Harvard Review of Psychiatry

Published by Lippincott, Williams & Wilkins
Online ISSN: 1465-7309
Publications
Article
The lifetime risk for major depression in women is well known to be twice the risk in men and is especially high during the reproductive years between menarche and menopause. A subset of reproductive-age women experience depressive episodes that are triggered by hormonal fluctuations. Such "reproductive depressions" involve episodes of depression that occur specifically during the premenstrual, postpartum, and perimenopausal phases in women. These reproductive subtypes of depression can be conceptualized as a specific biological response to the effects of hormonal fluctuations in the brain. The different types of reproductive depressions are associated with each other, have unique risk factors that are distinct from nonreproductive depression episodes, and respond to both hormonal and nonhormonal interventions. This review uses a PubMed search of relevant literature to discuss clinical, animal, and genetic evidence for reproductive depression as a specific subtype of major depression. Unique treatment options, such as hormonal interventions, are also discussed, and hypotheses regarding the underlying biology of reproductive depression-including interactions between the serotonergic system and estrogen, as well as specific effects on neurosteroids-are explored. This review will provide evidence supporting reproductive depression as a distinct clinical entity with specific treatment approaches and a unique biology that is separate from nonreproductive depression.
 
Article
Largely unknown in Anglophonic medicine, eighteenth-century Spanish physician-scholar Andrés Piquer-Arrufat was early to coin a name (affectio melancholico-maníaca, or "melancholic-manic illness") for the syndrome that emerged much later as manic-depressive illness and then bipolar disorder. He considered it a single, independent diagnostic entity, distinct from mania and melancholia, with varying manifestations over time. Piquer recognized mixed states, seasonality, and rapid cycling, and hypothesized "mental or cerebral damage" as underlying the disorder. His formulations evolved from clinical observations of patients over time, including his detailed longitudinal clinical description of Spanish King Ferdinand VI (1759), and as presented in his own medical textbook (1764). Piquer anticipated the often cited nineteenth-century works of Jean Falret and Jules Baillarger in Paris, and later, Emil Kraepelin in Heidelberg, by more than a century.
 
Article
Olfactory processing is thought to be mediated via the frontal and temporolimbic brain regions, both of which, as well as olfactory dysfunction, are implicated in schizophrenia. Likewise, several empirical studies of olfactory dysfunction--in particular, olfactory deficits in identification, odor detection threshold sensitivity, and odor memory, along with associated brain structural changes--have been conducted to illuminate the pathophysiology of schizophrenia. These anomalies have been investigated, more recently, as possible biological markers of that disabling illness. This article summarizes recent research on neuroimaging changes associated with olfactory impairments in schizophrenia patients and on related functional changes in psychophysiological measurements (e.g., odor identification, odor discrimination, odor detection threshold, and odor memory). The possible role of these changes as biological markers of the disorder will be discussed, as will potentially productive directions for future research.
 
Article
The field of psychiatric genetics is highly interdisci-plinary, with roots in human genetics, psychiatry, statistics, and epidemiology. A primary goal in psychiatric genetics is to clarify how genes influence psychiatric illnesses—that is, the pathway from genotype to phenotype. 1 Such knowledge about the etiology and pathogenesis of illnesses should provide a basis for improving treatment and prevention.
 
Oxytocin is synthesized in specialized cells in the PVN and SON of the hypothalamus, and serves dual roles, as both a central neurotransmitter/neuromodulator (for central effects, see Figure 2) and a peripheral hormone. Though there are receptors for oxytocin throughout the body, its primary effects are in the gravid uterus and breast, where it stimulates contractions and milk ejection. Abbreviations: PVN, paraventricular nuclei; SON, supraoptic nuclei. 
Article
Oxytocin is a neuropeptide involved in a wide variety of social behaviors in diverse species. Recent research on its effects in humans has generated an arresting picture of its role in the dynamic function of the social brain. This review presents a broad overview of this uniquely social peptide, with a particular focus on extant studies of its effects in humans. After a short discussion of the evolutionary history of the oxytocin system, critical aspects of its peripheral and central physiology, and several salient technical issues surrounding human oxytocin research, a systematic review of studies of the effects of intranasal oxytocin in humans is presented. These effects include alterations in social decision making, processing of social stimuli, certain uniquely social behaviors (e.g., eye contact), and social memory. Oxytocin's prosocial influence is then framed by an evolutionary perspective on its role in mammalian social bonding and attachment. Finally, limitations in current human oxytocin research and oxytocin's potential therapeutic applications are discussed. Key conclusions are (1) human research with intranasal oxytocin has uniquely enhanced our understanding of the microstructure and function of the human social brain, and (2) the oxytocin system is a promising target for therapeutic interventions in a variety of conditions, especially those characterized by anxiety and aberrations in social function.
 
Article
Louis-Victor Marcé, MD, of Paris compiled an extensive monograph published in 1858 that surveyed knowledge of psychiatric disorders of women during and following pregnancy. This work has largely been ignored for 150 years. We summarize here what is known about Marcé's life and work, and include selected passages from his monograph. Marcé provides extensive clinical descriptions of syndromes, with 79 case examples, and summarizes etiological theories and treatments characteristic of his era and place. This work was based on cases that he personally evaluated and on other reported cases, all drawn from broad social and economic backgrounds. Marcé shows an appreciation of epidemiological evidence and a critical approach to then conventional pathophysiological and therapeutic views. His work anticipated modern rediscovery of the high risk of depression in pregnancy and of both acute mood disorders and psychoses, postpartum. This comprehensive summary of clinical knowledge of perinatal psychiatric disorders of women is a landmark early contribution to a field that has only recently emerged as a psychiatric subspecialty.
 
Article
The syndrome of manic-depressive insanity (MDI), as conceptualized by Emil Kraepelin a century ago, with later refinements, continues to dominate research and clinical practice with mood disorder patients. Current understanding of Kraepelin's views by Anglophones is heavily influenced by the late, highly developed, MDI concept represented in the 1921 partial English translation of the last complete edition of his textbook, the product of gradual development over several decades. We reviewed all nine editions and revisions of Kraepelin's Textbook (1883-1926) and other writings by him to document the evolution of his views of MDI, and characterized salient developments within biographical and historical contexts. We found support for the traditional impression that Kraepelin's clinical perception of similarities of various forms of periodic psychiatric disorders marked by fundamental dysregulation of excitation and inhibition of thought and behavior, as well as of mood--as distinct from chronic psychotic illnesses--encouraged his broad, mature concept of MDI. However, our findings indicate a complex evolution of Kraepelin's MDI concept in the 1880s and 1890s, his use of more creative and less empirical clinical methods than traditionally believed, and his considerable personal uncertainty about making clear distinctions among MDI, dementia praecox, intermediate conditions, and paranoid disorders--an uncertainty that persisted to the end of his career in the 1920s. Kraepelin responded to a compelling international need for diagnostic order in nineteenth-century psychiatry, and effectively promoted his diagnostic proposals with a widely used and influential textbook. Though his methods were less empirical than is usually realized, his legacy includes analysis of large clinical samples to describe psychopathology and illness-course, along with efforts to define psychobiologically coherent and clinically differentiable entities, as steps toward defining psychiatric syndromes. Modern international "neo-Kraepelinian" enthusiasm for descriptive, criterion-based diagnosis should be tempered by Kraepelin's own appreciation of the tentative and uncertain nature of psychiatric nosology, particularly in classifying illnesses with both affective and psychotic features.
 
Article
The amobarbital interview has been a diagnostic and therapeutic tool for almost 70 years. Because safer alternatives, namely benzodiazepines, have become available over the past 30 years, its clinical use merits reexamination. Toward this end, the psychiatric literature on the amobarbital interview is reviewed. A Medline search using the key words "amobarbital interview" generated papers published in English since 1966. Most of the literature demonstrating utility of the amobarbital interview consists of uncontrolled case series or case reports on a variety of clinical applications. One controlled study in patients with catatonia demonstrated clear superiority of amobarbital over placebo in promoting verbalization and alertness, but six other controlled studies using various doses in heterogeneous patient groups failed to find differences between this drug and placebo. Additional rigorous, controlled studies comparing amobarbital with placebo and with possible alternatives such as benzodiazepines in specific patient populations are needed to define the place of this agent in the psychiatric armamentarium.
 
Article
Significant challenges exist in providing safe, effective, and culturally sound mental health and psychosocial services when an unforeseen disaster strikes in a low-resource setting. We present here a case study describing the experience of a transnational team in expanding mental health and psychosocial services delivered by two health care organizations, one local (Zanmi Lasante) and one international (Partners in Health), acting collaboratively as part of the emergency response to the 2010 Haiti earthquake. In the year and a half following the earthquake, Zanmi Lasante and Partners in Health provided 20,000 documented individual and group appointments for mental health and psychosocial needs. During the delivery of disaster response services, the collaboration led to the development of a model to guide the expansion and scaling up of community-based mental health services in the Zanmi Lasante health care system over the long-term, with potential for broader scale-up in Haiti. This model identifies key skill packages and implementation rules for developing evidence-based pathways and algorithms for treating common mental disorders. Throughout the collaboration, efforts were made to coordinate planning with multiple organizations interested in supporting the development of mental health programs following the disaster, including national governmental bodies, nongovernmental organizations, universities, foreign academic medical centers, and corporations. The collaborative interventions are framed here in terms of four overarching categories of action: direct service delivery, research, training, and advocacy. This case study exemplifies the role of psychiatrists working in low-resource settings as public health program implementers and as members of multidisciplinary teams.
 
Article
Schizophrenia is a syndrome, undoubtedly with multiple etiologies, that variably exhibits several features including positive and negative symptoms, cognitive deficits, onset in young adulthood, and deterioration from the previous level of function. This review will examine the growing evidence that dysfunction of corticolimbic glutamatergic neurotransmission may contribute to or account for the manifestations of schizophrenia. Glutamatergic neurons represent the primary excitatory afferent and efferent systems innervating the cortex, limbic regions, and striatum. The postsynaptic actions of glutamate are mediated by a family of glutamate-gated ion channels that permit the influx of sodium and calcium, thereby depolarizing (exciting) neurons. One of these receptors, the N-methyl-D-aspartate (NMDA) receptor, is the site of action of psychotomimetics such as phencyclidine and related anesthetics, which can reproduce in normal individuals most of the symptomatic features of schizophrenia. An endogenous antagonist at the NMDA receptor, N-acetyl-aspartyl glutamate, appears to have enhanced activity in the frontal cortex and hippocampal formation in persons with this disorder. Glutamatergic dysfunction may be particularly relevant to those forms of schizophrenia in which negative symptoms, cognitive deficits, and deterioration are prominent features. In support of this inference, clinical studies have shown that drugs that enhance NMDA-receptor function reduce negative symptoms and cognitive deficits in persons with chronic schizophrenia who are receiving neuroleptics. Thus, dysfunction of glutamatergic neurotransmission represents an important organizational focus for research on the complex manifestations of schizophrenia.
 
Article
Neurophysiologic processes underlie the uncontrolled, compulsive behaviors defining the addicted state. These"hard-wired"changes in the brain are considered critical for the transition from casual to addictive drug use. This review of preclinical and clinical (primarily neuroimaging) studies will describe how the delineation between pleasure, reward, and addiction has evolved as our understanding of the biologic mechanisms underlying these processes has progressed. Although the mesolimbic dopaminergic efflux associated with drug reward was previously considered the biologic equivalent of pleasure, dopaminergic activation occurs in the presence of unexpected and novel stimuli (either pleasurable or aversive) and appears to determine the motivational state of wanting or expectation. The persistent release of dopamine during chronic drug use progressively recruits limbic brain regions and the prefrontal cortex, embedding drug cues into the amygdala (through glutaminergic mechanisms) and involving the amygdala, anterior cingulate, orbitofrontal cortex, and dorsolateral prefrontal cortex in the obsessive craving for drugs. The abstinent, addicted brain is subsequently primed to return to drug use when triggered by a single use of drug, contextual drug cues, craving, or stress, with each process defined by a relatively distinct brain region or neural pathway. The compulsive drive toward drug use is complemented by deficits in impulse control and decision making, which are also mediated by the orbitofrontal cortex and anterior cingulate. Within this framework, future targets for pharmacologic treatment are suggested.
 
Article
In this paper we review studies of brain cellular high-energy phosphate metabolism, as measured by phosphorus-31 magnetic resonance spectroscopy (31P-MRS), in subjects with major depressive disorder (MDD). We also review the literature on the role of thyroid hormones on the cellular high-energy phosphate metabolism in multiple organs. Finally, we review data on the efficacy of thyroid hormones as adjuvant treatment in MDD. The framework established by these findings enables us to hypothesize that dysfunction of brain cellular energy metabolism is a vulnerability factor for MDD, and that correcting cellular energy metabolism (e.g., with thyroid hormones) is a valid therapeutic strategy for improving the symptoms of MDD. We discuss our hypothesis in the context of other current theories on the mechanism of thyroid hormones in MDD.
 
Article
Evidence from lesioning studies and neuroimaging has linked negative symptoms to dysfunction of the prefrontal cortex, the limbic system, and the basal ganglia. Although such symptoms have been most strongly associated with dopaminergic hypoactivity in the prefrontal cortex, other neurotransmitters including norepinephrine, serotonin, and the excitatory amino acids may also play a role. In some patients moderate doses of conventional neuroleptics clearly improve negative symptoms; the response of such symptoms is relatively greater with clozapine and probably with certain serotonin-dopamine antagonists. Recent studies demonstrating improvement of negative symptoms when conventional neuroleptics are augmented with selective serotonin-reuptake inhibitors or with agents active at the glycine-modulatory site of the glutamatergic N-methyl-D-aspartate receptor complex suggest that further amelioration of primary negative symptoms may be possible through pharmacological strategies involving multiple neurotransmitter systems.
 
Article
Managed care, in addition to affecting health care costs and patient care, challenges health care providers. New vocabularies and modes of discourse must be learned.’ Income is squeezed down. New ethical conflicts emerge.’ Professional autonomy is diluted because physicians must negotiate with benefits managers, faceless but powerful at the end of a telephone line.’ These challenges affect all physicians but fall most heavily on the physician-in-training - in part due to the tensions inherent in the position. Residents must function autonomously before they are sure they can do so. Being a trainee evokes earlier, dependent relationship^,^ sometimes resulting in temporary psychological regression.‘ And feeling little control over one’s life increases a resident’s sense of personal ~ulnerability.~.~ For decades psychiatric training managed these tensions through a supervisory structure that was mutually satisfying. Residents wanted clinical experience, and hospitals wanted care for patients. Residents wanted to learn, and supervisors wanted to teach. Residents wanted a sense of personal autonomy, and training programs wanted physicians who could function, under supervision, on their own, gradually assuming independent responsibility. Managed care has challenged this balance of clinical responsibility and professional development, most recently with proposals for on-site evaluation of patients in emergency wards by clinicians dispatched by the managed care organization. Under these proposals master’s-level clinicians from a mobile team arrive in the emergency department and perform an independent assessment “to determine the level of care needed,’’ in the hope of diverting the
 
Article
“Split treatment”—in which patients receive treatment from two or more caregivers—is extremely common in contemporary psychiatric practice and has been discussed from various viewpoints. The roles of supervisor, collaborator, and consultant have been distinguished, together with their implications for continuity of care and risk management. 1−5 A common pairing of roles seen in the community is treatment by both a psychopharmacologist—a physician (or, in some geographical areas, an advanced practice nurse) who prescribes the patient’s medication—and a psychotherapist, who may be a physician or nonphysician, whose role involves verbal exploration of the patient’s clinical issues.
 
Studies of Executive Function in Patients with Major Depressive Disorder 
Article
The deficits in attention and executive function characteristic of major depressive disorder (MDD) are reviewed. The networks underlying attention and executive function, the neuropsychological tests commonly used to evaluate these domains, and the neuroanatomy of MDD are also discussed. A neural network approach to the attentional and executive function deficits of MDD has ramifications for hypothesis-guided research, the cognitive model of depression, and application of the medical disease model to psychiatric disorders.
 
Article
Women with mood disorders, especially bipolar disorder (BD), have been shown to have high rates of reproductive and metabolic dysfunction. The available data on the functional, anatomic, and clinical neuroendocrine abnormalities in women with BD suggest a two-tiered relationship with mood pathology. First, many of the medications commonly used in the treatment of BD can have deleterious effects on blood levels of reproductive hormones and consequently on the hypothalamic-pituitary-gonadal (HPG) axis and reproductive function. Studies that have specifically addressed the association between psychotropic medications and menstrual abnormalities, polycystic ovary syndrome, and overall reproductive endocrine function in women with BD have found high rates of HPG irregularities in women with BD. Second, there is evidence of reproductive dysfunction in women with BD prior to treatment. In addition, many of the psychotropic medications used in the treatment of BD are associated with weight gain, insulin resistance, and dyslipidemia. These metabolic side effects further compound the neuroendocrine system dysregulation in women with BD. Current understanding of the reproductive and metabolic function in women with BD points to vulnerability, which in turn increases the risk of later-life cardiovascular disease and diabetes, among other morbidities, for women with BD.
 
Article
Postmortem, magnetic resonance, and event-related potential studies suggest the presence of temporal lobe abnormalities in schizophrenia. Analyses using convergent measurements of brain structure and function, however, have rarely been done in the same patients. We recently developed a protocol using high-spatial-resolution magnetic resonance scans, auditory P300 event-related potentials, and thought disorder scales to examine temporal lobe structure and function in the same patients. We report a case of schizophrenia that showed left-lateralized volume reduction in the superior temporal gyrus, hippocampus, and parahippocampal gyrus (also on right), with associated P300 amplitude reduction and thought disorder marked by word-finding difficulties and perseverations.
 
Article
Bleuler and Kraepelin are described as icons of the aggressively psychological and aggressively biologic approaches to schizophrenia. We suggest that methodologic advances in studying the function and structure of the brain now allow a reconciliation of these seemingly dissimilar approaches, particularly in the temporal lobe. We begin with a brief historic overview of these different approaches to schizophrenia and then describe structural (magnetic resonance imaging [MRI]), functional (event-related potential [ERP]), and neuropsychological studies in this disorder, including a summary of work conducted in our own laboratory. Recent MRI investigations agree on the presence of volume reductions in schizophrenia in the medial temporal lobe structures of the hippocampus-amygdala complex and of the para-hippocampal gyrus. Furthermore, two recent studies also indicate volume reductions in the superior temporal gyrus (STG). These volume reductions are most prominent in male patients and in the left hemisphere of right-handed patients with schizophrenia. Along with structural studies, there has been a burgeoning interest in MRI-clinical correlations, with volume reductions in the anterior STG being associated with hallucinations and those in the posterior STG being associated with thought disorder. Functional ERP studies also implicate the importance of the temporal lobe in schizophrenia; in addition, ERP abnormalities have been directly associated with a left greater than right MRI volume reduction of the posterior STG. Neuropsychological studies in nonpsychiatric patients are also consistent with a pattern of functional deficits shown to arise from temporal lobe abnormalities, whereas direct MRI-neuropsychological correlations in schizophrenic patients show that decreased performance on tests of verbal memory, abstraction, and categorization correlates with reduced MRI volume of left and right temporal lobe structures. Integration of these findings with those from basic neuroscience suggests a possible role of excitatory amino acid neurotransmission dysregulation and excitotoxicity in the pathology of schizophrenia. A data-based pathophysiologic characterization of schizophrenia is now becoming a reality, and the next few years should see a further unification of the Kraepelinian and Bleulerian approaches to this disorder.
 
Article
The autoimmune basis for schizophrenia has been investigated for the last 60 years. Although numerous immune abnormalities have been reported, the current literature is viewed with much skepticism because most of the studies have failed to control for extraneous factors that may have influenced the findings. Principally, antipsychotic medication, duration of illness, and current clinical state (acutely psychotic or remitted) may considerably alter immune response, as may other factors such as nutritional status, substance abuse, and concurrent medical illness. We review recent studies that employed current diagnostic criteria and modern immunologic techniques. (These studies were located by use of a Medline search on the terms schizophrenia and psychosis, cross-referenced with immune abnormalities, lymphokines, antibodies, lymphocytes, HLA, and medication, and by perusing the reference lists in the articles found through this search.) Immune abnormalities that have been replicated in studies of schizophrenic patients include increased prevalence of antinuclear antibodies, decreased production of interleukin-2, and increased serum concentrations of interleukin-2 receptor and interleukin-6. Given the current importance of autoimmunity as an etiologic mechanism in several branches of medicine, further studies are needed, especially those having a longitudinal design and including drug-naive patients.
 
Article
Multiple lines of evidence indicate that mood disorders are associated with abnormalities in the brain's cellular composition, especially in glial cells. Considered inert support cells in the past, glial cells are now known to be important for brain function. Treatments for mood disorders enhance glial cell proliferation, and experimental stimulation of cell growth has antidepressant effects in animal models of mood disorders. These findings suggest that the proliferation and survival of glial cells may be important in the pathogenesis of mood disorders and may be possible targets for the development of new treatments. In this article we review the evidence for glial abnormalities in mood disorders, and we discuss glial cell biology and evidence from postmortem studies of mood disorders. The goal is not to carry out a comprehensive review but to selectively discuss existing evidence in support of an argument for the role of glial cells in mood disorders.
 
Methodological Problems in Studies Used to Support Claims That Abortion Leads to Psychiatric Problems: Medical and Health Records and Physician Reports (Continued)
Standardized Measures or Self-Report of Physician Diagnosis
Standardized Measures or Self-Report of Physician Diagnosis (Continued)
Article
The objective of this review is to identify and illustrate methodological issues in studies used to support claims that induced abortion results in an "abortion trauma syndrome" or a psychiatric disorder. After identifying key methodological issues to consider when evaluating such research, we illustrate these issues by critically examining recent empirical studies that are widely cited in legislative and judicial testimony in support of the existence of adverse psychiatric sequelae of induced abortion. Recent studies that have been used to assert a causal connection between abortion and subsequent mental disorders are marked by methodological problems that include, but not limited to: poor sample and comparison group selection; inadequate conceptualization and control of relevant variables; poor quality and lack of clinical significance of outcome measures; inappropriateness of statistical analyses; and errors of interpretation, including misattribution of causal effects. By way of contrast, we review some recent major studies that avoid these methodological errors. The most consistent predictor of mental disorders after abortion remains preexisting disorders, which, in turn, are strongly associated with exposure to sexual abuse and intimate violence. Educating researchers, clinicians, and policymakers how to appropriately assess the methodological quality of research about abortion outcomes is crucial. Further, methodologically sound research is needed to evaluate not only psychological outcomes of abortion, but also the impact of existing legislation and the effects of social attitudes and behaviors on women who have abortions.
 
Article
Attention-deficit hyperactivity disorder (ADHD) and substance-use disorders are related to each other in a variety of ways. Although within the child-psychiatry literature earlier investigations were inconsistent regarding such a link, recent prospective studies that followed hyperactive children and normal controls into adulthood have found that hyperactive adults with a history of ADHD are more likely than controls to have substance-use disorders. The substance-abuse literature is less consistent regarding the potential association between ADHD and substance abuse. However, recent studies suggest that persons with a substance-use disorder, and particularly those with a cocaine-use disorder, may be more likely than the general population to have a childhood history of ADHD. Some of the inconsistency regarding this association is due to differences in diagnostic criteria, type of assessments used, and reliability of information obtained. Each of the potential relationships that may exist between ADHD and substance abuse has treatment implications for the clinician. Pharmacological as well as nonpharmacological approaches deserve further investigation. Because pharmacotherapy is a central component in the treatment of childhood ADHD, clinicians designing a strategy to treat both a substance-use disorder and ADHD need to consider pharmacological interventions. At present, the literature on pharmacological treatment for childhood ADHD is extensive and that for adult ADHD is growing; information regarding the treatment of cocaine abuse and concomitant ADHD symptoms remains limited.
 
Article
Buprenorphine, an opioid mixed agonist-antagonist, is a potent analgesic that appears to be effective for the treatment of opiate abuse. Recent preclinical studies have shown that buprenorphine also significantly reduces cocaine self-administration by rhesus monkeys for periods up to 120 days. This unexpected finding has led to clinical trials to evaluate buprenorphine's effectiveness for the treatment of dependence on both cocaine and opiates, as defined by DSM-III-R criteria. Buprenorphine's safety in combination with cocaine and opiates and its effects on electroencephalographic sleep patterns and regional cerebral blood flow were evaluated during inpatient studies. Buprenorphine (4 or 8 mg/day given sublingually) did not accentuate the cardiovascular and respiratory changes induced by an acute challenge dose of cocaine (30 mg given intravenously) or morphine (10 mg given intravenously) alone. In an outpatient open trial, buprenorphine significantly reduced both opiate and cocaine abuse by patients who had abused these drugs for more than 10 years. Most of these patients had failed in other drug abuse treatment programs. Reports of needle sharing also decreased significantly, and no patient tested positive for human immunodeficiency virus (HIV). The apparent safety and effectiveness of buprenorphine, combined with a high level of patient acceptance, led the Food and Drug Administration to grant a compassionate extension of the approved period for outpatient buprenorphine treatment from 26 to 52 weeks. Clinical trials of buprenorphine are ongoing. Possible mechanisms underlying buprenorphine-cocaine interactions are now under investigation.
 
Article
Although it is commonly accepted that interpersonal violence (IntPV) leads to adverse health consequences, the available data are far from decisive. To test the hypothesized link, the authors devised an evidence-based strategy to determine the data quality in studies purporting to link IntPV and some medically unexplained disorders in women (irritable bowel syndrome, chronic pelvic pain, fibromyalgia/chronic fatigue, and other chronic pain syndromes). English language studies with control groups of unaffected women were assessed for the quality of their methodologies. The number of studies, together with the consistency of their findings in each domain, was collated to determine the overall weight of evidence regarding the link for each condition. The quantity and quality of research in each clinical area proved to be sparse. In general, most research was limited to small, convenience samples, with insufficient attention to the design of control groups and to sample size. The evidence currently available regarding irritable bowel syndrome, fibromyalgia/chronic fatigue, chronic pelvic pain, and other chronic pain syndromes does not allow for any firm conclusion regarding their link to IntPV. More research - paying particular regard to the methodological concerns identified here - is required in order to generate any definitive conclusions.
 
Article
This review will examine issues related to the validity of memories of child abuse in patients with borderline personality disorder (BPD). A large body of research has shown that all memories are distorted by cognitive schema, and that "recovered memories" may be particularly unreliable. Empirical findings on trauma in BPD will be reviewed, as well as the difficulties in verifying trauma histories. Evidence will be examined suggesting that borderline patients have a distorted perception of interpersonal events. Clinical recommendations will be made for the evaluation of memories of abuse in patients with BPD.
 
Continued 
Article
After participating in this educational activity, the reader should be better able to identify the instruments that are currently being used to measure quality of life (QoL) in alcohol abuse and dependence; determine the impact of alcohol abuse and dependence on QoL; and evaluate the impact of treating alcohol abuse and dependence on QoL. Quality of life, which consists of the physical, mental, and social domains, has been shown to be negatively affected by alcohol abuse and dependence. This review aims to examine QoL in alcohol abuse and dependence by reviewing the instruments used to measure it and by analyzing the impact of alcohol abuse and dependence and of treatment on QoL. Studies were identified using a database search of PubMed and PsycINFO from the past 40 years (1971-2011) using the following keywords: abuse OR dependence, OR use AND alcohol, AND Quality of Life, QoL, Health-related quality of life, HRQOL. Two authors agreed independently on including 50 studies that met specific selection criteria. Although several global measures of QoL have established reliability and validity, many alcohol-specific measures of QoL have not yet been validated. Nevertheless, QoL has been shown to be significantly impaired in those with alcohol abuse and dependence, particularly in the domains of mental health and social functioning, the very areas that show the greatest improvement with abstinence and its maintenance. Moreover, the literature demonstrates the utility of using QoL measures throughout assessment and treatment as a motivational tool and as a marker for treatment efficacy. Measuring and monitoring QoL during assessment and treatment can add important value to patient recovery, for QoL improves with treatment and successful abstinence. Therefore, targeted, disease-specific assessments of QoL are warranted to address the impairments in the physical, mental, and social domains in alcohol abuse and dependence, thereby improving long-term outcomes.
 
Article
Despite the high prevalence of the psychoactive substance use disorders (PSUDs), relatively little is known about the childhood antecedents of these disorders. To examine this issue a comprehensive review of the English-language literature on studies of preadolescents (< 12 years) who subsequently developed PSUDs or were offspring of parents with PSUDs was undertaken. In all, nine longitudinal studies and 13 cross-sectional studies were identified. Data from studies of subjects at high risk for PSUDs indicate that children of parents with PSUDs are at increased risk for the development of temperamental, personality, non-PSUD psychiatric, cognitive, and psychosocial disturbances. Longitudinal studies also indicate that children with these neuropsychiatric disturbances are at increased risk for the development of PSUDs in adolescence and adulthood. We conclude that neuropsychiatrically impaired children of parents with PSUDs may represent those at highest risk for later development of PSUDs. Because these neuropsychiatric disorders are potentially treatable, their identification may lead to effective early intervention strategies.
 
Relationship of “common vulnerability” to vulnerability for each illicit drug category. 
Relationship of genetic aspects of “common vulnerability” to genetic aspects of vulnerability for each illicit drug category. Proportion of variance in drug abuse attributable to genetic factors: marijuana, 33%; stimulants, 33%; sedatives, 27%; heroin/opiates, 54%; PCP/psychedelics, 26%. 
Proportions of Variance in Abuse of/Dependence on Illicit Drugs Accounted for by Genetic and Environmental Influences
Relationship of family environmental aspects of “common vulnerability” to family environmental aspects of vulnerability for each illicit drug category. Proportion of variance in drug abuse attributable to family environmental factors: marijuana, 29%; stimulants, 18%; sedatives, 17%; heroin/opiates, 15%; PCP/ psychedelics, 19%. 
Relationship of nonfamily environmental aspects of “common vulnerability” to nonfamily environmental aspects of vulnerability for each illicit drug category. Proportion of variance in drug abuse attributable to nonfamily environmental factors: marijuana, 38%; stimulants, 48%; sedatives, 56%; heroin/opiates, 33%; PCP/psychedelics, 52%. 
Article
The Harvard Twin Study of Substance Abuse was carried out with the members of the Vietnam Era Twin (VET) Registry. The VET Registry comprises over 8000 male twins who served in the United States military between 1965 and 1975 and were subsequently interviewed regarding their use of licit and illicit substances, as well as various types of psychopathology. Our research has demonstrated significant influences by genetic, shared environmental, and unique environmental factors on the abuse of illicit substances. Multivariate analyses have indicated that the co-occurrence of abuse of various types of illicit drugs reflects a common vulnerability, influenced by both genetic and environmental factors, that cuts across all categories of illicit drugs. We have also demonstrated that some drugs have unique determinants, both genetic and environmental, that are not shared with other drugs. In part, the genetic influence on marijuana abuse is mediated by genetic influence on subjective effects in response to the drug. The determinants of transitions from one stage of drug use to another differ depending on which drug or which transition is examined. We determined significant genetic influences on several aspects of nicotine and alcohol use separately, as well as genetic influences shared by both substances. We found that the co-occurrence of illicit drug abuse and major depression is due to unique environmental influences. The phenotypic association between symptoms of conduct disorder and alcohol and marijuana dependence is due largely to shared environmental influences. Our results, thus far, indicate a complex pattern of genetic and environmental influences on substance use and abuse.
 
Article
Physician impairment is a serious public health issue affecting physicians as well as their families, colleagues, and patients. Though physicians generally display healthier habits than members of the general population, overall rates of impairment are similar among both groups, and prescription drug abuse (including prescription opioids) is particularly problematic among physicians. The current review focuses mainly on prescription opioid abuse and dependence among physicians. It includes a brief history of early physician experiences with anesthetic and analgesic agents, and explores several hypotheses regarding the etiology of prescription opioid abuse and dependence among physicians. Barriers to identification and to treatment entry among physicians are discussed. In addition, methods of assessment and successful treatment in specialized impaired physician programs are described. Medical and psychosocial interventions, 12-step involvement, and extensive use of evaluations are highlighted. Attention is paid to typical follow-up contracting and monitoring strategies, as well as strategies for prevention. Given the extremely positive outcomes demonstrated by specialized programs for treating impaired professionals, it is recommended that their methods be disseminated and utilized in treatment centers for the general public.
 
Article
The complex factors that can lead to either creative or destructive experiences in psychotherapy for both patients and therapists are explored with reference to the treatment of patients with a history of abuse. Particular emphasis is placed upon the formation of an intermediate space, in which a safe therapeutic environment is established, allowing for the creative interplay of past and present. The concepts of the transitional object, transitional phenomena, and projective identification are defined and amplified in explaining how they help to determine whether a safe therapeutic space is achieved, or whether destructive, abusive experiences are re-created, for both patient and therapist. In addition, the importance of the therapist's capacity to tolerate the ambiguity and uncertainty of psychotherapy is elaborated. The relationship between these formulations and the therapist's countertransference is emphasized. Also described is the importance of supervision in helping therapists--during training and throughout professional life--to discuss shame-arousing experiences with their patients.
 
Article
CASE HISTORY Mr. J. was a 41-year-old research assistant’when he was first referred for psychopharmacological consultation for depression. He and his psychotherapist, an experienced clinical psychologist, thought that their 18-month-long therapy was progressing too slowly. Both attributed this mainly to Mr. J.’s unremittingly negative opinion of himself. Mr. J. described himself as having been unhappy as far back as he could remember. He had first visited a therapist at the age of 5 and had seen therapists on and off when he was a teenager. He recalled feeling hopeless and socially isolated during adolescence. As a high school senior, he had tried to run his car off a bridge but had turned the steering wheel back at the last moment. He was gifted academically but had dropped out of college after a few semesters. Over the next two decades he married and divorced twice. He received psychotherapy for depression, but his chronic dysphoria continued unchanged. He had poor self-esteem and low energy but few other neurovegetative symptoms of depression. Although he functioned below his potential at his job, he was never unable to work. As an adult, he had not experienced periods of mania, hypomania, or psychosis, had never attempted suicide, and had not been hospitalized for depression. At age 40, after
 
Gender Differences in Stress-System Changes Following Acute Drug Administration 
Gender Differences in Stress-System Changes Following Stress or Drug Cue 
Article
Extensive research indicates that chronic substance abuse disrupts stress and reward systems of the brain. Gender variation within these stress-system alterations, including the impact of sex hormones on these changes, may influence sex-specific differences in both the development of, and recovery from, dependency. As such, gender variations in stress-system function may also provide a viable explanation for why women are markedly more vulnerable than men to the negative consequences of drug use. This article therefore initially reviews studies that have examined gender differences in emotional and biophysiological changes to the stress and reward system following the acute administration of drugs, including cocaine, alcohol, and nicotine. The article then reviews studies that have examined gender differences in response to various types of stress in both healthy and drug-abusing populations. Studies examining the impact of sex hormones on these gender-related responses are also reported. The implications of these sex-specific variations in stress and reward system function are discussed in terms of both comorbid psychopathology and treatment outcome.
 
Top-cited authors
Jean Frazier
  • University of Massachusetts Medical School
Kai Macdonald
  • University of California, San Diego
Ed Tronick
  • University of Massachusetts Boston
David Cochran
  • University of Massachusetts Medical School
Waguih William IsHak, MD, FAPA
  • Cedars-Sinai Medical Center