Anton J.L.M. van Balkom

Anxiety disorders in later life: a report from the longitudinal aging study Amsterdam

Objective. To study the prevalence and risk factors of anxiety disorders in the older (55–85) population of The Netherlands.

Comorbidity Patterns of Anxiety and Depressive Disorders in a Large Cohort Study: the Netherlands Study of Depression and Anxiety (NESDA)

BACKGROUND Comorbidity of depressive and anxiety disorders is common and has been shown to be a consistent predictor of chronicity. Comorbidity patterns among specific depressive and anxiety disorders have not been extensively reported. This study examines comorbidity patterns and temporal sequencing of separate depressive and anxiety disorders using data from a large psychiatric cohort. METHOD Baseline data (N = 1,783) of the Netherlands Study of Depression and Anxiety, collected between September 2004 and February 2007, were used. Current and lifetime comorbidity rates for depressive and anxiety disorders (DSM-IV-TR criteria) were calculated. Associations of comorbidity with sociodemographic, vulnerability, and clinical characteristics, and temporal sequencing of disorders were examined. RESULTS Of those with a depressive disorder, 67% had a current and 75% had a lifetime comorbid anxiety disorder. Of persons with a current anxiety disorder, 63% had a current and 81% had a lifetime depressive disorder. Comorbidity of depressive and anxiety disorders was associated with more childhood trauma (OR = 1.19; 95% CI, 1.06-1.33), higher neuroticism (OR = 1.05; 95% CI, 1.02-1.08), earlier age at onset of first disorder (OR = 1.59; 95% CI, 1.22-2.07), longer duration of depressive and/or anxiety symptoms (OR = 1.01; 95% CI, 1.01-1.01), and higher symptom severity (ORs ranging from 1.01 to 1.03; all P values < .05). In 57% of comorbid cases, anxiety preceded depression, and in 18%, depression preceded anxiety. Comorbidity with preceding depression compared to preceding anxiety was associated with a shorter duration of symptoms of depressive and/or anxiety symptoms (OR = 0.99; 95% CI, 0.98-0.99), earlier age at first onset (OR = 0.46; 95% CI, 0.31-0.68), and fewer fear symptoms (OR = 0.98; 95% CI, 0.97-0.99). CONCLUSIONS Comorbidity rates in anxiety and depressive disorders were very high, indicating that it is advisable to assess both disorders routinely regardless of the primary reason for consultation. This is especially important since comorbid patients showed a specific vulnerability pattern, with more childhood trauma, neuroticism, and higher severity and duration of symptoms.

Cognitive and behavioral therapies alone versus in combination with fluvoxamine in the treatment of obsessive Compulsive disorder

The purpose of this treatment package design study was to investigate the differential efficacy of cognitive therapy or exposure in vivo with response prevention for obsessive compulsive disorder (OCD) versus the sequential combination with fluvoxamine. Patients with OCD (N = 117) were randomized to one of the following five conditions: a) cognitive therapy for weeks 1 to 16, b) exposure in vivo with response prevention for weeks 1 to 16, c) fluvoxamine for weeks 1 to 16 plus cognitive therapy in weeks 9 to 16, d) fluvoxamine for weeks 1 to 16 plus exposure in vivo with response prevention in weeks 9 to 16, or e) waiting list control condition for weeks 1 to 8 only. Assessments took place before treatment (pretest) and after 8 (midtest), and 16 weeks (posttest). In the first 8 weeks, six treatment sessions were delivered. During weeks 9 to 16, another 10 sessions were given. Thirty-one patients dropped out. Outcome was assessed by patient-, therapist- and assessor-ratings of the Anxiety Discomfort Scale, the Yale-Brown Obsessive Compulsive Scale, and the Padua Inventory-Revised. In contrast with the four treatments, after 8 weeks the waiting list control condition did not result in a significant decrease of symptoms. After 16 weeks of treatment, all four treatment packages were effective on these OCD ratings, but they did not differ among each other in effectiveness. In OCD, the sequential combination of fluvoxamine with cognitive therapy or exposure in vivo with response prevention is not superior to either cognitive therapy or exposure in vivo alone.

Symptom Overlap between Autism Spectrum Disorder, Generalized Social Anxiety Disorder and Obsessive-Compulsive Disorder in Adults: A Preliminary Case-Controlled Study

Background: Obsessive-compulsive disorder (OCD) and social anxiety disorder (SAD) frequently co-occur in persons with autism spectrum disorder (ASD). We studied which features distinguish ‘pure’ anxiety disordered patients from those with co-morbid ASD. Method: In a case-controlled design in which groups were matched for age, sex and educational level, patients with OCD or SAD and co-morbid ASD were compared with patients with ‘pure’ (i.e. without ASD) OCD, with ‘pure’ SAD and a control group, using the Autism Questionnaire (AQ), Yale-Brown Obsessive-Compulsive Scales, Liebowitz Social Anxiety Scale, Beck Anxiety Inventory and questions on egodystonia of OC behaviors. Results: No between patient group differences were found on social or general anxiety measures. The AQ subscales communication problems and lack of imagination discriminated best between patients with comorbid ASD and the other groups, ASD patients showing elevated scores, whereas the other patient groups scored equal to controls. On the AQ social skill subscale all patient groups showed elevated scores. On OC symptom severity, pure OCD patients showed highest scores, whereas comorbid ASD subjects scored intermediate between controls and the pure OCD group, the differences being explained by lower obsession severity in the ASD group. There were no differences between the pure OCD and comorbid ASD groups on egodystonia. Conclusion: Patients with comorbid ASD differ from patients with pure OCD and SAD on autism-related problem behaviors, but there is also overlap between groups, possibly reflecting overlapping etiologies. Despite the relatively small sample size, these data strongly suggest that specific autism symptom domains should be assessed to pick up autism-related problems in OCD and SAD patients, and subsequently fine-tune treatment programs for these patients.

Presupplementary Motor Area Hyperactivity During Response Inhibition: A Candidate Endophenotype of Obsessive-Compulsive Disorder

OBJECTIVE Endophenotype studies of obsessive-compulsive disorder (OCD) may uncover heritable traits that are related to genetic susceptibility to OCD. Deficient response inhibition is a promising endophenotype of OCD, although its functional neural correlates have not been extensively studied. The authors sought to determine the functional neural correlates of response inhibition in a large sample of medication-free OCD patients and their unaffected siblings. METHOD Forty-one OCD patients, 17 of their siblings, and 37 matched healthy comparison subjects performed a stop-signal task during 3-T functional MRI. The stop-signal reaction time provided a behavioral measure of response inhibition. The neural correlates of response inhibition were assessed in a region-of-interest analysis that included the presupplementary motor area, inferior frontal gyrus, subthalamic nucleus, and inferior parietal cortex. RESULTS Patients with OCD had greater stop-signal reaction times relative to healthy comparison subjects. The numerical stop-signal reaction time difference between siblings and comparison subjects failed to reach significance. Both patients with OCD and their siblings showed greater activity in the left presupplementary motor area during successful inhibition relative to comparison subjects. Relative to both the comparison subjects and the siblings, patients with OCD showed decreased activity in the right inferior parietal cortex and inferior frontal gyrus. In patients and siblings, presupplementary motor area activity correlated negatively with stop-signal reaction time. CONCLUSIONS These findings suggest that presupplementary motor area hyperactivity is a neurocognitive endophenotype of OCD that is possibly related to inefficient neural processing within the presupplementary motor area itself. Patients with OCD further showed a state-dependent deficit in recruiting right inferior parietal cortex and inferior frontal gyrus, which may contribute to their inhibition deficit.

Reduced anterior cingulate and orbitofrontal volumes in child abuse-related complex PTSD

OBJECTIVE Classic posttraumatic stress disorder (PTSD) is associated with smaller hippocampus, amygdala, and anterior cingulate cortex (ACC) volumes. We investigated whether child abuse-related complex PTSD--a severe form of PTSD with affect dysregulation and high comorbidity--showed similar brain volume reductions. METHOD We used voxel-based morphometry to measure gray matter concentrations in referred outpatients with child abuse-related complex PTSD (n = 31) compared to matched healthy nontraumatized controls (n = 28). Complex PTSD was diagnosed using the Structured Clinical Interview for DSM-IV-TR and the Structured Clinical Interview for Disorders of Extreme Stress. All respondents were scanned on a 1.5-T magnetic resonance system at the VU Medical Center, Amsterdam, The Netherlands, between September 2005 and February 2006. RESULTS As was hypothesized, patients with child abuse-related complex PTSD showed reductions in gray matter concentration in right hippocampus (P(SVC corrected) = .04) and right dorsal ACC (P(SVC corrected) = .02) compared to controls. In addition, a reduction in gray matter concentration in the right orbitofrontal cortex (OFC) was found. Severity of child abuse and PTSD-hyperarousal correlated negatively with ACC volume. Impulsivity correlated negatively with hippocampus volume, and anger, with hippocampus and OFC volume. Comorbidity of borderline personality disorder--compared to comorbid cluster C personality disorder--accounted for more extensive reductions in the ACC and OFC volume. CONCLUSIONS In complex PTSD, not only the hippocampus and the ACC but also the OFC seem to be affected, even in the absence of comorbid borderline personality disorder. These results suggest that neural correlates of complex PTSD are more severe than those of classic PTSD.

Amygdala activity in obsessive-compulsive disorder with contamination fear: a study with oxygen-15 water positron emission tomography

Previous imaging studies of obsessive-compulsive symptom states have implicated frontal-striatal and limbic regions in the pathophysiology of obsessive-compulsive disorder (OCD). Functional imaging studies, however, have yielded inconsistent results, presumably due to methodological differences (patient inclusion criteria, stimulus paradigm, imaging technique, and absence of control groups). In the present study, randomized presentation of contamination-related and neutral visual stimuli was used to investigate the neurophysiological correlates of contamination fear in a group of medication-free OCD patients with washing behaviors and healthy controls. A total of 21 subjects (11 OCD patients and 10 healthy controls) were scanned using H(2)(15)O positron emission tomography (PET). Subjects were presented with pictures of clean and dirty surroundings and were requested to make indoor/outdoor decisions to control for attention differences. State anxiety and obsessionality were rated after each scan using visual analogue scales. Main effects of stimulus type (contamination vs. neutral) were found in bilateral occipital cortex in both groups. A significant group interaction effect was observed in the left amygdala reflecting enhanced activity in response to contamination stimuli in OCD patients. Sensitization effects were observed in the right amygdala in the OCD group; these paralleled an increase in levels of distress and obsessionality as well as a decrease in dorsolateral prefrontal activity. The findings of the present study are consistent with the hypothesis of decreased frontal-striatal control of limbic structures, specifically the amygdala, resulting in an inadequate fear response in OCD patients with contamination fear.

Symptom Dimensions in OCD: Item-Level Factor Analysis and Heritability Estimates

To reduce the phenotypic heterogeneity of obsessive-compulsive disorder (OCD) for genetic, clinical and translational studies, numerous factor analyses of the Yale-Brown Obsessive Compulsive Scale checklist (YBOCS-CL) have been conducted. Results of these analyses have been inconsistent, likely as a consequence of small sample sizes and variable methodologies. Furthermore, data concerning the heritability of the factors are limited. Item and category-level factor analyses of YBOCS-CL items from 1224 OCD subjects were followed by heritability analyses in 52 OCD-affected multigenerational families. Item-level analyses indicated that a five factor model: (1) taboo, (2) contamination/cleaning, (3) doubts, (4) superstitions/rituals, and (5) symmetry/hoarding provided the best fit, followed by a one-factor solution. All 5 factors as well as the one-factor solution were found to be heritable. Bivariate analyses indicated that the taboo and doubts factor, and the contamination and symmetry/hoarding factor share genetic influences. Contamination and symmetry/hoarding show shared genetic variance with symptom severity. Nearly all factors showed shared environmental variance with each other and with symptom severity. These results support the utility of both OCD diagnosis and symptom dimensions in genetic research and clinical contexts. Both shared and unique genetic influences underlie susceptibility to OCD and its symptom dimensions.

Increased activation of the left hippocampus region in Complex PTSD during encoding and recognition of emotional words: a pilot study.

To gain insight into memory disturbances in Complex Posttraumatic Stress Disorder (Complex PTSD), we investigated declarative memory function and medial temporal lobe activity in patients and healthy non-traumatized controls. A case-control study was performed in nine patients with Complex PTSD and nine controls. All respondents performed a declarative memory task with neutral and emotional, negative words during functional magnetic resonance imaging. Memory performance of neutral words was impaired in Complex PTSD with a relative conservation of recall of negative words. Deep encoding of later remembered negative words, as well as correct recognition of negative words and false alarms, was associated with an enhanced Blood Oxygenation Level Dependent (BOLD) response in the left hippocampus extending into the parahippocampal gyrus of Complex PTSD patients compared with controls. Post-hoc volumetric comparisons did not reveal significant anatomical differences in the medial temporal lobe between Complex PTSD patients and controls. We conclude that in Complex PTSD preferential recall of negative words is associated with increased activation in the left hippocampus and parahippocampal gyrus during both successful and false recall. These findings support a model of an abnormally functioning hippocampus in Complex PTSD.

The effectiveness of anxiety treatment on alcohol-dependent patients with a comorbid phobic disorder: a randomized controlled trial

OBJECTIVE Evidence has emerged which indicates that the post-treatment relapse rate for alcohol-dependent patients with a comorbid anxiety disorder is higher than for alcohol-dependent patients without a comorbid anxiety disorder. The question raised by this evidence is whether the relapse rate in these dually diagnosed patients could be reduced if they were given additional treatment for the comorbid anxiety disorder. We attempted to answer this question by conducting a trial among patients with a double diagnosis of alcohol dependence and agoraphobia or social phobia. METHOD We conducted a 32-week randomized controlled trial among 96 abstinent patients with a primary diagnosis of alcohol dependence and a comorbid anxiety disorder involving agoraphobia or social phobia. The patients were randomly assigned to an intensive psychosocial relapse-prevention program on its own (n = 49) or in combination with an anxiety treatment program comprising cognitive behavioral therapy (CBT) and optional pharmacotherapy consisting of an SSRI (n = 47). The primary outcome measure was the percentage of patients who suffered an alcohol relapse during a 32-week period. The secondary outcome measures were total abstinence, a reduction in the days of heavy drinking, and less severe anxiety symptoms. RESULTS Although the additional therapy clearly reduced the anxiety symptoms, it had no significant effect on the alcohol relapse rates. CONCLUSION Anxiety treatment for alcohol-dependent patients with a comorbid anxiety disorder can alleviate anxiety symptoms, but it has no significant effect on the outcome of alcohol treatment programs.