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Biomedical subjects

Christine Lochner

Publications and source records attributed to Christine Lochner.

At least 19 recordsLinked to original sources
PubMed2025

Human development, inequality, and their associations with brain structure across 29 countries.

BACKGROUND: The macro-social and environmental conditions in which people live, such as the level of a country's development or inequality, are associated with brain-related disorders. However, the relationship between these systemic environmental factors and the brain remains unclear. We aimed to determine the association between the level of development and inequality of a country and the brain structure of healthy adults. METHODS: We conducted a cross-sectional study pooling brain imaging (T1-based) data from 145 magnetic resonance imaging (MRI) studies in 7,962 healthy adults (4,110 women) in 29 different countries. We used a meta-regression approach to relate the brain structure to the country's level of development and inequality. RESULTS: Higher human development was consistently associated with larger hippocampi and more expanded global cortical surface area, particularly in frontal areas. Increased inequality was most consistently associated with smaller hippocampal volume and thinner cortical thickness across the brain. CONCLUSIONS: Our results suggest that the macro-economic conditions of a country are reflected in its inhabitants' brains and may explain the different incidence of brain disorders across the world. The observed variability of brain structure in health across countries should be considered when developing tools in the field of personalized or precision medicine that are intended to be used across the world.

Humans↗
PubMed2006

Genetics and personality traits in patients with social anxiety disorder: a case-control study in South Africa.

BACKGROUND: Social anxiety disorder (SAD) is among the most common of all psychiatric disorders with lifetime prevalence estimates ranging from 7% to 13%. Although there is evidence that SAD has a strong familial basis, there are few studies of potential candidate genes. In addition to a genetic association, there is also the possibility that temperamental risk factors for the disorder may be genetically transmitted. Against this background, our aims were threefold: i.) to compare patients and controls with respect to personality traits, ii.) to genotype a subgroup of these participants to investigate the role of genes encoding components of serotonergic (5-HT) and dopaminergic (DA) pathways in patients with SAD and iii.) to compare differences in temperament dimensions between carriers of different (dominant vs. recessive) alleles for selected polymorphisms in SAD patients. METHODS: Sixty-three patients (n=63; 35 male, 28 female) with a DSM-IV diagnosis of generalized SAD and SPIN-scores >18, and age-matched control participants (n=150; 31 male, 119 female) were included in the study. The Temperament and Character Inventory (TCI) was used to measure behaviours associated with specific personality dimensions (i.e. temperament/character). DNA was extracted and genotyped to investigate the role of select candidate genes encoding components in serotonergic and dopaminergic pathways in mediating the development of SAD. To achieve this, the frequency of variants in 5-HT and DA genes was compared between a Caucasian subset of SAD patients (n=41) and a convenience sample of Caucasian controls (n=88), using case-control association analyses. We also investigated the frequency of variants in 5-HT and DA-related genes across temperament characteristics in SAD patients, using analyses of variance (ANOVA). RESULTS: Patients scored significantly higher on harm avoidance (p<0.001) but lower on novelty seeking (p=0.04) and self-directedness (p=0.004) compared to controls. In the Caucasian subset, there was a difference between patients and controls in distribution of the 5-HT(2A)T102C polymorphism, with significantly more patients harboring T-containing genotypes (T-containing genotypes: [T/T+T/C] vs. [C/C]) (chi2=7.55; p=0.012). Temperament dimensions did not, however, differ significantly between carriers of different (dominant vs. recessive) alleles for the 5-HT(2A)T102C polymorphism in SAD patients. CONCLUSIONS: The results suggest a possible role for the 5-HT(2A)T102C polymorphism in the development of SAD. To date genetic findings in SAD have been inconsistent; nevertheless, serotonergic variants, and their associations with temperaments (e.g. reward dependence) deserve further exploration, in the hope that endophenotypes relevant to SAD can ultimately be delineated.

Adolescent↗
PubMed2006

Does work on obsessive-compulsive spectrum disorders contribute to understanding the heterogeneity of obsessive-compulsive disorder?

BACKGROUND: 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). METHODS: 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. RESULTS: OCSDs may lie on several different dimensions. Our cluster analysis found that in OCD there were 3 clusters of OCD spectrum symptoms: (1) "Reward deficiency" (including trichotillomania, pathological gambling, hypersexual disorder and Tourette's disorder), (2) "Impulsivity" (including compulsive shopping, kleptomania, eating disorders, self-injury and intermittent explosive disorder), and (3) "Somatic" (including body dysmorphic disorder and hypochondriasis). CONCLUSIONS: 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.

Cluster Analysis↗
PubMed2006

Obsessive-compulsive spectrum disorders: a multidimensional approach.

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.

Diagnostic and Statistical Manual of Mental Disord↗
PubMed2006

Topiramate in the treatment of trichotillomania: an open-label pilot study.

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.

Adult↗
PubMed2006

Disability and quality of life in post-traumatic stress disorder: impact of drug treatment.

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.

Clinical Trials as Topic↗
PubMed2006

Genetic correlates in trichotillomania--A case-control association study in the South African Caucasian population.

BACKGROUND: Trichotillomania (TTM), a prevalent and disabling psychiatric disorder characterized by repetitive hair-pulling, is presently classified as an impulse control disorder (ICD). Some have argued, however, that TTM is an obsessive-compulsive spectrum disorder (OCSD). There is some evidence that both disorders (OCD and TTM) are mediated by serotonergic (5-HT) and dopaminergic pathways. METHODS: The aim of the present investigation was to assess the role of candidate genes encoding components within the 5-HT and dopaminergic neurotransmitter pathways in mediating TTM. South African Caucasian TTM subjects (n=39), OCD (n=250) and control subjects (n=152) were genotyped for variants in 5-HT and dopaminergic candidate genes. RESULTS: Both genotypic and allelic distributions of the 5-HT receptor 2A (5-HT2A) T102C variant were found to be significantly different between the TTM and control subjects (p=0.028 and p=0.024, respectively), and a trend towards significance was noted between the TTM and OCD subjects (p=0.084 and p=0.080 for genotype and allele analyses, respectively), with the T102T-genotype found to confer susceptibility to the development of TTM. CONCLUSION: This investigation provides preliminary evidence for the involvement of 5-HT2A in the molecular aetiology of TTM and supports the need for further replication in a larger dataset. The present data are consistent with previous findings that 5-HT2A plays a role in mediating impulse dyscontrol.

Alleles↗
PubMed2005

Obsessive-compulsive disorder and trichotillomania: a phenomenological comparison.

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. RESULTS: OCD 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. CONCLUSIONS: These 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.

Adolescent↗
PubMed2005

Hoarding in obsessive-compulsive disorder: clinical and genetic correlates.

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.

Adult↗
PubMed2005

Obsessive compulsive disorder--prevalence in Xhosa-speaking schizophrenia patients.

Obsessive compulsive disorder (OCD) has been reported in up to 31% of schizophrenia sufferers. This study evaluated the presence of OCD in a Xhosa-speaking schizophrenia group. Xhosa patients (N = 509, including 100 sibships) with schizophrenia were recruited from hospital and community settings. The patients underwent a structured clinical interview for the presence of lifetime co-morbid schizophrenia and OCD. Only 3 patients (0.5%) fulfilled criteria for OCD. No concordance for OCD was noted in the sibship group. Our findings differ from those in other parts of the world, and if replicated, might suggest unique protective environmental or genetic factors for OCD in certain ethnic groups.

Adult↗
PubMed2004

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 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.

Adult↗
PubMed2004

Corrigendum to "gender in obsessive-compulsive disorder: clinical and genetic findings" [Eur. Neuropsychopharmacol. 14 (2004) 105-113].

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 G allele at the G861C variant of the 5HT1Dbeta 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.

Adolescent↗
PubMed2004

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.

Adolescent↗
PubMed2003

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.

Case-Control Studies↗
PubMed2002

Childhood trauma in obsessive-compulsive disorder, trichotillomania, and controls.

There is relatively little data on the link between childhood trauma and obsessive-compulsive/putative obsessive-compulsive spectrum disorders. The revised Childhood Trauma Questionnaire (CTQ), which assesses physical, emotional, and sexual abuse as well as physical and emotional neglect, was administered to female patients with obsessive-compulsive disorder (OCD; n = 74; age: 36.1 plus minus 16.3), TTM (n = 36; age: 31.8 plus minus 12.3), and a group of normal controls (n = 31; age: 21.5 plus minus 1.0). The findings showed a significantly greater severity of childhood trauma in general, and emotional neglect specifically, in the patient groups compared to the controls. Although various factors may play a role in the etiology of both OCD and trichotillomania (TTM), this study is consistent with some evidence from previous studies suggesting that childhood trauma may play a role in the development of these disorders.

Adolescent↗
PubMed2002

Trichotillomania and skin-picking: a phenomenological comparison.

Although trichotillomania and pathological skin-picking are both characterized by repetitive self-injurious stereotypic behaviors, the former is classified as an impulse control disorder, while the latter is not given a specific diagnostic category in the Diagnostic and Statistical Manual of Mental Disorders (4th edition) [APA, 1994]. There are, however, few empirical data on phenomenological similarities and differences between these disorders. Patients with trichotillomania and pathological skin-picking were compared in terms of several demographic (age, gender), clinical (comorbid axis I and II disorders), and personality variables. Trichotillomania and pathological skin-picking were very similar in demographics, psychiatric comorbidity, and personality dimensions. Dissociative symptoms may be more common in trichotillomania than in pathological skin-picking. These data support the concept of phenomenological overlap between trichotillomania and pathological skin-picking. Future work to assess the implications of overlap for clinical evaluation and intervention in the two conditions may be useful.

Adult↗