Christine Lochner - Academia.edu (original) (raw)

Papers by Christine Lochner

OBJECTIVE: In obsessive-compulsive disorder (OCD), symmetry-related symptoms may be important. Al... more OBJECTIVE:
In obsessive-compulsive disorder (OCD), symmetry-related symptoms may be important. Although clinical correlates of symmetry-related symptoms have been identified in OCD, few data exist on genetic associations. Animal studies indicate involvement of dopamine in symmetry-related behavior, suggesting this may be relevant to analogous symptoms in OCD. Alterations in dopamine may also reflect environmental influences. However, the association of symmetry-related symptomatology, early adversity, and polymorphisms in dopaminergic genes has not been investigated in OCD.
METHODS:
Clinical information and polymorphisms in key dopaminergic genes were compared between OCD patients with primary symmetry symptoms and those without.
RESULTS:
OCD patients with primary symmetry symptoms comprised 46.6% (n=210) of the sample (n=451), and were older (p < 0.01), had longer illness duration (p < 0.01), higher OCD severity scores (p = 0.01), and greater comorbidity (p < 0.01) than those without. In Caucasians (n=343), genotype frequency differed significantly between groups for ANKK1 rs1800497, with more OCD patients with symmetry symptoms being homozygous for the A2 (CC) genotype (χ2 = 7.296; p = 0.026).
CONCLUSION:
Symmetry symptoms have some distinct clinical features and may represent a marker of severity in OCD. However, clinical associations, in combination with the association found with the ANKK1 rs1800497 A2 variant, suggest that primary symmetry symptoms may represent a distinctive clinical and psychobiological profile.

Background Social anxiety disorder (SAD) is characterized by excessive anxiety about social inte... more Background

Social anxiety disorder (SAD) is characterized by excessive anxiety about social interaction or performance situations, leading to avoidance and clinically significant distress. A growing literature on the neurobiology of SAD has suggested that the reward/avoidance basal ganglia circuitry in general and the glutamatergic system in particular may play a role. In the current study, we investigated 1H-magnetic resonance spectroscopy (1H-MRS) concentrations in cortical, striatal, and thalamic circuitry, as well as their associations with measures of social anxiety and related symptoms, in patients with primary SAD.

Methodology

Eighteen adult individuals with SAD and 19 age- and sex- matched controls participated in this study. 1H-MRS was used to determine relative metabolite concentrations in the anterior cingulate cortex (ACC) using single voxel spectroscopy (reporting relative N-acetyl-aspartate (NAA), N-acetyl-aspartate with N-acetyl-aspartyl-glutamate (NAA + NAAG), glycerophosphocholine with phosphocholine (GPC + PCh), myo-inositol, glutamate (Glu), and glutamate with its precursor glutamine (Glu + Gln)), and the caudate, putamen and thalami bilaterally using two dimensional chemical shift imaging (reporting relative NAA + NAAG and GPC + PCh). Relationships between metabolite concentrations and measures of social anxiety and related symptoms were also determined. Measures of social anxiety included symptom severity, blushing propensity, and gaze anxiety/avoidance.

Results

We found, first, decreased relative glutamate concentration in the ACC of SAD and changes in myo-inositol with measures of social anxiety. Second, NAA metabolite concentration was increased in thalamus of SAD, and choline metabolite concentrations were related to measures of social anxiety. Lastly, choline metabolite concentration in the caudate and putamen showed changes in relation to measures of social anxiety.

Conclusion

These findings are consistent with evidence that the reward/avoidance basal ganglia circuitry, as well as the glutamatergic system, play a role in mediating SAD symptoms.

Introduction: There is a substantial body of evi- dence that obsessive-compulsive disorder (OCD) ... more Introduction: There is a substantial body of evi- dence that obsessive-compulsive disorder (OCD) symptoms can be grouped into a series of dis- crete dimensions, and some evidence that not all OCD symptom dimensions respond equally well to pharmacologic or psychotherapeutic interven- tion. The response of OCD symptom dimensions to 12 weeks of treatment with escitalopram or placebo was investigated. Methods:

Concepts and Controversies in Obsessive-Compulsive Disorder, 2005

1 In this chapter we argue that it is a useful heuristic to conceptualize trichotillomania (TTM) ... more 1 In this chapter we argue that it is a useful heuristic to conceptualize trichotillomania (TTM) as belonging to an obsessive-compulsive spectrum of disorders.

The Israel journal of psychiatry and related sciences, 2008

There is increasing evidence that obsessive-compulsive disorder (OCD) is a heterogeneous disorder... more There is increasing evidence that obsessive-compulsive disorder (OCD) is a heterogeneous disorder. Different clinical subtypes may be characterized by differing pathophysiological mechanisms and treatment outcomes. A cluster analysis was performed on 45 items of the Yale-Brown Obsessive-Compulsive Symptoms Checklist (YBOCS-CL) for 261 patients with OCD. Cluster solutions emerging at different linkage distance levels, and the associations of identified clusters with demographic, clinical and relevant genetic variables, were investigated. A 6-cluster solution emerged at a linkage distance level of 1.5, and a 3-cluster solution emerged at a linkage distance level of 2.1. The 3 clusters in the latter solution were labeled I) Contamination / washing, II) Hoarding / symmetry / ordering, and III) Obsessional / checking. Increased Cluster III scores were associated with earlier age of OCD onset and the Met/Met (L/L) genotype of the COMT Val158Met polymorphism. The data here are consistent w...

CNS spectrums, 2008

There is a substantial body of evidence that obsessive-compulsive disorder (OCD) symptoms can be ... more 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. 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. Exploratory factor analysis of individual Yale-Brown Obsessive-Compulsive Scale items yielded 5 factors (contamination/cleaning, harm/checking, hoar...

Behavioural brain research, Jan 15, 2015

Skin picking disorder (SPD) and trichotillomania (hair pulling disorder, or HPD) significantly ov... more Skin picking disorder (SPD) and trichotillomania (hair pulling disorder, or HPD) significantly overlap in terms of clinical features. However, few studies have directly compared structural brain data in these disorders. The aim of this study was to compare volumes of brain structures and cortical thickness in patients with SPD and HPD, and determine involvement of fronto-striatal pathways. Seventeen female SPD, 17 HPD and 15 healthy age-matched controls underwent clinical assessment and structural MRI imaging. Group differences were determined in brain volume and cortical thickness, controlling for illness severity. Participants with SPD had greater volume of the ventral striatum bilaterally; and reduced cortical thickness in right hemisphere frontal areas, and greater thickness of the cuneus bilaterally compared to HPD and control participants. HPD participants demonstrated reduced thickness of the right parahippocampal gyrus compared to SPD and control participants. The findings h...

BMC Psychiatry, 2005

Background: Similarities between obsessive-compulsive disorder (OCD) and trichotillomania (TTM) h... more Background: Similarities 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. Methods: Two 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.

Journal of the American Academy of Child and Adolescent Psychiatry, 2014

Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental d... more Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large…

Progress in neuro-psychopharmacology & biological psychiatry, Jan 27, 2014

Social anxiety disorder (SAD) is characterized by excessive anxiety about social interaction or p... more Social anxiety disorder (SAD) is characterized by excessive anxiety about social interaction or performance situations, leading to avoidance and clinically significant distress. A growing literature on the neurobiology of SAD has suggested that the reward/avoidance basal ganglia circuitry in general and the glutamatergic system in particular may play a role. In the current study, we investigated (1)H-magnetic resonance spectroscopy ((1)H-MRS) concentrations in cortical, striatal, and thalamic circuitry, as well as their associations with measures of social anxiety and related symptoms, in patients with primary SAD. Eighteen adult individuals with SAD and 19 age- and sex- matched controls participated in this study. (1)H-MRS was used to determine relative metabolite concentrations in the anterior cingulate cortex (ACC) using single voxel spectroscopy (reporting relative N-acetyl-aspartate (NAA), N-acetyl-aspartate with N-acetyl-aspartyl-glutamate (NAA+NAAG), glycerophosphocholine wit...

Behavioural Brain Research, 2011

In non-pregnant individuals, the prefrontal cortex (PFC) is involved in the regulation of emotion... more 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

Psychopathology, 2010

There has been debate about whether obsessive-compulsive disorder (OCD) should be classified as o... more There has been debate about whether obsessive-compulsive disorder (OCD) should be classified as one of the anxiety disorders, or should rather be categorized with obsessive-compulsive spectrum conditions. The question of where OCD should be located in the diagnostic system was addressed by investigating the relationship of OCD, obsessive-compulsive spectrum disorders (OCSDs), and anxiety disorders. We administered a structured diagnostic interview (the SCID-OCSD) for assessing putative OCSDs in patients who presented with a primary diagnosis of OCD, panic disorder with/out agoraphobia (PD) or social anxiety disorder (SAD) in an attempt to address the proposed differentiation of OCD from the other DSM-IV anxiety disorders. Patients with OCD were significantly more likely to have multiple comorbid putative OCSDs than patients with PD or SAD. Some OCSDs, i.e. any tic disorder/Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disorder as well as body-focused repetitive behaviors (self-injury, trichotillomania), and certain impulsive/reward-focused disorders (kleptomania, hypersexual disorder) were more common in OCD. Some of the putative OCSDs (e.g. hypochondriasis and body dysmorphic disorder) were more common in PD and SAD, respectively. Depression had equally high comorbidity with OCD, PD, and SAD, while generalized anxiety disorder and alcohol dependence were particularly associated with SAD. These findings suggest that some putative OCSDs may be related to OCD, while some may have a closer relationship to other anxiety disorders. From a nosological perspective, it may be useful to include OCD and certain OCSDs under the rubric of an enlarged category of anxiety and OCSDs.

Psychopathology, 2003

Background: There is growing recognition that the anxiety disorders are disabling disorders assoc... more 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.

Psychiatry Research, 2004

There is increasing evidence that obsessive -compulsive disorder (OCD) is mediated by genetic fac... more 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 disorder's 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, Tourette's 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.

Psychiatric Clinics of North America, 2006

One advantage of conceptualizing two disorders as related lies in the possibility that a similar ... more One advantage of conceptualizing two disorders as related lies in the possibility that a similar treatment is effective for both conditions. The approach taken in this paper is somewhat different, however. The authors have argued that although a particular psychobiologic process may be relevant to OCD and obsessive-compulsive conditions, it may be disrupted indifferent ways in various conditions that fall along a spectrum. If so, differ-ent obsessive-compulsive spectrum disorders may well require different treatments. Thus, although OCD and trichotillomania can be conceptualized in terms of the pathologic release of motor programs, they may require rather different treatment approaches. Furthermore, in the absence of a detailed understanding of the psycho-biology of OCD and related disorders, conceptualizations of obsessive-compulsive spectrum disorders can remain only preliminary in nature. The involvement of cortico-striatal circuitry in OCD suggests that obsessive-compulsive spectrum disorders may be characterized by involvement of these paths. Striatal circuits mediate many different functions (including reward processes), however, and are involved in many disorders. Similarly, the involvement of serotonergic neurotransmitters in OCD suggests that these neurotransmitters are central to defining spectrum disorders.Again, however, serotonin plays a role in many functions (including impulse control) and mediates many different disorders. Much work remains to be done to delineate optimally the obsessive-compulsive spectrum of disorders. Nevertheless, significant progress has been made. Empiric data demonstrate involvement of cortico-striatal circuitry in a number of putative obsessive-compulsive spectrum disorders [43]. Similarly, data demonstrate that a selective response to serotonin-reuptake inhibitors is seen in a range of these different spectrum disorders. As further progress is made in understanding the cognitive-affective neuroscience of OCD and related conditions, constructs about obsessive-compulsive spectrum disorders will become increasingly sharp.

Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2011

Introduction: Comorbid obsessive-compulsive personality disorder (OCPD) is well-described in obse... more Introduction: Comorbid obsessive-compulsive personality disorder (OCPD) is well-described in obsessivecompulsive 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.

Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2006

There is a growing literature on the concept of an obsessive-compulsive spectrum of disorders. He... more There is a growing literature on the concept of an obsessive-compulsive spectrum of disorders. Here, we consider the different dimensions on which obsessive-compulsive spectrum (OCSDs) lie, and focus on how the concepts from this literature may help understand the heterogeneity of obsessive-compulsive disorder (OCD). A computerized literature search (MEDLINE: 1964-2005) was used to collect studies addressing different dimensions on which the OCSDs lie. Against this backdrop, we report on a cluster analysis of OCSDs within OCD. OCSDs may lie on several different dimensions. Our cluster analysis found that in OCD there were 3 clusters of OCD spectrum symptoms: (1) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Reward deficiency&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; (including trichotillomania, pathological gambling, hypersexual disorder and Tourette&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disorder), (2) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Impulsivity&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; (including compulsive shopping, kleptomania, eating disorders, self-injury and intermittent explosive disorder), and (3) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Somatic&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; (including body dysmorphic disorder and hypochondriasis). It is unlikely that OC symptoms and disorders fall on any single phenomenological dimension; instead, multiple different constructs may be required to map this nosological space. Although there is evidence for the validity of some of the relevant dimensions, additional work is required to delineate more fully the endophenotypes that underlie OC symptoms and disorders.

Primary Care Psychiatry, 2001

Olfactory reference syndrome (ORS) has been defined as a psychiatric condition characterized by p... more Olfactory reference syndrome (ORS) has been defined as a psychiatric condition characterized by persistent preoccupation about body odour accompanied by shame, embarrassment, significant distress, avoidance behaviour and social isolation.

PharmacoEconomics, 2006

The degree of functional disability and quality of life (QOL) impairment in patients with post-tr... more The degree of functional disability and quality of life (QOL) impairment in patients with post-traumatic stress disorder (PTSD) is at least comparable with, and in many instances greater than, that of patients with other anxiety and mood disorders. Multidimensional QOL assessments in PTSD have utility in capturing aspects of individual patient experience and satisfaction related to health and treatment, and have fairly robust sensitivity to treatment effects. Despite the growing number of epidemiological and clinical studies detailing QOL in PTSD, there are few studies of the impact of pharmacological agents on QOL outcomes, and none that have included an economic component to evaluate the resource consequences of the disorder. To date, the selective serotonin reuptake inhibitors have been shown to confer significant acute (and longer term) QOL and psychosocial benefits. Further investigation of the relationship of QOL to PTSD symptom severity, disability, treatment outcome and cost, among the different drug treatment modalities, is clearly needed.

Neuropsychobiology, 2007

Dissociation is defined as the disruption of the usually integrated functions of consciousness, s... more Dissociation is defined as the disruption of the usually integrated functions of consciousness, such as memory, identity, and perceptions of the environment. Causes include various psychological, neurological and neurobiological mechanisms, none of which have been consistently supported. To our knowledge, the role of gene-environment interactions in dissociative experiences in obsessive-compulsive disorder (OCD) has not previously been investigated. Eighty-three Caucasian patients (29 male, 54 female) with a principal diagnosis of OCD were included. The Dissociative Experiences Scale was used to assess dissociation. The role of childhood trauma (assessed with the Childhood Trauma Questionnaire), and a functional 44-bp insertion/deletion polymorphism in the promoter region of the serotonin transporter, or 5-HTT, in mediating dissociation, was investigated using multiple regression analysis and path analysis using the partial least squares model. Both analyses indicated that an interaction between physical neglect and the S/S genotype of the 5-HTT gene significantly predicted dissociation in patients with OCD. Dissociation may be a predictor of poorer treatment outcome in patients with OCD; therefore, a better understanding of the mechanisms that underlie this phenomenon may be useful. Here, two different but related statistical techniques (multiple regression and partial least squares), confirmed that physical neglect and the 5-HTT genotype jointly play a role in predicting dissociation in OCD.