Professor Emeritus, Psychiatry and Behavioral Sciences
Eating disorders ; anorexia nervosa: endocrinology and subtypes; risk factors for restricting anorexia nervosa: personality traits and starvation-induced mental and behavioral activation. Women’s health: depression with atypical physical symptoms; depression during pregnancy and postnatal depression: effects on the offspring.
This study evaluated the question whether length of in utero exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants might affect neonatal outcome and psychomotor development in infancy.Birth outcome was determined in the offspring of 55 women with major depressive disorder who used SSRI medication for different durations during their pregnancies. At an average age of 14 months, children underwent a pediatric examination and an evaluation with the Bayley Scales of Infant Development (BSID-II).Duration of in utero exposure to SSRIs was negatively associated with total Apgar scores, specifically the activity subscale. Odds ratios for a low score (<2) on this scale were 3.8 and 6.0 at 1 and 5 min, respectively. Newborns with longer exposure were more often admitted to the Neonatal Intensive Care Unit (p?.03). Mental Development Index scores of the infants were not associated with the length of gestational exposure to SSRIs. A longer duration of exposure increased the risk for lower Psychomotor Developmental Index and Behavioral Rating Scale scores in infancy (p?=?0.012 and p?=?0.007, respectively) on the BSID-II.The findings provide evidence that the length of prenatal SSRI antidepressant use can affect neonatal adjustment and can have an effect on psychomotor test scores in infancy. Importantly, the children's mental development and motor function by neurological examination were within the normal range. Timing of exposure to SSRIs during susceptible periods of fetal development and variations in the severity of maternal depression may have contributed to the associations.
View details for DOI 10.1007/s00213-011-2270-z
View details for Web of Science ID 000294224800006
View details for PubMedID 21499702
This review addresses the role animal models play in contributing to our knowledge about the eating disorders anorexia nervosa (AN) and bulimia nervosa (BN) and obesity.Explore the usefulness of animal models in complex biobehavioral familial conditions, such as AN, BN, and obesity, that involve interactions among genetic, physiologic, psychological, and cultural factors.The most promising animal model to mimic AN is the activity-based anorexia rodent model leading to pathological weight loss. The paradigm incorporates reward elements of the drive for activity in the presence of an appetite and allows the use of genetically modified animals. For BN, the sham-feeding preparation in rodents equipped with a gastric fistula appears to be best suited to reproduce the postprandial emesis and the defects in satiety. Animal models that incorporate genes linked to behavior and mood may clarify biobehavioral processes underlying AN and BN. By contrast, a relative abundance of animal models has contributed to our understanding of human obesity. Both environmental and genetic determinants of obesity have been modeled in rodents. Here, we consider single gene mutant obesity models, along with models of obesigenic environmental conditions. The contributions of animal models to obesity research are illustrated by their utility for identifying genes linked to human obesity, for elucidating the pathways that regulate body weight and for the identification of potential therapeutic targets. The utility of these models may be further improved by exploring the impact of experimental manipulations on the behavioral determinants of energy balance.
View details for DOI 10.1007/s00213-008-1102-2
View details for Web of Science ID 000257383200003
View details for PubMedID 18317734
This paper discusses the hypothesis that a 'drive for activity" in the presence of physiological and endocrine changes consistent with starvation is a characteristic symptom of acute anorexia nervosa (AN). This 'drive for movement', along with alertness and lack of fatigue, so unlike the motor slowing and loss of energy observed in simple starvation has been recognized in AN throughout history, but has received little attention in the past fifty years. Clinical reports and experimental evidence suggest that 'restlessness' and a 'drive for activity' vary in intensity, they appears to be starvation-dependent and to wane with food intake. Central nervous system (CNS) systems known to be involved in mediating activity and arousal levels that are altered by the negative energy expenditure in AN are reviewed. Among these, the corticotropin-releasing hormone (CRH) system, the melanocyte stimulating hormone/agouti-related protein (MSH/AGRP) system and the norepinephrine/epinephrine (NE/EPI) and dopamine (DA) system may contribute to the 'drive for activity' and alertness in AN. AN appears to represent a disorder of gene/environment interaction. Future research will reveal whether in individuals predisposed to AN, the 'drive for activity' reflects the reactivation of mechanisms important in food scarcity, controlled by one or more evolutionary conserved genes including those regulating foraging behavior. Recognition of the 'drive for activity' as a diagnostic symptom of AN and its assessment prior to re-nutrition would permit clarification of its role in the etiology of AN.
View details for DOI 10.1016/j.jad.2005.12.039
View details for Web of Science ID 000238136800013
View details for PubMedID 16448703
Human neurodevelopment is the result of genetic and environmental interactions. This paper examines the role of prenatal nutrition relative to psychiatric disorders and explores the relationship among nutrients, mood changes, and mood disorders. Epidemiologic studies have found that adults who were born with a normal, yet low birth weight have an increased susceptibility to diseases such as coronary heart disease, diabetes, and stroke in adulthood. Prenatal caloric malnutrition, low birth weight, and prematurity also increase the risk for neurodevelopmental disorders, schizophrenia, affective disorders, and schizoid and antisocial personality disorders. Placebo-controlled studies in medicated patients suggest that add-on treatment with omega-3 fatty acids, particularly eicosapentaenoic acid, may ameliorate symptoms of major depressive disorder. Additional studies are necessary to confirm any benefits for bipolar disorders.
View details for PubMedID 15538990
Anorexia nervosa (AN) is a complex disorder of unclear etiology. We argue that the current DSM-IV criteria do not adequately describe the cardinal symptoms of this "eating disorder". Our reasoning is based on the lack of empirical evidence supporting the terminology of some of the criteria, which underlie the core of our current conceptualisation of AN. We propose alternative criteria which allow a better integration of biologically derived hypotheses addressing the nosology and the symptomatology of AN.
View details for DOI 10.1007/s00702-004-0136-9
View details for Web of Science ID 000222514400006
View details for PubMedID 15206001
Patients with anorexia nervosa (AN) often show normal to elevated physical activity levels despite severe weight loss and emaciation. This is seemingly in contrast to the loss of energy and fatigue characteristic of other starvation states associated with weight loss. Despite the fact that historical accounts and clinical case studies of AN have regularly commented on the elevated activity levels, the behavior has become only recently the subject of systematic study. Because rodents and other species increase their activity upon food restriction leading to weight loss when given access to an activity wheel--a phenomenon referred to as activity-based anorexia or semi-starvation-induced hyperactivity (SIH)-it has been proposed that the hyperactivity in AN patients may reflect the mobilization of phylogenetically old pathways in individuals predisposed to AN. Exogeneous application of leptin in this animal model of AN has recently been shown to suppress completely the development of SIH. Hypoleptinemia, as a result of the food restriction, may represent the initial trigger for the increased activity levels in AN patients and in food-restricted rats. In the first and second parts of our review, we will summarize the relevant findings pertaining to hyperactivity in AN patients and in the rat model, respectively. We conclude with a synopsis and implications for future research.
View details for DOI 10.1016/S0031-9384(03)00102-1
View details for Web of Science ID 000183846800004
View details for PubMedID 12818707
To compare the structural growth and developmental outcome of children born to mothers diagnosed with major depressive disorder during pregnancy who were exposed or not exposed to selective serotonin reuptake inhibitors (SSRIs) in utero.Children whose mothers were diagnosed with major depressive disorder in pregnancy and elected not to take medication (n = 13) were compared with children of depressed mothers treated with SSRIs (n = 31) on birth outcomes and postnatal neurodevelopmental functioning between ages 6 and 40 months. Children underwent blinded standardized pediatric and dysmorphology examinations and evaluations of their mental and psychomotor development with the use of the Bayley Scales of Infant Development (BSID II).The Bayley mental developmental indexes were similar in both groups. Children exposed to SSRIs during pregnancy had lower APGAR scores and scored lower on the Bayley psychomotor development indexes and the motor quality factor of the Bayley Behavioral Rating Scale than unexposed children.The findings that SSRIs during fetal development might have subtle effects on motor development and motor control are consistent with the pharmacologic properties of the drugs.
View details for DOI 10.1067/mpd.203.139
View details for Web of Science ID 000182733800011
View details for PubMedID 12712058
The eating disorders anorexia nervosa (AN) and bulimia nervosa (BN) are multifactorial syndromes of unknown origin which occur typically in female adolescents or young women. Nowadays, AN and BN are most often triggered by dietary restriction. Both are treatable conditions. As in other psychiatric disorders, a lower comorbidity, a shorter duration of illness, less familial psychopathology, and, in AN, a higher minimal weight have been shown to be associated with a better outcome. So far, no abnormalities specific to AN or BN that would shed light on their etiology have been identified. Controlled and uncontrolled studies testing antipsychotic, antidepressant, weight-promoting, and prokinetic drugs have demonstrated that the core symptoms of AN are refractory to currently available psychotropic medication. For relapse prevention, however, antidepressant medication may be useful. Renutrition, psychotherapy, and family therapy remain the cornerstones of treatment for AN. Placebo-controlled studies with antidepressant drugs have been far more promising for treating BN in the short term. Recent studies have found that lasting symptomatic improvement and remission require the addition of psychological treatments in the form of cognitive and interpersonal psychotherapy. The steady stream of newly identified peptides and other molecules involved in appetite and body weight control may ultimately provide cues to better targeted treatments of eating disorders.
View details for PubMedID 12397843
This study investigated family functioning in adolescents with the restricting and bulimic type of anorexia nervosa (AN) and in healthy controls.Fifty-one parents and their children (17 with AN and 34 healthy adolescents) completed the Family Assessment Measure, a self-report instrument that provides information about the functional strengths and weaknesses of the family and each family member.AN patients with the bulimic subtype and their mothers were significantly more likely to perceive family functioning as impaired than were healthy adolescents or restricting AN patients. Restricting AN patients and their families did not differ from healthy control families.The results suggest that the problems faced by bulimic patients color their and their parents' view of each other and the family. Symptomatic and personality differences between the subtypes of AN with better control, fewer symptoms, and denial of conflict characterizing restricting AN families may be reflected in family interaction styles.
View details for Web of Science ID 000170823400014
View details for PubMedID 11767716
View details for Web of Science ID 000171042500005
This study was designed to compare placebo responses in men and women.Data for 501 women and 375 men with major depressive disorder treated with placebo from seven investigational randomized double-blind trials comparing fluoxetine with placebo were analyzed. Changes in major depressive disorder symptoms with placebo administration were measured as changes in total Hamilton Depression Rating Scale scores and adverse (nocebo) effects were measured by comparing treatment-emergent signs and symptoms.Both women and men with major depressive disorder showed significant symptomatic improvement following placebo administration, similar in magnitude and time course of response. Women on placebo reported slightly more nocebo effects than men.The finding that women and men with major depressive disorder demonstrated a similar therapeutic outcome after placebo administration suggests that gender is not a predictor of placebo response.
View details for Web of Science ID 000166675000008
View details for PubMedID 11164762
The core symptoms of anorexia nervosa have remained points of debate. The goal of this paper is a close study of unexpected and paradoxical symptoms in anorexia nervosa which are described in the literature but which, for the most part, have escaped the attention of investigator.Following a brief examination of psychological influences: developmental psychodynamics issues, psychiatric comorbidity and personality features, as well as the physical consequences of starvation, all of which are considered probable contributors to the pathological process, the symptoms of denial, lack of concern, contentment, liveliness, and overactivity in anorexia nervosa are discussed.If these symptoms are accepted as specific for anorexia nervosa, their presence suggests that starvation might generate in individuals with a vulnerability for anorexia nervosa a condition of mental and physical activation.Areas of research to test this hypothesis, positing starvation-induced arousal or activation as a physiological dysregulation in anorexia nervosa which would powerfully support food avoidance, are discussed.
View details for Web of Science ID 000076770900005
View details for PubMedID 9813763
Anorexia nervosa (AN) and bulimia nervosa (BN) are currently classified as eating disorders. Both disorders are the product of a complex interaction between psychological and physiological processes and both show considerable comorbidity with other psychiatric disorders. Physiological and endocrine abnormalities, including primary or secondary amenorrhea and menstrual dysfunction, are common and for the most part a function of the severity of weight loss, malnutrition and/or abnormal eating habits. Therefore, assessment needs to include several steps: (1) Clinical evaluation to ascertain the diagnosis, including weight and height measurements; (2) Determination of co-existing psychiatric illnesses; and (3) Physical examination and evaluation of the physiological and endocrine status. Eating disorders interfere with reproductive function. In view of the fact that dieting has reached epidemic proportions among the young female population, and given the high association between eating disorders and endocrine abnormalities as well as menstrual disturbances, all women participating in research studies should be screened for the presence of eating disorders, disordered eating, and excessive exercise.
View details for Web of Science ID 000078297300008
View details for PubMedID 9803752
Both depressive disorders and eating disorders are multidimensional and heterogeneous disorders. This paper examines the nature of their relationship by reviewing clinical descriptive, family-genetic, treatment, and biological studies that relate to the issue. The studies confirm the prominence of depressive symptoms and depressive disorders in eating disorders. Other psychiatric syndromes which occur with less frequency, such as anxiety disorders and obsessive-compulsive disorders in anorexia nervosa, or personality disorders, anxiety disorders, and substance abuse in bulimia nervosa, also play an important role in the development and maintenance of eating disorders. Since few studies have controlled for starvation-induced physical, endocrine, or psychological changes which mimic the symptoms considered diagnostic for depression, further research will be needed. The evidence for a shared etiology is not compelling for anorexia nervosa and is at most suggestive for bulimia nervosa. Since in contemporary cases dieting-induced weight loss is the principal trigger, women with self-critical or depressive features will be disproportionately recruited into eating disorders. The model that fits the data best would accommodate a relationship between eating disorders and the full spectrum of depressive disorders from no depression to severe depression, with somewhat higher rates of depression in bulimic anorectic and bulimia nervosa patients than in restricting anorexia nervosa patients, but the model would admit a specific pathophysiology and psychopathology in each eating disorder.
View details for PubMedID 9809221
The goal of this study was to determine whether family and individual psychopathology mediate the relationship between unwanted sexual experiences and bulimic eating behavior.Sixty-one women diagnosed with bulimia nervosa and 92 women students and university staff who had never met critia for an eating disorder completed standardized questionnaires on eating behavior, sexual abuse, individual psychopathology, and family psychopathology.Linear regression showed bulimic eating behavior to be significantly related to sexual abuse (beta = .40; p < .0001; R2 = 8.9%). However, multiple regression analyses with family and individual psychopathology as independent variables in addition to sexual abuse showed only individual psychopathology to predict significantly abnormal eating behavior (beta = .53, p < .0001; overall R2 = 49.6%). Specifically, depressive symptoms, suicidality, and impulsive behavior, but not substance abuse, were the components of individual psychopathology most directly associated with bulimia.The findings suggest that the primary focus in treatment should not be the traumatic events themselves, but their long-term consequences for the individual.
View details for Web of Science ID A1997WQ64500003
View details for PubMedID 9097196
To study late-onset cases of eating disorders in order to (1) document the occurrence of these cases as truly new onset, even if postmenopausal; (2) to alert clinicians to the category of late-onset eating disorders, especially clinical features and treatment response; (3) to challenge some prevailing assumptions of etiology.Selection of cases of eating disorders with first onset after age 40 that met DSM-IV criteria, by review of eating disorders admissions to three university hospital programs.Eleven patients, approximately 1% of all cases of eating disorders, had first onset of an eating disorder after age 40 and as late as 77, with an average onset of 56 and clinical presentation at 60 years. They met DSM-IV criteria for all subtypes of eating disorders. In general, concurrent medical and comorbid psychiatric symptoms made recognition and treatment more complex.Truly late-onset cases do occur, challenging etiological theories requiring adolescent age of onset, premenopausal endocrine functioning, or adolescent psychodynamic conflicts. Late-occurring cases, after accurate diagnosis, require an appreciation of psychological themes pertinent to this age group, such as bereavement or unresolved body image issues. Age by itself is no barrier to onset of eating disorders, which may occur whenever self-starvation and/or binge-purge behaviors become entrenched as sustaining behaviors for amelioration of psychodynamic conflicts, mood disorders, or interpersonal distress.
View details for Web of Science ID A1996VV63600006
View details for PubMedID 8953326
View details for Web of Science ID A1996VJ20900008
Findings of studies of carbohydrate metabolism in anorexia nervosa are reviewed. Topics covered included fasting blood sugar concentrations; serum insulin concentrations, insulin receptor binding activity, insulin sensitivity, and insulin resistance; plasma ketone bodies and free fatty acids; glucose tolerance tests; growth hormone, cortisol, intestinal hormones, and norepinephrine. Metabolic changes reported in anorexia nervosa are similar to those found in human and animal studies of states of caloric and carbohydrate restriction. Restoration of normal body weight is associated with normalization of virtually all measures. It is concluded that published studies offer no conclusive evidence for a syndrome-specific impairment in carbohydrate metabolism in anorexia nervosa.
View details for Web of Science ID A1996UL14200011
View details for PubMedID 8739118
To study gender differences in psychiatric symptoms and their relationship to minor delinquent behavior in high school seniors.This was a cross-sectional study of symptoms experienced during the past 2 weeks and the past year. Male (n = 249) and female (n = 248) high school seniors attending an inner-city and two suburban high schools rated themselves on a 46-item Hopkins Symptom Checklist and a 19-item Delinquency questionnaire.Female adolescents, regardless of race, reported significantly higher levels of emotional distress, in particular depressed mood and anxiety, than did male adolescents. A separate factor analysis of male and female students generated anger-tension, school problems, and sadness-irritation, lethargy, respectively, as the first two factors. Trouble paying attention in school and marijuana, alcohol, and other drug use were associated with significantly higher levels of psychiatric symptoms. Black and white adolescents were similar in psychological adjustment.This survey confirms sex differences in the level of psychiatric symptoms for 16- to 18-year-old adolescents, suggests gender-related qualitative differences in negative emotions, and emphasizes the importance of controlling for education when studying adolescents from different ethnic or racial backgrounds.
View details for Web of Science ID A1996UB75900016
View details for PubMedID 8919712
View details for Web of Science ID A1996TU73400001
The aging process alone has no significant adverse consequences for the caloric intake and the nutritional status of healthy elderly individuals. Epidemiological data suggest that in humans, in contrast to rodents, undernutrition reduces the life span. In the Western World, malnutrition in old age has become uncommon and is, for the most part, the result of physical illness and/or of psychological and socio-economic factors, such as depressive disorders, social isolation, smoking, alcohol abuse, and poverty. Body weight shows a U- or J-shaped relationship to mortality risk with the highest survival rates found at normal to moderate overweight. However, studies that have controlled for disease already present, smoking status, serum cholesterol level, or hypertension, suggest an increased mortality risk for lower and upper extremes of body weight, only. Populations with healthy lifestyles have significantly greater life expectancy that the average normal population. Even in the very old, exercise has been shown to improve muscle strength and function. The studies suggest that nutritional intake and nutritional status in old age is multifactorial and dependent not only on appetite and availability of diverse food, but also on physical activity, body mass, education, and an involved social lifestyle.
View details for Web of Science ID A1995RA38100009
View details for PubMedID 7556509
The study describes a sequential analysis of depression-related physical symptoms and their relationship to imipramine and amitriptyline plasma levels over 4 weeks of treatment in 79 unipolar and bipolar patients hospitalized for major depressive disorder. Insomnia diminished in all patients after 2 weeks of drug administration. After 4 weeks, the sleep of patients whose depressive disorder has significantly improved was nearly normal, whereas patients who remained depressed showed continued sleep impairment. Reductions in loss of appetite, weight and sexual interest paralleled mood improvement. Tricyclic plasma levels significantly correlated with improved sleep. The findings suggest a close link between depressed mood and physical symptoms during recovery from major depressive disorder.
View details for Web of Science ID A1994NX89100001
View details for PubMedID 7963067
View details for Web of Science ID A1994NM21000007
Attitudes toward body weight and dieting and the relations of these attitudes to psychological adjustment were investigated in 497 randomly selected adolescents who were in their senior year in one urban and two suburban midwestern high schools. Most students reported feeling physically healthy. Two thirds of female adolescents were preoccupied with weight and dieting compared with only a small number (approximately 15%) of male adolescents. Black female adolescents were found to be less weight- and diet-conscious than white female adolescents. Increased weight and dieting concerns were associated with greater body and self-image dissatisfaction, with a depressed mood, and greater overall symptomatic distress in both male and female adolescents. The fairly common fear of being overweight and thoughts about dieting experienced by contemporary female adolescents, in part, seem to reflect the greater aesthetic value that contemporary society places on thinness for women. Overall, the findings suggest that preoccupation with weight and/or dieting concerns in either male or female adolescents are likely to indicate psychological problems.
View details for Web of Science ID A1990DW64600011
View details for PubMedID 2388787
Personality characteristics were assessed in women who had physically and, in the majority, psychologically recovered from restricting anorexia nervosa at an 8- to 10-year follow-up. Personality dimensions were evaluated using the Multidimensional Personality Questionnaire, the California Personality Inventory, and the Reid-Ware Scale. Women who had recovered from anorexia nervosa rated higher on risk avoidance, displayed greater restraint in emotional expression and initiative, and showed greater conformance to authority than age-matched normal women. On comparison with their sisters, the recovered women reported a greater degree of self- and impulse control and less enterprise and spontaneity; sisters, however, endorsed equally high moral standards. The differences in personality characteristics remained significant after statistically controlling for depressive symptoms and eating behavior. The results suggest that a temperamental disposition toward emotional and behavioral restraint combined with a strong sense for traditional values may be psychological risk factors for the development of the restricting type of anorexia nervosa.
View details for Web of Science ID A1990CY40600004
View details for PubMedID 2330389