The search for the causes of medical and psychiatric disorders has gone through 3 historical phases. First, up until the mid-19th century, causes of illness were anecdotally recorded from individual ...cases, resulting in long and diverse lists for all disorders. Second, in the latter half of the 19th century, with the use of microbiological methods, single causes were found for many infectious diseases that led to specific diagnostic tests, effective preventions, and, in some cases, treatments. Causal thinking in medicine shifted from the earlier multicausal approaches to monocausal theories of etiology. Indeed, proving monocausal etiology became a way to establish the legitimacy of a disorder. Through the writings of Kahlbaum and Hecker, psychiatry was deeply influenced by this monocausal perspective, the importance of which was substantially amplified by a twist of fate: the increasing clinical importance of general paresis of the insane throughout the 19th century and the eventual proof that it too was a monocausal condition. However, in the mid-20th century, the third phase began. With decreasing deaths from infectious diseases, epidemiology and clinical medicine shifted to a chronic disease model in which paradigmatic disorders, such as cancer and cardiovascular disease, were shown to be highly multicausal. Biostatistics evolved from deterministic to probabilistic models of disease risk factors. Paradoxically, at this time, biological psychiatry, then rising to dominance in American psychiatry, vigorously pursued monocausal theories, first of neurochemical origin and then of genetic origin. We were trying to establish the legitimacy of our field by pursuing an outmoded model—that “real” diseases are monocausal. Despite ample evidence to the contrary, monocausal thinking continues to influence our field, for example, in the popular but improbable view that we can, with a few key advances, move easily from descriptive to etiologically based diagnoses.
How should DSM criteria relate to the disorders they are designed to assess? To address this question empirically, the author examines how well DSM-5 symptomatic criteria for major depression capture ...the descriptions of clinical depression in the post-Kraepelin Western psychiatric tradition as described in textbooks published between 1900 and 1960. Eighteen symptoms and signs of depression were described, 10 of which are covered by the DSM criteria for major depression or melancholia. For two symptoms (mood and cognitive content), DSM criteria are considerably narrower than those described in the textbooks. Five symptoms and signs (changes in volition/motivation, slowing of speech, anxiety, other physical symptoms, and depersonalization/derealization) are not present in the DSM criteria. Compared with the DSM criteria, these authors gave greater emphasis to cognitive, physical, and psychomotor changes, and less to neurovegetative symptoms. These results suggest that important features of major depression are not captured by DSM criteria. This is unproblematic as long as DSM criteria are understood to index rather than constitute psychiatric disorders. However, since DSM-III, our field has moved toward a reification of DSM that implicitly assumes that psychiatric disorders are actually just the DSM criteria. That is, we have taken an index of something for the thing itself. For example, good diagnostic criteria should be succinct and require minimal inference, but some critical clinical phenomena are subtle, difficult to assess, and experienced in widely varying ways. This conceptual error has contributed to the impoverishment of psychopathology and has affected our research, clinical work, and teaching in some undesirable ways.
The genetics of major depression Flint, Jonathan; Kendler, Kenneth S
Neuron (Cambridge, Mass.),
02/2014, Letnik:
81, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Major depression is the commonest psychiatric disorder and in the U.S. has the greatest impact of all biomedical diseases on disability. Here we review evidence of the genetic contribution to disease ...susceptibility and the current state of molecular approaches. Genome-wide association and linkage results provide constraints on the allele frequencies and effect sizes of susceptibility loci, which we use to interpret the voluminous candidate gene literature. We consider evidence for the genetic heterogeneity of the disorder and the likelihood that subtypes exist that represent more genetically homogenous conditions than have hitherto been analyzed.
IMPORTANCE: This article aims to determine the degree to which modern operationalized diagnostic criteria for schizophrenia reflect the main clinical features of the disorder as described ...historically by diagnostic experts. OBSERVATIONS: Amazon.com, the National Library of Medicine, and Forgottenbooks.com were searched for articles written or translated into English from 1900 to 1960. Clinical descriptions of schizophrenia or dementia praecox appearing in 16 textbooks or review articles published between 1899 and 1956 were reviewed and compared with the criteria for schizophrenia from 6 modern US operationalized diagnostic systems. Twenty prominent symptoms and signs were reported by 5 or more authors. A strong association was seen between the frequency with which the symptoms/signs were reported and the likelihood of their presence in modern diagnostic systems. Of these 20 symptoms/signs, 3 (thought disorder, delusions, and hallucinations) were included in all diagnostic systems and were among the 4 most frequently reported. Three symptoms/signs were added then kept in subsequent criteria: emotional blunting, changes in volition, and changes in social life. Three symptoms/signs were added but then dropped: bizarre delusions, passivity symptoms, and mood incongruity. Eleven symptoms/signs were never included in any diagnostic system. Compared with historical authors, modern criteria favored symptoms over signs. Odd movements and postures, noted by 16 of 18 historical authors, were absent from all modern criteria. DSM-5 criteria contain 6 of the 20 historically noted symptoms/signs. CONCLUSIONS AND RELEVANCE: Although modern operationalized criteria for schizophrenia reflect symptoms and signs commonly reported by historical experts, many clinical features emphasized by these experts are absent from modern criteria. This is not necessarily problematic as diagnostic criteria are meant to index rather than thoroughly describe syndromes. However, the lack of correspondence in schizophrenia between historically important symptoms/signs and current diagnostic systems highlights the limitations of clinical evaluations and research studies that restrict the diagnostic assessments to current diagnostic criteria. We should not confuse our DSM diagnostic criteria with the disorders that they were designed to index.
Psychiatric genetics has taught us a great deal about the nature of psychiatric disorders. Traditional family, twin and adoption studies have demonstrated the substantial role of genetic factors in ...their etiology, clarified the role of genetic factors in comorbidity, elucidated development pathways, and documented the importance of gene-environment correlation and interaction. We have also received some hard lessons when we were unable to detect replicable genes of large effect size and found that our much-valued candidate genes did not live up to their expected promise. With more mature molecular and statistical methods, we are entering now a different era. Statistical analyses of aggregate molecular signals are validating earlier heritability estimates. Replicated findings from genome-wide association studies are beginning to emerge, as are discoveries of large-effect size rare genomic variants. The number of such findings is likely to soon grow dramatically. The most pressing question facing the field is what biological picture these results will reveal. I articulate four possible scenarios that reflect (i) no, (ii) minimal, (iii) moderate and (iv) high biological coherence in the replicated molecular variant findings, which are soon likely to emerge. I discuss the factors that will likely influence these patterns, including the problems of etiological heterogeneity and multiple realizability. These findings could provide critical insights into the underlying biology of our psychiatric syndromes and potentially permit us to perceive, 'through a glass darkly,' the levels of the mind-brain system that are disordered.
While psychiatric genetics has emerged as one of our most dynamic research fields, the historical context in which we view these developments is limited. To provide such a perspective, the author ...reviews 48 representative texts, published from 1780 to 1910, examining the inheritance of insanity. Six main conclusions emerge. First, most authors viewed heredity as among the strongest risk factors for insanity. Second, most writers concluded that a predisposition to illness rather than the illness itself was transmitted in families. Third, the probabilistic nature of the transmission was noted, as insanity often skipped generations or affected only a few of many siblings. Fourth, authors discussed the homogeneity versus heterogeneity of familial transmission of the various forms of insanities. Heterogeneous transmission was usually seen as the rule—with relatives of insane patients affected with a wide variety of psychiatric, and sometimes neurological, illnesses. Homogeneous transmission (“like begets like”) was the exception. Fifth, writers noted that odd and eccentric personality features were common in the relatives of their insane patients. Finally, inheritance was commonly understood to include prior environmental parental experiences, and some authors noted that parent-offspring transmission of insanity could arise from psychological or intrauterine effects. Many of these conclusions, arising solely from clinical experience and without an understanding of biological mechanisms, statistical analyses, or necessary controls, are supported by later, more rigorous methods. Rather than entirely rejecting its value, we might view this literature as a complementary resource, likely more biased, but suffused with the extensive clinical knowledge of our forebears.
IMPORTANCE: Associations between putative risk factors and psychiatric and substance use disorders are widespread in the literature. Basing prevention efforts on such findings is hazardous. Applying ...causal inference methods, while challenging, is central to developing realistic and potentially actionable etiologic models for psychopathology. OBSERVATIONS: Causal methods can be divided into randomized clinical trials (RCTs), natural experiments, and statistical models. The first 2 approaches can potentially control for both known and unknown confounders, while statistical methods control only for known and measured confounders. The criterion standard, RCTs, can have important limitations, especially regarding generalizability. Furthermore, for ethical reasons, many critical questions in psychiatric epidemiology cannot be addressed by RCTs. We review, with examples, methods that try to meet as-if randomization assumptions, use instrumental variables, or use pre-post designs, regression discontinuity designs, or co-relative designs. Each method has strengths and limitations, especially the plausibility of as-if randomization and generalizability. Of the large family of statistical methods for causal inference, we examine propensity scoring and marginal models, which are best applied to samples with strong predictors of risk factor exposure. CONCLUSIONS AND RELEVANCE: Causal inference is important because it informs etiologic models and prevention efforts. The view that causation can be definitively resolved only with RCTs and that no other method can provide potentially useful inferences is simplistic. Rather, each method has varying strengths and limitations. We need to avoid the extremes of overzealous causal claims and the cynical view that potential causal information is unattainable when RCTs are infeasible. Triangulation, which applies different methods for elucidating causal inferences to address to the same question, may increase confidence in the resulting causal claims.
The modern concept of depression arose from earlier diagnostic formulations of melancholia over the hundred years from the 1780s to the 1880s. In this historical sketch, this evolution is traced from ...the writings of 12 authors outlining the central roles played by the concepts of faculty psychology and understandability. Five of the authors, writing from 1780 through the 1830s, including Cullen, Pinel, and Esquirol, defined melancholia as a disorder of intellect or judgment, a “partial insanity” often, but not always, associated with sadness. Two texts from the 1850s by Guislain, and Bucknill and Tuke were at the transition between paradigms. Both emphasized a neglected disorder—melancholia without delusions—arguing that it reflected a primary disorder of mood—not of intellect. In the final phase in the 1860s to 1880s, 5 authors (Griesinger, Sankey, Maudsley, Krafft-Ebing, and Kraepelin) all confronted the problem of the cause of delusional melancholia. Each author concluded that melancholia was a primary mood disorder and argued that the delusions emerged understandably from the abnormal mood. In this 100-year period, the explanation of delusional melancholia in faculty psychology terms reversed itself from an intellect to mood to a mood to intellect model. The great nosologists of the 19th century are often seen as creating our psychiatric disorders using a simple inductive process, clustering the symptoms, signs, and later the course of the patients. This history suggests 2 complexities to this narrative. First, in addition to bottom-up clinical studies, these nosologists were working top-down from theories of faculty psychology proposed by 18th century philosophers. Second, for patient groups experiencing disorders of multiple faculties, the nosologists used judgments about understandability to assign primary causal roles. This historical model suggests that the pathway from patient observation to the nosologic categories—the conceptual birth of our diagnostic categories—has been more complex than is often realized.
While sufferers of major depression to the present day sometimes describe their experience as "mental pain," limited attention has been given to one of the major etiologic theories of 19th century ...psychiatry: melancholia as psychalgia. I illustrate the development of this theory, which arose in the context of the early phases of the application of psychophysiology to mental illness, through German, French, and English psychiatric texts from the 1830-1870s. As clinical pathological correlation became a dominant paradigm in early 19th medicine, nervous diseases stood out as potential exceptions, sometimes demonstrating "pain without lesions" or neuralgia. Tic Douloureux was a paradigmatic example. The first descriptions of reflex actions in the spinal cord in the early 19th century resulted in a range of theories of reflexes in brain that expanded to include "ganglia" that could react to diverse complex social and mental stimuli, and whose actions could impact key mental functions including mood. Theories of neuralgia included a constitutional predisposition and an acute physical trauma producing a hypersensitivity so that normal stimuli (e.g., touch) were misinterpreted as excruciating pain. A parallel framework was conceptualized in the brain to produce psychalgia. A predisposition combined with a mental trauma could produce hypersensitivity in key brain ganglia. This psychophysiological framework explained how normal social and introspective experiences would, in melancholic patients, be interpreted in a distorted manner, reinforcing themes of inadequacy, failure, and worthlessness, and produce a sustained mood state of intense mental pain or psychalgia. I illustrate the development of this theory, which integrated brain and mind-based perspectives on mental illness, through the writings of four major 19th alienists: Guislain, Griesinger, Maudsley, and Krafft-Ebing.
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