SEARCH · PubMed Health

Results for “Endophenotypes”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 379 records · Page 21Linked to original sources

PubMed2005

Psychological, autonomic, and serotonergic correlates of parasuicide among adolescent girls.

Although parasuicidal behavior in adolescence is poorly understood, evidence suggests that it may be a developmental precursor of borderline personality disorder (BPD). Current theories of both parasuicide and BPD suggest that emotion dysregulation is the primary precipitant of self-injury, which serves to dampen overwhelmingly negative affect. To date, however, no studies have assessed endophenotypic markers of emotional responding among parasuicidal adolescents. In the present study, we compare parasuicidal adolescent girls (n=23) with age-matched controls (n=23) on both psychological and physiological measures of emotion regulation and psychopathology. Adolescents, parents, and teachers completed questionnaires assessing internalizing and externalizing psychopathology, substance use, trait affectivity, and histories of parasuicide. Psychophysiological measures including electrodermal responding (EDR), respiratory sinus arrhythmia, and cardiac pre-ejection period (PEP) were collected at baseline, during negative mood induction, and during recovery. Compared with controls, parasuicidal adolescents exhibited reduced respiratory sinus arrhythmia (RSA) at baseline, greater RSA reactivity during negative mood induction, and attenuated peripheral serotonin levels. No between-group differences on measures of PEP or EDR were found. These results lend further support to theories of emotion dysregulation and impulsivity in parasuicidal teenage girls.

Adolescent↗

PubMed2001

Progress toward discovery of susceptibility genes for bipolar manic-depressive illness and schizophrenia.

The inconsistency in linkage results that has bedeviled psychiatric genetics has been observed to occur regularly in common diseases with complex inheritance. Nonetheless, in two such instances--noninsulin-dependent diabetes mellitus (NIDDM) and inflammatory bowel disease (IBD)--susceptibility genes have been discovered based on the follow-ups of linkage findings. In bipolar illness disorder (BPD) and schizophrenia (SZ), there are some linkage reports with replication of other studies similar to the situation in NIDDM and IBD before the successful positional cloning efforts. Two of the regions with linkage reports, BPD and SZ, on the long arms of chromosomes 13 and 22, show linkage to the same markers in both diseases. This lends some plausibility to the hypothesis of some shared genetic predispositions for both disorders. Cytogenetic evidence offers another positional approach to susceptibility genes. The velocardiofacial syndrome is associated with deletions very close to the linkage region on chromosome 22, and with psychiatric manifestations of both BPD and SZ. Endophenotypes of SZ, previously demonstrated to the be heritable, have been found to have chromosomal linkage in at least one study. These include eye-tracking abnormalities linked to 6p, and an abnormality of the P50 cortical evoked potential linked to chromosome 15. Variants in specific genes have been associated with susceptibility to the psychiatric illnesses. These genetic findings may contribute to etiologic subcategorization of BPD and SZ, and the development of new treatment approaches. A table of genetic terms is included for review

Journal Article↗

PubMed2004

Freeze, flight, fight, fright, faint: adaptationist perspectives on the acute stress response spectrum.

This article reviews the existing evolutionary perspectives on the acute stress response habitual faintness and blood-injection-injury type-specific phobia (BIITS phobia). In this article, an alternative evolutionary perspective, based on recent advances in evolutionary psychology, is proposed. Specifically, that fear-induced faintness (eg, fainting following the sight of a syringe, blood, or following a trivial skin injury) is a distinct Homo sapiens-specific extreme-stress survival response to an inescapable threat. The article suggests that faintness evolved in response to middle paleolithic intra-group and inter-group violence (of con-specifics) rather than as a pan-mammalian defense response, as is presently assumed. Based on recent literature, freeze, flight, fight, fright, faint provides a more complete description of the human acute stress response sequence than current descriptions. Faintness, one of three primary physiological reactions involved in BIITS phobia, is extremely rare in other phobias. Since heritability estimates are higher for faintness than for fears or phobias, the author suggests that trait-faintness may be a useful complement to trait-anxiety as an endophenotype in research on the human fear circuitry. Some implications for the forthcoming Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition as well as for clinical, health services, and transcriptomic research are briefly discussed.

Adaptation, Psychological↗

PubMed2006

What is the optimal way to subdivide obsessive-compulsive disorder?

The clinical presentation of obsessive-compulsive disorder (OCD) varies not only across patients but over the course of the disorder. This diversity indicates that OCD is a heterogeneous disorder, which may have an important impact on psychopathological, longitudinal, genetic, and treatment research. To better understand OCD heterogeneity, more homogeneous phenotypic descriptions are necessary to delimiting clinically meaningful subgroups of patients. Besides phenotypic descriptions, another method of delimiting OCD patient subgroups includes the search for endophenotypes (extended phenotypes) based on neurophysiological, immunological, genetic, neuropsychological, or neuroanatomic (neuroimaging) paradigms. This article will describe some strategies that deal with OCD heterogeneity, including the identification of more homogeneous phenotypical categories, an improved understanding of obsessive-compulsive symptom dimensions and how to use them as quantitative traits, and broadening the diagnostic boundaries of OCD to include other related conditions. The relevance and limitations of each approach are also discussed. Since the etiological mechanisms associated with the expressions of OCD are unknown, there is probably not one but several heuristic strategies to search for more homogeneous OCD subgroup, that combined may provide the most fruitful results.

Cytogenetics↗

PubMed2002

Finding genes for bipolar disorder in the functional genomics era: from convergent functional genomics to phenomics and back.

Psychiatric genetics, while promising to unravel the mechanisms of psychiatric disorders, has proven to be a challenging field. Psychiatric disorders, like other common genetic traits, are complex and heterogeneous. Psychiatric genetics has also suffered from a lack of quantifiable, biology-based phenotypes. However, the field is currently at an opportune moment. The work of various investigators is on the verge of paying rich dividends. Efforts at positional cloning are being greatly accelerated by the fruits of the Human Genome Project. New tools of functional genomics, such as expression profiling and proteomics, are being applied to animal models. These two methods can complement each other in an approach we have termed convergent functional genomics. Lastly, improvements in the measurement of biologically distinct endophenotypes--or phenomic--will lead to a better understanding of the mapping of genes to phenotypes in both animal and human systems.

Journal Article↗

PubMed2002

Genetic factors and neurocognitive traits.

Genetic contributions to phenotypic variation in general intelligence have been studied extensively. Less research has been conducted on genetic contributions to specific cognitive abilities, such as attention, memory, working memory, language, and motor functions. However, the existing data indicate a significant role of genetic factors in these abilities. Stages of information processing, such as sensory gating, early sensory registration, and cognitive analysis, also show evidence of genetic contributions. Recent molecular studies have begun to identify candidate genes for specific cognitive functions. Future research, identifying endophenotypes based on cognitive profiles of neuropsychiatric disorders, may also assist in the detection of genes that increase susceptibility to major psychiatric disorders.

Journal Article↗

PubMed2005

Update on the biology of seasonal affective disorder.

The etiology and pathophysiology of seasonal affective disorder (SAD) has been linked to the seasons and to light since its first conceptualization. Aspects of SAD that make it particularly amenable to biological investigation include the predictable recurrent episodes, the rapid response to a nonpharmacologic treatment, the specific neurovegetative features, and the availability of rich animal models of seasonality. This paper reviews new findings for the major biological hypotheses for SAD, focusing on circadian rhythms, neurotransmitters, and molecular genetics. Integrative issues and future directions for the study of SAD, including the heuristic value of a dual-vulnerability hypothesis that conceptualizes seasonality as a dimensional construct and the importance of studying endophenotypes, will be discussed.

Chronobiology Disorders↗

PubMed2003

Genetic linkage in bipolar disorder.

Bipolar disorder is an etiologically complex syndrome that is clearly heritable. Multiple genes, working singly or in concert, are likely to cause susceptibility to bipolar disorder. Bipolar disorder genetics has progressed rapidly in the last few decades. However, specific causal genetic mutations for bipolar disorder have not been identified. Both candidate gene studies and complete genome screens have been conducted. They have provided compelling evidence for several potential bipolar disorder susceptibility loci in several regions of the genome. The strongest evidence suggests that bipolar disorder susceptibility loci may lie in one or more genomic regions on chromosomes 18, 4, and 21. Other regions of interest, including those on chromosomes 5 and 8, are also under investigation. New approaches, such as the use of genetically isolated populations and the use of endophenotypes for bipolar disorder, hold promise for continued advancement in the search to identify specific bipolar disorder genes.

Animals↗

PubMed2002

Eye movement abnormality suggestive of a spatial working memory deficit is present in parents of autistic probands.

Autistic probands exhibit impaired spatial accuracy and impaired response suppression errors during a delayed oculomotor response task. Family members of autistic probands, and thus the possible familial nature of these deficits, have not been assessed. Eleven parents of autistic probands and 17 adults from unaffected families, ages 25-50 years, completed oculomotor delayed-response tasks. Parents of autistic probands demonstrated poorer spatial accuracy than the comparison group (p = .002), with no significant differences between groups on percentage of premature saccades or latency of remembered saccades. Spatial working memory deficits, as measured by the delayed oculomotor response task, appear to be familial in families with an autistic proband. These deficits deserve further evaluation as a potential endophenotypic marker for genetic risk for autism.

Adult↗

PubMed2003

Heritability of daytime cortisol levels in children.

Individual differences in the level of the stress hormone cortisol play a prominent role as an explanatory variable in studies on psychopathology. Relatively few studies have paid attention to individual differences in cortisol levels and the etiology of these differences, in particular their possible genetic basis. All these studies have been in adults. The aim of this study was to estimate genetic and environmental influences on basal cortisol levels in 12-year-old children. To this end, four samples of salivary cortisol were collected on two consecutive days in a sample of 180 twin pairs. Low correlations were found between cortisol levels at different points in time during the day. A significant genetic contribution was found to the variation of basal cortisol levels in the morning and afternoon samples, but not in the evening sample. Heritability did not differ for boys and girls and was highest (60%) for cortisol levels during the sample taken about 45 minutes after awakening. This cortisol awakening response provides a useful endophenotype in the search for genes that may affect hypothalamic-pituitary adrenocortical functioning in children.

Biomarkers↗

PubMed2003

Toward an animal model for antisocial behavior: parallels between mice and humans.

The goal of this article is to examine whether mouse lines genetically selected for short and long attack latencies are good animal models for antisocial behavior in humans. To this end, we compared male Short and Long Attack Latency mice (SAL and LAL, respectively) with the extremes of the Dunedin Multidisciplinary Health and Development Study (men who persistently displayed antisocial behavior [Persisters] and men who never manifested antisocial behavior [Abstainers]). Groups were compared on the basis of five distinct domains: aggression/violence, reproduction, cognition, behavioral disorders, and endophenotypes. Our observations point to considerable parallels between, on one side, SAL and Persisters, and, on the other side, between LAL and Abstainers (but to a lesser extent). We believe that SAL and LAL are good mouse models to study the development of antisocial behavior and will yield valuable and testable hypotheses with regard to the neurobiological and genetical architecture of antisocial behavior.

Aggression↗

PubMed2001

Review of studies of child and adolescent offspring of bipolar parents.

OBJECTIVE: The authors reviewed studies of child and adolescent offspring of bipolar (BP) parents. Findings from these studies are critically discussed with respect to methodological issues that can inform future designs. METHODS: A Medline search was performed to identify studies that examined child and adolescent offspring of BP parents. Publications were excluded if they did not separate offspring of BP parents from offspring of major depressive disorder or schizoaffective parents ("affective offspring") or did not separately analyze data from child- and adolescent-age versus adult offspring. RESULTS: Seventeen studies fit these review criteria. Rates of mood disorders in child and adolescent offspring of BP parents ranged from 5 to 67% compared with rates in offspring of healthy volunteers of 0-38%. Rates of non-mood disordered psychopathology ranged from 5 to 52% in offspring of BP parents and from 0 to 25% in offspring of healthy volunteers. Rates of mood disorders and of other psychopathology were increased in offspring of BP parents compared with offspring of healthy volunteers in all of the eight studies that included a comparison group of offspring of healthy volunteers. CONCLUSIONS: Studies suggest that children (< or =21 years) of BP parents are at increased risk for developing mood and other disorders (e.g., disruptive, anxiety). Therefore, additional investigations are clearly warranted. In the context of current research on diagnosis, assessment, longitudinal course and comorbidity of childhood mania, the following suggestions for the design of future studies should be considered: 1) Phenotypic specification of bipolar manifestations (e.g., BP-I, BP-II, BP-NOS) in child/adolescent offspring and in bipolar parents themselves. 2) Control groups that are pediatric-age relevant and thus include attention-deficit hyperactivity disorder. 3) Assessments that include items for prepubertal mania and for onsets and offsets of all occurrences of symptoms and of environmental factors (e.g., life events) in offspring and in parents so that trajectories of overlap and sequence between child and parental mania can be investigated. 4) These detailed onsets and offsets of symptoms are also necessary to investigate prodromal manifestations of mania in the offspring. 5) Unaffected offspring present a unique opportunity to study pre- and postmorbid cognitive and physiological endophenotypes and structural and functional brain abnormalities. Findings from offspring studies will be crucial to inform research on the development of early intervention and prevention strategies.

Adolescent↗

PubMed2003

EEG phenotype in alcoholism: increased coherence in the depressive subtype.

OBJECTIVE: Electroencephalography (EEG) power and coherence changes may be trait markers for alcoholism providing clues to brain mechanisms of vulnerability. However, it is unclear whether alpha power and coherence differences reflect reversible toxic or withdrawal effects of alcohol. METHOD: The EEGs of 10 non-abstinent and 16 long-term abstinent alcoholics (7.7 +/- 5.8 years) and 25 controls were analyzed. Levels of anxiety and depression were assessed by questionnaire. RESULTS: No statistically significant EEG power differences were observed between groups, although the numerical difference between alcoholics and controls was similar to that previously reported. Bilateral, intrahemispheric, posterior coherences were significantly increased in the alpha and beta frequency bands both in long-term abstinent and non-abstinent alcohol-dependent subjects - particularly when depressiveness was included as a covariate. CONCLUSION: These results suggest that increased EEG-coherence (cortical synchronization) may serve as endophenotype for alcoholism in conjunction with increased depressiveness and point to a possible involvement of GABAergic and/or glutamatergic neurotransmission.

Adult↗

PubMed2003

Gray matter features of schizotypal disorder patients exhibiting the schizophrenia-related code types of the Minnesota Multiphasic Personality Inventory.

OBJECTIVE: Previous studies have suggested that several code types of the Minnesota Multiphasic Personality Inventory (MMPI) are useful markers for identifying schizophrenia. We hypothesized that schizotypal disorder (STD) patients with such schizophrenia-related code types have the morphological brain abnormalities associated with schizophrenia. METHOD: Voxel-based morphometric analysis with statistical parametric mapping (SPM) 99 software was used to investigate the differences in brain morphology between 14 STD patients with the schizophrenia-related code types of the MMPI and 28 normal individuals. RESULTS: The STD patients showed significantly decreased gray matter volume in the insular regions bilaterally and in the left entorhinal cortex, compared with the controls. CONCLUSION: Our findings suggest that STD patients with the schizophrenia-related code types have volume reductions in these regions as an endophenotype that overlaps with schizophrenia.

Adolescent↗

PubMed2002

Mapping of the associated phenotype of an absent granular layer in ichthyosis vulgaris to the epidermal differentiation complex on chromosome 1.

Ichthyosis vulgaris (IV) is a mild to severe scaling disorder of uncertain etiology estimated to affect as many as 1 : 250 in the population. Family studies have shown that in many cases IV follows an autosomal dominant inheritance pattern, but gene mapping studies have not been reported. To investigate the genetic basis for inherited IV, we have performed gene linkage studies in two multigenerational families where affected individuals have clinical features of IV but distinct histological features. The epidermis in this disorder characteristically displays non-specific orthohyperkeratosis. Notably, a subset of IV patients with a reduced or absent granular epidermal layer (AGL) have been reported, and decreased filaggrin levels have been described in others. The prominent role of profilaggrin in human keratohyalin suggests that defects in the gene for profilaggrin (FLG), its processing of profillagrin to filaggrin, or a gene involved in profilaggrin regulation may underlie or modify the pathology in IV. Family 1 had seven individuals with IV, severe heat intolerance and epidermis with 1-3 granular layers (consistent with normal epidermal histology). Ichthyosis vulgaris in this family did not segregate with FLG or other genes in the epidermal differentiation complex. In contrast, five of the six IV patients in Family 2, all siblings, had epidermis with no granular layer. Significant evidence was obtained for linkage of IV with the associated AGL phenotype to the epidermal differentiation complex (which includes FLG) assuming either a recessive (max Lod 3.4) or dominant (max Lod 3.6) inheritance model. Sequence analysis of FLG did not reveal a mutation in the amino or carboxyl terminal portions of the coding sequence adjacent to filaggrin repeats. The AGL may represent an endophenotype for IV, and the presence of a modifier of IV pathology at this locus is discussed.

Adult↗

PubMed2005

The primacy of cognition in schizophrenia.

Cognitive tasks and concepts are used increasingly in schizophrenia science and treatment. Recent meta-analyses show that across a spectrum of research domains only cognitive measures distinguish a majority of schizophrenia patients from healthy people. Average effect sizes derived from common clinical tests of attention, memory, language, and reasoning are twice as large as those obtained in structural magnetic resonance imaging and positron emission tomography studies. Chronic stress, genes, brain disturbances, task structure, gender, and sociocultural background may all enhance the sensitivity of cognitive performance to schizophrenia. At the same time, disease heterogeneity and the presence of endophenotypes and subtypes within the patient population may place upper limits on the strength of any specific cognitive finding. Schizophrenia is a complex biobehavioral disorder that manifests itself primarily in cognition.

Adult↗

PubMed2000

Neuropsychological functioning in nonreferred siblings of children with attention deficit/hyperactivity disorder.

The goal of this study was to assess neuropsychological functioning in nonreferred siblings of children with attention deficit/hyperactivity disorder (ADHD). Participants were 156 siblings of ADHD probands with (N = 40) and without (N = 116) ADHD (according to criteria of the Diagnostic and Statistical Manual of Mental Disorders (3rd edition, revised; American Psychiatric Association, 1987) and 118 siblings of non-ADHD normal controls of similar age, IQ, and grade level. Information on attention, executive, and memory functions was obtained in a standardized manner without knowledge of clinical status. Compared with siblings of controls, siblings with ADHD were significantly impaired on the Stroop test and on verbal learning and memory. In contrast, siblings without ADHD were similar to controls on virtually all measures. These data suggest that some executive, attention, and verbal learning deficits are found in nonreferred individuals with ADHD but that neuropsychological deficits are unlikely to constitute an endophenotype to ADHD.

Adolescent↗

PubMed2006

Schizotypy and sustained attention: confirming evidence from an adult community sample.

Sustained attention deficits represent one of the most robust findings in the study of schizophrenia and schizotypy. However, very little is known about the nature of sustained attention performance and schizotypy in the general adult population. The present study assessed sustained attention performance in a large, normative adult community sample (N = 305) with no history of psychosis using the Continuous Performance Test-identical pairs version (CPT-IP). Associations between overall CPT-IP performance and schizotypal personality disorder features, controlling for the effects of age, sex, and educational level, revealed diminished sensitivity (d', discriminability), and increased random errors were related to increased reality distortion features. These data, drawn from a general population sample, provided support for overall sustained attention deficits as an endophenotype for schizophrenia liability.

Adolescent↗