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Biomedical subjects

Frank Johnson

Publications and source records attributed to Frank Johnson.

15 recordsLinked to original sources

Differentiation of obsessive-compulsive-, panic-, obsessive-compulsive personality-, and non-disordered individuals by variation in the promoter region of the serotonin transporter gene.

Past research investigating the role of the serotonin transporter gene in OCD has produced mixed findings. One possible reason for the mixed findings is comorbidity. In this study, non-comorbid OCD individuals were compared to non-disordered controls. A sample of panic disordered individuals was also compared to a non-disordered group. Finally, as an exploratory analysis, individuals were assessed for OCPD and their allelic frequencies were also compared to non-disordered individuals. Analyses revealed that there were higher frequencies of the s/s genotype among the OCD group when compared to non-disordered controls. There were no differences in allelic frequencies on the serotonin transporter gene between the panic disordered group, the OCPD group, and the non-disordered control group. This study found that non-comorbid OCD individuals tended to have a higher percentage of the homozygous short genotype than non-disordered individuals. The s/s genotype might serve as a contributory risk factor for OCD.

Adult↗

Singing-driven gene expression in the developing songbird brain.

Neural and behavioral development arises from an integration of genetic and environmental influences, yet specifying the nature of this interaction remains a primary problem in neuroscience. Here, we review molecular and behavioral studies that focus on the role of singing-driven gene expression during neural and vocal development in the male zebra finch (Taeniopygia guttata), a songbird that learns a species-typical vocal pattern during juvenile development by imitating an adult male tutor. A primary aim of our lab has been to identify naturally-occurring environmental influences that shape the propensity to sing. This ethological approach underlies our theoretical perspective, which is to integrate the significance of singing-driven gene expression into a broader ecological context.

Age Factors↗

Estrogen regulation of cell proliferation and distribution of estrogen receptor-alpha in the brains of adult female prairie and meadow voles.

Adult female prairie (Microtus ochrogaster) and meadow (M. pennsylvanicus) voles were compared to examine neural cell proliferation and the effects of estrogen manipulation on cell proliferation in the amygdala, ventromedial hypothalamus (VMH), and dentate gyrus of the hippocampus (DG). Unlike prior studies, our study focused on the amygdala and VMH, because they are involved in social behaviors and may underlie behavioral differences between the species. Meadow voles had a higher density of cells labeled with the cell proliferation marker 5-bromo-2'-deoxyuridine (BrdU) in the amygdala and DG than did prairie voles. Treatment with estradiol benzoate (EB) for 3 days increased the density of BrdU-labeled cells in the amygdala, particularly in the posterior cortical (pCorA) and medial (pMeA) nuclei, in meadow, but not prairie, voles. Furthermore, the majority of the BrdU-labeled cells in the pCorA and pMeA displayed either a neuronal or a glial progenitor phenotype, but no species or treatment differences were found in the percentage of neuronal or glial progenitor cells. To understand better estrogen's effects on adult neurogenesis, we also examined estrogen receptor-alpha (ERalpha) distribution. Meadow voles had more ERalpha-labeled cells in the pCorA and VMH, but not in the pMeA or DG, than did prairie voles. In addition, more than one-half of the BrdU-labeled cells in the amygdala of both species coexpressed ERalpha labeling. Together, these data indicate that estrogen alters cell proliferation in a species- and region-specific manner, and some of these effects may lie in the specific localization of estrogen receptors in the adult vole brain.

Age Factors↗

Gender specific gene-environment interactions on laboratory-assessed aggression.

We examined gene-environment interactive effects on aggressive behavior among men and women genotyped (short versus long alleles) for the serotonin transporter gene. Aggressive behavior was indexed via a laboratory paradigm that measured the intensity and duration of shocks delivered to a putative "employee". Half of the participants were exposed to a physical stressor during the procedure (stress) and half were not (no-stress). Participants' physiological responses were gauged via acoustic startle eyeblink reactions (startle reactivity). Results were that men with the homozygous short (s/s) genotype showed increased aggression only under stress, whereas women and men carrying the long allele did not show differences in aggression in stress versus no-stress. However, although stress exposure produced increases in startle reactivity, there were no genotype or gender differences in physiology. These results replicate longitudinal research findings confirming the interactive effects of genes and environment on behavioral reactivity and on the development of externalizing psychopathological syndromes, at least in men.

Adult↗

Motor-induced transcription but sensory-regulated translation of ZENK in socially interactive songbirds.

The ZENK gene, depending upon singing activity, is transcribed within all the telencephalic nuclei controlling vocal behavior in songbirds. We show here that singing by deafened or completely isolated adult zebra finches induced high levels of ZENK transcription. This mRNA however, was not translated into high levels of ZENK protein. Instead, high levels of singing-driven ZENK protein translation were found in socially interactive birds. This dissociation between ZENK mRNA and ZENK protein was regionally specific to the robust nucleus of the arcopallium (RA), a region that is well known for its control of vocal-motor behavior in birds. Our results suggest cooperation between motor and sensory processes for regulating mRNA induction and subsequent protein synthesis in socially active songbirds.

Animals↗

Personality subtyping and bulimia nervosa: psychopathological and genetic correlates.

BACKGROUND: There is empirical evidence suggesting that individuals with bulimia nervosa vary considerably in terms of psychiatric co-morbidity and personality functioning. In this study, latent profile analysis was used to attempt to identify clusters of bulimic subjects based on psychiatric co-morbidity and personality. METHOD: A total of 178 women with bulimia nervosa or a subclinical variant of bulimia nervosa completed a series of self-report inventories of co-morbid psychopathology and personality, and also provided a buccal smear sample for genetic analyses. RESULTS: Three clusters of bulimic women were identified: an affective-perfectionistic cluster, an impulsive cluster, and a low co-morbid psychopathology cluster. The clusters showed expected differences on external validation tests with both personality and eating-disorder measures. The impulsive cluster showed the highest elevations on dissocial behavior and the lowest scores on compulsivity, while the affective-perfectionistic cluster showed the highest levels of eating-disorder symptoms. The clusters did not differ on genetic variations of the serotonin transporter gene. CONCLUSIONS: This study corroborates previous findings suggesting that the bulimia nervosa diagnostic category is comprised of three classes of individuals based on co-morbid psychopathology and personality. These differences may have significant etiological and treatment implications.

Adolescent↗

Inhibitors of carbohydrate metabolism reduce undirected song production at doses that do not alter food intake in singly housed male zebra finches.

Previous findings in our laboratory indicate that food availability and/or the balance of metabolic fuels may play a role in the production of undirected song in singly housed adult male zebra finches (Taeniopygia guttata). In this study, 2-deoxyglucose (2-DG) or 2,5-anhydro-d-mannitol (2,5-AM) were used to attenuate the circadian shift from lipid to carbohydrate metabolism, which normally occurs at the onset of the light phase in free-feeding, singly housed zebra finches, in order to evaluate the possibility that carbohydrate metabolism influences the production of undirected song. Food intake was also measured. Both drugs (which block carbohydrate metabolism and increase reliance on lipid metabolism) produced dose-dependent reductions in undirected singing, while food intake was not altered. Our results suggest that undirected singing (and possibly other voluntary and/or social behaviors) is sensitive to the availability of dietary fuels, whereas, food intake may show a greater regulation by the availability of stored fuels.

Animals↗

CB1 cannabinoid receptor activation inhibits a neural correlate of song recognition in an auditory/perceptual region of the zebra finch telencephalon.

A notable consequence of CB1 cannabinoid receptor activation in vertebrates is an impairment of cognitive function related to learning and short-term memory. The mechanisms of this impairment remain unclear, but one possibility is that cannabinoids influence encoding of stimuli at sensory and/or perceptual levels. Here, by treating zebra finches with the cannabinoid agonist WIN55212-2 and then measuring expression of the transcription factor zenk following presentation of novel zebra finch song, we show that cannabinoid receptor activation differentially influences zenk expression in sensory versus perceptual regions of the songbird auditory telencephalon. That is, WIN55212-2 dose-dependently inhibited zenk expression in a region for auditory perception (NCM, the caudomedial neostriatum), but had no effect on zenk expression in the primary auditory area, the Field L complex. The inhibitory effects of WIN55212-2 on zenk expression in NCM were reversed by coadministration of the CB1-selective antagonist SR141716A. Moreover, we found that the habituation of the NCM zenk response to repeated presentation of the same song, a well-established neural correlate of song recognition, was blocked when birds were treated with WIN55212-2 during habituation trials. Our data suggest that activation of CB1 cannabinoid receptors can selectively influence perceptual and mnemonic aspects of auditory experience.

Animals↗

Cannabinoid exposure alters learning of zebra finch vocal patterns.

Using a well-established songbird model of juvenile vocal development, we have found that daily cannabinoid exposure at modest dosages alters sensory-motor vocal learning. Adult exposure did not change song that had already been learned. Our results demonstrate the potential for cannabinoid exposure to produce distinct effects during post-natal CNS development.

Animals↗

Is there an association between serotonin transporter gene polymorphism and family history of depression?

BACKGROUND: To date, research examining the relationship between the serotonin transporter gene and depression has yielded both positive and negative results. This study will attempt to add further evidence to that body of literature by examining the relationship between the serotonin transporter gene and a family history of depression while controlling for a family history of completed suicide. METHODS: Forty-seven volunteers responded to questionnaires regarding family history of depression and suicide, and provided buccal swabs to allow for analysis of the 5-HTTLPR polymorphism. RESULTS: Individuals with the s/s genotype were significantly more likely to have two or more first-degree relatives with a history of depression even when controlling for a family history of completed suicides. LIMITATIONS: The small sample size, particularly in the group of individuals with the s/s genotype, is a limitation of this study. Assessment of family history was conducted in abbreviated fashion. Information regarding participants' personal history of depression and suicide was not collected, so no conclusions regarding participants' own mental health can be drawn. CONCLUSIONS: A significant relationship between family history of depression and the s/s genotype was found, despite the small sample size and while controlling for family history of suicide. Whatever risk short alleles may confer for depression may be distinct from the risk they confer for suicidality.

Adult↗

Birth month and suicidal and depressive symptoms in Australians born in the Southern vs. the Northern hemisphere.

To test whether Australians in utero during the Southern hemisphere flu peak would show increased suicidal and depressive symptoms, as would those born in the Northern hemisphere and who were in utero during the Northern hemisphere flu peak. A sample of 2514 adolescents and young adults presenting to general practitioners completed measures of depressive and suicidal symptoms. Patients' date and country of birth were recorded. Those born in the Southern hemisphere in September-November showed the highest suicidal and depressive symptoms, as did those born in the Northern hemisphere in March-May. Season of birth may be a risk factor for depressive and suicidal symptoms.

Adolescent↗

Food availability but not cold ambient temperature affects undirected singing in adult male zebra finches.

Adult male zebra finches (Taeniopygia guttata) produce hundreds of song bouts per day, even when housed in social isolation. Whether the production of this "undirected song" is influenced by specific environmental factors is unclear, although we previously found that short-term food (but not water) deprivation leads to a prompt cessation of singing. Here, male zebra finches were placed on a schedule of restricted feeding for 11 days to ask whether stimulus features associated with food influenced undirected song independent of the effect of food on body mass. We also evaluated the within-day effects of ambient temperature (Ta) variation on metabolic rate and then, based on these data, placed male zebra finches on 5 days of cold Ta (8 degrees C) to determine whether a moderately increased energy demand associated with cold Ta would influence undirected song. Daily song production and several energetic variables were measured during each manipulation, and data obtained during baseline and recovery periods (food and water available ad libitum, Ta=26 degrees C) provided a standard for comparison. Our results showed that the schedule of restricted feeding produced more than two-thirds reduction in the daily production of undirected song, while cold Ta had no effect. Daily food intake and body mass were well defended under both manipulations. Thus, undirected singing by adult male zebra finches appears to show a specific relationship to the availability of food. Possible mechanisms linking food availability to singing are discussed.

Animals↗

Quantifying song bout production during zebra finch sensory-motor learning suggests a sensitive period for vocal practice.

Using an event-triggered recording system, the quantity of daily song bout production was measured weekly in male zebra finches (Taeniopygia guttata) during sensory-motor learning and at one year of age. Our aim was to ask whether the development of a stereotyped vocal pattern involves a practice-driven component. If so, we hypothesized that juvenile males learning song should sing more often than adults reciting a vocal pattern they had already learned, and that greater levels of juvenile singing should be associated with improvement in the quality of the adult song. Across the period measured (36-365 days of age), subjects showed an inverted U-shaped pattern of daily song bout production. Song bout production was lowest during subsong, with increased production associated with plastic song and song crystallization, although individual differences were large. Daily song bout production decreased in adulthood. Higher levels of song bout production during plastic song correlated with fewer sequencing errors in adult song patterns (r(2)=0.77). In contrast, quantity of singing during song crystallization showed no relationship to vocal stereotypy (r(2)=0.002). Our data suggest a sensitive period for vocal practice during zebra finch sensory-motor learning with consequences for the note-sequence fidelity of the adult vocal pattern.

Aging↗

Association between serotonin transporter gene polymorphism and family history of attempted and completed suicide.

The purpose of this study was to examine the association of the serotonin transporter gene to family history of suicidality. Forty-seven volunteers responded to questionnaires about family history of suicide, and provided buccal swabs for analysis of the polymorphism. Allelic homozygocity (the short variant) was associated with family history of suicidality. These data, to be interpreted with the study's limitations in mind, suggest a link between the serotonin transporter gene polymorphism and suicide-related variables, which should be the focus of future research.

Adult↗