Dana Niehaus

Quality of Life in Anxiety Disorders: A Comparison of Obsessive-Compulsive Disorder, Social Anxiety Disorder, and Panic Disorder

Background: There is growing recognition that the anxiety disorders are disabling disorders associated with substantial morbidity and impaired quality of life (QOL). Nevertheless, there have been few studies comparing QOL across these conditions. Sampling and Methods: 337 outpatients with obsessive-compulsive disorder (OCD; n = 220), panic disorder (PD; n = 53), or social anxiety disorder (SAD; n = 64) were compared using a number of assessment scales to compare objective and subjective impairment in QOL. The association of QOL with symptom severity and comorbid depression was also assessed. Results: The extent of impairment due to OCD, PD or SAD appears to be similar across the QOL scales. However, various domains are differentially affected in each of the disorders; OCD patients had more impairment in family life and activities of daily living; SAD patients had more impairment in social life and leisure activities, and PD patients were less able to avoid the use of nonprescribed drugs. QOL was lower in patients with increased symptom severity as well as in those with comorbid depression. Conclusions: While the extent of impairment appears similar across a number of different anxiety disorders, characteristic symptoms of each disorder may be associated with differential impairment of various domains of function, and may require specifically tailored interventions.

Gender in obsessive–compulsive disorder: clinical and genetic findings

BACKGROUND There is increasing recognition that obsessive-compulsive disorder (OCD) is not a homogeneous entity. It has been suggested that gender may contribute to the clinical and biological heterogeneity of OCD. METHODS Two hundred and twenty patients (n=220; 107 male, 113 female) with DSM-IV OCD (age: 36.40+/-13.46) underwent structured interviews. A subset of Caucasian subjects (n=178), including subjects from the genetically homogeneous Afrikaner population (n=81), and of matched control subjects (n=161), was genotyped for polymorphisms in genes involved in monoamine function. Clinical and genetic data were statistically analyzed across gender. RESULTS Compared with females, males with OCD (1) had an earlier age of onset, and a trend toward having more tics and worse outcome, (2) had somewhat differing patterns of OCD symptomatology and axis I comorbidity, and (3) in the Caucasian group, were more likely to have the high activity T allele of the EcoRV variant of the monoamine oxidase A (MAO-A) gene compared to controls, and (4) in the Afrikaner subgroup, were more frequently homozygous for the C allele at the G861C variant of the 5HT(1D beta) gene than controls. Females with OCD (1) reported more sexual abuse during childhood than males, (2) often noted changes in obsessive-compulsive symptoms in the premenstrual/menstrual period as well as during/shortly after pregnancy, and with menopause, and (3) in the Caucasian subgroup, were more frequently homozygous for the low activity C allele of the EcoRV variant of the MAO-A gene compared to controls, with this allele also more frequent in female patients than controls. CONCLUSION This study supports the hypothesis that gender contributes to the clinical and biological heterogeneity of OCD. A sexually dimorphic pattern of genetic susceptibility to OCD may be present. Further work is, however, needed to delineate the mechanisms that are responsible for mediating the effects of gender.

Early- versus late-onset obsessive–compulsive disorder: investigating genetic and clinical correlates

There is increasing evidence that obsessive-compulsive disorder (OCD) is mediated by genetic factors. Although the precise mechanism of inheritance is unclear, recent evidence has pointed towards the involvement of the serotonergic and dopaminergic systems in the disorders development. Furthermore, early-onset OCD appears to be a subtype that exhibits distinct clinical features and that is associated with greater familial loading. In the present investigation, South African OCD patients (n=252) were stratified according to age of onset and were clinically assessed. Additionally, selected variants in genes encoding serotonergic and dopaminergic components were investigated in a Caucasian OCD subset (n=180). This subgroup was further stratified to evaluate the role that these candidate genes may play in the genetically homogeneous Afrikaner subset (n=80). Analysis of the clinical data revealed an association between early age of onset and an increased frequency of tics, Tourettes disorder, and trichotillomania (TTM). The genetic studies yielded statistically significant results when the allelic distributions of genetic variants in the dopamine receptor type 4 gene (DRD4) were analysed in the Caucasian OCD cohort. These data support a role for the dopaminergic system, which may be relevant to the development of early-onset OCD.

Investigating the role of dopaminergic and serotonergic candidate genes in obsessive-compulsive disorder

There is increasing evidence that the aetiology of obsessive-compulsive disorder (OCD) has a marked genetic component, although the precise mechanism of inheritance is unclear. Clinical and pharmacological studies have implicated the serotonergic and dopaminergic systems in disease pathogenesis. This study investigated the role of attractive candidate genes in the serotonergic and dopaminergic pathways in the development of OCD. The distribution of selected polymorphic variants in the serotonin receptor type 2A and 1Dbeta (5-HT(2A), 5-HT(1Dbeta)), dopamine transporter (DAT), dopamine receptor type 4 (DRD4) and monoamine-oxidase A (MAO-A) genes were analysed in 71 OCD cases and 129 control individuals in the genetically homogeneous Afrikaner population, by means of case-control association studies. Although no statistically significant genotypic or allelic associations were detected, the data yielded interesting preliminary results that warrant further discussion and investigation.

Long-acting injectable risperidone in the treatment of subjects with recent-onset psychosis: a preliminary study.

Using a long-acting antipsychotic to improve adherence early in the illness may reduce relapse rates and promote sustained remission, thereby improving the long-term outcome of schizophrenia. We assessed whether risperidone long-acting injection (RLAI) could be used safely and effectively in the treatment of recent-onset psychosis. Fifty patients aged 15 to 43 years with newly diagnosed schizophreniform disorder or schizophrenia were treated with RLAI 25 to 50 mg every 2 weeks for 2 years. Thirty-six patients (72%) completed the trial. Of 39 (78%) who showed a clinical response of 50%, 4 relapsed. Thirty-two patients (64%) achieved remission. Mean maximum increase in Extrapyramidal Symptoms Rating Scale total score was 1.4 (95% confidence interval, 0.61-2.10; n = 50); 10 patients required anticholinergic medication, and 1 subject developed persistent dyskinesia. Prolactin levels were elevated in 18 patients, 4 of whom reported possible prolactin-related adverse events. Mean increase in body mass index to last visit for all patients was 4.8 kg/m2 (SD, 3.8 kg/m2). The final RLAI dose was 25 mg for 54% of patients, 37.5 mg for 30%, and 50 mg for 16%. This preliminary study suggests that RLAI was overall well tolerated and appears to be effective in recent-onset psychosis. Further investigation is warranted.

Remission in patients with first-episode schizophrenia receiving assured antipsychotic medication: A study with risperidone long-acting injection

Recently proposed criteria for remission by a ‘Remission in Schizophrenia Working Group’ have generated considerable interest. We assessed rates, predictors, and correlates of remission in a sample of patients with first-episode schizophrenia treated with injectable, long-acting risperidone. This allowed us to examine remission among patients known to be receiving medication. This was a single-site open-label study in which 50 newly diagnosed cases of schizophreniform disorder or schizophrenia aged 16 to 43 years were treated with injectable, long-acting risperidone 25–50 mg every 2 weeks for 2 years. Remission, according to Remission in Schizophrenia Working Group criteria, was achieved in 64% of the patients. Of those achieving remission, 97% maintained this status until study completion. Remission was associated with greater improvements in other symptom domains, insight, and social and occupational functioning. Patients in remission received lower doses of antipsychotic medication, had fewer extrapyramidal symptoms, and a more favorable attitude toward medication. The results of this open-label study suggest that a majority of first-episode patients who receive long-acting injectable antipsychotic medication may achieve sustained remission. Double-blind-controlled studies using long-acting injectable antipsychotics in early psychosis are warranted to further test this.

Obsessive-compulsive disorder and trichotillomania: a phenomenological comparison

BackgroundSimilarities between obsessive-compulsive disorder (OCD) and trichotillomania (TTM) have been widely recognized. Nevertheless, there is evidence of important differences between these two disorders. Some authors have conceptualized the disorders as lying on an OCD spectrum of conditions.MethodsTwo hundred and seventy eight OCD patients (n = 278: 148 male; 130 female) and 54 TTM patients (n = 54; 5 male; 49 female) of all ages were interviewed. Female patients were compared on select demographic and clinical variables, including comorbid axis I and II disorders, and temperament/character profiles.ResultsOCD patients reported significantly more lifetime disability, but fewer TTM patients reported response to treatment. OCD patients reported higher comorbidity, more harm avoidance and less novelty seeking, more maladaptive beliefs, and more sexual abuse. OCD and TTM symptoms were equally likely to worsen during menstruation, but OCD onset or worsening was more likely associated with pregnancy/puerperium.ConclusionsThese findings support previous work demonstrating significant differences between OCD and TTM. The classification of TTM as an impulse control disorder is also problematic, and TTM may have more in common with conditions characterized by stereotypical self-injurious symptoms, such as skin-picking. Differences between OCD and TTM may reflect differences in underlying psychobiology, and may necessitate contrasting treatment approaches.

Single photon emission computed tomography (SPECT) of anxiety disorders before and after treatment with citalopram.

BackgroundSeveral studies have now examined the effects of selective serotonin reuptake inhibitor (SSRI) treatment on brain function in a variety of anxiety disorders including obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and social anxiety disorder (social phobia) (SAD). Regional changes in cerebral perfusion following SSRI treatment have been shown for all three disorders. The orbitofrontal cortex (OFC) (OCD), caudate (OCD), medial pre-frontal/cingulate (OCD, SAD, PTSD), temporal (OCD, SAD, PTSD) and, thalamic regions (OCD, SAD) are some of those implicated. Some data also suggests that higher perfusion pre-treatment in the anterior cingulate (PTSD), OFC, caudate (OCD) and antero-lateral temporal region (SAD) predicts subsequent treatment response. This paper further examines the notion of overlap in the neurocircuitry of treatment and indeed treatment response across anxiety disorders with SSRI treatment.MethodsSingle photon emission computed tomography (SPECT) using Tc-99 m HMPAO to assess brain perfusion was performed on subjects with OCD, PTSD, and SAD before and after 8 weeks (SAD) and 12 weeks (OCD and PTSD) treatment with the SSRI citalopram. Statistical parametric mapping (SPM) was used to compare scans (pre- vs post-medication, and responders vs non-responders) in the combined group of subjects.ResultsCitalopram treatment resulted in significant deactivation (p = 0.001) for the entire group in the superior (t = 4.78) and anterior (t = 4.04) cingulate, right thalamus (t = 4.66) and left hippocampus (t = 3.96). Deactivation (p = 0.001) within the left precentral (t = 4.26), right mid-frontal (t = 4.03), right inferior frontal (t = 3.99), left prefrontal (3.81) and right precuneus (t= 3.85) was more marked in treatment responders. No pattern of baseline activation distinguished responders from non-responders to subsequent pharmacotherapy.ConclusionsAlthough each of the anxiety disorders may be mediated by different neurocircuits, there is some overlap in the functional neuro-anatomy of their response to SSRI treatment. The current data are consistent with previous work demonstrating the importance of limbic circuits in this spectrum of disorders. These play a crucial role in cognitive-affective processing, are innervated by serotonergic neurons, and changes in their activity during serotonergic pharmacotherapy seem crucial.

The effects of eicosapentaenoic acid in tardive dyskinesia: A randomized, placebo-controlled trial

OBJECTIVE Worldwide, conventional antipsychotic medication continues to be used extensively, and tardive dyskinesia (TD) remains a serious complication. The primary objective of the present study was to compare the efficacy of EPA versus placebo in reducing symptoms of TD. METHOD This was a 12-week, double-blinded, randomized study of ethyl-EPA 2g/day versus placebo as supplemental medication, in patients with schizophrenia or schizoaffective disorder, with established TD. RESULTS Eighty-four subjects were randomized, of whom 77 were included in the analysis. Both the EPA and placebo groups displayed significant baseline to endpoint improvements in Extrapyramidal Symptom Rating Scale dyskinesia scores, but there were no significant between-group differences (p=0.4). Response rates (>or=30% improvement in TD symptoms) also did not differ significantly between EPA-treated subjects (45%) and placebo-treated subjects (32%) (p=0.6). However, a post-hoc linear mixed model repeated measures analysis of variance indicated an effect for treatment group and duration of TD. The EPA-treated patients had significantly greater mean reductions in dyskinesia scores initially, although this was not sustained beyond 6 weeks. CONCLUSIONS This trial failed to demonstrate an anti-dyskinetic effect for ethyl-EPA 2g/day on the primary efficacy measure. However, a modest and transient benefit is suggested in patients with more recent onset of TD. The lack of clear-cut efficacy could be explained on the basis of the dose of EPA being too low, the study being underpowered, TD being too chronic in the majority of cases, differences in dietary fatty acid intake, or that EPA lacks an anti-dyskinetic action.

Perceptions of a South African schizophrenia population with regards to community attitudes towards their illness

BackgroundWith the worldwide shift towards a more community-based psychiatric service delivery approach, stigma and the issues surrounding it have received much attention. However, very little South African data exist and the aim of our study was therefore to investigate the experience of internalized stigma in a South African schizophrenia population with specific emphasis on abuse as a form of stigmatization.MethodsA total of 100 subjects at various stages of schizophrenic illness were subjected to a the Internalized Stigma of Mental Illness scale (ISMI) that was modified to include six items focusing specifically on investigating the experience of stigmatization within the South African context.ResultsA high overall degree of stigmatization was perceived by most subjects, but not equally so for all ISMI areas. When looking at the modified items, 29% felt media-influence to be negative, this seemed to be specifically true for those with matriculation and higher as well as a home-language other than Afrikaans. Thirty nine percent indicated that they had been victims of physical abuse due to their mental illness, with the data suggesting that especially Xhosa-speaking patients, male subjects and those with more admissions and a longer duration of illness experienced this excessively.DiscussionOur study confirmed a high overall degree of perceived stigmatization as well as suggesting some evidence for cultural influences on stigma. It was the first to provide South African data and as such can be regarded as central to our efforts in restructuring psychiatric services and clinical practices in a way that would minimize the effects of stigma and ultimately benefit our clients.