3 supplements on cognition and mood of recovered depressed individuals. Seventy-one participants were randomized to receive either omega-3 or placebo for four weeks in a randomized double-blind design. Results showed small effects of omega-3 supplementation on aspects of emotional decision-making and on self-reported states of depression and tension. Some of the effects were confounded by learning effects. No significant effects were observed on memory, attention, cognitive reactivity and depressive symptoms. While inconclusive, the present findings may indicate that omega-3 supplementation has selective effects on emotional cognition and mood in recovered depressed participants.

Clinical and physiological correlates of irritability in depression: results from the Netherlands study of depression and anxiety.

Objective. Irritable and nonirritable depressed patients differ on demographic and clinical characteristics. We investigated whether this extends to psychological and physiological measures. Method. We compared irritable and nonirritable unipolar depressed patients on symptomatology, personality, and (psycho)physiological measures (cortisol, cholesterol, and heart rate variability). Symptomatology was reassessed after one year, and we also compared depressed patients who were irritable or non-irritable at both time points (Irr++ versus Irr--). Results. Almost half (46%; N = 420) of the sample was classified as irritable. These patients scored higher on depression severity, anxiety, hypomanic symptoms, and psychological variables. No differences were observed on physiological markers after correction for depression severity. The same pattern was found when comparing Irr++ and Irr-- groups. Conclusion. Irritable and non-irritable depressed patients differ on clinical and psychological variables, but not on the currently investigated physiological markers. The clinical relevance of the distinction and the significance of the hypomanic symptoms remain to be demonstrated.

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.

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.

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.

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 (ß=.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.

Emotional processing as a predictor of symptom change: an acute tryptophan depletion study in depressed patients.

Acute tryptophan depletion (ATD) in currently depressed patients has no immediate effect on symptoms, but leads to transient symptom improvement or worsening the next day. In view of recent findings concerning the cognitive effects of serotonin manipulations, we used ATD in fourteen depressed patients to investigate whether cognitive effects following ATD predict symptom changes. We found that symptom improvement 24h after ATD was associated with an improved recall of positive words and with less attentional bias and recall of negative words, 5h after ATD. These results indicate that serotonergic alterations affect emotional processing which may subsequently lead to symptom changes.

The efficacy of n-3 fatty acids DHA and EPA (fish oil) for perinatal depression.

Depressive symptoms are common during pregnancy and the post-partum period. Although essential n-3 PUFA may have beneficial effects on depression, it remains unclear whether they are also effective for perinatal depression. The purpose of the present study was to assess the efficacy of n-3 supplementation for perinatal depression, by performing a meta-analysis on currently available data. After a thorough literature search, we included seven randomised controlled trials in the meta-analysis, all with EPA and/or DHA supplementation. Most studies were judged to be of low-to-moderate quality, mainly due to small sample sizes and failure to adhere to Consolidated Standards of Reporting Trials guidelines. Some studies were not primarily designed to address perinatal depression. A total of 309 women on n-3 fatty acid supplementation were compared with 303 women on placebo treatment. n-3 Supplementation was not found to be significantly more effective than placebo at post-treatment with a pooled effect size (Hedges's g) of - 0.03 (95 % CI - 0.18, 0.13; P = 0.76) using a fixed-effects model. Heterogeneity was low-to-moderate (I2 = 30 %). In a subgroup analysis of three small studies of pregnant women with major depression, there was some indication of effectiveness (effect size 0.17; 95 % CI - 0.21, 0.55). In conclusion, the question of whether EPA and DHA administration is effective in the prevention or treatment of perinatal depression cannot be answered yet. Future research should focus on women who are clinically depressed (or at risk). The quality of research in this area needs to improve.

Heart-focused anxiety as a mediating variable in the treatment of noncardiac chest pain by cognitive-behavioral therapy and paroxetine.

OBJECTIVE: We compared the efficacy of cognitive behavior therapy (CBT), paroxetine and placebo in the treatment of noncardiac chest pain (NCCP). We also investigated whether pre- to mid-treatment reduction of (heart-focused) anxiety mediated mid- to post-treatment pain reduction. METHODS: Sixty-nine adults with NCCP were randomly assigned to 16 weeks of outpatient treatment with CBT, paroxetine or placebo. The comparison between placebo and paroxetine was carried out in a double-blind fashion. The main outcome measure was a chest pain index (duration*intensity) as derived from daily pain diaries. Putative mediator measures were general anxiety (HADS:A) and heart-focused anxiety (Cardiac Anxiety Questionnaire). RESULTS: Eleven patients treated with paroxetine or placebo dropped out prematurely. Intent-to-treat analysis showed that CBT was significantly superior to placebo and to paroxetine in reducing NCCP at posttreatment. Only CBT significantly reduced heart-focused anxiety compared to placebo at mid- and post-treatment. Pre- to mid-treatment reduction of heart-focused anxiety predicted mid- to post-treatment NCCP reduction. The indirect effect of CBT on pain reduction by reducing heart-focused anxiety was significant compared to placebo but not to paroxetine. CONCLUSION: CBT is an effective treatment option for patients with NCCP. Paroxetine is not more effective than placebo on the short term. Reduction of heart-focused anxiety by CBT seems to mediate subsequent reduction of NCCP compared to placebo. The results provide further support for cognitive-behavioral models of NCCP and point to the potential benefits of, in particular, cognitive-behavioral interventions to modify heart-focused anxiety.

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.

Residual cognitive impairments in remitted depressed patients.

Depressive disorders are associated with various cognitive impairments. Studies on whether or not these impairments persist into the euthymic phase have shown conflicting results, due to differences in test versions and in study samples. In this paper, we aimed to compare the cognitive performance of remitted depressed patients with that of age- and gender-matched healthy volunteers across a wide range of cognitive domains. In two studies, we found few differences on neutral as well as emotional information processing tests. The findings indicate that remitted depressed patients who use antidepressant medication still show an increased recognition of facial expression of fear compared to healthy controls. Patients also performed worse on a test of recognition of abstract visual information from long-term memory. No other residual cognitive impairments were found. These results indicate that most of the cognitive impairments associated with depression resolve with recovery through medication, even when recovery is incomplete. Considering the finding that remitted depressed patients have higher levels of cognitive reactivity, future studies may investigate the possibility that these cognitive impairments have not resolved but have become latent, and may therefore easily be triggered by small changes in mood state.

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.

Cognitive behavior therapy and paroxetine in the treatment of hypochondriasis: a randomized controlled trial.

OBJECTIVE: This study, to the authors' knowledge, is the first randomized controlled trial comparing the efficacy of cognitive behavior therapy (CBT), paroxetine, and a placebo (administered in a double blind fashion) in the treatment of hypochondriasis. METHOD: The authors randomly assigned 112 subjects with hypochondriasis according to DSM-IV criteria to 16 weeks of outpatient treatment with CBT, paroxetine, or a placebo. The main outcome measure was the Whiteley Index. The authors made pretest and posttest assessments and analyzed all outcome measures using a General Linear Model 3x2 repeated measures analysis of variance with Helmert contrasts. The authors considered subjects who scored at least one standard deviation below the mean pretest score on the Whiteley Index as responders. All analyses were conducted on intent-to-treat and completer bases. RESULTS: On the Whiteley Index, Helmert contrasts on the intent-to-treat and completer cohorts revealed that pooled CBT and paroxetine were significantly superior to placebo, but did not differ significantly from each other. The responder analysis on the intent-to-treat cohort and completer cohort, respectively, revealed the following percentages of responders per group: CBT group, 45% and 54%; paroxetine group, 30% and 38%; and placebo group, 14% and 12%. In the intent-to-treat analysis, only CBT differed significantly from the placebo. In the completer analysis, both paroxetine and CBT differed significantly from the placebo. CONCLUSIONS: CBT or paroxetine are effective short-term treatment options for subjects with hypochondriasis.

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.