Aliza P. Wingo

Neurocognitive impairment in bipolar disorder patients: functional implications

BACKGROUND Functional recovery among treated bipolar disorder (BPD) patients is far less likely than syndromal and even symptomatic recovery. We hypothesized that increasingly well-documented aspects of cognitive impairment may contribute to poor functional outcomes in BPD patients, and reviewed the available research on the topic. METHODS Computerized literature searching identified 12 studies with 13 comparisons that simultaneously evaluated cognitive and functional status in euthymic (n = 8) or non-euthymic (n = 5 comparisons) adult BPD patients versus otherwise similar healthy controls. RESULTS In 6/8 studies of euthymic BPD patients and 5/5 studies of non-euthymic BPD patients, neurocognitive impairment was significantly associated with impaired psychosocial functioning, even after adjusting for residual mood symptoms and relevant demographic and clinical variables. Cognitive status was consistently assessed with standardized, performance-based neuropsychological tests, but functional status usually was based on subjective self-appraisals. Approximately 55% of BPD patients were unemployed. CONCLUSIONS Available studies are limited by subjective assessments of functional status rather than objective, performance-based measures. Nevertheless, they support the hypothesis that enduring aspects of cognitive impairment found even in euthymic BPD patients are associated with inferior functioning. These findings encourage further studies with better assessment methods and greater rehabilitative efforts in BPD patients.

Moderating effects of resilience on depression in individuals with a history of childhood abuse or trauma exposure.

BACKGROUND Influences of resilience on the presence and severity of depression following trauma exposure are largely unknown. Hence, we examined effects of resilience on depressive symptom severity in individuals with past childhood abuse and/or other trauma exposure. METHODS In this cross-sectional study of 792 adults, resilience was measured with the Connor-Davidson Resilience Scale, depression with the Beck Depression Inventory (BDI), childhood abuse with the Childhood Trauma Questionnaire, and other traumas with the Trauma Events Inventory. RESULTS Multiple linear regression modeling with depression severity (BDI score) as the outcome yielded 4 factors: childhood abuse (β=2.5, p<0.0001), other trauma (β=3.5, p<0.0001), resilience (β=-0.5, p<0.0001), and other trauma × resilience interaction term (β=-0.1, p=0.0021), all of which were significantly associated with depression severity, even after adjusting for age, sex, race, education, employment, income, marital status, and family psychiatric history. Childhood abuse and trauma exposure contributed to depressive symptom severity while resilience mitigated it. CONCLUSIONS Resilience moderates depressive symptom severity in individuals exposed to childhood abuse or other traumas both as a main effect and an interaction with trauma exposure. Resilience may be amenable to external manipulation and could present a potential focus for treatments and interventions.

Long-term antidepressant treatment in bipolar disorder: meta-analyses of benefits and risks

Objective:  Long‐term antidepressant (AD) treatment for depression in bipolar disorder (BPD) patients is highly prevalent, but its benefits and risks remain uncertain, encouraging this meta‐analysis of available research.

Cognition and disability in bipolar disorder: lessons from schizophrenia research

BACKGROUND Cognitive and functional impairments occur in patients diagnosed with bipolar disorder (BPD), although they are usually less severe and far less studied than in schizophrenia. There may be value in applying approaches developed in schizophrenia research to study cognitive functioning among BPD patients in areas including performance-based disability assessment, cognitive remediation treatments, enhancement of the accuracy of real-world functioning, and studying cognition and disability in relatives. METHODS We reviewed current research on cognitive and functional disability in BPD, noted areas of similarity and discrepancy to research on schizophrenia, and highlighted methods and approaches used to study schizophrenia that can be applied to study unmet needs of BPD patients. RESULTS Research in schizophrenia increasingly separates potential functional capacity from real-world outcome status, and has assessed contributions of cognitive impairment and other illness factors to functional outcomes. For schizophrenia, various behavioral and pharmacological treatments aimed at cognitive enhancement have been attempted, with moderate success, compared to rare studies of treatment effects on cognitive impairment in BPD. Very little research has been performed in the occurrence of cognitive impairments in first-degree relatives of people with BPD, despite evidence that cognitive impairments may be stable traits across symptomatic status in people with BPD. CONCLUSIONS Research and treatment approaches developed for schizophrenia can productively be applied to the study and treatment of patients diagnosed with BPD, notably including studies of the characteristics of and treatments for functional impairment related to cognitive deficits.

Association between childhood maltreatment and adult emotional dysregulation in a low-income, urban, African American sample: Moderation by oxytocin receptor gene

The ability to effectively regulate emotions and a secure attachment style are critical for maintaining mental health across the life span. The experience of childhood maltreatment interferes with normal development of emotional regulation and dramatically increases risk for a wide range of psychiatric disorders in adulthood. The central nervous system oxytocin systems are critically involved in mediating social attachment and buffering psychophysiological responses to stress. We therefore investigated the impact of childhood maltreatment and an oxytocin receptor (OXTR) single nucleotide polymorphism (rs53576) and their interaction on emotional dysregulation and attachment style in adulthood in a sample of low-income, African American men and women recruited from primary care clinics of an urban, public hospital. Consistent with prior research, we found that the severity of childhood maltreatment was associated with increased levels of emotional dysregulation in adulthood. Childhood maltreatment was also positively associated with ratings of disorganized/unresolved adult attachment style and negatively associated with ratings of secure adult attachment style. There was no direct association between rs53576 and emotional dysregulation or ratings of adult attachment style. However, there were significant interactions between rs53576 and childhood maltreatment in predicting level of adult emotional dysregulation and attachment style. Specifically, G/G genotype carriers were at risk for increased emotional dysregulation when exposed to three or more categories of childhood abuse. In addition, G/G genotype carriers exhibited enhanced disorganized adult attachment style when exposed to severe childhood abuse compared to A/A and A/G carriers. Our findings suggest that A allele carriers of OXTR rs53576 are resilient against the effects of severe childhood adversity, by protection against emotional dysregulation and disorganized attachment.

Family environment and adult resilience: contributions of positive parenting and the oxytocin receptor gene

Background Abundant research shows that childhood adversity increases the risk for adult psychopathology while research on influences of positive family environment on risk for psychopathology is limited. Similarly, a growing body of research examines genetic and gene by environment predictors of psychopathology, yet such research on predictors of resilience is sparse. Objectives We examined the role of positive factors in childhood family environment (CFE) and the OXTR rs53576 genotype in predicting levels of adult resilient coping and positive affect. We also examined whether the relationship between positive factors in the CFEs and adult resilient coping and positive affect varied across OXTR rs53576 genotype. Methods We gathered self-report data on childhood environment, trauma history, and adult resilience and positive affect in a sample of 971 African American adults. Results We found that positive CFE was positively associated with higher levels of resilient coping and positive affect in adulthood after controlling for childhood maltreatment, other trauma, and symptoms of posttraumatic stress disorder. We did not find a direct effect of OXTR 53576 on a combined resilient coping/positive-affect-dependent variable, but we did find an interaction of OXTR rs53576 with family environment. Conclusions Our data suggest that even in the face of adversity, positive aspects of the family environment may contribute to resilience. These results highlight the importance of considering protective developmental experiences and the interaction of such experiences with genetic variants in risk and resilience research.

Pain Symptomatology and Pain Medication Use in Civilian PTSD

Summary Participants with posttraumatic stress disorder (PTSD) had higher self‐reported pain and were significantly more likely to have used opioid analgesics for pain control compared to those without PTSD. Abstract The comorbidity of pain syndromes and trauma‐related syndromes has been shown to be high. However, there have been limited data, especially in civilian medical populations, on the role of trauma‐related disorders such as posttraumatic stress disorder (PTSD) on chronic pain and pain medication use. We analyzed 647 general hospital patients in primary care and obstetrics and gynecological waiting rooms for the experience of trauma and PTSD‐related stress disorders. PTSD symptoms were found to be significantly positively correlated with pain ratings (r = .282, P < 0.001) and pain‐related functional impairment (r = 0.303, P < 0.001). Those with a current PTSD diagnosis had significantly higher subjective pain and pain‐related impairment ratings than those with no PTSD. Furthermore, those with a current diagnosis of PTSD were significantly more likely to have used opioid analgesics for pain control compared to those without a diagnosis of PTSD (χ2 = 8.98, P = 0.011). When analyzing the separate PTSD symptom subclusters (re‐experiencing, avoidance, and hyperarousal), all symptom clusters were significantly related to pain and pain‐related impairment ratings, but only the avoidance cluster was significantly related to prior opioid pain medication use. We conclude that PTSD and trauma‐related disorders are common in impoverished medical populations and that their presence should be examined in patients with pain syndromes. Furthermore, these data suggest that PTSD and pain may share a vulnerability pathway, including the endogenous opioid neurotransmission systems.

The Renin-Angiotensin Pathway in Posttraumatic Stress Disorder: Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Are Associated With Fewer Traumatic Stress Symptoms

OBJECTIVE Posttraumatic stress disorder (PTSD) is a debilitating stress-related illness associated with trauma exposure. The peripheral and central mechanisms mediating stress response in PTSD are incompletely understood. Recent data suggest that the renin-angiotensin pathway, essential to cardiovascular regulation, is also involved in mediating stress and anxiety. In this study, the authors examined the relationship between active treatment with blood pressure medication, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and PTSD symptom severity within a highly traumatized civilian medical population. METHOD Cross-sectional, observational data were analyzed from a larger study; patients were recruited from Grady Memorial Hospitals outpatient population from 2006 to November 2010. Multivariable linear regression models were fit to statistically evaluate the independent association of being prescribed an ACE inhibitor or ARB with PTSD symptoms, using a subset of patients for whom medical information was available (n = 505). Categorical PTSD diagnosis was assessed using the modified PTSD Symptom Scale (PSS) based on DSM-IV criteria, and PTSD symptom severity (the primary outcome of interest) was measured using the PSS and Clinician Administered PTSD Scale. RESULTS A significant association was determined between presence of an ACE inhibitor/ARB medication and decreased PTSD symptoms (mean PSS score 11.4 vs 14.9 for individuals prescribed vs not prescribed ACE inhibitors/ARBs, respectively [P = .014]). After adjustment for covariates, ACE inhibitor/ARB treatment remained significantly associated with decreased PTSD symptoms (P = .044). Notably, other blood pressure medications, including β-blockers, calcium channel blockers, and diuretics, were not significantly associated with reduced PTSD symptoms. CONCLUSIONS These data provide the first clinical evidence supporting a role for the renin-angiotensin system in the regulation of stress response in patients diagnosed with PTSD. Further studies should examine whether available medications targeting this pathway should be considered for future treatment and potential protection against PTSD symptoms.

Resilience characteristics mitigate tendency for harmful alcohol and illicit drug use in adults with a history of childhood abuse: A cross-sectional study of 2024 inner-city men and women

Resilience refers to abilities to cope adaptively with adversity or trauma. A common psychological sequella of childhood abuse or other traumatic experiences is substance use problems. There are, however, very limited data on relationships among resilience traits, childhood abuse, and alcohol or drug use problems. Hence, we aimed to examine associations between resilience characteristics and lifetime alcohol and illicit drug use in 2024 inner-city adults with high rates of childhood abuse and other trauma exposure. In this cross-sectional study, resilience was assessed with the Connor-Davidson Resilience Scale, childhood abuse with the Childhood Trauma Questionnaire, lifetime alcohol and illicit drug use with the Alcohol Use Disorder Identification Test and Drug Abuse Screening Test. Associations between resilience and substance use were examined with linear regression models, adjusting for trauma load, age, and sex. We found that resilience characteristics mitigated tendency for lifetime alcohol use problems both as a main effect (β = -0.11; p = 0.0014) and an interaction with severity of childhood abuse (β = -0.06; p = 0.0115) after trauma severity, age, and sex were controlled for. Similarly, resilience reduced lifetime illicit drug use both as a main effect (β = -0.03; p = 0.0008) and as an interaction with severity of childhood abuse (β = -0.01; p = 0.0256) after trauma load, age, and sex were adjusted for. Our findings add to a nascent body of literature suggesting that resilience characteristics mitigate risks not only for PTSD, major depression, and suicidality, but also for substance use problems in adults exposed to childhood abuse or other traumatic experiences.

Factors Associated with Functional Recovery in Bipolar Disorder Patients

OBJECTIVES Among bipolar disorder (BPD) patients, functional recovery, defined as regaining individual premorbid residential and vocational status, is far less common than symptomatic recovery. As several factors have tentatively been implicated in outcomes in BPD, we investigated predictors of functional recovery among BPD patients, including demographic, clinical, and neurocognitive factors. METHODS We assessed functional recovery status with standardized residential and occupational indices, assessed neurocognitive functioning with performance-based neuropsychological tests, and collected demographic and clinical information for 65 euthymic or residually depressed Structured Clinical Interview for DSM-IV-defined type I or II BPD patients. We examined predictors of functional recovery with multiple logistic regression modeling. RESULTS More education (p = 0.006), fewer years of illness (p = 0.037), and being married (p = 0.045) were associated independently with functional recovery, even after controlling for residual depressive symptoms, diagnostic type (I versus II), and psychiatric comorbidity. Functionally unrecovered BPD patients performed less well than recovered patients on verbal fluency (effect size = 0.54, p = 0.03), a measure of executive functioning, but this difference was not significant when adjusted for residual mood symptoms and education. CONCLUSIONS Among euthymic or mildly depressed BPD patients, functional recovery was associated with more education, being married, and fewer years of illness.