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Hippocampal lesions, species-typical behaviours and anxiety in mice.

The hippocampus is believed to play an important role in spatial cognition and anxiety. Much of the supporting evidence is derived from rat studies. Recent reports on hippocampal lesioned mice also showed impairments in spatial function, but anxiety was not uniformly diminished. There were, however, striking impairments in several "species typical" behaviours; lesioned mice made poorer nests, and hoarded and burrowed less. In the present experiments, mice with excitotoxic hippocampal lesions were tested in a well-established anxiety paradigm, the light-dark box. As in previous anxiety tests, the results were mixed; some measures (reduced dark time) suggested lesioned mice were less anxious; others (fewer light-dark transits) suggested greater anxiety. However, lesioned mice only made fewer transits when the door was small. This suggested that the tendency to enter small holes, so characteristic of small rodents, was reduced; subsequent tests showed lesioned mice preferred to explore in an alley rather than enter its attached tunnels. Further tests of "species typical" behaviours revealed that lesioned mice spent less time digging and climbing, and made less use of cardboard shelters in their cages. This was not due to inactivity; lesions did not reduce grooming or locomotion. Finally, tests of hyponeophagia showed hippocampal lesions reduced this measure of anxiety, so long as the control baseline was sufficiently high. Overall, the results suggest that the hippocampus is important in many species-typical behaviours, potentially influencing performance in a range of behavioural tests. However, species-typical behaviours offer easy and economical ways to test for hippocampal dysfunction, for example, in genetically modified mice.

Animals↗

Medial preoptic area interactions with the nucleus accumbens-ventral pallidum circuit and maternal behavior in rats.

Several experiments explored the roles of nucleus accumbens (NA), ventral pallidum (VP) and medial preoptic area (MPOA) in the regulation of maternal behavior in rats. A preliminary experiment found that bilateral radiofrequency lesions of medial NA did not disrupt maternal behavior. Experiment 1 found that bilateral infusions of muscimol into VP, but not into medial NA, reversibly disrupted maternal behavior. Experiment 2 found that unilateral muscimol injections into VP disrupted maternal behavior to a greater extent when paired with a contralateral N-methyl-d-aspartic acid (NMDA) MPOA lesion than when paired with a sham MPOA lesion. Experiment 3 showed that a unilateral NMDA MPOA lesion paired with a contralateral NMDA VP lesion (Contra group) disrupted maternal behavior to a much greater extent than did sham NMLA lesions or NMDA lesions of MPOA and VP ipsilateral to one another. Experiment 3 focused on the specificity of the maternal behavior disruptions and found that the primary maternal deficit in the Contra females was a severe deficit in retrieval behavior. Importantly, these females showed normal hoarding behavior, home cage activity, and elevated plus maze activity. Experiment 3 used Neu N immunohistochemistry to define the extent of MPOA and VP excitotoxic lesions. It is hypothesized that MPOA acts to facilitate the active components of maternal behavior by inhibiting NA, which then releases VP from GABAergic inhibition, and such disinhibition of VP allows pup stimuli to trigger appropriate maternal responses.

Analysis of Variance↗

The Concentric Square Field: a multivariate test arena for analysis of explorative strategies.

In this study, we describe the behavior of laboratory rats in a recently developed observation arena, the Concentric Square Field (CSF). The CSF contains a number of areas designed to provoke exploration and behaviors associated with risk assessment, risk taking and security seeking in an environment not previously experienced. The model includes sheltered, open and elevated areas, a hole board device, areas with different light conditions, and wall-enclosed corridors. The rationale behind the CSF is to meet the demand for multivariate test situations that are not predictive in the sense of previous definition of a specific purpose of measuring a certain mental state. We define multivariate as being a free choice of where to stay in areas of different qualities. In the present study, identification of risky as opposed to safe areas is based on the retrieval behavior in lactating females and hoarding of food pellets in food-deprived males. Furthermore, we describe the effects of pre-trial food deprivation, immobilization, social stress, strain differences (Sprague-Dawley, Wistar and Lister Hooded males), sex differences (Sprague-Dawley) and repeated testing. Besides the conventional statistics, a principal component analysis (PCA) helped to discriminate between the various categories tested. Our conclusion is that the multivariate and non-predictive test situation (CSF) and the use of PCA provide a good tool for ethoexperimental analysis.

Analysis of Variance↗

Familiality of factor analysis-derived YBOCS dimensions in OCD-affected sibling pairs from the OCD Collaborative Genetics Study.

BACKGROUND: Identification of familial, more homogenous characteristics of obsessive-compulsive disorder (OCD) may help to define relevant subtypes and increase the power of genetic and neurobiological studies of OCD. While factor-analytic studies have found consistent, clinically meaningful OCD symptom dimensions, there have been only limited attempts to evaluate the familiality and potential genetic basis of such dimensions. METHODS: Four hundred eighteen sibling pairs with OCD were evaluated using the Structured Clinical Interview for DSM-IV and the Yale-Brown Obsessive Compulsive Scale (YBOCS) Symptom Checklist and Severity scales. RESULTS: After controlling for sex, age, and age of onset, robust sib-sib intraclass correlations were found for two of the four YBOCS factors: Factor IV (hoarding obsessions and compulsions (p = .001) and Factor I (aggressive, sexual, and religious obsessions, and checking compulsions; p = .002). Smaller, but still significant, familiality was found for Factor III (contamination/cleaning; p = .02) and Factor II (symmetry/ordering/arranging; p = .04). Limiting the sample to female subjects more than doubled the familiality estimates for Factor II (p = .003). Among potentially relevant comorbid conditions for genetic studies, bipolar I/II and major depressive disorder were strongly associated with Factor I (p < .001), whereas ADHD, alcohol dependence, and bulimia were associated with Factor II (p < .01). CONCLUSIONS: Factor-analyzed OCD symptom dimensions in sibling pairs with OCD are familial with some gender-dependence, exhibit relatively specific relationships to comorbid psychiatric disorders and thus may be useful as refined phenotypes for molecular genetic studies of OCD.

Comorbidity↗

Principal components analysis of obsessive-compulsive disorder symptoms in children and adolescents.

BACKGROUND: Obsessive-compulsive disorder (OCD) has a broadly diverse clinical expression that may reflect etiologic heterogeneity. Several adult studies have identified consistent symptom dimensions of OCD. The purpose of this study was to conduct an exploratory principal components analysis of obsessive-compulsive (OC) symptoms in children and adolescents with OCD to identify improved phenotypes for future studies. METHODS: This study examined lifetime occurrence of OC symptoms included in the 13 symptom categories of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Principal components analysis with promax rotation was performed on 231 children and adolescents with OCD and compared with results of similar adult studies. RESULTS: A four-factor solution emerged explaining 59.8% of symptom variance characterized by 1) symmetry/ordering/repeating/checking; 2) contamination/cleaning/aggressive/somatic; 3) hoarding; and 4) sexual/religious symptoms. All factors included core symptoms that have been consistently observed in adult studies of OCD. CONCLUSIONS: In children and adolescents, OCD is a multidimensional disorder. Symptom dimensions are predominantly congruent with those described in similar studies of adults with OCD, suggesting fairly consistent covariation of OCD symptoms through the developmental course. Future work is required to understand changes in specific symptom dimensions observed across the life span.

Adolescent↗

The relationship between miscellaneous symptoms and major symptom factors in obsessive-compulsive disorder.

The diverse symptomatology of obsessive-compulsive disorder (OCD) is being increasingly regarded as reducible to a few symptom dimensions. However, prevailing factor-analytically derived models of symptom structure omit a number of the well-recognized "miscellaneous" symptoms of OCD. This study sought to determine whether miscellaneous OCD symptoms, ascertained by the Yale-Brown Obsessive-Compulsive Scale symptom checklist, could be differentially and reliably predicted by four symptom factors (obsessions and checking, symmetry and ordering, contamination and cleaning, and hoarding) in two independent groups of individuals with OCD (n=381 and n=107). Logistic regression analyses were used to determine the association of each of the miscellaneous symptoms with the symptom factors; then a single confirmatory factor analysis was conducted to test the model of associations in the smaller sample. Sixteen (89%) of the 18 symptoms examined were reliably predicted by one (11 items) or two (5 items) of the factors, with obsessions and checking and symmetry and ordering emerging as foremost predictors. The expanded four-factor model showed good fit with data from the second sample. Results are conceptually meaningful, but suggest the inadequacy of groupings based solely upon overt behaviors. These findings may aid clinical understanding of OCD and be of value to studies using symptom factors to guide investigation of its causes and correlates.

Adult↗

The role of cognitive factors in the pathogenesis of obsessive-compulsive symptoms: a prospective study.

Cognitive models of obsessive-compulsive disorder (OCD) posit that specific kinds of dysfunctional beliefs (e.g., pertaining to responsibility and the significance of intrusive thoughts) underlie the development of this disorder. The present study was designed to prospectively evaluate whether dysfunctional beliefs thought to underlie OCD act as a specific vulnerability factor in the pathogenesis of obsessive-compulsive symptomatology. Eighty-five individuals were prospectively followed over a period of time thought to be associated with an increased onset of OCD symptoms -- childbirth and the postpartum. The majority of these new mothers and fathers experienced intrusive infant-related thoughts and performed neutralizing behaviors similar to, but less severe than, those observed in OCD. Scores on a measure of dysfunctional beliefs thought to underlie OCD predicted the development of obsessive-compulsive symptoms after controlling for pre-existing OCD symptoms, anxiety, and depression. Dysfunctional beliefs also predicted the severity of checking, washing, and obsessional OCD symptom dimensions, but not neutralizing, ordering, or hoarding symptom dimensions. These data provide evidence for specific dysfunctional beliefs as risk factors in the development of some types of OCD symptoms.

Adolescent↗

Temporal stability of symptom dimensions in adult patients with obsessive-compulsive disorder.

BACKGROUND: Although symptoms of obsessive-compulsive disorder (OCD) are heterogeneous, considerable advances have been made in subtyping OCD based on factor-analysed symptom dimensions. However, there is very little empirical data on the longitudinal course of symptom dimensions in adult OCD. METHODS: We examined prospectively the temporal symptom stability in adult OCD patients. Of 54 baseline OCD inpatients, 43 (80%) were re-assessed with the Yale-Brown Obsessive-Compulsive Scale symptom checklist after 6 years on average. RESULTS: Significant changes occurred within the symptom dimensions aggressive/checking, symmetry/ordering, and contamination/cleaning, whereas the others (hoarding, sexual/religious) remained unchanged from baseline to follow-up. Shifts between different dimensions from baseline to follow-up were rare, the score of each dimension at follow-up was most strongly predicted from the score of the same dimension at baseline. LIMITATIONS: The main limitation of the present study is the relatively small sample size. Furthermore, not the same raters conducted the baseline and follow-up assessments. CONCLUSIONS: Symptom dimensions seem to be remarkably stable over several years in adult OCD, despite various treatments and significant improvements in symptom severity. This underlines the usefulness of these symptom dimensions for studies of biological and genetic markers, comorbidity and treatment response predictors.

Adult↗

Could obsessive-compulsive disorder have originated as a group-selected adaptive trait in traditional societies?

Obsessive-compulsive disorder (OCD) possesses distinctive characteristics inviting evolutionary and anthropological explanations. A genetically based condition with low fecundity persisting through generations is paradoxical. The concept of group selection is an evolutionary principle capable of clarifying the perplexing epidemiology of OCD. Using a group-selection paradigm, the authors propose that OCD reflects an ancient form of behavioural specialization. The majority of compulsions such as checking, washing, counting, needing to confess, hoarding and requiring precision, all carry the potential to benefit society. Focussing primarily on hunting and gathering cultures, the potential evolutionary advantages of OCD are explored.

Adaptation, Biological↗

Early influences on human energy regulation: thrifty genotypes and thrifty phenotypes.

Early influences on human ingestive behavior and other aspects of energy homeostasis can be defined according to two very different time scales: the evolutionary time frame responsible for selection of behavioral and metabolic traits embedded within the genome; and the life-course time frame responsible for setting the phenotype. Evolutionary influences: Famine has been a constant threat to human survival leading to the selection of thrifty genes. Thriftiness can take many forms: metabolic (an 'energy-sparing' super-efficient metabolism); adipogenic (a propensity to rapid fat gain); physiologic (an ability to switch off non-essential processes); gluttony (a tendency to gorge when food is available); sloth (a tendency to conserve energy through inactivity); or behavioral (hoarding, meanness, theft, etc). Life-course influences: The nutritional environment of the early embryo can have a major impact on its survival, and its immediate and later physiology. Subsequently, the fetus is sensitive to its nutrient supply that in turn is affected by maternal fuel supply and by the constraints of the utero-placental unit. Adaptive plasticity also continues through infancy. Ingestive behavior in terms of appetite and satiety could theoretically be affected by some of these metabolic adaptations. This paper will describe the key elements of the thrifty genotype and phenotype and review the evidence base relating these early effects to differences in ingestive behavior.

Animals↗

Pathophysiology of obsessive-compulsive disorder: a necessary link between phenomenology, neuropsychology, imagery and physiology.

Obsessive-compulsive disorder (OCD) is characterized by repetitive intrusive thoughts and compulsive time-consuming behaviors classified into three to five distinct symptom dimensions including: (1) aggressive/somatic obsessions with checking compulsions; (2) contamination concerns with washing compulsions; (3) symmetry obsessions with counting/ordering compulsions; (4) hoarding obsessions with collecting compulsions; and (5) sexual/religious concerns. Phenomenologically, OCD could be thought of as the irruption of internal signals centered on the erroneous perception that "something is wrong" in a specific situation. This generates severe anxiety, leading to recurrent behaviors aimed at reducing the emotional tension. In this paper, we examine how the abnormalities in brain activity reported in OCD can be interpreted in the light of physiology after consideration of various approaches (phenomenology, neuropsychology, neuroimmunology and neuroimagery) that contribute to proposing the central role of several cortical and subcortical regions, especially the orbitofrontal cortex (OFC), the anterior cingulate cortex (ACC), the dorsolateral prefrontal cortex (DLPC), the head of the caudate nucleus and the thalamus. The OFC is involved in the significance attributed to the consequences of action, thereby subserving decision-making, whereas the ACC is particularly activated in situations in which there are conflicting options and a high likelihood of making an error. The DLPC plays a critical part in the cognitive processing of relevant information. This cortical information is then integrated by the caudate nucleus, which controls behavioral programs. A dysfunction of these networks at one or several stages will result in the emergence and maintenance of repetitive thoughts and characteristic OCD behavior.

Diagnostic Imaging↗

Influence of different sources of information on attitude toward organ donation: a factor analysis.

OBJECTIVES: To determine media through which the population receives information on donation; to analyze the association between the sources of information and the psychosocial variables with respect to the opinion on donation; and to determine how each source of information influences this opinion. MATERIALS AND METHODS: A questionnaire on donation was administered to a random sample of 2000 persons stratified by age, gender, and geographical location, of whom 1143 respondents claimed to have no experience with donation and/or transplantation. A statistical analysis was done between the sources of information or the psychosocial variables or their co-variation to determine their specific impact on the population. RESULTS: The medium with the greatest impact on the population is television; the second factor is the press and radio; the third is magazines and talks with friends/family; the fourth is hoardings and posters, and campaigns about organ donation; and the last factor is information given by health professionals. In the factor analysis between sources of information and psychosocial variables, an association was observed between press, radio, and information given by health professionals and a higher education level; and between information provided by discussions in schools, by age, and a higher level of education. Sources of Information sources as that have a favorable effect on donation include discussions, (P = .0079), and information by health professionals (P < .0005) and by friends (P = .0132) and by family (P = .0044). CONCLUSIONS: Opinion on donation is more favorable among subjects who have received information on an individual basis and at specialized meetings. The only psychosocial variable associated with some sources of information is the level of education.

Adolescent↗

How to develop and implement pandemic preparedness plans? The need for a coherent European policy.

How should public health authorities confront the threat of pandemic influenza? Is massive stockpiling the answer? If so, the costs could be overwhelming. Or is vaccination of pre-selected segments of the population the best approach? If so, then what about the tough ethical question that must be addressed: for whom--and by whose decision? Are local and national health authorities operating on the same wavelength? Just how all-encompassing should a national preparedness plan be? Finally, can we count on one national government to shuttle vaccines across Europe's internal borders where they are needed to deal with an outbreak--or will hoarding and panic ensue? These issues and more were the focus of debate during the conference's session on preparedness plans, chaired by Dr. D. Fedson, former professor of medicine at the University of Virginia. As participants observed, Europe faces an alarming diversity of approaches and states of readiness from one country to the next, which cries out for a coherent European policy.

Disaster Planning↗

Metabolic and hormonal control of the desire for food and sex: implications for obesity and eating disorders.

During evolution, the ability to overeat and store the extra energy as glycogen and lipids in specialized tissues must have conferred a reproductive advantage by releasing animals from the need to eat constantly, enabling them to engage in behaviors that improved reproductive success. Mechanisms that inhibited ingestive behavior might have been most adaptive when they caused individuals to stop foraging, hoarding and eating in order to find and court potential mates. Conversely, the ability to abstain from reproductive activities to engage in foraging and eating was probably critical for individual survival during severe energetic challenges because reproductive processes are energetically costly and can be delayed until the energetic conditions improve. The mechanisms that control ingestive behavior most likely evolved under conditions in which both food and mates were available, and thus, our understanding might be limited by our narrow focus on food intake in animals isolated from potential mates, and reproductive behaviors in the absence of food. Our understanding of obesity and eating disorders will be enriched by the study of the choice between ingestive and reproductive behaviors and by a renewed attention to "reproductive" hormones such as gonadal steroids and hypothalamic releasing hormones. Furthermore, leptin and reproductive hormones have both organizational and activational effects on the energy balancing system including those mechanisms that control appetite, body fat content and body fat distribution. Understanding these organizational and activational effects on body fat distribution might lead to a better understanding of sex differences in the propensity to develop obesity, type II diabetes and eating disorders.

Animals↗

The relationship between disgust sensitivity, anxiety and obsessions.

Three hundred participants, including volunteers from an obsessional support group, filled in questionnaires relating to disgust sensitivity, health anxiety, anxiety, fear of death, fear of contamination and obsessionality as part of an investigation into the involvement of disgust sensitivity in types of obsessions. Overall, the data supported the hypothesis that a relationship does exist between disgust sensitivity and the targeted variables. A significant predictive relationship was found between disgust sensitivity and total scores on the obsessive compulsive inventory (OCI; Psychological Assessment 10 (1998) 206) for both frequency and distress of symptomatology. Disgust sensitivity scores were significantly related to health anxiety scores and general anxiety scores and to all the obsessional subscales, with the exception of hoarding. Additionally, multiple regression analyses revealed that disgust sensitivity may be more specifically related to washing compulsions: frequency of washing behaviour was best predicted by disgust sensitivity scores. Washing distress scores were best predicted by health anxiety scores, though disgust sensitivity entered in the second model. It is suggested that further research on the relationship between disgust sensitivity and obsessionality could be helpful in refining the theoretical understanding of obsessions.

Adult↗

Symptom structure in obsessive-compulsive disorder: a confirmatory factor-analytic study.

Although obsessive-compulsive disorder (OCD) has long been a unitary diagnosis, there is much recent interest in its potential heterogeneity, as manifested by symptom subgroups. This study evaluated existing models of symptom structure in a sample of 203 individuals with OCD. Using confirmatory factor analysis, we examined the ability of each model to account for two levels of data: a priori symptom groupings (second-order) and individual symptoms, identified by the Yale-Brown Obsessive Compulsive Scale symptom checklist. Four models were examined: a single-factor, a two-factor (i.e., obsessions and compulsions), and two multidimensional models, comprising three and four factors. Adequate fit was found solely for the four-factor model--specifying obsessions/checking, symmetry/ordering, contamination/cleaning, and hoarding--but only at the second-order level; it did not account for relationships among discrete symptoms. Parameter estimates showed within-factor heterogeneity, as well as overlap between factors, most notably the two representing checking and contamination-related symptoms. The implications of these findings are discussed. Results provide evidence for the multidimensionality of OCD symptoms, but suggest that a comprehensive model has yet to be identified. They also point to the inadequacy of groupings based solely upon overt behavioural similarities (e.g., 'checking'). Recommendations are made for future research.

Adult↗

Obsessive-compulsive disorder subgroups: a symptom-based clustering approach.

Although obsessive-compulsive disorder (OCD) is often considered a heterogeneous condition, there is no generally accepted subtype typology. Cluster analysis was used to identify definitive symptom-based groupings of 106 OCD patients. A stable cluster solution was achieved and five patient subgroups were identified based on their pattern of symptoms on the Yale-Brown (Y-BOCS) symptom checklist: harming, hoarding, contamination, certainty and obsessionals. The five subgroups were characterized by dominant symptom patterns and significant secondary concerns reflecting the symptom heterorgenaity often seen in the clinical presentation of obsessional patents. Between cluster differences on multiple symptom measures were evaluated and several meaningful differences were identified. Cluster analytic procedures may prove to be a useful tool for identifying a functional taxonomy of OCD subtypes.

Adult↗

Increased alcohol intake and behavioral disinhibition in rats with ventral striatal neuron loss.

A previous study of ours reported excessive alcohol intake, enhanced defensive aggressiveness (hyperreactivity towards the experimenter), impulsive behavior, and reduced cortical serotonin levels in rats following extensive basal forebrain axon-sparing lesions involving the septal area and the ventral striatum. This constellation of signs resembles that seen clinically in "Dionysian" alcoholics. The present investigation aimed at examining the effect of ibotenic acid lesions restricted to the septal area or the ventral striatum on this behavioral profile. Experiment 1 indicated that medium-sized lesions (induced by infusing 0.35 microl ibotenic acid in each hemisphere) encompassing the septal area or the ventral striatum elicited a qualitatively similar behavioral profile. Both lesion types markedly enhanced the intake of 6% ethanol, and both groups were significantly more hyperreactive towards the experimenter. A brief doorbell signal elicited significantly more fleeing in rats with basal forebrain lesions, and licking from an electrified waterspout in the punished drinking test caused lesser suppression of locomotor activity than normal. Both groups also showed significant deficits in food hoarding. Histological examination revealed that the posterior portion of the ventral striatal lesion typically overlapped with the anterior portion of the septal lesion. Experiment 2 avoided this neuropathological overlap, and examined groups bearing small discrete lesions (induced by infusing 0.15 microl ibotenic acid in each hemisphere) restricted to either the accumbens part of the ventral striatum or the dorsal septal area. Lesions to the nucleus accumbens were associated with an increase in home-cage alcohol drinking, no hyperreactivity towards the experimenter, potentiation of fleeing at the expense of freezing in response to a sudden auditory signal, and disinhibited behavior in the punished drinking test with increased punished responding and reduced behavioral suppression. Rats with small septal lesions showed a weak enhancement of defensive aggression, but no other behavioral alterations. Our results suggest that ventral striatal neuron loss gives rise to excessive alcohol drinking and enhanced impulsivity.

Acoustic Stimulation↗