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Socratic questioning is used to enhance the process of guided discovery in psychotherapy sessions. OBJECTIVE: Socratic questioning and guided discovery are defined, and assorted clinical examples are provided. METHODS: The limited research on the impact of Socratic questioning is reviewed and integrated with 30 + years of clinical experience. RESULTS: The scant research suggests that Socratic questioning significantly reduces depression from one session to the next, particularly for patients with a pessimistic cognitive bias, but there is no research on patient improvements at the end of psychotherapy. CONCLUSION: Socratic questions and guided discovery can facilitate sensitivity to issues related to diversity and can be useful in psychotherapy training. The Socratic approach relies on an integration of the research evidence, ancient philosophy, and contemporary cognitive therapy.
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Terapia Cognitivo-Conductual , Humanos , PsicoterapiaRESUMEN
The Psyche Awards were developed to recognize the best journal articles published during the previous year. Each award confronts a specific topic within the field of mental health care, identifying articles that integrate the science and practice of psychology. For the current awards, 161 journals were screened, and 223 relevant articles were identified. The papers were then narrowed down to 46 papers distributed across 11 award categories. A panel of four expert judges read each article and rated all papers for their contribution to the field. The current award categories highlight some of the best articles published during 2021, capturing important information about psychological assessment, treatment of depression, working with suicidal clients, technology-assisted psychotherapy, the impact of Covid-19 on mental health, lessons from a review of history, recent innovations in the field, and strategies to expand the integration of science and practice.
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Psychotherapy relies on a strong integration of theory, empirical research, and clinical experience. Furthermore, publishing journal articles on the diagnosis and treatment of mental illness requires creativity, persistence and a scientific approach. The present article examines recent publications on assessment and diagnosis, case conceptualization and treatment planning and generic issues related to the therapeutic alliance. The article includes a review of papers on common diagnostic problems including anxiety disorders, depression, eating disorders, addictions, and personality pathology. In each of ten categories, the best papers are identified that were published during the past year, and the top article is highlighted as an award winner that should be read by all mental health professionals.
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Objectives: Hope/hopelessness is an important determinant of health and death, and is a modifiable risk factor for older adults. The present review aimed to evaluate the effectiveness of interventions on hope among older populations. Methods: PsychINFO and PubMed were systematically searched. Publications reporting on interventions delivered to older adults that included quantitative data on hope/hopelessness were systematically reviewed. Results: Thirty-six studies were included, most with hope/hopelessness as a secondary outcome. Interventions based on CBT alone or combined with antidepressants significantly decreased hopelessness in depressed older adults. Psychological interventions based on life review effectively improved hope/hopelessness in a range of samples, including depressed, bereaving, or medically ill older adults. Little to no support was found for exercise programs for healthy older adults, educational interventions for medically ill individuals, or Dignity Therapy for palliative care patients. Conclusions: Hope/hopelessness in older adults can be improved using psychological interventions based on CBT and life review. Controlled trials with hope/hopelessness as a primary objective are needed to more clearly demonstrate effectiveness. Clinical implications: Cognitive-behavioral interventions can improve hopelessness in depressed older adults. Life-review based interventions can positively impact hope in a range of older populations. Dignity Therapy, physical exercise, and educational programs may not effectively improve hope/hopelessness in older adults.
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Terapia Cognitivo-Conductual , Esperanza , Afecto , Anciano , Antidepresivos , Humanos , Cuidados PaliativosRESUMEN
OBJECTIVE: The present study aimed to understand how key risk factors of older adult suicide interact to ultimately lead to death by suicide using data collected post-mortem. METHOD: A psychological autopsy was used to gather detailed information about psychiatric diagnosis, medical problems, social isolation, and negative attitudes expressed by the individual during the six months prior to their death. Interviews with next-of-kin, medical and psychiatric records, and the Cumulative Illness Rating Scale for Geriatrics were used. Subjects included 32 older adults who died by suicide and 45 older adults who died by natural causes. RESULTS: Hopelessness, depression, and negative health attitudes were strongly correlated with suicide. Older age was associated with social isolation, suggesting an indirect relationship with suicide via hopelessness, depression, and negative health attitudes. Physical illness did not increase risk. Multivariate analyses suggested that hopelessness fully mediated the effects of social isolation, negative health attitudes, and depression on suicide. CONCLUSIONS: Psychological factors played the largest role in suicide deaths compared to social isolation and physical illness. Suicide interventions aimed at older adults should ensure hopelessness, depression, and negative health attitudes are primary targets.
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Trastornos Mentales , Suicidio , Anciano , Humanos , Factores de Riesgo , Autoimagen , Aislamiento SocialRESUMEN
Every spring, media coverage emphasizes the "award season", highlighting contributions made by musicians, actors, and professional athletes. Unfortunately, psychologists are not included in these gala celebrations. It seems appropriate to take time to praise the hard work and dedication that is required to publish in an academic journal. The present article summarizes the results from the 3rd annual psychotherapy award program designed to highlight the valuable contributions made in eleven different categories. A total of 81 academic journals were reviewed for their articles published during 2019, and 150 papers were found useful and relevant to the field of psychotherapy. The list was then shortened to 44 articles that were organized into eleven award categories, and the best paper in each category was selected by a panel from the journal's editorial board. The hope is that all psychotherapists will value the contributions being made in these articles.
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BACKGROUND: Opiate misuse has reached epidemic levels. Prevention efforts depend on distinguishing opiate users from abusers. The current study compared opioid users who died by natural cases, accidents, and suicide using psychological autopsy methods. Groups were compared on substance use characteristics, treatment history, experiences of negative life events, and circumstances at the time of death. METHODS: Substance use and suicide risk were evaluated using psychological autopsy methods in 63 decedents with positive toxicology for opiates at death divided into three groups: adults dying by suicide (n = 19), accident (n = 19), and natural causes (n = 25). Groups were compared on several dependent measures, using chi-square analyses to examine categorical variables and one-way analyses of variance (ANOVA) to examine continuous variables. RESULTS: Individuals who died by suicide were similar in many ways to adults who died by an accidental overdose. However, suicide completers were more likely to have struggled with severe depression, and previously attempted suicide, whereas the accidental overdose sample was more likely to display a chronic pattern of severe drug abuse. CONCLUSIONS: The current study helps to distinguish between opiate users who are at risk for death by an accidental or intentional overdose. In the ongoing opiate crisis, clinicians must understand the risk of overdose and the nuances of accidental behaviors compared to purposeful ones. Signs of suicidal planning, relevant psychopathology, and ongoing life stress may be useful points of intervention for stopping the increasing number of deaths among opiate users.
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Accidentes/mortalidad , Causas de Muerte , Alcaloides Opiáceos/efectos adversos , Sobredosis de Opiáceos/mortalidad , Estrés Psicológico/mortalidad , Suicidio , Accidentes/clasificación , Accidentes/psicología , Adulto , Anciano , Autopsia/clasificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sobredosis de Opiáceos/clasificación , Sobredosis de Opiáceos/psicología , Trastornos Relacionados con Opioides/clasificación , Trastornos Relacionados con Opioides/mortalidad , Trastornos Relacionados con Opioides/psicología , Factores de Riesgo , Estrés Psicológico/psicología , Suicidio/clasificación , Suicidio/psicología , Adulto JovenRESUMEN
Neurasthenia was a popular diagnosis from 1869 through 1930. Despite being discarded, the core symptoms of neurasthenia can still be found throughout modern society. The present article reviews the symptoms, common course, proposed causes, and common treatments for neurasthenia. Similarities are seen in several familiar diagnoses, including depression, chronic fatigue syndrome, and fibromyalgia. Through reviewing the trends of neurasthenia, modern doctors may learn more about the subtleties of the diagnostic process, as well as the patient-physician relationship. The goal is to learn from the past as it relates to current problems that may be related to the stress of modern living. The history of neurasthenia is presented as it relates to problems that may remain today.
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Neurastenia , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Neurastenia/etiología , Neurastenia/historia , Neurastenia/fisiopatología , Neurastenia/terapiaRESUMEN
Dorsolateral prefrontal cortex (DLPFC) and temporal pole (TP) are brain regions that display abnormalities in bipolar disorder (BD) patients. DNA methylation - an epigenetic mechanism both heritable and sensitive to the environment - may be involved in the pathophysiology of BD. To study BD-associated DNA methylomic differences in these brain regions, we extracted genomic DNA from the postmortem tissues of Brodmann Area (BA) 9 (DLPFC) and BA38 (TP) gray matter from 20 BD, ten major depression (MDD), and ten control age-and-sex-matched subjects. Genome-wide methylation levels were measured using the 850â¯K Illumina MethylationEPIC BeadChip. We detected striking differences between cortical regions, with greater numbers of between-brain-region differentially methylated positions (DMPs; i.e., CpG sites) in all groups, most pronounced in the BD group, and with substantial overlap across groups. The genes of DMPs common to both BD and MDD (hypothetically associated with their common features such as depression) and those distinct to BD (hypothetically associated with BD-specific features such as mania) were enriched in pathways involved in neurodevelopment including axon guidance. Pathways enriched only in the BD-MDD shared list pointed to GABAergic dysregulation, while those enriched in the BD-only list suggested glutamatergic dysregulation and greater impact on synaptogenesis and synaptic plasticity. We further detected group-specific between-brain-region gene expression differences in ODC1, CALY, GALNT2, and GABRD, which contained significant between-brain-region DMPs. In each brain region, no significant DMPs or differentially methylated regions (DMRs) were found between diagnostic groups. In summary, the methylation differences between DLPFC and TP may provide molecular targets for further investigations of genetic and environmental vulnerabilities associated with both unique and common features of various mood disorders and suggest directions of future development of individualized treatment strategies.
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Trastorno Bipolar/metabolismo , Metilación de ADN/fisiología , Trastorno Depresivo Mayor/metabolismo , Expresión Génica/fisiología , Genoma/fisiología , Corteza Prefrontal/metabolismo , Lóbulo Temporal/metabolismo , Adulto , Anciano , Autopsia , Islas de CpG , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
In a sample of 114 military veterans with depression histories, perceived burden was related to depression symptoms and suicide attempt history. After accounting for perceived burden, sense of belonging was negatively related to depression. Among the areas of social support, family support was inversely related to both depression and suicide history. After accounting for family support, personal meaning from relationships and friend support were related to depression. The results of this study suggest that perceived burdensomeness may be a stronger determinant of suicidality than sense of belonging or social support. This study highlights the contribution of perceived burdensomeness to suicide and depression.
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Costo de Enfermedad , Depresión/psicología , Familia/psicología , Percepción Social , Prevención del Suicidio , Suicidio , Veteranos/psicología , Adulto , Femenino , Humanos , Relaciones Interpersonales , Masculino , Persona de Mediana Edad , Apoyo Social , Ideación Suicida , Suicidio/psicología , Estados UnidosRESUMEN
Major Depressive Disorder (MDD) is a common psychiatric disorder for which available medications are often not effective. The high prevalence of MDD and modest response to existing therapies compels efforts to better understand and treat the disorder. Decreased hippocampal volume with increasing duration of depression suggests altered gene expression or even a decrease in neurogenesis. Tissue punches from the dentate gyrus were collected postmortem from 23 subjects with MDD and 23 psychiatrically-normal control subjects. Total RNA was isolated and whole transcriptome paired-end RNA-sequencing was performed using an Illumina NextSeq 500. For each sample, raw RNA-seq reads were aligned to the Ensembl GRCh38 human reference genome. Analysis revealed 30 genes differentially expressed in MDD compared to controls (FDR<0.05). Down-regulated genes included several with inflammatory function (ISG15, IFI44L, IFI6, NR4A1/Nur-77) and GABBR1 while up-regulated genes included several with cytokine function (CCL2/MCP-1), inhibitors of angiogenesis (ADM, ADAMTS9), and the KANSL1 gene, a histone acetyltransferase. Similar analyses of specific subsets of MDD subjects (suicide vs. non-suicide, single vs. multiple episodes) yielded similar, though not identical, results. Enrichment analysis identified an over-representation of inflammatory and neurogenesis-related (ERK/MAPK) signaling pathways significantly altered in the hippocampal dentate gyrus in MDD. Together, these data implicate neuro-inflammation as playing a crucial role in MDD. These findings support continued efforts to identify adjunctive approaches towards the treatment of MDD with drugs including anti-inflammatory and neuroprotective properties.
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Giro Dentado/metabolismo , Trastorno Depresivo Mayor/metabolismo , Expresión Génica , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Regulación de la Expresión Génica , Humanos , Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Transcriptoma , Adulto JovenRESUMEN
Functional imaging studies consistently report abnormal amygdala activity in major depressive disorder (MDD). Neuroanatomical correlates are less clear: imaging studies have produced mixed results on amygdala volume, and postmortem neuroanatomic studies have only examined cell densities in portions of the amygdala or its subregions in MDD. Here, we present a stereological analysis of the volume of, and the total number of, neurons, glia, and neurovascular (pericyte and endothelial) cells in the basolateral amygdala in MDD. Postmortem tissues from 13 subjects with MDD and 10 controls were examined. Sections (~15/subject) taken throughout the rostral-caudal extent of the basolateral amygdala (BLA) were stained for Nissl substance and utilized for stereological estimation of volume and cell numbers. Results indicate that depressed subjects had a larger lateral nucleus than controls and a greater number of total BLA neurovascular cells than controls. There were no differences in the number or density of neurons or glia between depressed and control subjects. These findings present a more detailed picture of BLA cellular anatomy in depression than has previously been available. Further studies are needed to determine whether the greater number of neurovascular cells in depressed subjects may be related to increased amygdala activity in depression.
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Complejo Nuclear Basolateral/patología , Trastorno Depresivo Mayor/patología , Adolescente , Adulto , Anciano , Recuento de Células , Células Endoteliales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuroglía/patología , Neuronas/patología , Pericitos/patología , Adulto JovenRESUMEN
BACKGROUND: People who feel they have become a burden on others may become susceptible to suicidal ideation. When people no longer feel capable or productive, they may assume that friends and family members would be better off without them. AIM: The present study was designed to assess preliminary psychometric properties of a new measure, the Perceived Burdensomeness (PBS) Scale. METHOD: Depressed psychiatric patients (N = 173) were recruited from a veterans affairs medical center. Patients were assessed with a structured diagnostic interview and self-report measures assessing perceived burdensomeness, depression severity, hopelessness, and suicidal ideation. RESULTS: The present study supported preliminary evidence of reliability and concurrent validity of the PBS. Additionally, perceived burdensomeness was significantly associated with higher levels of hopelessness and suicidal ideation. CONCLUSION: It is hoped that with the aid of the PBS clinicians may be able to intervene more specifically in the treatment of suicidality.
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Trastornos de Adaptación/psicología , Trastorno Depresivo Mayor/psicología , Trastorno Distímico/psicología , Autoimagen , Ideación Suicida , Veteranos/psicología , Adulto , Anciano , Trastornos de Ansiedad/psicología , Trastorno Depresivo/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Teoría Psicológica , Psicometría , Reproducibilidad de los Resultados , Trastornos por Estrés Postraumático/psicología , Trastornos Relacionados con Sustancias/psicología , Suicidio/psicología , Adulto JovenRESUMEN
OBJECTIVE: Sense of belonging has demonstrated significant relationships with depression and suicidal thoughts, highlighting its potential utility in refining assessment of suicide risk. METHOD: Structured clinical interviews and self-report measures were used to assess depression, suicidal behaviors, hopelessness, life stress, social support, and sense of belonging in a sample of 116 depressed psychiatric patients. RESULTS: Lower sense of belonging was significantly associated with greater severity of depression, hopelessness, suicidal ideation, and history of prior suicide attempt(s). However, sense of belonging did not predict suicidal ideation and history of prior suicide attempt(s) beyond the association between suicidal behaviors and established risk factors. Sense of belonging displayed a significant relationship with depression and hopelessness and is likely to play a critical role in both the development of and recovery from depression. CONCLUSIONS: Sense of belonging is directly related to depression and hopelessness, while indirectly related to suicidal ideation. Low sense of belonging provides an important target for assessment and intervention in the treatment of depression. Cognitive, behavioral, and interpersonal interventions may help improve an individual's sense of belonging and decrease symptoms of depression and hopelessness.
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Depresión/psicología , Aislamiento Social/psicología , Apoyo Social , Ideación Suicida , Suicidio/psicología , Adolescente , Adulto , Anciano , Trastorno Depresivo Mayor/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Psicológicos , Factores de Riesgo , Estrés Psicológico/psicología , Adulto JovenRESUMEN
The present study explored gender differences in suicidal methods, aiming to identify ways to improve our identification of individuals at risk for suicide. Preferred suicide methods vary by demographics; however, method-specific risk factors have not been consistently identified. All suicidal deaths (N=2,347) in a large urban county were identified over a 15-year period (1994-2008). The majority of men used shooting and hanging. In contrast, women relied on a variety of methods, including self-poisoning, shooting, hanging, and carbon monoxide poisoning. Significant demographic differences are evident among individuals who die by shooting and self-poisoning.
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Asfixia/mortalidad , Ahogamiento/mortalidad , Prevención del Suicidio , Suicidio , Heridas por Arma de Fuego/mortalidad , Adulto , Consumo de Bebidas Alcohólicas , Causas de Muerte/tendencias , Demografía , Femenino , Necesidades y Demandas de Servicios de Salud , Humanos , Masculino , Salud Mental , Persona de Mediana Edad , Ohio/epidemiología , Factores de Riesgo , Factores Sexuales , Suicidio/clasificación , Suicidio/psicología , Suicidio/estadística & datos numéricos , Suicidio/tendenciasRESUMEN
Major depressive disorder (MDD) has been linked to changes in function and activity of the hippocampus, one of the central limbic regions involved in regulation of emotions and mood. The exact cellular and molecular mechanisms underlying hippocampal plasticity in response to stress are yet to be fully characterized. In this study, we examined the genetic profile of micro-dissected subfields of post-mortem hippocampus from subjects diagnosed with MDD and comparison subjects matched for sex, race and age. Gene expression profiles of the dentate gyrus and CA1 were assessed by 48K human HEEBO whole genome microarrays and a subgroup of identified genes was confirmed by real-time polymerase chain reaction (qPCR). Pathway analysis revealed altered expression of several gene families, including cytoskeletal proteins involved in rearrangement of neuronal processes. Based on this and evidence of hippocampal neuronal atrophy in MDD, we focused on the expression of cytoskeletal, synaptic and glutamate receptor genes. Our findings demonstrate significant dysregulation of synaptic function/structure related genes SNAP25, DLG2 (SAP93), and MAP1A, and 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid receptor subunit genes GLUR1 and GLUR3. Several of these human target genes were similarly dysregulated in a rat model of chronic unpredictable stress and the effects reversed by antidepressant treatment. Together, these studies provide new evidence that disruption of synaptic and glutamatergic signalling pathways contribute to the pathophysiology underlying MDD and provide interesting targets for novel therapeutic interventions.
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Trastorno Depresivo Mayor/genética , Hipocampo/metabolismo , Hipocampo/patología , Proteínas del Tejido Nervioso/genética , Receptores de Glutamato/genética , Sinapsis/genética , Adulto , Anciano , Anciano de 80 o más Años , Animales , Trastorno Depresivo Mayor/metabolismo , Trastorno Depresivo Mayor/patología , Femenino , Regulación de la Expresión Génica , Guanilato-Quinasas/biosíntesis , Guanilato-Quinasas/genética , Humanos , Masculino , Proteínas Asociadas a Microtúbulos/biosíntesis , Proteínas Asociadas a Microtúbulos/genética , Persona de Mediana Edad , Proteínas del Tejido Nervioso/biosíntesis , Ratas , Ratas Sprague-Dawley , Receptores AMPA/biosíntesis , Receptores AMPA/genética , Receptores de Glutamato/biosíntesis , Sinapsis/metabolismo , Proteína 25 Asociada a Sinaptosomas/biosíntesis , Proteína 25 Asociada a Sinaptosomas/genética , Proteínas Supresoras de Tumor/biosíntesis , Proteínas Supresoras de Tumor/genéticaRESUMEN
OBJECTIVE: Late-life depression has been associated with risk for cerebrovascular pathology, as demonstrated in neuroimaging studies of older depressed patients, as well as mood disorder following cerebrovascular accidents. However, more research is needed on neuroanatomical changes in late-life depression, where there has been no clearly documented link to brain injury. Such studies should examine morphological changes in medium and small sized vessels that supply the cortical gray and white matter. METHODS: The present study used a non-specific histological Nissl staining and a more vessel-specific immunolabeling with endothelial marker von Willebrand Factor (vWF) to estimate density and size of blood vessel segments in the orbitofrontal cortex of 16 older subjects with major depressive disorder (MDD) and 9 non-psychiatric comparison subjects. RESULTS: The density of Nissl-stained vessel segments and of segments with perivascular spaces was higher in subjects with MDD than in comparison subjects in gray (GM) and white matter (WM). In GM, the density of vWF-immunoreactive segments with cross-sectional areas greater than 800 µm2 was higher in MDD. In WM, only the density of vWF-immunoreactive segments with patent perivascular spaces and diameters larger than 60 µm was higher in subjects with MDD. Also in the WM, only subjects with late-onset MDD presented a significantly higher density of vWF-positive segments than comparison subjects. CONCLUSIONS: In older subjects with MDD, there appear to be morphological changes that increase visibility of medium-sized vessel segments with some labeling techniques, and this increased visibility may be related to increased patency of perivascular spaces around arterioles.
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Trastorno Depresivo Mayor/patología , Corteza Prefrontal/irrigación sanguínea , Anciano , Anciano de 80 o más Años , Autopsia , Estudios de Casos y Controles , Circulación Cerebrovascular , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Neuroimaging consistently reveals smaller hippocampal volume in recurrent or chronic major depressive disorder (MDD). The underlying cellular correlates of the smaller volume are not clearly known. Postmortem tissues from 17 pairs of depressed and control subjects were obtained at autopsy, and informant-based retrospective psychiatric assessment was performed. Formalin-fixed left temporal lobes were sectioned (40 µm), stained for Nissl substance, and every 60th section selected throughout the entire hippocampus. Total volume of the hippocampal formation was calculated, and total numbers of pyramidal neurons (in hippocampal fields CA1, CA2/3, hilus), dentate gyrus (DG) granule cells, and glial cells were estimated stereologically. While hippocampal volume in all MDD subjects was not significantly smaller versus control subjects, in recurrent/chronic MDD, total volume decreased with duration of depressive illness (r = -0.696, p < 0.026). There was no significant difference between MDD and controls in total number or density of pyramidal neurons/granule cells or glial cells in CA1, CA2/3, hilus, or DG. However, CA1 pyramidal neuron density increased with duration of illness in recurrent/chronic MDD (r = 0.840, p < 0.002). Granule cell (r = 0.971, p < 0.002) and glial cell numbers (r = 0.980, p < 0.001) increased with age in those taking antidepressant medication (n = 6). Increasing DG granule cell and glial cell numbers with age in antidepressant-treated subjects may reflect proliferative effects of antidepressant medications. Decreasing total volume and increasing CA1 pyramidal neuron density with duration of illness in recurrent/chronic MDD lends support to the neuropil hypothesis of MDD.
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Trastorno Depresivo Mayor/patología , Hipocampo/patología , Neuronas/patología , Recuento de Células , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadísticas no Paramétricas , Técnicas EstereotáxicasRESUMEN
Despite its high sensitivity, the Beck Hopelessness Scale (BHS) has demonstrated low specificity, has an ambiguous factor structure, and includes inadequate items. The current study examined the psychometric properties of a modified BHS (mBHS) using a Likert scale format that would allow for improved reliability, validity, and clinical utility. Measures of hopelessness and depression were administered to 116 undergraduates. The mBHS demonstrated reliability over 10 weeks (r = .78) and internal consistency (alpha = .91). The BHS and mBHS were similarly effective in identifying suicidal ideation. The mBHS provides clinicians with a simple alternative for assessing hopelessness and suicide risk.
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Depresión/diagnóstico , Tamizaje Masivo , Pruebas Psicológicas , Ideación Suicida , Prevención del Suicidio , Adolescente , Adulto , Emociones , Análisis Factorial , Femenino , Humanos , Estudios Longitudinales , Masculino , Análisis Multivariante , Psicometría , Reproducibilidad de los Resultados , Autoinforme , Suicidio/psicología , Estados Unidos , Adulto JovenRESUMEN
A-to-I RNA editing is a post-transcriptional modification of single nucleotides in RNA by adenosine deamination, which thereby diversifies the gene products encoded in the genome. Thousands of potential RNA editing sites have been identified by recent studies (e.g. see Li et al, Science 2009); however, only a handful of these sites have been independently confirmed. Here, we systematically and quantitatively examined 109 putative coding region A-to-I RNA editing sites in three sets of normal human brain samples by ultra-high-throughput sequencing (uHTS). Forty of 109 putative sites, including 25 previously confirmed sites, were validated as truly edited in our brain samples, suggesting an overestimation of A-to-I RNA editing in these putative sites by Li et al (2009). To evaluate RNA editing in human disease, we analyzed 29 of the confirmed sites in subjects with major depressive disorder and schizophrenia using uHTS. In striking contrast to many prior studies, we did not find significant alterations in the frequency of RNA editing at any of the editing sites in samples from these patients, including within the 5HT(2C) serotonin receptor (HTR2C). Our results indicate that uHTS is a fast, quantitative and high-throughput method to assess RNA editing in human physiology and disease and that many prior studies of RNA editing may overestimate both the extent and disease-related variability of RNA editing at the sites we examined in the human brain.