Browsing by Author "Lochner C."
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- ItemAltered prefrontal cortical function during processing of fear-relevant stimuli in pregnancy(2011-05-25) Roos A.; Robertson F.; Lochner C.; Vythilingum B.; Stein D.J.In non-pregnant individuals, the prefrontal cortex (PFC) is involved in the regulation of emotion, and appears to play a role in anxiety. Near-infrared spectroscopy (NIRS) detects cortical neural activation without harmful radiation making it safe for use in pregnancy. The aims of this study were to assess neural circuitry involved in processing fear-relevant stimuli during pregnancy using NIRS, and to determine associations between activation of this circuitry, distress and anxiety symptoms, attention to threat, cortisol, estrogen, progesterone and testosterone levels. There was significant activation of the PFC in response to fearful faces compared to rest in both pregnant and control groups. Within pregnancy, the activation was most pronounced at trimester 2, compared to the other trimesters. In pregnant women only (all trimesters), PFC activation was significantly associated with increased distress and anxiety, but with decreased selective attention to masked fear. PFC activation was also significantly associated with increased levels of cortisol and testosterone in pregnancy. PFC function appears to be altered during processing of fear-relevant stimuli in pregnancy. Changes in hormone levels may lead to changes in PFC function, and in turn to changes in cognitive-affective processing and anxiety. Further work is needed, however, to explore precisely how PFC function is altered in pregnancy; it is possible that certain changes reflect altered processing of threat stimuli, while others reflect attempts to compensate for distressing and anxious symptoms that emerge during pregnancy. © 2011 Elsevier B.V.
- ItemChanges in regional brain volumes in social anxiety disorder following 12 weeks of treatment with escitalopram(2010) Cassimjee N.; Fouche J.-P.; Burnett M.; Lochner C.; Warwick, James M.; Dupont P.; Stein D.J.; Cloete K.J.; Carey P.D.It has been suggested that antidepressants, including the selective serotonin reuptake inhibitors have neurotrophic effects. Nevertheless, the impact of treatment with a selective serotonin re-uptake inhibitor on regional brain volumes in social anxiety disorder has not been studied. 11 subjects with social anxiety disorder completed magnetic resonance imaging both before and after 12-weeks of treatment with 20 mg/day escitalopram. No increases in structural grey matter were found, but there were decreases in bilateral superior temporal cortex, vermis and the left cerebellum volumes following 12 weeks of treatment with escitalopram. These preliminary findings require replication to determine their reliability, and extension to determine whether or not they are disorder specific. © 2010 Springer Science+Business Media, LLC..
- ItemComorbid obsessive-compulsive personality disorder in obsessive-compulsive disorder (OCD): A marker of severity(2011) Lochner C.; Serebro P.; Van der Merwe, L.; Hemmings, Sian M. J.; Kinnear C.; Seedat S.; Stein D.J.Introduction: Comorbid obsessive-compulsive personality disorder (OCPD) is well-described in obsessive-compulsive disorder (OCD). It remains unclear, however, whether OCPD in OCD represents a distinct subtype of OCD or whether it is simply a marker of severity in OCD. Materials and methods: The aim of this study was to compare a large sample of OCD subjects (n = 403) with and without OCPD on a range of demographic, clinical and genetic characteristics to evaluate whether comorbid OCPD in OCD represents a distinct subtype of OCD, or is a marker of severity. Results: Our findings suggest that OCD with and without OCPD are similar in terms of gender distribution and age at onset of OC symptoms. Compared to OCD. -OCPD (n = 267, 66%), those with OCD. +. OCPD (n = 136, 34%) are more likely to present with the OC symptom dimensions which reflect the diagnostic criteria for OCPD (e.g. hoarding), and have significantly greater OCD severity, comorbidity, functional impairment, and poorer insight. Furthermore there are no differences in distribution of gene variants, or response to treatment in the two groups. Conclusion: The majority of our findings suggest that in OCD, patients with OCPD do not have a highly distinctive phenomenological or genetic profile, but rather that OCPD represents a marker of severity. © 2011 Elsevier Inc.
- ItemDifferential effects of escitalopram challenge on disgust processing in obsessive-compulsive disorder(2012) Lochner C.; Simmons C.; Kidd Michael; Chamberlain S.R.; Fineberg N.A.; van Honk J.; Ipser J.; Stein D.J.
- ItemDopamine transporter binding in social anxiety disorder: The effect of treatment with escitalopram(2012) Warwick, James M.; Carey P.D.; Cassimjee N.; Lochner C.; Hemmings, Sian M. J.; Moolman-Smook H.; Beetge E.; Dupont P.; Stein D.J.Social anxiety disorder (SAD) is characterised by fear of social or performance situations where the individual is exposed to unfamiliar people or to possible scrutiny by others. The literature on dopamine ligands and dopamine genotypes in SAD is however inconsistent. In this study we measured the effects of SSRI pharmacotherapy on dopamine transporter (DAT) binding in patients with SAD, also addressing variability in DAT genotype. Adult subjects meeting DSM-IV criteria for generalised SAD were studied before and after 12 weeks of pharmacotherapy with the selective serotonin reuptake inhibitor (SSRI) escitalopram. DAT single photon emission computed tomography (SPECT) using 123I-FP-CIT was performed at baseline, and repeated at 12 weeks. Striatal DAT binding was analysed for changes following therapy, and for correlations with clinical efficacy, in the whole group as well as for a subgroup with the A10/A10 DAT genotype. The study included 14 subjects (9 male, 5 female) with a mean (SD) age of 41 (±13) years. The subjects' Liebowitz Social Anxiety Scale (LSAS) score was significantly decreased following pharmacotherapy. In the combined group the left caudate and left putamen showed clusters of increased DAT binding after therapy. The left caudate changes were also observed in the subgroup of 9 A10/A10 homozygotes. However no correlation was found between improved symptoms and DAT binding. The changes found in DAT binding in the caudate and putamen may be due to serotonergic activation of dopamine function by SSRI therapy. This is consistent with previous work indicating decreased DAT binding in SAD, and increased DAT binding after SSRI administration. © Springer Science+Business Media, LLC 2012.
- ItemEscitalopram in obsessive-compulsive disorder: Response of symptom dimensions to pharmacotherapy(2008) Stein D.J.; Carey P.D.; Lochner C.; Seedat Soraya; Fineberg N.; Andersen E.W.Introduction: There is a substantial body of evidence that obsessive-compulsive disorder (OCD) symptoms can be grouped into a series of discrete dimensions, and some evidence that not all OCD symptom dimensions respond equally well to pharmacologic or psychotherapeutic intervention. The response of OCD symptom dimensions to 12 weeks of treatment with escitalopram or placebo was investigated. Methods: Data from a randomized, double-blind, placebo-controlled study of escitalopram in 466 adults with OCD were analyzed. Exploratory factor analysis of individual items of the Yale-Brown Obsessive-Compulsive Scale checklist was performed and subscale scores based on the extracted factors were determined. Analyses of covariance were undertaken to determine whether inclusion of each subscale score in these models impacted on the efficacy of escitalopram versus placebo. Results: Exploratory factor analysis of individual Yale-Brown Obsessive-Compulsive Scale items yielded 5 factors (contamination/cleaning, harm/checking, hoarding/symmetry, religious/ sexual, and somatic/hypochondriacal). Analyses of covariance including all the subscales demonstrated that escitalopram was more effective than placebo. There was a significant interaction for the hoarding/symmetry factor, which was associated with a poor treatment response. Conclusion: Escitalopram shows good efficacy across the range of OCD symptom dimensions. Nevertheless, hoarding/symmetry was associated with a poorer treatment response. Hoarding/symmetry may be particularly characteristic of an early-onset group of OCD patients, with the involvement of neurotransmitters other than serotonin. Further work is needed to delineate fully the subtypes of OCD, and their correlates with underlying psychobiology and treatment responsivity.
- ItemEvidence for fractional anisotropy and mean diffusivity white matter abnormalities in the internal capsule and cingulum in patients with obsessive-compulsive disorder(2012) Lochner C.; Fouche J.-P.; du Plessis S.; Spottiswoode B.; Seedat S.; Fineberg N.; Chamberlain S.R.; Stein D.J.Background: There is evidence to suggest that obsessive-compulsive disorder (OCD) is associated with structural abnormalities in cortico-striato-thalamic circuits, yet the extent of white matter abnormalities is not well established. In this study, we used diffusion tensor imaging (DTI) to examine white matter integrity in specific regions of interest (ROIs) in patients with OCD. Methods: Patients with OCD and sex-, age- and IQ-matched healthy controls underwent DTI. The primary objective was to explore whether patients with OCD had white matter abnormalities in the anterior limb of the internal capsule (ALIC), the uncinate fasciculus, the genu of the corpus callo-sum and the cingulum. The secondary objective was to evaluate the relation between fractional anisotropy and mean diffusivity in these ROIs and other clinical variables (including age at onset of OCD, OCD severity and levels of depressive and anxiety symptomatology) in patients with OCD. Results: There were 15 patients and 17 controls enrolled in our study. Compared with healthy controls, patients with OCD showed increased fractional anisotropy in bilateral regions of the ALIC adjacent to the body of the caudate, as well as decreased fractional anisotropy in the right anterior limb near the head of the caudate. Patients also had decreased mean diffusivity in the body of the right cingulum and the left anterior cingulum compared with controls. Correlational analyses revealed significant associations of fractional anisotropy and mean diffusivity in select circuits with OCD, depression and anxiety severity scores. Limitations: Inclusion of patients with OCD receiving pharmacotherapy may have been a limitation. In addition, the patients were heterogeneous in terms of their obsessive-compulsive symptom profiles; we did not distinguish between different obsessive-compulsive symptom dimensions. Conclusion: The study results provide further evidence for OCD-related white matter abnormalities in the ALIC and cingulum, consistent with a cortico striatal model of OCD. © 2012 Canadian Medical Association.
- ItemGrey matter abnormalities in social anxiety disorder: A pilot study(2012) Syal S.; Hattingh C.J.; Fouche J.-P.; Spottiswoode B.; Carey P.D.; Lochner C.; Stein D.J.While a number of studies have explored the functional neuroanatomy of social anxiety disorder (SAD), data on grey matter integrity are lacking. We conducted structural MRI scans to examine the cortical thickness of grey matter in individuals with SAD. 13 unmedicated adult patients with a primary diagnosis of generalized social anxiety disorder and 13 demographically (age, gender and education) matched healthy controls underwent 3T structural magnetic resonance imaging. Cortical thickness and subcortical volumes were estimated using an automated algorithm (Freesurfer Version 4.5). Compared to controls, social anxiety disorder patients showed significant bilateral cortical thinning in the fusiform and post central regions. Additionally, right hemisphere specific thinning was found in the frontal, temporal, parietal and insular cortices of individuals with social anxiety disorder. Although uncorrected cortical grey matter volumes were significantly lower in individuals with SAD, we did not detect volumetric differences in corrected amygdala, hippocampal or cortical grey matter volumes across study groups. Structural differences in grey matter thickness between SAD patients and controls highlight the diffuse neuroanatomical networks involved in both social anxiety and social behavior. Additional work is needed to investigate the causal mechanisms involved in such structural abnormalities in SAD. © Springer Science+Business Media, LLC 2012.
- ItemHoarding in obsessive-compulsive disorder: Clinical and genetic correlates(2005) Lochner C.; Kinnear C.J.; Hemmings, Sian M. J.; Seller C.; Niehaus D.J.H.; Knowles J.A.; Daniels W.; Moolman-Smook J.C.; Seedat S.; Stein D.J.Objective: Hoarding may be an important symptom dimension in obsessive-compulsive disorder (OCD). Hoarding in OCD has been associated with poor insight, poorer response to selective serotonin reuptake inhibitors than other OCD symptom dimensions, and a distinctive psychobiological profile. The clinical and genetic correlates of hoarding in OCD therefore deserve additional investigation. Method: Adult OCD patients (N = 315) underwent a comprehensive clinical assessment that included the Structured Clinical Interview for DSM-IV Axis I Disorders (Patient Edition) and for Diagnosis of Obsessive-Compulsive Spectrum Disorders. DNA extracted from venous blood (10-30 mL) in a Caucasian subset of the interviewed OCD patients (N = 204) and Caucasian controls (N = 169), including patients (N = 94) and controls (N = 138) of Afrikaner descent, was genotyped to investigate polymorphisms in genes involved in monoamine function and previously hypothesized to be relevant to OCD. Data were collected from 1998 through 2004. Results: OCD patients with hoarding made up 18.1% of the total sample. Compared with nonhoarding OCD, OCD with hoarding was associated with a number of comorbid Axis I disorders, obsessive-compulsive personality disorder, significantly higher OCD severity scores, and more functional impairment. In subjects of Afrikaner descent, the L/L genotype of the COMT Val158Met polymorphism was significantly more common in the OCD hoarding group, with a preponderance of low activity alleles, compared with nonhoarding patients and controls. Conclusions: These data are consistent with the hypothesis that hoarding represents a unique symptom subtype in OCD with a distinctive clinical and psychobiological profile. Further work is needed to determine the psychobiological mechanisms responsible for hoarding and to replicate the genetic findings noted here.
- ItemLatent class analysis of the Yale-Brown Obsessive-Compulsive Scale symptoms in obsessive-compulsive disorder(2011) Delucchi K.L.; Katerberg H.; Stewart S.E.; Denys D.A.J.P.; Lochner C.; Stack D.E.; Den Boer J.A.; Van Balkom A.J.L.M.; Jenike M.A.; Stein D.J.; Cath D.C.; Mathews C.A.Objective: Obsessive-compulsive disorder (OCD) is phenomenologically heterogeneous, and findings of underlying structure classification based on symptom grouping have been ambiguous to date. Variable-centered approaches, primarily factor analysis, have been used to identify homogeneous groups of symptoms; but person-centered latent methods have seen little use. This study was designed to uncover sets of homogeneous groupings within 1611 individuals with OCD based on symptoms. Method: Latent class analysis models using 61 obsessive-compulsive symptoms collected from the Yale-Brown Obsessive-Compulsive Scale were fit. Relationships between latent class membership and treatment response, sex, symptom severity, and comorbid tic disorders were tested for relationship to class membership. Results: Latent class analysis models of best fit yielded 3 classes. Classes differed only in frequency of symptom endorsement. Classes with higher symptom endorsement were associated with earlier age of onset, being male, higher Yale-Brown Obsessive-Compulsive Scale symptom severity scores, and comorbid tic disorders. There were no differences in treatment response between classes. Conclusions: These results provide support for the validity of a single underlying latent OCD construct, in addition to the distinct symptom factors identified previously via factor analyses. © 2011 Elsevier Inc. All rights reserved.
- ItemSelective attention to fearful faces during pregnancy(2012-01-18) Roos A.; Lochner C.; Kidd M.; van Honk J.; Vythilingum B.; Stein D.J.
- ItemThe validity of DSM-IV-TR criteria B and C of hair-pulling disorder (trichotillomania): Evidence from a clinical study(2011) Lochner C.; Stein D.J.; Woods D.; Pauls D.L.; Franklin M.E.; Loerke E.H.; Keuthen N.J.In both DSM-IV-TR and the ICD-10, hair-pulling disorder (trichotillomania, or TTM) is described as hair-pulling, with a rising urge or tension prior to pulling or when attempting to resist, and pleasure, relief or gratification during or after pulling. However, it has been questioned whether all patients with hair-pulling experience these other phenomena, and whether they occur with all pulling episodes. The objective of this study was to examine the DSM-IV-TR requirement of criteria B and C for a diagnosis of TTM in a sample of people with hair-pulling. A multi-site sample of adults with hair-pulling who met both DSM-IV-TR diagnostic criteria B and C (n=82, 89.13%) were compared to those who failed to satisfy both B and C (n=10, 10.87%) on a number of clinical variables. There were no differences in hair-pulling severity, levels of comorbid depressive and anxiety symptoms, number of comorbid body-focused repetitive behaviors, or impairment between those patients who did and did not meet criteria B and C. Our study does not provide convincing support for the inclusion of the current diagnostic criteria B and C for TTM in DSM-5. © 2011 Elsevier Ireland Ltd.
- ItemTopiramate in the treatment of trichotillomania: An open-label pilot study(2006) Lochner C.; Seedat S.; Niehaus D.J.H.; Stein D.J.There is a need for an effective medication for the treatment of trichotillomania (TTM), which is an impulse control disorder characterized by chronic hair-pulling. Topiramate has shown promising results in the treatment of impulse-control disorders. The present open-label pilot study investigated the efficacy and safety of topiramate in 14 adults with TTM. Patients received 16 weeks of flexible dose treatment (50-250 mg/day), followed by a flexible dose taper over 2-4 weeks. The primary outcome measure was the Massachusetts General Hospital Hair-Pulling Scale (HPS), whereas secondary outcome measures were the Clinical Global Impression (CGI) Scale, the Montgomery-Asberg Depression Rating Scale, the Hamilton Rating Scale for Anxiety and the Disability Profile. A repeated measures analysis of variance on the intent-to-treat sample was implemented to evaluate treatment response. The primary outcome measure (HPS) indicated that the severity of hair-pulling in adults with TTM who completed the 16-week study (n=9) decreased significantly from baseline to the treatment endpoint (F=5.05; P=0.0002). Although the CGI-Improvement scores suggested that hair-pulling was not significantly reduced, six of nine trial completers were classified as responders. None of the other measures showed significant differences compared to baseline. Five patients dropped out owing to adverse effects. These results suggest that topiramate may be useful in the treatment of TTM. Future studies should investigate the efficacy of topiramate in an appropriately powered randomized placebo-controlled trial. © 2006 Lippincott Williams & Wilkins.