Developmental imaging genetics: Linking dopamine function to adolescent behavior

Adolescence is a period of development characterized by numerous neurobiological changes that significantly influence behavior and brain function. Adolescence is of particular interest due to the alarming statistics indicating that mortality rates increase two to three-fold during this time compared to childhood, due largely to a peak in risk-taking behaviors resulting from increased impulsivity and sensation seeking. Furthermore, there exists large unexplained variability in these behaviors that are in part mediated by biological factors. Recent advances in molecular genetics and functional neuroimaging have provided a unique and exciting opportunity to non-invasively study the influence of genetic factors on brain function in humans. While genes do not code for specific behaviors, they do determine the structure and function of proteins that are essential to the neuronal processes that underlie behavior. Therefore, studying the interaction of genotype with measures of brain function over development could shed light on critical time points when biologically mediated individual differences in complex behaviors emerge. Here we review animal and human literature examining the neurobiological basis of adolescent development related to dopamine neurotransmission. Dopamine is of critical importance because of (1) its role in cognitive and affective behaviors, (2) its role in the pathogenesis of major psychopathology, and (3) the protracted development of dopamine signaling pathways over adolescence. We will then focus on current research examining the role of dopamine-related genes on brain function. We propose the use of imaging genetics to examine the influence of genetically mediated dopamine variability on brain function during adolescence, keeping in mind the limitations of this approach.     

The association between dopamine D4 receptor exon III polymorphism and intensity of PTSD symptoms among flood survivors

Abstract

Thanks to the development of molecular genetics methods it is now possible to look for the genes which may contribute to posttraumatic stress disorder (PTSD). Polymorphism located in exon III of dopamine receptor type 4 (DRD4) gene was related to maladaptive stress responses as well as temperament traits related to PTSD. This study analyzed the association between the variable number tandem repeat (VNTR) DRD4 exon III polymorphism and intensity of PTSD symptoms in 107 (57 women and 50 men) survivors of a flood aged 14–62. Intensity of PTSD symptoms was measured using PTSD-F and PTSD-C questionnaires. Multivariate analysis of covariance (MANCOVA) was conducted to test the main and interactive effects of genotype and level of trauma exposure. Participants with at least one copy of the DRD4 long allele (seven or eight repetitions) had more intense PTSD symptoms on the Avoidance/Numbing scale (Cohen's f = .22) and the Total Scale (Cohen's f = .2) of the PTSD-F than participants who did not have these alleles in genotype. The results must be treated with caution, however, due to methodological restrictions and they need to be replicated on a larger sample.     

Individual differences in flow proneness are linked to a dopamine D2 receptor gene variant

Flow is a special mental state characterized by deep concentration that occurs during the performance of optimally challenging tasks. In prior studies, proneness to experience flow has been found to be moderately heritable. In the present study, we investigated whether individual differences in flow proneness are related to a polymorphism of the dopamine D2 receptor coding gene (DRD2 C957T rs6277). This polymorphism affects striatal D2 receptor availability, a factor that has been shown to be related to flow proneness. To our knowledge, this is the first study to investigate the association between this trait and a specific gene variant. In a sample of 236 healthy Hungarian adults, we found that CC homozygotes report higher flow proneness than do T allele carriers, but only during mandatory activities (i.e., studying and working), not during leisure time. We discuss implications of this result, e.g., the potential mediators of the relationship.     

DRD2基因TaqIA多态性与同伴侵害对青少年早期抑郁的交互作用

本研究运用问卷法与DNA分型技术,对1063名青少年(初次测评年龄为12.32±0.47岁,50.3%女生)进行间隔2年的追踪调查,考察DRD2基因TaqIA多态性与同伴身体侵害和关系侵害对青少年早期抑郁的交互作用及其性别差异。结果发现,TaqIA多态性与身体侵害、关系侵害均对男青少年抑郁存在显著的交互作用。在携带A2A2基因型的男生中,身体侵害和关系侵害可以显著正向预测其抑郁水平,而在携带A1等位基因的男生中,同伴侵害对抑郁无预测作用。此外,TaqIA多态性与身体侵害、关系侵害对女生抑郁均无显著交互作用。研究结果提示,同伴侵害是一种重要的候选环境指标,与TaqIA多态性交互影响青少年早期抑郁,并且性别在这一基因×环境交互作用中起到重要的调节效应。     

Association of polymorphisms in BDNF, MTHFR, and genes involved in the dopaminergic pathway with memory in a healthy Chinese population

The contribution of genetic factors to the memory is widely acknowledged. Research suggests that these factors include genes involved in the dopaminergic pathway, as well as the genes for brain-derived neurotrophic factor (BDNF) and methylenetetrahydrofolate reductase (MTHFR). The activity of the products of these genes is affected by single nucleotide polymorphisms (SNPs) within the genes. This study investigates the association between memory and SNPs in genes involved in the dopaminergic pathway, as well as in the BDNF and MTHFR genes, in a sample of healthy individuals. The sample includes 134 Taiwanese undergraduate volunteers of similar cognitive ability. The Chinese versions of the Wechsler Memory Scale (WMS-III) and Wechsler Adult Intelligence Scale (WAIS-III) were employed. Our findings indicate that the BDNF Met66Val polymorphism and dopamine receptor D3 (DRD3) Ser9Gly polymorphism are associated significantly with long-term auditory memory. Further analysis detects no significant associations in the other polymorphisms and indices. Future replicated studies with larger sample sizes, and studies that consider different ethnic groups, are encouraged.     

The Dopamine D4 Receptor (DRD4) Exon 3 VNTR Contributes to Adaptive Personality Differences in an Italian Small Island Population

The search for evolutionary forces shaping the diversity of human personality traits encouraged studies that have found that islanders are relatively closed and introverted, with little interest in the external world. The ‘personality gene flow’ hypothesis was proposed to explain the mechanism underlying this difference, suggesting that the frequency of alleles that influence islander personality traits might progressively increase in the gene pools on islands because of selective emigration of individuals not displaying these alleles. We genotyped 96 individuals from the Italian mainland and 117 from Giglio Island, whose residents were previously assessed regarding their personality traits. We genotyped three polymorphisms: the dopamine D4 receptor (DRD4) exon 3 repeat region, the serotonin‐transporter SLC6A4 5‐HTTLPR indel and the dopamine transporter SLC6A3 DAT1 3′UTR repeat region. Only the DRD4 exon 3 repeat was hypothesised to show varying allele frequencies because this polymorphism could be associated with human migration and personality traits such as extraversion, openness and novelty seeking. As predicted, no differences in allele frequencies were found for the SLC6A4 and SLC6A3 polymorphisms, whereas significant differences were observed in the frequency of the DRD4 exon 3 alleles. The DRD4.2 repeat was more common in mainlanders, as expected, whereas the DRD4.7 allele was over‐represented among islanders who never emigrated. This last result contradicts the suggested association of this allele with long‐distance migrations. We suggest that emigration might have caused gene flow out the island that resulted in somewhat unpredictable changes in the frequencies of specific alleles, thus influencing islander personality traits. Copyright © 2013 European Association of Personality Psychology     

The dopamine D4 receptor gene,birth weight,maternal depression,maternal attention,and the prediction of disorganized attachment at 36 months of age: A prospective gene × environment analysis

BackgroundEfforts to understand the developmental pathways for disorganized attachment reflect the importance of disorganized attachment on the prediction of future psychopathology. The inconsistent findings on the prediction of disorganized attachment from the dopamine D4 receptor (DRD4) gene, birth weight, and maternal depression as well as the evidence supporting the contribution of early maternal care, suggest the importance of exploring a gene by environment model.MethodsOur sample is from the Maternal Adversity, Vulnerability, and Neurodevelopment project; consisting of 655 mother–child dyads. Birth weight was cross-referenced with normative data to calculate birth weight percentile. Infant DRD4 genotype was obtained with buccal swabs and categorized according to the presence of the 7-repeat allele. Maternal depression was assessed with the Center for Epidemiologic Studies Depression Scale at the prenatal, 6-, 12-, and 24-month assessments. Maternal attention was measured at 6-months using a videotaped session of a 20-min non-feeding interaction. Attachment was assessed at 36-months using the Strange Situation Procedure.ResultsThe presence of the DRD4 7-repeat allele was associated with less disorganized attachment, β = −1.11, OR = 0.33, p = 0.0008. Maternal looking away frequency showed significant interactions with maternal depression at the prenatal assessment, β = 0.003, OR = 1.003, p = 0.023, and at 24 months, β = 0.004, OR = 1.004, p = 0.021, as at both time points, women suffering from depression and with frequent looking away behavior had an increased probability of disorganized attachment in their child, while those with less looking away behavior had a decreased probability of disorganized attachment in their child at 36 months.ConclusionsOur models support the contribution of biological and multiple environmental factors in the complex prediction of disorganized attachment at 36 months.     

DRD4基因与亲社会行为的关联及其潜在脑机制

DRD4基因是亲社会行为的重要候选基因,且与环境交互影响亲社会行为的发生发展。通过梳理既有研究,本文从性别差异、亲社会行为的不同类型及发展动态性等角度探讨了亲社会行为遗传研究存在分歧的原因,并在此基础上探索了DRD4基因作用于亲社会行为的潜在脑机制。未来研究应采用纵向设计探究DRD4基因影响亲社会行为的发展动态性问题,并深入探索其性别差异;采用多质多法分析考察不同类型亲社会行为遗传机制的差异性;采用影像遗传学设计揭示“DRD4基因—脑—亲社会行为”作用机制。     

Sources of Cognitive Exploration: Genetic Variation in the Prefrontal Dopamine System Predicts Openness/Intellect

The personality trait Openness/Intellect reflects the tendency to be imaginative, curious, perceptive, artistic, and intellectual - all characteristics that involve cognitive exploration. Little is known about the biological basis of Openness/Intellect, but the trait has been linked to cognitive functions of prefrontal cortex, and the neurotransmitter dopamine plays a key role in motivation to explore. The hypothesis that dopamine is involved in Openness/Intellect was supported by examining its association with two genes that are central components of the prefrontal dopaminergic system. In two demographically different samples (children: N = 608; adults: N = 214), variation in the dopamine D4 receptor gene (DRD4) and the catechol-O-methyltransferase gene (COMT) predicted Openness/Intellect, as main effects in the child sample and as a gene-gene interaction in adults.     

Together – apart: in touch in a time of separation

This paper explores the experience of working as a Jungian analyst through the various phases of the global COVID-19 pandemic, examining the importance of the physical containing space alongside the analyst’s internal mind and how technology can both help and hinder understanding. A number of clinical vignettes illustrate the challenge of communicating over a distance, paying particular attention to the way countertransference phenomena can become re-attuned. Reference is made to mythology and symbols of hope, and consideration given to the meaning and purpose of the pandemic.     

The Possibility of Meaning in Human Evolution

Science undermines the certitude of non-naturalistic answers to the question of whether human life has meaning. I explore whether evolution can provide a naturalistic basis for existential meaning. Using the work of philosopher Daniel Dennett and scientist Ursula Goodenough, I argue that evolution is the locus of the possibility of meaning because it has produced intentionality, the matrix of consciousness. I conclude that the question of the meaning of human life is an existentialist one: existential meaning is a product of the individual and collective tasks human beings undertake.     

Phenotypic plasticity and archetype: a response to common objections to the biological theory of archetype and instinct

Since Jung’s death in 1961, scholars have attempted to integrate growing biological science data into Jungian concepts such as the collective unconscious, instincts and the archetypes. This enterprise has been challenging due to persistent false dichotomies of gene and environment occasionally arising. Recent works by Roesler (2022a, 2022b) for example, have raised objections to the biological theory of archetypes, but the objections are plagued by such dichotomies. The concept of phenotypic plasticity, however, helps to both avoid this problem as well as bridge the gap between competing theories into a more integrated model with solid biological foundations.     

When is it time to stop? When good enough becomes bad enough

This article draws on Winnicott’s concept of the good enough mother to discuss how to know whether a therapeutic situation is good enough to continue or bad enough to end. This dilemma is explored in terms of clinical syndromes, such as anorexia and pathological gambling, but focuses mainly on analyst-initiated endings, which are termed the ‘Casablanca dilemma’, based on an amplification of the ending of the film Casablanca. The author goes on to discuss such one-sided endings, drawing on interviews with 40 analysts and therapists about their clinical experience. A typology of bad enough endings is presented. The psychological differences between a good enough analysis as opposed to a bad enough one are explored through the ideas of Winnicott and Neumann.     

Kann Es Ein Argument Für Den Skeptizismus Geben? Das Epistemische Problem Der Irrtumsmöglichkeit

Summary  Is there any argument for scepticism? The epistemic problem of the possibility of error. Arguments for scepticism rest on the assumption that knowledge claims are fallible. For this reason the concept of knowledge appears to be questionable. Since it is necessary to distinguish doubts from possible doubts, the arguments for scepticism appear to be unconvincing. If we take it into account that we know something that is immune to doubt, we should draw the conclusion that, contrary to scepticism, knowledge claims have to be compatible with being fallible. Thus any knowledge claim is capable of being doubted.     

The transcendent function in Spitteler’s Prometheus and Epimetheus

In August 2020, John Beebe and Steve Myers met via Zoom to discuss their differing interpretations of psychological typology and the different sources within Jung’s writings that influenced their books: Integrity in Depth: Energies and Patterns in Psychological Type (Beebe), and Myers-Briggs Typology vs Jungian Individuation (Myers). The discussion centred on Spitteler’s epic poem Prometheus und Epimetheus, which forms the basis of chapter V of Psychological Types. This is both the largest chapter and one of two chapters that Jung highlighted in the Argentine foreword as containing the essence of the book. Jung’s book is primarily about the transformation of personality rather than the categorization of people. Although it contains a critical psychology that deconstructs the nature of consciousness, that is only one half of the book and a stepping-stone to the other half, which is the reconciliation of opposites with particular emphasis on the relation of consciousness and the unconscious. Jung assumed that readers were already familiar with Prometheus und Epimetheus, an understanding of which sheds light on the nature of the transformation that Jung described – the development of a new attitude towards attitude itself.     

Chapter 6: Biblical Foundations for a Practical Theology of Aging

SUMMARY

This article reviews Biblical sources pertaining to the elderly, particularly the frail elderly. Founded on these sources, implications for elderly with Alzheimer's Disease and other forms of dementia are addressed through a personal perspective informed by writings of Christian mystics.     

Seeing in the Dark: A View into Dissociation and Healing

In this paper, I will explore the role of art-making, the experience of trauma and dissociation, and the process of working with self-states from an analytic and creative frame. Relevant literature on dissociation, trauma, and the use of art will be discussed. A case involving my work with an adolescent girl who had experienced sexual abuse from a family member will be shared, with an emphasis on the meaningful role images played during the therapeutic process. Both Jungian and psychoanalytic models of conceptualizing and working with dissociation are included, following Donald Kalsched’s (2013) recommendation for a “binocular stance” to treatment, including both a focus on the inner, intrapsychic world and the interpersonal, relational realm, and how art images both illuminated and expressed these realms. Within the therapeutic process, art images allowed the therapist a view into the client’s unconscious process, and created a meeting ground for dissociative barriers to be gradually seen, felt and known, by both therapist and client. The experience of dissociation, in images and in session, provided a reference point for myself and my client, Taylor, to develop a shared understanding and a framework for growth.     

Mythological Underpinnings of Feminine Development

In the manner of Oedipus Rex, the myth of Myrrha—a story about a daughter's initiation of sex with her father—promises to divulge insights about feminine development. Given parallels between these two myths, the author asks why Jung identified Electra rather than Myrrha as the feminine counterpart to Oedipus, and revisits Freud's and Jung's differing interpretations of the incest theme in personality development. To break open the metaphor of Myrrha's incest, the author analyzes a similar account of incest in the Old Testament story of Lot and his wife and finds that they share a theme of female bitterness related to wounding of the mother and its arresting effect on the daughter's maturation. The article then considers the Demeter-Persephone myth, a tale not of incest but rape in Persephone's initiation into womanhood. In contrast to Myrrha, Persephone's development unfolds with strong maternal support tempered by the opposing claims on her by the masculine. The article draws these stories together to illuminate the archetypal forces that drive feminine development as well as the human affairs that resist and complicate them. The article concludes with a case study of a client whose developmental “stuckness” follows the contours of the Myrrha myth.