Genetic association of SLC6A3 (dopamine transporter) gene polymorphisms with personality disorders and substance abuse disorders: a systematic review and meta-analysis.

INTRODUCTION: Personality disorders (PD) are characterized by socially dysfunctional behavioral patterns that affect patients and show higher incidence rates within families. Substance abuse disorders (SAD) are exemplified by extensive and prolonged use of substances, including alcohol, nicotine, or illegal drugs. Genetic predisposition for both PD and SAD has been reported to involve gene variants regulating dopaminergic pathways. Yet, discrepancy among reported results necessitates further elucidation of potential hereditary-related risk factors. Because both disorders impose a societal burden, knowledge on the impact of certain genetic backgrounds on these diseases could help develop evidence-based strategies for efficacious treatment approaches. MATERIALS AND METHODS: In the present study a systematic review was performed, and the association between dopamine transporter gene polymorphism (SLC6A3), particularly rs28363170 entailing a 40-bp variable number tandem repeat, and PD as well as SAD was investigated recruiting meta-analysis approach. RESULTS: Initial literature search for PD yielded 1577, from which nine fulfilled eligibility criteria to be used in a meta-analysis including 729 cases and 2113 controls. From the 934 studies retrieved for SAD, only 29 articles with 5221 cases and 4822 controls were used for meta-analysis. A statistically significant association was seen between rs28363170 (for the 9-repeat allele) and PD in European populations according to the co-dominant mode of inheritance. For SAD no statistically significant correlation under any mode of inheritance was observed. There was no indication of time-trend phenomena. CONCLUSION: Our findings demonstrate the association of SLC6A3 gene polymorphism with PD, thus underling the need to understand neurobiological mechanisms inherent to the above disorders to guide treatment strategies under the perspective of personalized medicine.

Personality, subjective well-being, and the serotonin 1a receptor gene in common marmosets (Callithrix jacchus).

Studies of personality traits in common marmosets (Callithrix jacchus) indicate that there are five or six constructs-Sociability, Dominance, Neuroticism, Openness, and two related to Conscientiousness. The present study attempted to determine whether our earlier study of laboratory-housed individuals only yielded three-Dominance, Sociability, and Neuroticism-because of a low amount of between-subjects variance. To do so, we increased our sample size from 77 to 128. In addition, we ascertained the reliability and validity of ratings and whether polymorphisms related to the serotonin 1a receptor were associated with personality. We found Sociability, Dominance, and Negative Affect factors that resembled three domains found in previous studies, including ours. We also found an Openness and Impulsiveness factor, the latter of which bore some resemblance to Conscientiousness, and two higher-order factors, Pro-sociality and Boldness. In further analyses, we could not exclude the possibility that Pro-sociality and Boldness represented a higher-level of personality organization. Correlations between personality factors and well-being were consistent with the definitions of the factors. There were no significant associations between personality and genotype. These results suggest that common marmoset personality structure varies as a function of rearing or housing variables that have not yet been investigated systematically.

Coupling of autism genes to tissue-wide expression and dysfunction of synapse, calcium signalling and transcriptional regulation.

Autism Spectrum Disorder (ASD) is a heterogeneous disorder that is often accompanied with many co-morbidities. Recent genetic studies have identified various pathways from hundreds of candidate risk genes with varying levels of association to ASD. However, it is unknown which pathways are specific to the core symptoms or which are shared by the co-morbidities. We hypothesised that critical ASD candidates should appear widely across different scoring systems, and that comorbidity pathways should be constituted by genes expressed in the relevant tissues. We analysed the Simons Foundation for Autism Research Initiative (SFARI) database and four independently published scoring systems and identified 292 overlapping genes. We examined their mRNA expression using the Genotype-Tissue Expression (GTEx) database and validated protein expression levels using the human protein atlas (HPA) dataset. This led to clustering of the overlapping ASD genes into 2 groups; one with 91 genes primarily expressed in the central nervous system (CNS geneset) and another with 201 genes expressed in both CNS and peripheral tissues (CNS+PT geneset). Bioinformatic analyses showed a high enrichment of CNS development and synaptic transmission in the CNS geneset, and an enrichment of synapse, chromatin remodelling, gene regulation and endocrine signalling in the CNS+PT geneset. Calcium signalling and the glutamatergic synapse were found to be highly interconnected among pathways in the combined geneset. Our analyses demonstrate that 2/3 of ASD genes are expressed beyond the brain, which may impact peripheral function and involve in ASD co-morbidities, and relevant pathways may be explored for the treatment of ASD co-morbidities.

The Relationship between the Level of Anterior Cingulate Cortex Metabolites, Brain-Periphery Redox Imbalance, and the Clinical State of Patients with Schizophrenia and Personality Disorders.

Schizophrenia is a complex mental disorder whose course varies with periods of deterioration and symptomatic improvement without diagnosis and treatment specific for the disease. So far, it has not been possible to clearly define what kinds of functional and structural changes are responsible for the onset or recurrence of acute psychotic decompensation in the course of schizophrenia, and to what extent personality disorders may precede the appearance of the appropriate symptoms. The work combines magnetic resonance spectroscopy imaging with clinical evaluation and laboratory tests to determine the likely pathway of schizophrenia development by identifying peripheral cerebral biomarkers compared to personality disorders. The relationship between the level of metabolites in the brain, the clinical status of patients according to International Statistical Classification of Diseases and Related Health Problems, 10th Revision ICD-10, duration of untreated psychosis (DUP), and biochemical indices related to redox balance (malondialdehyde), the efficiency of antioxidant systems (FRAP), and bioenergetic metabolism of mitochondria, were investigated. There was a reduction in the level of brain N-acetyl-aspartate and glutamate in the anterior cingulate gyrus of patients with schisophrenia compared to the other groups that seems more to reflect a biological etiopathological factor of psychosis. Decreased activity of brain metabolites correlated with increased peripheral oxidative stress (increased malondialdehyde MDA) associated with decreased efficiency of antioxidant systems (FRAP) and the breakdown of clinical symptoms in patients with schizophrenia in the course of psychotic decompensation compared to other groups. The period of untreated psychosis correlated negatively with glucose value in the brain of people with schizophrenia, and positively with choline level. The demonstrated differences between two psychiatric units, such as schizophrenia and personality disorders in relation to healthy people, may be used to improve the diagnosis and prognosis of schizophrenia compared to other heterogenous psychopathology in the future. The collapse of clinical symptoms of patients with schizophrenia in the course of psychotic decompensation may be associated with the occurrence of specific schizotypes, the determination of which is possible by determining common relationships between changes in metabolic activity of particular brain structures and peripheral parameters, which may be an important biological etiopathological factor of psychosis. Markers of peripheral redox imbalance associated with disturbed bioenergy metabolism in the brain may provide specific biological factors of psychosis however, they need to be confirmed in further studies.

Effects of Omega 3 Fatty Acids on Main Dimensions of Psychopathology.

The usefulness of polyunsaturated fatty acids on inflammatory, cardiovascular, and the nervous system was studied in the last decades, but the mechanisms underlying their benefic properties are still partially unknown. These agents seem to express their action on the membrane phospholipid composition and permeability and modulation of second messenger cascades. In psychiatry, the efficacy and tolerability of omega-3 fatty acids were investigated in several psychiatric disorders, including major depression, bipolar disorder, personality disorders, high-risk conditions to develop psychosis, attention-deficit hyperactivity disorder, and autism spectrum disorders. Initial findings in this field are promising, and some relevant questions need to be addressed. In particular, the effects of these agents on the main symptom dimensions have to be investigated in a trans-diagnostic perspective. The present systematic review is aimed to examine the available data on the efficacy of omega-3 fatty acids on domains of psychotic symptoms, affective symptoms, impulsivity, and aggressiveness, and harmful behaviors, and suicide risk.

Swiprosin-1/ EFhd2: from Immune Regulator to Personality and Brain Disorders.

BACKGROUND/AIMS: Swiprosin-1/ EF-hand domain 2 (EFhd2) is a Ca2+ sensor protein that plays an important role in the immune system. Its abundant expression in the brain, however, suggested also a role in neuronal circuits and behavior. METHODS: Here we review recent discoveries on the structure and molecular function, its role in immunity and its function in the brain regarding behavioral control and pathologies. RESULTS: While EFhd2 did not emerge as a vital protein for brain development, changes in its expression may nevertheless shape the adult behavioral repertoire significantly and contribute to adult personality traits. A defective function of EFhd2 may also render individuals more prone to the development of psychiatric disorders. Most prominently, EFhd2 proved to be a resilience factor protecting from fast establishment of drug addiction. Moreover, EFhd2 is critical for adult neurogenesis and as a modulator of monoaminergic systems. CONCLUSION: Dysregulated activity of EFhd2 is increasingly considered as a contributing factor for the development of numerous neurodegenerative disorders. Whether EFhd2 can be used as biomarker or in therapeutic approaches has to be addressed in future research.

Extraversion modulates cortisol responses to acute social stress in chronic major depression.

BACKGROUND: Chronic Major Depressive Disorder (CMDD) is a common, disabling illness that is often complicated by high reactivity to social stress. To further elucidate the nature of this reactivity, the current study evaluated whether the personality dimensions of neuroticism and extraversion influenced cortisol responses to a social challenge in CMDD patients vs. controls. METHODS: Fifty participants with CMDD and 58 healthy controls completed the Trier Social Stress Test (TSST) using a standard protocol. Neuroticism and extraversion were measured using the Revised NEO Personality Inventory. Hierarchical linear regressions assessed associations between independent variables neuroticism and extraversion and dependent variable cortisol area-under-the-curve increase (AUCi) in response to the TSST in the two study groups. RESULTS: The extraversion-by-group interaction was a significant predictor of cortisol AUCi, while no significant findings related to neuroticism were found. Simple slopes analysis revealed a significant negative association between extraversion and AUCi in the CMDD group, but not in healthy controls. Post-hoc analysis of the raw cortisol data over time found that CMDD participants with higher extraversion scores had significantly higher pre-challenge cortisol levels than did other study participants, however this did not explain or confound the AUCi results. CONCLUSIONS: In participants with CMDD but not in controls, higher levels of extraversion were associated with higher pre-challenge cortisol levels and decreased cortisol reactivity during the TSST, however these two findings were statistically independent. These findings underline the importance of considering personality factors when studying stress biology in CMDD patients. Extraversion may prove to be an important intermediate target for both research and clinical work in this complex, heterogenous and often treatment-resistant population.

Neuroticism predicts the impact of serotonin challenges on fear processing in subgenual anterior cingulate cortex.

The personality trait neuroticism is associated with increased vulnerability to anxiety and mood disorders, conditions linked with abnormal serotonin neurotransmission and emotional processing. The interaction between neuroticism and serotonin during emotional processing is however not understood. Here we investigate how individual neuroticism scores influence the neural response to negative emotional faces and their sensitivity to serotonergic tone. Twenty healthy participants performed an emotional face task under functional MRI on three occasions: increased serotonin tone following infusion of a selective serotonin reuptake inhibitor (SSRI), decreased serotonin tone following acute tryptophan depletion (ATD) protocol, and no serotonin challenge (control). During the task, participants performed a gender-discrimination task of neutral, fearful or angry facial expressions. Individual variations in neuroticism scores were associated with neural response of subgenual anterior cingulate cortex to fearful facial expressions. The association was however opposite under the two serotoninergic challenges. The fear-related response in this region and individual neuroticism scores correlated negatively during citalopram challenge and positively during ATD. Thus, neuroticism scores were associated with the relative impact of serotonin challenges on fear processing in subgenual anterior cingulate cortex. This finding may link to a neural mechanism for the variable therapeutic effect of SSRI treatment observed in clinical populations.

Brain neuroreceptor density and personality traits: towards dimensional biomarkers for psychiatric disorders.

Positron emission tomography has, for 30 years, been used in numerous case-control studies searching for hypothesized differences in the density of neuroreceptor or transporter proteins in psychiatric disorders such as schizophrenia and depression. In most cases, the results have not been conclusive. One reason could be the sizeable interindividual variability in biochemical markers, which in twin studies have shown to emanate from both environmental and genetic factors, leading to low statistical power for the detection of group effects. On the other hand, the same interindividual variability has served as an opportunity for correlative studies on the biological underpinning of behaviour. Using this approach, a series of studies has linked markers for the dopamine and serotonin system to personality traits associated with psychiatric conditions. Based on increasing evidence for the view that many psychopathological states represent extremes of a continuum rather than distinct categories, this research strategy may lead to new biological insights about the vulnerability to and pathophysiology of major psychiatric disorders.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.

Genetic association analysis of serotonin and signal transduction pathways in suicide attempters from an Italian sample of psychiatric patients.

Genetic factors have been reported to contribute to the liability of suicide. We aimed to investigate functional polymorphisms in eight genes (serotonin transporter, SLC6A4; receptors, 5HTR1A, 1B, 5HTR2A; Tryptophan Hydroxylase, TPH1, TPH2; Monoamine Oxidase, MAOA and G Protein Subunit Beta 3, GNB3) to investigate their predictive value for suicide. The possible confounding effects of gender and phenotypic patients dissection were also valued. A sample of 111 consecutive psychiatric inpatients was recruited and assessed using specific psychometric instruments. Genomic DNA was isolated from peripheral white blood cell samples and polymorphisms were genotyped by pyrosequencing technology. Although no differences were observed between allele and genotype frequencies for all polymorphisms and suicide attempt (SA), a polygenic risk score was detected for three genes HTR2A (A-1438G), TPH1 and TPH2 increasing the prediction of SA risk (Thresh=0.43, p=0.038, R2=0.053). Moreover some nominal associations were obtained after gender and phenotypic dissection stratification (TEMPS-A, TEMPs-H, GSMD, SHSS, GAF, CGI) for SLC6A4 (5-HTTLPR), HTR1A (C-1019G), HTR2A (A-1438G), TPH1 (A799C) and GNB3 (C825T) genes, that were lost after Bonferroni correction. This is a first evidence that specific additive combinations of genes could increase the prediction of SA risk and that gender and phenotypic dissection could influence the association of the genes with SA. This could represent a further study also for future meta-analyses on larger samples.

Emotional personality disorders in patients with vibration disease associated with androgen deficiency.

Comparative analysis covered emotional personality disorders in vibration disease patients'in dependence on presence and intensity of androgen deficiency. Parameters of depression, personal and actual anxiety in vibration disease patients are reliably higher in those with marked clinical and laboratory signs of androgen deficiency.

Sex determines cortisol and alpha-amylase responses to acute physical and psychosocial stress in patients with avoidant personality disorder.

INTRODUCTIONS: Avoidant personality disorder (AVPD) has excessive and pervasive anxiety and discomfort in social situations. The aims of this study were to explore the relationship between AVPD and physical and psychological stress and psychological tests. METHODS: We evaluated 93 AVPD patients and 355 nonpatient controls by salivary amylase and cortisol responses during exposure to the Trier Social Stress Test (TSST) and electrical stimulation stress. Spielberger state-trait anxiety inventory (STAI), Profile of Mood State (POMS), Beck Depression Inventory (BDI), Depression and Anxiety Cognition Scale (DACS), and Childhood Trauma Questionnaire (CTQ) were administered. RESULTS: Following electrical stimulation, salivary cortisol levels in female AVPD decreased significantly less than that in female's controls, but salivary cortisol levels did not show a difference between male AVPD patients and controls. Salivary alpha-amylase (sAA) levels did not show a difference between females or male AVPD patients and controls. Following TSST exposure, sAA levels did not show a difference between females or male AVPD patients and controls. Salivary cortisol levels did not show a difference between females or male AVPD patients and controls. In the AVPD patients, POMS scores were significantly higher compared with the controls. STAI, BDI, DACS scores, and CTQ significantly increased in the AVPD patients compared with the controls. LF in heart rate variability in AVPD significantly increased more compared with controls. CONCLUSIONS: These results suggest that heightened sympathetic reactivity in female AVPD co-occurs with attenuated salivary cortisol responses to electric stimulation stress and there is a significant difference between AVPD and controls in mood, anxiety, social cognition, and automatic nerve systems.

Borderline and cluster C personality disorders manifest distinct physiological responses to psychosocial stress.

BACKGROUND: Maladaptive emotional control is a defining feature of personality disorders. Yet little is known about the underlying physiological dynamics of emotional reactivity to psychosocial stress across distinct personality disorders. The current study compared subjective emotional responses with autonomic nervous system and HPA axis physiological responses to psychosocial stress in women with cluster C personality disorder (CPD) and borderline personality disorder (BPD). METHODS: Subjective mood ratings, salivary cortisol, heart rate (HR), and skin conductance level (SCL) were assessed before, during, and after exposure to a standardized psychosocial stress paradigm (Trier Social Stress Test, TSST) in 26 women with BPD, 20 women with CPD, and 35 healthy female controls. Subjects were free of any medication including hormonal contraceptives, had a regular menstrual cycle, and were tested during the luteal phase of their menstrual cycle. RESULTS: Both CPD and BPD patients reported a similar burden of subjective mood disturbance. However, only BPD patients demonstrated reduced baseline cortisol levels with a blunted cortisol and HR reactivity to the TSST. In addition, BPD patients exhibited a generalized increase of SCL. No significant differences in baseline or TSST reactivity of cortisol, HR, or SCL were observed between CPD patients and healthy controls. CONCLUSION: These findings indicate that patients with BPD have significant alterations in their physiological stress reactivity, which is notably distinct from patients with CPD and those of healthy controls.

Childhood trauma and parental style: Relationship with markers of inflammation, oxidative stress, and aggression in healthy and personality disordered subjects.

Recent studies suggest that early life trauma is associated with elevations in circulating markers of inflammation in human subjects. History of aggression as a behavior, or aggression as a personality trait, is also associated with elevations of these inflammatory markers. Since early life trauma is associated with the development and maintenance of aggression in later life we examined the relationship of early life adversity, plasma inflammation markers (IL-6 and CRP) and oxidative stress markers (8-OH-DG and 8-ISO), and aggression in adult subjects with (n=79) and without (n=55) personality disorder. We used a series of mediated and moderated path models to test whether the effects of early adversity on later aggression may be mediated through markers of inflammation. Childhood abuse and parental control were associated with basal IL-6 and CRP concentrations. Path modeling suggested that childhood abuse was associated with aggression indirectly through CRP while parental control influenced aggression indirectly through IL-6 and CRP. Furthermore, these effects were independent of the effect of current depression. The results suggest that disruption of inflammatory processes represent one pathway by which early adversity influences aggression.

Estradiol and cortisol interactions in youth externalizing psychopathology.

Growing evidence has indicated that gonadal and stress hormones interact to shape socially dominant behavior and externalizing psychopathology; however, such work to date has focused exclusively on the testosterone-cortisol interaction, despite expectations that estradiol should be associated with similar behavioral outcomes to testosterone. Here, we present the first empirical test of the hypothesis that adolescent males and females (N=105, ages 13-18) with high estradiol and low cortisol concentrations are at highest risk for externalizing problems, but - replicating previous work - only among adolescents high on pathological personality traits. Parents reported on youth psychopathology and personality, and hormone concentrations were measured via passive drool. Results confirmed the hypothesis: high estradiol was associated with more externalizing behaviors, but only when cortisol was low and personality traits of disagreeableness and emotional instability were high. Further, these associations held when controlling for testosterone concentrations. These findings provide the first empirical evidence of a hypothalamic pituitary adrenal (HPA)×hypothalamic pituitary gonadal (HPG) axis interaction that extends the "dual hormone" hypothesis beyond testosterone.

[Very low magnesium levels in red blood cells as a significant factor in the etiopathogenesis of borderline disorders].

AIM: Basic studies indicate magnesium deficiency as one of the important, but often neglected, risk factors aggravating the course of borderline disorders (BD). A clinical verification of this notion has been conducted. MATERIAL AND METHODS: Authors studied 62 patients with BD, aged 25-65 years, of inpatient and outpatient settings. Contents of magnesium and other blood electrolytes were determined. RESULTS: Authors found an extremely high prevalence of very low levels of magnesium (Mg) in erythrocytes (<0.3 mmol/l) in patients with BD compared to controls (patients without BD, Mg (er.) 1.62±0.48 mmol/l). It has been shown that low Mg levels in the plasma and red blood cells are associated with a significantly increased risk of the following diagnoses: F07 «Personality and behavioral disorder due to brain disease, damage and dysfunction¼ (p<0.0016), F21 «Schizotypal disorder¼ (p<0.0005) and F34 «Persistent mood [affective] disorders¼ (p<0.0001). The use of Magne B6 Forte (4 tablets/day, 30 days, then 2 tablets/day for 1 year) resulted in a significant increase in the Mg levels in the plasma and erythrocytes, the compensation of anxiety and depressive symptoms, improvement of sleep and general health of the patients, reduced consumption of antidepressants (by 30%). CONCLUSION: Administration of the drugs based on organic salts of magnesium per os improves the condition of patients and reduces their need in pharmacotherapy.

Personality × hormone interactions in adolescent externalizing psychopathology.

The "dual-hormone" hypothesis predicts that testosterone and cortisol will jointly regulate aggressive and socially dominant behavior in children and adults (e.g., Mehta & Josephs, 2010). The present study extends research on the dual-hormone hypothesis by testing the interaction between testosterone, cortisol, and personality disorder (PD) traits in predicting externalizing problems in a community sample of adolescent males and females. Participants were 106 youth from the community, ranging in age from 13-18 (Mage = 16.01 years, SDage = 1.29), and their parents. Parents and youth provided ratings on an omnibus measure of personality pathology and externalizing problems. Youth provided saliva samples via passive drool from which testosterone and cortisol levels were obtained. Robust moderation of the joint effects of testosterone and cortisol on parent-reported externalizing problems was found for both higher-order PD traits associated with externalizing psychopathology (Disagreeableness and Emotional Instability). Higher testosterone was associated with externalizing outcomes, but only when cortisol was low, and only among youth with high levels of Disagreeableness and Emotional Instability. These findings provide the first evidence for the dual-hormone hypothesis in a mixed-sex sample of community adolescents, but importantly offer novel evidence for the importance of personality traits. Examination of the joint regulation of externalizing problems by testosterone and cortisol in the context of adolescent personality may help to clarify inconsistent main effects of testosterone and cortisol on clinical externalizing phenotypes.

Dorsal prefrontal cortical serotonin 2A receptor binding indices are differentially related to individual scores on harm avoidance.

Although the serotonergic system has been implicated in healthy as well as in pathological emotional states, knowledge about its involvement in personality is limited. Earlier research on this topic suggests that post-synaptic 5-HT2A receptors could be involved in particular in frontal cortical areas. In drug-naïve healthy individuals, we examined the relationship between these 5-HT2A receptors and the temperament dimension harm avoidance (HA) using 123I-5-I-R91150 single photon emission computed tomography (SPECT). HA is a personality feature closely related to stress, anxiety and depression proneness, and it is thought to be mediated by the serotonergic system. We focused on the prefrontal cortices as these regions are frequently implicated in cognitive processes related to a variety of affective disorders. We found a positive relationship between dorsal prefrontal cortical (DPFC) 5-HT2A receptor binding indices (BI) and individual HA scores. Further, our results suggest that those individuals with a tendency to worry or to ruminate are particularly prone to display significantly higher 5-HT2A receptor BI in the left DPFC. Although we only examined psychologically healthy individuals, this relationship suggests a possible vulnerability for affective disorders.

Hormones: empirical contribution. Cortisol reactivity and recovery in the context of adolescent personality disorder.

The present study examined whether the associations between stress responses and psychopathology were moderated by adolescent personality disorder (PD) traits. Participants were a community sample of 106 adolescents (47 male, Mage = 16.01) and their parents. Parents reported on adolescents' PD traits and behavioral problems. Changes in salivary cortisol were assessed in response to a laboratory-based stress induction. Moderated regression analyses revealed significant linear and quadratic interactions between cortisol recovery and PD traits in the prediction of behavioral problems. Although typically conceptualized as "adaptive," steeper poststressor recovery was associated with more behavioral problems when PD traits were high. These findings suggest that, in the presence of maladaptive personality traits, premature recovery from environmental stressors may indicate an inability to respond appropriately to negative environmental stimuli, thus reflecting a core disturbance in PD trait functioning. The results underscore the informative role that personality plays in illuminating the nature of hormone functioning in adolescents and are interpreted in a developmental psychopathology framework.

Hormones: commentary. Riding the physiological roller coaster: adaptive significance of cortisol stress reactivity to social contexts.

The authors conjecture that to understand normal stress regulation, including cortisol stress reactivity, it is important to understand why these biomarkers are released and what they function to accomplish within the individual. This perspective holds that high (or rising) cortisol has advantages and disadvantages that must be understood within a context to understand how individual differences unfold. This perspective is juxtaposed with a popular vantage point of this stress hormone or of stress exposure that emphasizes the deleterious consequences or problems of this hormone. While the costs and benefits of cortisol are emphasized for normal stress regulation, this dynamic context-dependent purpose of stress hormones should extend to the development of psychopathology as well. This functional and dynamic view of cortisol is helpful for interpreting why Tackett and colleagues (2014) appear to observe advantageous cortisol recovery from stress in individuals with elevated personality disorder symptoms.