From Temperament to Personality: Genetic Codes and the Burden of Trauma

I would say that this issue of Bilim ve Ütopya, with its cover theme of “Personality Disorders,” has become a resource worth revisiting from time to time, thanks to its important articles, both for those interested in the subject and in psychology and for clinicians and researchers working in the field. Bringing together highly esteemed researchers in this area, this issue offers a comprehensive look at different forms of personality pathology. In this first article on personality disorders, I will try to present a different perspective on personality pathology. There is a point frequently emphasized by psychotherapists, theorists, and trainers who work with personality pathology. Among the components that shape character, there are innate traits that exist independently of all other factors. These are the inherited characteristics we possess at birth… In addition, traumatic stress experienced from birth onward (and some publications now include stress in the womb), particularly during the early years of life, also plays a very important role in personality development. This article will discuss these innate characteristics and the effects of postnatal traumatic stress on the formation of character.

Temperament, Personality, and Character

Temperament, character, and personality are distinct concepts. Character consists of learned attitudes developed under the influence of the environment and upbringing. It therefore includes characteristics that change over time. Temperament consists of inherited constitutional traits that change very little throughout life [1]. The term “temperament,” used in the literature, derives from the word “temperare,” meaning “to mix.” It describes attitudes and behaviors with a constitutional, genetic, and biological basis [2]. Personality, in turn, is formed by the combination of genetically inherited temperament and character that develops later [3,4]. Personality traits characteristically influence a person's typical ways of thinking, feeling, perceiving, and relating to others. These become clearly established in late childhood or adolescence and, setting aside the effects of exposure to traumatic life events or receiving psychotherapy, generally remain stable throughout life.

A Historical Perspective on Personality and Temperament

It has been known since the time of Hipokrat that human beings have different temperamental traits.

Emil Kraepelin was a German psychiatrist who lived from 1856 to 1926. He is known for being the first to classify mental disorders, laying the foundations for diagnostic classification manuals used today, such as the DSM and ICD. One of his greatest achievements was identifying the connection between brain pathology and psychiatric disorders.

In 1921, Kraepelin proposed a relationship between affective temperament and affective (mood) disorders [5]. Affect is the outward expression of an individual's emotional responses to events, thoughts, and stimuli. Mood, by contrast, is the more sustained emotional state that constitutes an individual's temperament.

Hagop S. Akiskal was born in Lebanon in 1944 to an Armenian family. Known for his research on temperament and bipolar disorder, the psychiatrist currently serves as an emeritus professor at the University of California, San Diego.

Akiskal argued that affective temperament underlies mood disorders (the umbrella term for conditions such as bipolar disorder and major depression) and defined five basic affective temperaments: depressive, hyperthymic, cyclothymic, irritable, and anxious temperament [6].

Claude Robert Cloninger is an American professor of psychiatry and genetics known for his psychobiological theory, developed through his research into the psychological, biological, and social foundations of mental health and mental disorders. Through this theory, Cloninger proposed that personality could predict vulnerability to mental disorders and developed the Temperament and Character Inventory.

Cloninger developed a general psychobiological theory to describe the structure and development of personality [7,8]. This model proposes four temperament dimensions assumed to be genetically independent, moderately stable throughout life, and invariant across cultural influences: novelty seeking, harm avoidance, reward dependence, and persistence. He defined character traits, which are assumed to develop and mature in adulthood and to influence self-concepts, under three headings: self-directedness, self-transcendence, and cooperativeness.

Cloninger described novelty seeking, the first temperament dimension, as arising from a heritable bias toward the activation of behaviors such as frequent exploratory activity in response to novelty, impulsive decision-making, exuberance when the possibility of reward arises, a quick temper, and avoidance of frustration. He described the second temperament factor, “harm avoidance,” as a heritable bias toward behavioral inhibition, expressed in avoidant behaviors such as pessimistic worry, fear of uncertainty, and shyness with strangers, as well as easy fatigability. The third temperament factor, reward dependence, was described as a heritable predisposition associated with behaviors such as excessive sentimentality, excessive attachment in relationships, and dependence on others' approval. He described the fourth temperament factor, persistence, as a heritable bias associated with maintaining behavior despite frustration, fatigue, and intermittent reinforcement [8,9].

Returning to the three character dimensions thought to develop and mature in adulthood—self-directedness, self-transcendence, and cooperativeness: self-directedness consists of accepting responsibility for one's choices, setting meaningful goals, and developing competence and confidence in problem-solving. Cooperativeness consists of social acceptance, empathy, compassion, and being principled. Self-transcendence consists of self-forgetfulness, transpersonal identification, and spiritual acceptance [7].

Temperament plays an important role in many areas of life. For example, a study investigating how spouses evaluate each other in couples experiencing marital difficulties found that their evaluations differed from those of couples without such difficulties, and that these differences were influenced by temperamental traits [10].

Temperament can manifest in various ways in diseases and syndromes. In bipolar disorder, a neurobiological disorder, patients with different temperamental traits have been shown to have different clinical features and illness courses [11]. Individuals with low reward dependence, self-directedness, and cooperativeness have been shown to be more prone to suicidal behavior. It has been reported that when people with this predisposition encounter adverse life events and stressors or experience depression, they respond with greater hopelessness, pessimism, and reactivity and are more inclined to harm themselves [12].

Childhood Trauma

Exposure to traumatic stress such as abuse or neglect in childhood is unfortunately very common worldwide and is a major risk factor for mental health problems in general [13]. Childhood trauma includes harmful and adverse experiences such as sexual abuse, physical abuse, emotional abuse, and physical and emotional neglect [14].

Childhood trauma has profound effects on children's emotional, behavioral, cognitive, social, and physical functioning. Developmental experiences shape the brain's organization and functioning as it matures. The effects of traumatic experiences on brain development and function are considered within the framework of the fundamental principles of neurodevelopment. Humans show various mental and physical responses to trauma, including physiological hyperarousal and dissociation.

Psychologically, dissociation is a state in which thoughts, feelings, and memories are excluded from consciousness in a way that threatens the individual's psychological integrity. Derealization (a sense of detachment from one's surroundings) and depersonalization (a sense of detachment from oneself) are examples of dissociative symptoms [15].

The developing brain organizes itself in response to new information and, as it internalizes that information, transfers it to adaptive memory networks. A previously calm child may develop neuropsychiatric symptoms following trauma. Responses that could be considered acute and adaptive behaviors during a traumatic event may subsequently become enduring, maladaptive traits [16].

Childhood Trauma and Illness

Although there is robust evidence linking childhood trauma and mental disorders, little is known about the underlying mechanisms. Current “stress sensitivity” models of childhood trauma suggest that psychological trauma makes individuals more sensitive to events [17–27].

As demonstrated in various studies, early-life stressors are a major risk factor for the development and persistence of mental disorders. Increased rates of major depression, post-traumatic stress disorder, attention-deficit/hyperactivity disorder (ADHD), and other behavioral disorders have been reported in maltreated children [18,27]. In particular, individuals with a history of childhood trauma are more likely to be traumatized by life events in adulthood. Childhood trauma also predicts chronic post-traumatic stress disorder with persistent symptoms. At this point, as we have discussed in previous issues, the emphasis on “treatment resistance” can be understood as a characterization that predates recent developments in psychotherapy. Research over the past 30 years has provided us with highly effective methods for treating PTSD symptoms. Returning to our subject, studies have shown that, because of reduced psychological flexibility, people who experienced childhood trauma continue to use the primitive psychological defenses employed during that trauma in maladaptive ways in adult life [28]. In a study of approximately 2,000 women, those with a history of childhood sexual or physical abuse had higher levels of depressive symptoms and anxiety than those without such a history, and were found to attempt suicide more frequently [29]. Studies indicate that, in addition to female sex, a family history of psychiatric illness, and a personal history of depression, early-life trauma increases the likelihood of developing major depression [30]. Exposure to extraordinary life stressors before adolescence, such as parental loss or sexual or physical abuse, has been documented to increase the risk of major depression and suicide [31–33]. Childhood trauma is also closely associated with vulnerability to substance use [34]. Many conditions, including major depression and anxiety disorders, as well as panic disorder and post-traumatic stress disorder, occur more frequently in adults who experienced childhood neglect and abuse than in healthy controls [35].

Studies have demonstrated an association between childhood trauma, such as sexual [14,21,36–39], physical [17,40–44], and emotional [36,39] abuse, and the likelihood of experiencing psychotic symptoms in adolescence and adulthood. Early trauma has been associated with an increased risk not only of psychiatric conditions such as schizophrenia and substance use disorder, but also of diabetes, heart disease, and immune-related diseases [35,45–48]. The onset of these psychiatric and other medical disorders in adulthood, or the worsening of an existing illness, is associated with acute life events or ongoing stress [49–52]. Adverse experiences during development are therefore thought to create sensitivity to the effects of stress later in life, making these individuals more vulnerable to developing mental illness or experiencing a worsening of existing illness in connection with acute or chronic life events [32]. In individuals with such childhood trauma, psychotherapy, either alone or as an adjunctive treatment, has also been shown to be more effective than medication alone [53].

The Neurobiological Effects of Childhood Trauma

The human brain and immune system are not fully mature at birth. Rather, both emerge from life in the womb with a small number of functions that allow the newborn to "adapt to a limited range of stimuli." Through experiences during the early stages of development after birth, the brain and immune system gradually expand their repertoire, probably to maximize adaptation to stimuli in the individual's environment [54–56]. The organism's aim is to find a solution that meets environmental demands, regardless of how positive or negative its experiences are [57]. Stress-induced changes in brain development affect myelination, synaptogenesis, and neurogenesis, all processes involved in nervous system development. The effects of events we define as traumatic on brain development depend not directly on the apparent type of experience, but on the extent to which it is perceived and experienced as stressful [58].

Studies provide evidence that childhood abuse or neglect is associated with an overall reduction in the volume of the hippocampus [59–62], as well as changes in the corpus callosum [57–63], prefrontal cortex, and frontal lobes [64].

The hippocampus is a brain region located in the temporal lobe that plays an important role in memory and navigation. It is a structure of the limbic system involved in converting short-term memory into long-term memory.

The prefrontal cortex is the part of the frontal lobe cortex containing feedback pathways and connections between major sensory and motor systems. The frontal lobe, located at the front of the brain, accounts for one-third of the brain and is responsible for conscious thought; it supports functions such as planning, impulse control, sustained attention, and problem-solving.

There is also evidence that childhood trauma in these individuals causes problems related to altered cortical symmetry [64] and leads to impaired neuronal integrity or reduced neuronal density in the temporal gyrus [63] and anterior cingulate.

Carter, Henry Vandyke, and Henry Gray. “Cingulate Gyrus.” Wikimedia, 2020, commons.wikimedia.org/wiki/File:Gray727.svg#/media/File:Gray727.svg.

A study investigating findings of reduced hippocampal volume in patients with depression found that these findings occurred largely in the subgroup of patients with early-life trauma [62].

One study identified “sensitive periods” in which particular age ranges are more sensitive to specific types of trauma, with differences between males and females. For example, sexual trauma occurring early in childhood was associated with reduced hippocampal volume, whereas trauma during adolescence was associated with changes in prefrontal cortex volume. Interestingly, the two sexes were also shown to have different periods of sensitivity to types of childhood trauma such as physical neglect or sexual abuse [58]. In other words, the brain structures of individuals of different sexes are more sensitive to different types of trauma at different ages.

Developmental plasticity is the brain's capacity to undergo physiological and structural changes. These changes encompass a range of systematic adjustments, from neurons forming new connections to remapping at the cortical level.

Although developmental plasticity has been well studied in relation to basic brain functions such as visual pathways [65,66], the principal determinants of complex brain and immune functions have not yet been adequately identified. Our knowledge in this area is growing over time [56,67]. Early trauma is known to affect inflammatory processes in the brain and can disrupt immune function. Trauma-related immune activation in early life may affect brain function and development, making individuals who have experienced trauma more sensitive to the effects of subsequent stressors [28].

An epidemiological twin study demonstrated that genetic factors, early-life trauma, and recent life stressors jointly play an important role in the onset of major depression [68]. Early adverse experiences may shape a pre-existing genetic vulnerability to stress and illness, thereby creating a phenotype at risk of developing a syndrome triggered by stress exposure [32]. How, then, might early adverse experiences create a vulnerable phenotype? They probably cause lasting sensitization of stress-sensitive neural circuits. Numerous studies have examined the neurobiological consequences of early developmental stress in animals [46,69,70]. (Figure 2)

Figure 1 Psychological Trauma and Phenotype

YAŞAR Alişan Burak (2017). Juvenil miyoklonik epilepsi hastalarında mizaç özellikleri ve çocukluk çağı travmaları ile hastalık özelliklerinin araştırılması, Sağlık Bilimleri Üniversitesi Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, Uzmanlık Tezi. İstanbul

Stress during sensitive periods of life can have long-term effects on immunity [71]. The effects of early trauma on cytokines, an important signaling system in the blood, have recently been studied extensively. For example, serum TNF-α and IL-6 levels in patients with major depression have been associated with childhood trauma. These are important cytokines involved in inflammatory processes in the blood. The severity of childhood sexual abuse has even been found to be associated with increased TNF-α and IL-6 levels. Childhood maltreatment in particular has been shown to produce long-term effects through these neuroinflammatory cytokines [72,73]. Chronic inflammatory states associated with childhood maltreatment have also been shown to occur independently of current clinical comorbidities such as major depression [73]. A similar finding has been reported in healthy adults with a history of childhood trauma [74].

Childhood Trauma and Stress

Studies show increased stress sensitivity, reduced resilience, and consequently an increased risk of mental health disorders in people exposed to childhood trauma [75]. For example, these experiences are known to be associated with depressive symptoms, anxiety symptoms, and even psychotic symptoms in adolescents and young adults [75]. Nevertheless, the effect of childhood trauma on stress sensitivity has received relatively little research attention. Stress sensitivity may influence the disorders mentioned here and others as well. Interventions targeting heightened stress sensitivity in everyday life may offer promising new therapeutic benefits. In addition to the primary prevention of childhood trauma and thorough assessment of patients' trauma histories, evaluating all patients with physical or psychological conditions from this perspective and providing the necessary evidence-based interventions may offer new therapeutic benefits [75].

Other studies have gone further, linking childhood trauma to a range of conditions, from psychiatric comorbidities (e.g., major depression, anxiety disorders, post-traumatic stress disorder, and eating disorders) to general medical conditions (obesity, asthma, and coronary artery disease). Research in this area has provided evidence that early childhood trauma may cause disruption or abnormal development of stress-regulatory systems, including the hypothalamic-pituitary-adrenal axis, an important hormonal pathway [76,77], and the central noradrenergic system [78].

Of course, as noted above, sensitivity to stress and vulnerability to illness are influenced not only by childhood trauma but also by genetic characteristics [46]. In other words, genetic factors and early-life or chronic stress jointly contribute to individual stress responses and to the onset of psychiatric and other illnesses [53].

Childhood Trauma and Personality Disorders

There is a substantial body of well-established research on the relationship between trauma and personality disorders, particularly borderline personality disorder (BPD) [79]. A study comparing veterans with combat trauma, outpatients with sexual trauma, and inpatients with sexual trauma against groups without trauma found that certain characteristics traditionally defined in terms of personality disorders were shared by all trauma groups. Traits associated with paranoid, borderline, schizotypal, and self-defeating (masochistic) personality disorders were frequently observed across individuals with traumatic experiences [79].

Many adults with personality disorders have reported early traumatic experiences [80]. Similarly, numerous studies have documented that individuals with personality disorders, particularly borderline personality disorder, report substantial childhood trauma compared with those with other disorders in related categories [81,82]. These findings reveal that personality disorders are common among patients with trauma, while traumatic childhood events are common among patients with personality disorders, suggesting a relationship between personality disorders and childhood trauma. Research in the literature indicates that childhood trauma plays a role in the development of personality disorders. Studies on the co-occurrence of borderline personality disorder and trauma are particularly common.

In borderline personality disorder, emotional and sexual abuse, as subtypes of childhood trauma, together with depressive symptoms, have been identified as important risk factors for impulsive behavior, self-harm, and suicidal behavior. (Anadolu Psikiyatri Derg 2019; 20(4):341-349). The borderline group's scores for depressive symptoms, childhood trauma and its subdimensions, impulsivity, self-harming behavior, and suicidal behavior differed significantly from those of the control group (p<0.01).

In summary, traumatic experiences, especially childhood trauma, have the potential to cause severe harm to a person's life and mental well-being. This harm may affect various domains or functions, such as attachment, personality traits, cognitions, and brain development, leading to adverse relational, psychological, neuropsychiatric, and functional outcomes. These adverse outcomes can vary in scope, including impaired functioning of emotions, thoughts, and behaviors, increased vulnerability to certain disorders, various psychological symptoms, and the development of mental disorders. Temperament, character and attachment characteristics, neurobiological developmental characteristics, vulnerabilities, and psychological health can determine the extent to which a person is affected by trauma. At the same time, psychological trauma can also affect personality traits. Character traits, meanwhile, are influenced by environmental factors and traumatic experiences, but are also related to the innate, genetically inherited temperamental traits an individual possesses.

References

1. traits in a cross-cultural twin sample: support for a hierarchical model of personality. J Pers Soc Psychol. 1998;74(6):1556.
2. Goodwin FK, Jamison KR. Manic-depressive illness, creativity and leadership. Manic-depressive Illn. 1990.
3. Svrakic DM, Cloninger CR. Personality disorder. BJ Sadock, VA Sadock (Eds.), Comprehensive Textbook of Psychiatry. 2004.
4. Akiskal HS, Hirschfeld RMA, Yerevanian BI. The relationship of personality to affective disorders: A critical review. Arch Gen Psychiatry. 1983;40(7):801-810.
5. Akiskal HS, Pinto O. The soft bipolar spectrum: footnotes to Kraepelin on the interface of hypomania, temperament and depression. In: Bipolar Disorders. Springer; 2000:37-62.
6. Akiskal HS. Criteria for the" soft" bipolar spectrum: treatment implications. Psychopharmacol Bull. 1987;23:68-73.
7. Cloninger CR, Svrakic DM, Przybeck TR. A psychobiological model of temperament and character. Arch Gen Psychiatry. 1993;50(12):975-990.
8. Cloninger CR. A systematic method for clinical description and classification of personality variants: A proposal. Arch Gen Psychiatry. 1987;44(6):573-588.
9. Cloninger CR. A unified biosocial theory of personality and its role in the development of anxiety states. Psychiatr Dev. 1986;3(2):167-226.
10. Erdoğan S. Evlilik uyumu ile psikiyatrik rahatsızlıklar, bağlanma stilleri ve mizaç ve karakter özellikleri arasındaki ilişkilerin incelenmesi. Gazi Üniversitesi/Tıp Fakültesi Psikiyatr Anabilim Dalı, Ankara. 2007:33.
11. Kesebir S, Vahip S, Akdeniz F, Yüncü Z. Bipolar bozuklukta mizaç ile klinik özelliklerin ilişkisi. Türk Psikiyatr Derg. 2005;16(3):164-169.
12. Ak M, Özmenler KN, Özşahin A. İntihar Girişimi İle Mizaç ve Karakter Özellikleri Arasındaki İlişkinin Major Depresif Bozukluk Örnekleminde İrdelenmesi. Klin Psikiyatr Derg. 2008;11(1).
13. Lange A, de Beurs E, Dolan C, Lachnit T, Sjollema S, Hanewald G. Long-term effects of childhood sexual abuse: Objective and subjective characteristics of the abuse and psychopathology in later life. J Nerv Ment Dis. 1999;187(3):150-158.
14. Morgan C, Fisher H. Environment and schizophrenia: environmental factors in schizophrenia: childhood trauma—a critical review. Schizophr Bull. 2007;33(1):3-10.
15. Şar V. Travma ve Dissosiyasyon Nedir? https://www.vedatsar.com/travma-ve-dissosiyasyon-nedir/. Published 2020.
16. Perry BD, Pollard RA, Blakley TL, Baker WL, Vigilante D. Childhood trauma, the neurobiology of adaptation, and “use‐dependent” development of the brain: How “states” become “traits.” Infant Ment Health J. 1995;16(4):271-291.
17. Bentall RP, de Sousa P, Varese F, et al. From adversity to psychosis: pathways and mechanisms from specific adversities to specific symptoms. Soc Psychiatry Psychiatr Epidemiol. 2014;49(7):1011-1022.
18. Famularo R, Kinscherff R, Fenton T. Psychiatric diagnoses of maltreated children: preliminary findings. J Am Acad Child Adolesc Psychiatry. 1992;31(5):863-867.
19. Wichers M, Schrijvers D, Geschwind N, et al. Mechanisms of gene-environment interactions in depression: evidence that genes potentiate multiple sources of adversity. Psychol Med. 2009;39(7):1077.
20. Hammen C, Henry R, Daley SE. Depression and sensitization to stressors among young women as a function of childhood adversity. J Consult Clin Psychol. 2000;68(5):782.
21. Holshausen K, Bowie CR, Harkness KL. The relation of childhood maltreatment to psychotic symptoms in adolescents and young adults with depression. J Clin Child Adolesc Psychol. 2016;45(3):241-247.
22. Howes OD, Murray RM. Schizophrenia: an integrated sociodevelopmental-cognitive model. Lancet. 2014;383(9929):1677-1687.
23. Kendler KS, Kuhn JW, Prescott CA. Childhood sexual abuse, stressful life events and risk for major depression in women. Psychol Med. 2004;34(8):1475.
24. Morgan C, Charalambides M, Hutchinson G, Murray RM. Migration, ethnicity, and psychosis: toward a sociodevelopmental model. Schizophr Bull. 2010;36(4):655-664.
25. Morgan C, Reininghaus U, Fearon P, et al. Modelling the interplay between childhood and adult adversity in pathways to psychosis: initial evidence from the AESOP study. Psychol Med. 2014;44(2):407.
26. Myin-Germeys I, van Os J, Schwartz JE, Stone AA, Delespaul PA. Emotional reactivity to daily life stress in psychosis. Arch Gen Psychiatry. 2001;58(12):1137-1144.
27. Pelcovitz D, Kaplan S, Goldenberg B, Mandel F, Lehane J, Guarrera J. Post-traumatic stress disorder in physically abused adolescents. J Am Acad Child Adolesc Psychiatry. 1994;33(3):305-312.
28. Crittenden PM, Heller MB. The roots of chronic posttraumatic stress disorder: Childhood trauma, information processing, and self-protective strategies. Chronic Stress. 2017;1:2470547016682965.
29. McCauley J, Kern DE, Kolodner K, et al. Clinical characteristics of women with a history of childhood abuse: unhealed wounds. Jama. 1997;277(17):1362-1368.
30. Regier DA, Hirschfeld RM, Goodwin FK, Burke JD, Lazar JB, Judd LL. The NIMH Depression Awareness, Recognition, and Treatment Program: structure, aims, and scientific basis. Am J Psychiatry. 1988;145(11):1351-1357.
31. Kendler KS, Kessler RC, Walters EE, et al. Stressful life events, genetic liability, and onset of an episode of major depression in women. Focus (Madison). 2010;8(3):459-470.
32. Heim C, Nemeroff CB. The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biol Psychiatry. 2001;49(12):1023-1039.
33. Dube SR, Anda RF, Felitti VJ, Chapman DP, Williamson DF, Giles WH. Childhood abuse, household dysfunction, and the risk of attempted suicide throughout the life span: findings from the Adverse Childhood Experiences Study. Jama. 2001;286(24):3089-3096.
34. Lopez-Patton M, Kumar M, Jones D, Fonseca M, Kumar AM, Nemeroff CB. Childhood trauma and METH abuse among men who have sex with men: Implications for intervention. J Psychiatr Res. 2016;72:1-5.
35. Agid O, Shapira B, Zislin J, et al. Environment and vulnerability to major psychiatric illness: a case control study of early parental loss in major depression, bipolar disorder and schizophrenia. Mol Psychiatry. 1999;4(2):163-172.
36. Varese F, Smeets F, Drukker M, et al. Childhood adversities increase the risk of psychosis: a meta-analysis of patient-control, prospective-and cross-sectional cohort studies. Schizophr Bull. 2012;38(4):661-671.
37. Matheson SL, Shepherd AM, Pinchbeck RM, Laurens KR, Carr VJ. Childhood adversity in schizophrenia: a systematic meta-analysis. Psychol Med. 2013;43(2):225.
38. Heins M, Simons C, Lataster T, et al. Childhood trauma and psychosis: a case-control and case-sibling comparison across different levels of genetic liability, psychopathology, and type of trauma. Am J Psychiatry. 2011;168(12):1286-1294.
39. Daalman K, Diederen KMJ, Derks EM, van Lutterveld R, Kahn RS, Sommer IEC. Childhood trauma and auditory verbal hallucinations. Psychol Med. 2012;42(12):2475.
40. Arseneault L, Cannon M, Fisher HL, Polanczyk G, Moffitt TE, Caspi A. Childhood trauma and children’s emerging psychotic symptoms: a genetically sensitive longitudinal cohort study. Am J Psychiatry. 2011;168(1):65-72.
41. McGrath JJ, McLaughlin KA, Saha S, et al. The association between childhood adversities and subsequent first onset of psychotic experiences: a cross-national analysis of 23,998 respondents from 17 countries. Psychol Med. 2017;47(7):1230.
42. Read J, van Os J, Morrison AP, Ross CA. Childhood trauma, psychosis and schizophrenia: a literature review with theoretical and clinical implications. Acta Psychiatr Scand. 2005;112(5):330-350.
43. Kelleher I, Harley M, Lynch F, Arseneault L, Fitzpatrick C, Cannon M. Associations between childhood trauma, bullying and psychotic symptoms among a school-based adolescent sample. Br J Psychiatry. 2008;193(5):378-382.
44. Harley M, Kelleher I, Clarke MC, et al. Cannabis use and childhood trauma interact additively to increase the risk of psychotic symptoms in adolescence. 2010.
45. Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: The Adverse Childhood Experiences (ACE) Study. Am J Prev Med. 1998;14(4):245-258.
46. Francis DD, Caldji C, Champagne F, Plotsky PM, Meaney MJ. The role of corticotropin-releasing factor–norepinephrine systems in mediating the effects of early experience on the development of behavioral and endocrine responses to stress. Biol Psychiatry. 1999;46(9):1153-1166.
47. Wallace DJ. The role of stress and trauma in rheumatoid arthritis and systemic lupus erythematosus. In: Seminars in Arthritis and Rheumatism. Vol 16. Elsevier; 1987:153-157.
48. Kendler KS, Bulik CM, Silberg J, Hettema JM, Myers J, Prescott CA. Childhood sexual abuse and adult psychiatric and substance use disorders in women: an epidemiological and cotwin control analysis. Arch Gen Psychiatry. 2000;57(10):953-959.
49. Hammen C, Davila J, Brown G, Ellicott A, Gitlin M. Psychiatric history and stress: predictors of severity of unipolar depression. J Abnorm Psychol. 1992;101(1):45.
50. Mooy JM, De Vries H, Grootenhuis PA, Bouter LM, Heine RJ. Major stressful life events in relation to prevalence of undetected type 2 diabetes: the Hoorn Study. Diabetes Care. 2000;23(2):197-201.
51. Norman RMG, Malla AK. A prospective study of daily stressors and symptomatology in schizophrenic patients. Soc Psychiatry Psychiatr Epidemiol. 1994;29(6):244-249.
52. Twisk JWR, Snel J, Kemper HCG, van Mechelen W. Changes in daily hassles and life events and the relationship with coronary heart disease risk factors: a 2-year longitudinal study in 27–29-year-old males and females. J Psychosom Res. 1999;46(3):229-240.
53. Nemeroff CB, Heim CM, Thase ME, et al. Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma. Proc Natl Acad Sci. 2003;100(24):14293-14296.
54. Greenough WT, Black JE, Wallace CS. Experience and brain development. Child Dev. 1987:539-559.
55. Bateson P, Barker D, Clutton-Brock T, et al. Developmental plasticity and human health. Nature. 2004;430(6998):419-421.
56. Danese A, McEwen BS. Adverse childhood experiences, allostasis, allostatic load, and age-related disease. Physiol Behav. 2012;106(1):29-39.
57. Teicher MH. Scars that won’t heal: The neurobiology of child abuse. Sci Am. 2002;286(3):68-75.
58. Teicher MH, Tomoda A, Andersen SL. Neurobiological consequences of early stress and childhood maltreatment: are results from human and animal studies comparable? Ann N Y Acad Sci. 2006;1071(1):313-323.
59. Bremner JD, Randall P, Vermetten E, et al. Magnetic resonance imaging-based measurement of hippocampal volume in posttraumatic stress disorder related to childhood physical and sexual abuse—a preliminary report. Biol Psychiatry. 1997;41(1):23-32.
60. Stein MB, Koverola C, Hanna C, Torchia MG, McClarty B. Hippocampal volume in women victimized by childhood sexual abuse. Psychol Med. 1997;27(4):951-959.
61. Driessen M, Herrmann J, Stahl K, et al. Magnetic resonance imaging volumes of the hippocampus and the amygdala in women with borderline personality disorder and early traumatization. Arch Gen Psychiatry. 2000;57(12):1115-1122.
62. Vythilingam M, Heim C, Newport J, et al. Childhood trauma associated with smaller hippocampal volume in women with major depression. Am J Psychiatry. 2002;159(12):2072-2080.
63. De Bellis MD, Keshavan MS, Frustaci K, et al. Superior temporal gyrus volumes in maltreated children and adolescents with PTSD. Biol Psychiatry. 2002;51(7):544-552.
64. Carrion VG, Weems CF, Eliez S, et al. Attenuation of frontal asymmetry in pediatric posttraumatic stress disorder. Biol Psychiatry. 2001;50(12):943-951.
65. Hubel DH, Wiesel TN. Brain and Visual Perception: The Story of a 25-Year Collaboration. Oxford University Press; 2004.
66. Hensch TK. Critical period plasticity in local cortical circuits. Nat Rev Neurosci. 2005;6(11):877-888.
67. Rook GAW, Lowry CA, Raison CL. Hygiene and other early childhood influences on the subsequent function of the immune system. Brain Res. 2015;1617:47-62.
68. Kendler KS, Kessler RC, Neale MC, Heath AC, Eaves LJ. The prediction of major depression in women: toward an integrated etiologic model. Am J Psychiatry. 1993;150:1139.
69. Kaufman J, Plotsky PM, Nemeroff CB, Charney DS. Effects of early adverse experiences on brain structure and function: clinical implications. Biol Psychiatry. 2000;48(8):778-790.
70. Ladd CO, Huot RL, Thrivikraman K V, Nemeroff CB. Long-term behavioral and neuroendocrine adaptations to adverse early experience. Prog Brain Res. 1998;122(3):2000.
71. Grosse L, Ambrée O, Jörgens S, et al. Cytokine levels in major depression are related to childhood trauma but not to recent stressors. Psychoneuroendocrinology. 2016;73:24-31.
72. Baumeister D, Akhtar R, Ciufolini S, Pariante CM, Mondelli V. Childhood trauma and adulthood inflammation: a meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-α. Mol Psychiatry. 2016;21(5):642-649.
73. Coelho R, Viola TW, Walss‐Bass C, Brietzke E, Grassi‐Oliveira R. Childhood maltreatment and inflammatory markers: a systematic review. Acta Psychiatr Scand. 2014;129(3):180-192.
74. Hartwell KJ, Moran-Santa Maria MM, Twal WO, et al. Association of elevated cytokines with childhood adversity in a sample of healthy adults. J Psychiatr Res. 2013;47(5):604-610.
75. Rauschenberg C, Van Os J, Cremers D, Goedhart M, Schieveld JNM, Reininghaus U. Stress sensitivity as a putative mechanism linking childhood trauma and psychopathology in youth’s daily life. Acta Psychiatr Scand. 2017;136(4):373-388.
76. Trickett PK, Noll JG, Susman EJ, Shenk CE, Putnam FW. Attenuation of cortisol across development for victims of sexual abuse. Dev Psychopathol. 2010;22(1):165.
77. Keeshin BR, Strawn JR, Out D, Granger DA, Putnam FW. Cortisol awakening response in adolescents with acute sexual abuse related posttraumatic stress disorder. Depress Anxiety. 2014;31(2):107-114.
78. Pervanidou P, Chrousos GP. Metabolic consequences of stress during childhood and adolescence. Metabolism. 2012;61(5):611-619.
79. Yen S, Shea MT. Recent developments in research of trauma and personality disorders. Curr Psychiatry Rep. 2001;3(1):52-58.
80. Flory JD, Yehuda R, Grossman R, New AS, Mitropoulou V, Siever LJ. Childhood trauma and basal cortisol in people with personality disorders. Compr Psychiatry. 2009;50(1):34-37.
81. Paris J. Childhood trauma as an etiological factor in the personality disorders. J Pers Disord. 1997;11(1):34-49.
82. Paris J. Does childhood trauma cause personality disorders in adults? Can J Psychiatry. 1998;43(2):148-153.
83. YAŞAR Alişan Burak (2017). Juvenil miyoklonik epilepsi hastalarında mizaç özellikleri ve çocukluk çağı travmaları ile hastalık özelliklerinin araştırılması, Sağlık Bilimleri Üniversitesi Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, Uzmanlık Tezi. İstanbul

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This article was first published in the issue of Bilim ve Ütopya with the cover theme “Personality Disorders” (2020).