Jacqueline A. Samson

Childhood Maltreatment and Psychopathology: A Case for Ecophenotypic Variants as Clinically and Neurobiologically Distinct Subtypes

OBJECTIVE Childhood maltreatment increases risk for psychopathology. For some highly prevalent disorders (major depression, substance abuse, anxiety disorders, and posttraumatic stress disorder) a substantial subset of individuals have a history of maltreatment and a substantial subset do not. The authors examined the evidence to assess whether those with a history of maltreatment represent a clinically and biologically distinct subtype. METHOD The authors reviewed the literature on maltreatment as a risk factor for these disorders and on the clinical differences between individuals with and without a history of maltreatment who share the same diagnoses. Neurobiological findings in maltreated individuals were reviewed and compared with findings reported for these disorders. RESULTS Maltreated individuals with depressive, anxiety, and substance use disorders have an earlier age at onset, greater symptom severity, more comorbidity, a greater risk for suicide, and poorer treatment response than nonmaltreated individuals with the same diagnoses. Imaging findings associated with these disorders, such as reduced hippocampal volume and amygdala hyperreactivity, are more consistently observed in maltreated individuals and may represent a maltreatment-related risk factor. Maltreated individuals also differ from others as a result of epigenetic modifications and genetic polymorphisms that interact with experience to increase risk for psychopathology. CONCLUSIONS Phenotypic expression of psychopathology may be strongly influenced by exposure to maltreatment, leading to a constellation of ecophenotypes. While these ecophenotypes fit within conventional diagnostic boundaries, they likely represent distinct subtypes. Recognition of this distinction may be essential in determining the biological bases of these disorders. Treatment guidelines and algorithms may be enhanced if maltreated and nonmaltreated individuals with the same diagnostic labels are differentiated.

Annual research review: enduring neurobiological effects of childhood abuse and neglect

BACKGROUND Childhood maltreatment is the most important preventable cause of psychopathology accounting for about 45% of the population attributable risk for childhood onset psychiatric disorders. A key breakthrough has been the discovery that maltreatment alters trajectories of brain development. METHODS This review aims to synthesize neuroimaging findings in children who experienced caregiver neglect as well as from studies in children, adolescents and adults who experienced physical, sexual and emotional abuse. In doing so, we provide preliminary answers to questions regarding the importance of type and timing of exposure, gender differences, reversibility and the relationship between brain changes and psychopathology. We also discuss whether these changes represent adaptive modifications or stress-induced damage. RESULTS Parental verbal abuse, witnessing domestic violence and sexual abuse appear to specifically target brain regions (auditory, visual and somatosensory cortex) and pathways that process and convey the aversive experience. Maltreatment is associated with reliable morphological alterations in anterior cingulate, dorsal lateral prefrontal and orbitofrontal cortex, corpus callosum and adult hippocampus, and with enhanced amygdala response to emotional faces and diminished striatal response to anticipated rewards. Evidence is emerging that these regions and interconnecting pathways have sensitive exposure periods when they are most vulnerable. CONCLUSIONS Early deprivation and later abuse may have opposite effects on amygdala volume. Structural and functional abnormalities initially attributed to psychiatric illness may be a more direct consequence of abuse. Childhood maltreatment exerts a prepotent influence on brain development and has been an unrecognized confound in almost all psychiatric neuroimaging studies. These brain changes may be best understood as adaptive responses to facilitate survival and reproduction in the face of adversity. Their relationship to psychopathology is complex as they are discernible in both susceptible and resilient individuals with maltreatment histories. Mechanisms fostering resilience will need to be a primary focus of future studies.

The effects of psychiatric disorders and symptoms on quality of life in patients with Type I and Type II diabetes mellitus.

The purpose of this study was to evaluate the influence of psychiatric symptoms and illness status on the health-related quality of life (HRQOL) of outpatients with Type I and Type II diabetes mellitus. Using a two-stage design, all patients were assessed by two measures of quality of life (Diabetes Quality of Life Measure; Medical Outcome Study Health Survey) and a psychiatric symptoms checklist (SCL-90-R). Patients scoring 63 or greater on the global severity index of the SCL-90-R and 30% below this cutoff were then evaluated using the Structured Clinical Interview for the DSM-III-R (SCID). Quality of life in both Type I and Type II diabetes was influenced by the level of current psychiatric symptoms and presence of co-morbid psychiatric disorder, after controlling for number of diabetic complications (e.g. effect of lifetime psychiatric illness on diabetes-related HRQOL; F=46.8; df=3, 135; p < 0.005). These effects were found consistently across specific domains. Both recent and past psychiatric disorders influenced HRQOL. Separate analyses comparing patients with and without depression showed similar effects. No interaction effects between diabetes type, number of complications, and psychiatric status were found in analyses. Finally, increased severity of psychiatric symptoms was correlated with decreased HRQOL in patients without current, recent, or past psychiatric diagnosis. This study shows the consistent, independent contribution of psychiatric symptoms and illness to the HRQOL of patients with a co-existing medical illness. Thus, psychiatric interventions addressing common conditions, such as depression, could improve the HRQOL of patients without changing medical status.

The effects of childhood maltreatment on brain structure, function and connectivity

Maltreatment-related childhood adversity is the leading preventable risk factor for mental illness and substance abuse. Although the association between maltreatment and psychopathology is compelling, there is a pressing need to understand how maltreatment increases the risk of psychiatric disorders. Emerging evidence suggests that maltreatment alters trajectories of brain development to affect sensory systems, network architecture and circuits involved in threat detection, emotional regulation and reward anticipation. This Review explores whether these alterations reflect toxic effects of early-life stress or potentially adaptive modifications, the relationship between psychopathology and brain changes, and the distinction between resilience, susceptibility and compensation.

Glycemic control and major depression in patients with type 1 and type 2 diabetes mellitus

The current study evaluated the association of glycemic control and major depression in 33 type 1 and 39 type 2 diabetes mellitus patients. Type 1 patients with a lifetime history of major depression showed significantly worse glycemic control than patients without a history of psychiatric illness (t = 2.09; df = 31, p < 0.05). Type 2 diabetes patients with a lifetime history of major depression did not have significantly worse control than those with no history of psychiatric illness. Findings from this study indicate different relationships between lifetime major depression and glycemic control for patients with type 1 and type 2 diabetes. Treatment implications for glycemic control in type 1 and type 2 diabetes patients are discussed.

The Association of Lifetime Psychiatric Illness and Increased Retinopathy in Patients With Type I Diabetes Mellitus

Forty-nine patients with Type I diabetes mellitus were assessed to examine the relationship between lifetime prevalence of psychiatric illness and retinopathy severity. The subjects with a history of psychiatric illness had significantly worse retinopathy than the subjects without psychiatric illness. Eighty-nine percent of the subjects with severe nonproliferative retinopathy or proliferative retinopathy had a history of psychiatric illness, predominantly affective illness. In addition, the subjects with a history of psychiatric illness had significantly higher current glycohemoglobin levels than those with no psychiatric history. This studys findings suggest that psychiatric illness may be a risk factor for development of retinopathy in Type I diabetic patients.

Diabetes, the brain, and behavior: Is there a biological mechanism underlying the association between diabetes and depression?

In summary, our review of the literature suggests that diabetes, especially type 1 diabetes, may place patients at risk for a depressive disorder through a biological mechanism linking the metabolic changes of diabetes to changes in brain structure and function. Further studies are warranted examining these relationships in order to better understand the impact of diabetes on brain functioning and structure as well as one potential manifestation of such changes--affective disorder. Moreover, such studies could play a useful role in better understanding mechanisms that commonly underlie the development of depression in individuals without diabetes but with other medical problems or conditions.

Diurnal variation of plasma cortisol and homovanillic acid in healthy subjects

We investigated the relationship between plasma levels of cortisol, the dopamine metabolite homovanillic acid (HVA) and norepinephrine in healthy human subjects. Plasma cortisol and HVA levels were measured at 0800h, and in an integrated sampling procedure involving samples every 15 min between 1300 and 1600h. Plasma norepinephrine was measured at 0800 and 1300h. Cortisol, HVA and norepinephrine indices did not show significant correlations with each other. Both cortisol and HVA showed significant decreases over time. Longitudinal Random Effects (LRE) models were used to test whether individual cortisol and HVA curves over time were correlated; significant correlations were not found with this procedure. While significant correlations between cortisol and catecholamine indices have been reported in depressed patients, our results do not suggest such correlations in healthy subjects.

Hypothalamic-pituitary-adrenal axis activity and 1-year outcome in depression.

The relationships of longitudinal biological measures to longer-term outcome in depressed patients have not been well explored. This study was designed to investigate whether in a sample of depressed patients: (a) symptomatic and functional outcome at 1 year was significantly different in psychotic major depressed (PMD) patients as compared with nonpsychotic major depressed (NPMD) patients and (b) high urinary or plasma cortisol levels at baseline or 1 year were associated with poorer outcomes at 1 year. Forty-two depressed patients (9 psychotic, 33 nonpsychotic) were evaluated at baseline and at 1 year using a battery of clinical ratings and measures of cortisol. A group of normal, healthy control subjects were similarly evaluated at baseline. At 1-year follow-up, PMD patients did not differ from NPMD patients in their Hamilton Depression Rating Scale (HDRS) and Brief Psychiatric Rating Scale scores (BPRS), but PMD patients demonstrated significantly poorer social and occupational functioning. Significant correlations were observed (n = 18) between higher levels of urinary and plasma cortisol at 1 year and poorer social and occupational functioning at 1 year, independent of the degree of residual depression. In contrast, baseline measures of urinary and plasma cortisol did not predict social and occupational functioning at 1 year.

Hypothalamic–pituitary–adrenal axis effects on plasma homovanillic acid in man

BACKGROUND Effects of the hypothalamic-pituitary-adrenal (HPA) axis on central dopaminergic systems have been proposed to underlie the development of psychotic symptoms in depression. This study examined HPA axis hormone effects on plasma levels of homovanillic acid (HVA), the dopamine metabolite, in healthy volunteers, using a placebo-controlled, double-blind, random-assignment, crossover design. On the basis of preliminary studies, we hypothesized that HPA axis hormones would produce delayed effects on plasma HVA levels measured in the afternoon. METHODS Ten healthy subjects underwent a standard protocol on four occasions and each time received ovine corticotropin-releasing hormone, synthetic adrenocorticotropic hormone (ACTH), cortisol, or placebo. Plasma HVA was measured at 9 AM and 4 PM on Day 1, immediately prior to administration of the test substance at 7 PM, then at 30-60-min intervals until 11 PM. Plasma HVA levels were subsequently obtained at 9 AM and 4 PM on Days 2 and 3. RESULTS As predicted, there were significant differences between test substances in delayed effects on afternoon HVA levels measured on Days 2 and 3, with cortisol and ACTH producing greater increases in HVA than placebo. Acute effects of HPA axis hormones on HVA were not found, while differences between test substances in delayed effects on morning HVA levels approached significance. CONCLUSIONS HPA axis hormones exert delayed effects on plasma HVA levels in healthy humans.