Are There Differences Among Evidence-Based Psychotherapies for Treating Different DSM-5 PTSD Symptom Clusters? A Systematic Review and Meta-analysis of Controlled Clinical Trials.

ABSTRACT: Posttraumatic stress disorder (PTSD) is a heterogeneous disease defined by four Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) symptom clusters: reexperiencing, avoidance, negative alterations in cognitions and mood, and hyperarousal. There are effective evidence-based psychotherapies (EBPs) for PTSD. However, given the variety of PTSD clinical presentations, we conducted the first meta-analysis investigating whether DSM-5 PTSD symptom clusters show different responses to EBPs. We systematically reviewed the literature for controlled clinical trials in five databases, performed a meta-analysis, and evaluated the methodological quality of the studies. We screened 633 studies and included seven. Three showed high risk, two showed some concerns, and one showed a low risk of bias. The symptom clusters do not seem to respond differently to EBPs (SMD cluster B: -0.40; 95% confidence interval [CI], -0.87 to 0.08; cluster C: -0.49; 95% CI, -0.90 to -0.08; cluster D: -0.44; 95% CI, -0.94 to 0.05; cluster E: -0.54; 95% CI, -1.07 to -0.0), even when analyzed by the therapeutic focuses. The findings dovetail nicely with the network theory of PTSD symptom, as although it is a heterogeneous disorder, the EBPs seem to promote a kind of cascade of symptom improvement.

Post-traumatic stress disorder as a predictor for incident hypertension: a 3-year retrospective cohort study.

BACKGROUND: The goal of the present study was to investigate the association between PTSD and the onset of hypertension in previously normotensive individuals in a population living in the stressful environment of the urban slums while controlling for risk factors for cardiovascular disease (CVD). METHODS: Participants were 320 normotensive individuals who lived in slums and were attending a family doctor program. Measurements included a questionnaire covering sociodemographic characteristics, clinical status and life habits, the Posttraumatic Stress Disorder Checklist - Civilian Version, and the Beck Depression Inventory. Incident hypertension was defined as the first occurrence at the follow-up review of the medical records of (1) systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher, (2) the participant started taking antihypertensive medication, or (3) a new diagnosis of hypertension made by a physician. Differences in sociodemographic, clinical, and lifestyle characteristics between hypertensive and non-hypertensive individuals were compared using the χ2 and t tests. Multivariate Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Six variables - age, educational level, body mass, smoking, diabetes, and PTSD diagnosis - showed a statistically significant (p ≤ 0.20) association with the hypertensive status. In the Cox regression, only PTSD diagnosis was significantly associated with incident hypertension (multivariate HR = 1.94; 95% CI 1.11-3.40). CONCLUSIONS: The present findings highlight the importance of considering a diagnostic hypothesis of PTSD in the prevention and treatment of cardiovascular diseases.

Machine learning applied to fMRI patterns of brain activation in response to mutilation pictures predicts PTSD symptoms.

BACKGROUND: The present study aimed to apply multivariate pattern recognition methods to predict posttraumatic stress symptoms from whole-brain activation patterns during two contexts where the aversiveness of unpleasant pictures was manipulated by the presence or absence of safety cues. METHODS: Trauma-exposed participants were presented with neutral and mutilation pictures during functional magnetic resonance imaging (fMRI) collection. Before the presentation of pictures, a text informed the subjects that the pictures were fictitious ("safe context") or real-life scenes ("real context"). We trained machine learning regression models (Gaussian process regression (GPR)) to predict PTSD symptoms in real and safe contexts. RESULTS: The GPR model could predict PTSD symptoms from brain responses to mutilation pictures in the real context but not in the safe context. The brain regions with the highest contribution to the model were the occipito-parietal regions, including the superior parietal gyrus, inferior parietal gyrus, and supramarginal gyrus. Additional analysis showed that GPR regression models accurately predicted clusters of PTSD symptoms, nominal intrusion, avoidance, and alterations in cognition. As expected, we obtained very similar results as those obtained in a model predicting PTSD total symptoms. CONCLUSION: This study is the first to show that machine learning applied to fMRI data collected in an aversive context can predict not only PTSD total symptoms but also clusters of PTSD symptoms in a more aversive context. Furthermore, this approach was able to identify potential biomarkers for PTSD, especially in occipitoparietal regions.

The top-100 cited articles on post-traumatic stress disorder: a historical bibliometric analysis.

This is a bibliometric analysis of the most-cited articles on post-traumatic stress disorder (PTSD) with the objective of identifying citation patterns for researchers, journals, centers, periods, topics, and nations. A search was conducted in Thomson Reuters' WoS Core Collection employing the expression TI = (posttraumatic stress disorder OR post-traumatic stress disorder OR PTSD). The 100 most-cited articles were downloaded, and the relevant data were extracted and analyzed. These studies had a total of 69,649 citations, ranging from a minimum of 360 to a maximum of 6029 citations, with an average of 696.49, a standard deviation of 720.92, mode of 369, and a median of 512. Eighty-eight percent of the most-cited articles on PTSD originated from the USA, with just six cities accounting for 52% of the publications and the Boston area alone responsible for almost one-fifth of the total output. The universities of Yale and Harvard headed the ranking of institutions with larger numbers of highly-cited articles. Female researchers represented 42.3% of all authors, 51% of the first authors, and 48% of the corresponding authors. The proportion of M.D. authors decreased significantly between the 1980-1999 (42%) and the 2000-2019 (27.2%) periods while that of Ph.D. authors increased from 44% to 57.4%. The most studied population was military veterans (28%). Female victims of sexual or physical violence, traumatized children, and adult survivors of childhood abuse were assessed in only 6-7% of the most-cited publications. Ten clinical trials evaluated psychological interventions but only three investigated pharmacotherapy. We concluded that influential research on PTSD remains centralized in the USA. A balanced gender representation in publications was found. There was a heavy reliance on combat veterans as the study population. Few highly-cited studies on the pharmacotherapy for PTSD were identified. Focused efforts are needed to address these challenges.

Stuck in a Moment: Tonic Immobility Predicts Poor Quality of Life in Treated PTSD Patients.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a prevalent and disabling multisystem disorder, with significant physical and psychiatric morbidity and poor quality of life (QOL). Although peritraumatic reactions - tonic immobility and dissociation - are established predictors of PTSD severity and development, there is a dearth of investigation assessing the impact of peritraumatic reactions on QOL of PTSD patients. Quality of life has become increasingly important in health care and research as a reliable outcome measure. It comprises psychological, physical, social and environmental domains, providing important information about the impact of diseases on patient's life. This study aims to investigate the impact of peritraumatic tonic immobility and peritraumatic dissociation on QOL of PTSD civilian outpatients. SUBJECTS AND METHODS: It is a cross-sectional study of 50 victims of urban violence with current PTSD, recruited in a specialized outpatient clinic. Instruments used were: Structured Clinical Interview IV, Peritraumatic Dissociative Experiences Questionnaire, Tonic Immobility Scale and WHOQOL-BREF (psychological, physical, social and environmental domains). Linear regression models were fitted to evaluate the impact of peritraumatic reactions - tonic immobility and dissociation - on WHOQOL-BREF scores. We controlled for sex as potential confounding. RESULTS: The severity of peritraumatic tonic immobility negatively impacted on psychological and environment domains of quality of life. For each additional point on the Tonic Immobility Scale, there was a decreased of 0.8 points on the scores of these domains of WHOQOL-BREF. Neither the peritraumatic reactions showed effects on physical nor social domains. Possible limitations of this study include cross-sectional design, relatively small sample size of tertiary center outpatients and recall bias. CONCLUSIONS: Peritraumatic tonic immobility is related to poor quality of life, adding new insights about the relationship between this immobility reaction and PTSD.

Unveiling the neural underpinnings of optimism: a systematic review.

Optimism is a personality trait strongly associated with physical and psychological well-being, with correlates in nonhuman species. Optimistic individuals hold positive expectancies for their future, have better physical and psychological health, recover faster after heart disease and other ailments, and cope more effectively with stress and anxiety. We performed a systematic review of neuroimaging studies focusing on neural correlates of optimism. A search identified 14 papers eligible for inclusion. Two key brain areas were linked to optimism: the anterior cingulate cortex (ACC), involved in imagining the future and processing of self-referential information; and the inferior frontal gyrus (IFG), involved in response inhibition and processing relevant cues. ACC activity was positively correlated with trait optimism and with the probability estimations of future positive events. Behavioral measures of optimistic tendencies investigated through the belief update task correlated positively with IFG activity. Elucidating the neural underpinnings of optimism may inform both the development of prevention and treatment strategies for several mental disorders negatively associated with optimism, such as depression, as well as help to foster new resilience promotion interventions targeting healthy, vulnerable, and mentally ill individuals.

The invisible scars of emotional abuse: a common and highly harmful form of childhood maltreatment.

BACKGROUND: Childhood maltreatment (CM) is unfortunately widespread globally and has been linked with an increased risk of a variety of psychiatric disorders in adults, including posttraumatic stress disorder (PTSD). These associations are well established in the literature for some maltreatment forms, such as sexual and physical abuse. However, the effects of emotional maltreatment are much less explored, even though this type figures among the most common forms of childhood maltreatment. Thus, the present study aims to investigate the impact of each type of childhood maltreatment, both individually and conjointly, on revictimization and PTSD symptom severity using a nonclinical college student sample. METHODS: Five hundred and two graduate and undergraduate students participated in the study by completing questionnaires assessing lifetime traumatic experiences in general, maltreatment during childhood and PTSD symptoms. Bivariate and multivariate negative binomial regressions were applied to examine the associations among childhood maltreatment, revictimization, and PTSD symptom severity. RESULTS: Our results showed that using bivariate models, all types of CM were significantly associated with revictimization and PTSD symptom severity. Multivariate models showed that emotional abuse was the type of maltreatment associated with the highest incidence rates of revictimization and PTSD symptom severity. CONCLUSIONS: These data provide additional evidence of the harmful effects of childhood maltreatment and its long-term consequences for individuals' mental health. Notably, the findings highlight the importance of studying the impacts of emotional abuse, which seems to be a highly prevalent, understudied, and chronic form of maltreatment that is as toxic as other maltreatment forms.

Absence of definitive scientific evidence that benzodiazepines could hinder the efficacy of exposure-based interventions in adults with anxiety or posttraumatic stress disorders: A systematic review of randomized clinical trials.

BACKGROUND AND OBJECTIVES: Exposure-based interventions (EBIs) are the first-line treatment for anxiety disorders and posttraumatic stress disorder. Although common, the association between EBIs and benzodiazepines is controversial. Therefore, we systematically reviewed the literature to evaluate if benzodiazepines could undermine the efficacy of EBIs in treating these disorders. METHODS: We conducted a systematic review aiming for randomized clinical trials (RCTs) in ISI Web of Science, Scopus, PubMed/MEDLINE, and PsycINFO databases. We scrutinized the reference list of selected papers and other systematic reviews. Finally, we evaluated the methodological quality and the scientific evidence of the studies. RESULTS: We screened 1,529 studies and included 12 RCTs in this review (all showing some concerns or high risk of bias). Benzodiazepines did not impact the efficacy of EBIs in nine studies at posttreatment, improved efficacy in two, and reduced it in one. In the follow-up, benzodiazepines (after its discontinuation) did not impact the efficacy in six studies and reduced it in five. The scientific level of evidence achieved was B for both phases. CONCLUSIONS: Until now there is no definitive evidence that benzodiazepines could hinder the EBIs' efficacy for treating posttraumatic stress disorder and anxiety disorders.

PTSD Predicts Smoking Cessation Failure in a Trauma-Exposed Population.

OBJECTIVE: The objective of the study was to investigate whether a diagnosis of posttraumatic stress disorder (PTSD; full or partial) or specific PTSD symptom clusters predicted failure in quitting smoking in a trauma-exposed population. Methods: Participants were 310 smokers who attempted quitting smoking, either successfully (quitters, n = 213) or not (relapsers, n = 97), who lived in slums and were attending a family doctor program. Measurements included a general questionnaire covering sociodemographic characteristics, clinical status and life habits, and the Posttraumatic Stress Disorder Checklist - Civilian Version. Differences in sociodemographic, clinical and lifestyle characteristics between quitters and relapsers were compared using a chi-square test. Because of the small sample size, full and partial PTSD were collapsed into a single category. Results: Significant differences (p ≤ .15) between quitters and relapsers were found in age, body mass index (BMI), income, alcohol consumption, and in the presence of full/partial PTSD diagnosis and of all three symptom clusters separately. Four logistic regression models predicting smoking cessation were modeled to control for confounding factors and included as independent variables a full/partial PTSD diagnosis and the three posttraumatic symptom clusters. The avoidance/numbing cluster presented the strongest association with relapse status (ORa 2.04, 95% CI [1.15, 3.63], p = .015), followed by the full/partial PTSD (ORa 1.80, 95% CI [1.04, 3.14], p = .038). The re-experiencing and the hyperarousal clusters were non-significantly associated with smoking cessation (ORa 1.34, 95% CI [0.80, 2.31], ns and ORa 1.65, 95% CI [0.96, 2.84], ns, respectively). Conclusions: Full/partial PTSD and posttraumatic symptom clusters uniquely predict risk for smoking relapse and thus may be a useful therapeutic target in trauma-exposed smokers.

Pre-traumatic vs post-traumatic OCD in PTSD patients: Are differences in comorbidity rates and functional health status related to childhood abuse?

OBJECTIVE: The goal of this study was to compare the clinical and functional status and the trauma-related characteristics of PTSD patients with comorbid OCD whose onset predated the index traumatic event (pre-traumatic OCD) with those of PTSD patient whose comorbid OCD only emerged after the exposure to the traumatic event (post-traumatic OCD). METHODS: Sixty-three individuals with PTSD and comorbid OCD were evaluated with the Structured Clinical Interview for DSM-IV AXIS I Disorders and completed the Posttraumatic Stress Disorder Checklist - Civilian Version, the Beck Depression Inventory, the Beck Anxiety Inventory, the Trauma History Questionnaire and the 36-Item Short-Form Health Survey. RESULTS: A history of childhood abuse was significantly more frequent among PTSD patients with pre-traumatic OCD (45.2%) than among their counterparts with post-traumatic OCD (16%). PTSD patients with pre-traumatic OCD had higher rates of psychiatric comorbidity in general and showed a lower functional health status in a physical domain (SF-36 Role Limitation due to Physical Health). In contrast, PTSD patients with post-traumatic OCD had a decreased functional health status in a psychological domain (SF-36 Emotional Well Being). The effect sizes were in the medium to large range. CONCLUSIONS: A history of child abuse may be an important, but often neglected, factor accounting for clinical, functional, and trauma-related differences between pre-traumatic and posttraumatic OCD in PTSD patients.

The worldwide incidence of neonaticide: a systematic review.

Neonaticide is the killing of a neonate on the day of its birth by his/her own mother. Neonaticidal women were reported to be predominantly young, unmarried, and primiparous. The motive for murdering the newborn relates to the shame, the fear of rejection, and abandonment by significant others, and the social stigmas associated with an illegitimate birth. The goal of the present study was to conduct a systematic review of the scientific literature and identify population-based studies reporting the incidence of neonaticide in different countries. A total of 485 abstracts were screened. After applying the inclusion/exclusion criteria, 10 studies were selected. Additional searches identified two more articles. Most of these studies were from Europe, where incidence varied from 0.07 (Finland, 1980-2000 period) to 8.5 neonaticides per 100000 births (Austria, 1975-2001 period). More recent studies have indicated that a growing proportion of neonaticidal women are married, multiparous, and suffers from mental disorders. Preventive measures, such as anonymous free delivery, were shown to reduce the incidence of neonaticide, although this effect may be short-lived. Despite social and institutional changes, neonaticide persists even in the most socially advanced, liberal, and prosperous societies in the world.

The impact of posttraumatic symptoms and comorbid mental disorders on the health-related quality of life in treatment-seeking PTSD patients.

BACKGROUND: There is a dearth of literature dealing with the impact of the severity of posttraumatic symptoms and of comorbid mental disorders on the health-related quality of life (HRQOL) of victims of civilian violence with a primary diagnosis of PTSD. OBJECTIVES: To investigate the influence of the severity of posttraumatic symptoms and of presence of comorbid mental disorders on the HRQOL of treatment-seeking outpatients with PTSD. METHODS: A sample of 65 PTSD patients was recruited in a specialized outpatient clinic. The volunteers had the diagnoses of PTSD and of comorbid mental disorders established with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). The severity of posttraumatic, depression and anxiety symptoms was measured with the PCL-C, BDI and BAI, respectively. HRQOL was assessed by means of the SF-36, a 36-item self-administered scale that measures eight domains of quality of life: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. Multiple linear regression models were fitted to investigate the relationship between the severity of posttraumatic, mood, and anxiety symptoms; the presence of specific current comorbid disorders and of psychotic symptoms, and the number of current comorbid conditions for each of the eight domains of HRQOL, after adjusting for the effect of sociodemographic characteristics. RESULTS: The severity of PTSD symptoms predicted worse HRQOL in all eight domains of SF-36, even after controlling for the severity of depression and anxiety symptoms, the presence of panic disorder, OCD, specific and social phobia, psychotic symptoms, and the number of comorbid disorders. The strongest negative association between PTSD symptoms severity and HRQOL was found in the Social Functioning domain. Although the inclusion of the depressive symptoms in the models led to a reduction of the magnitude of the negative association between the severity of PTSD symptoms and the HRQOL domain scores, the former still accounted for most of the explained variance of the latter. CONCLUSIONS: We found that even in the presence of comorbid mental disorders, the severity of posttraumatic symptoms remained the strongest predictor for impaired HRQOL in PTSD outpatients. Our results suggest that improvement of HRQOL should be considered a therapeutic objective and an essential outcome measure in the treatment of PTSD.

Comorbid depressive symptoms in treatment-seeking PTSD outpatients affect multiple domains of quality of life.

PURPOSE: No study has examined the impact of the comorbid Axis I conditions on the quality of life (QoL) of patients with a primary diagnosis of PTSD. Our goal was to investigate the influence of comorbid disorders on the QoL of treatment-seeking outpatients with PTSD. METHODS: The diagnoses of PTSD and of the comorbid disorders were established using the SCID-I. The 54 volunteers also completed the Posttraumatic Stress Disorder Checklist - Civilian Version, the BDI, the BAI, the Trauma History Questionnaire, and a socio-demographic questionnaire. Quality of life was assessed by means of the WHOQOL-BREF, a 26-item self-administered scale that measures four domains of QoL: psychological, physical, social, and environmental. Multiple linear regression models were fitted to investigate the relationship between the severity of post-traumatic, mood, and anxiety symptoms; the presence of specific current comorbid disorders and of psychotic symptoms, the number of current comorbid conditions, and a history of child abuse for each of the four domains of QoL, after adjusting for the effect of socio-demographic characteristics. RESULTS: The severity of PTSD symptoms impacted negatively on the psychological and physical domains. The severity of depressive symptoms correlated negatively with QoL in all domains, independently of sex, age, occupation, and marital status. The psychotic symptoms impacted negatively on the environmental domain. A history of child abuse was negatively associated with the psychological and the social domains. CONCLUSIONS: The severity of comorbid depressive symptoms is one of the most important factors in the determination of the QoL in patients with PTSD.

Exaggerating, mislabeling or simulating obsessive-compulsive symptoms: case reports of patients claiming to have obsessive-compulsive disorder.

BACKGROUND: There are no reported cases of factitious or simulated obsessive-compulsive disorder (OCD). However, over the last years, our clinic has come across a number of individuals that seem to exaggerate, mislabel or even intentionally "produce" obsessive and/or compulsive symptoms in order to be diagnosed with OCD. METHODS: In this study, experienced clinicians working on a university-based OCD clinic were requested to provide clinical vignettes of patients who, despite having a formal diagnosis of OCD, were felt to display non-genuine forms of this condition. RESULTS: Ten non-consecutive patients with a self-proclaimed diagnosis of OCD were identified and described. Although patients were diagnosed with OCD according to various structured interviews, they exhibited diverse combinations of the following features: (i) overly technical and/or doctrinaire description of their symptoms, (ii) mounting irritability, as the interviewer attempts to unveil the underlying nature of these descriptions; (iii) marked shifts in symptom patterns and disease course; (iv) an affirmative "yes" pattern of response to interview questions; (v) multiple Axis I psychiatric disorders; (vi) cluster B features; (vii) an erratic pattern of treatment response; and (viii) excessive or contradictory drug-related side effects. CONCLUSIONS: In sum, reliance on overly structured assessments conducted by insufficiently trained or naïve personnel may result in invalid OCD diagnoses, particularly those that leave no room for clinical judgment.

The role of childhood cumulative trauma in the risk of lifetime PTSD: An epidemiological study.

Cumulative trauma is usually devastating and can lead to severe psychological consequences, including posttraumatic stress disorder (PTSD). Exposure to various types of traumas, particularly during childhood, can be even more deleterious than the sheer number of events experienced. This epidemiological study is the first to investigate the impact of discrete childhood traumatic exposure on the risk of developing lifetime PTSD in a representative sample of the general population of the two biggest Brazilian cities. Participants were aged between 15 and 75 years old, living in São Paulo and Rio de Janeiro, Brazil, who had experienced traumatic events (N = 3,231). The PTSD diagnosis was assessed using the DSM-IV criteria through the version 2.1 of Composite International Diagnostic Interview. To operationalize childhood cumulative trauma, we considered the sum of 15 different childhood trauma categories that occurred before PTSD onset. The final multivariate logistic regression model indicated a strong relationship between the number of discrete types of childhood traumas and the likelihood of the lifetime PTSD development. The lifetime PTSD risk increased 28 % with each different type of childhood trauma when adjusted by confounds. Our study strengthens the evidence associating childhood cumulative trauma to increased lifetime PTSD risk.

Tonic immobility triggered by COVID-19-related trauma is associated with long-term PTSD symptoms.

During the COVID-19 pandemic healthcare workers were repeatedly exposed to traumatic experiences. Facing life-threatening events and repeated exposure to traumatic duty-related situations may cause posttraumatic stress disorder (PTSD). While tonic immobility has been considered a key vulnerability factor for PTSD, little is known about this relationship in the long term. In this study, we aimed to determine whether peritraumatic tonic immobility triggered by COVID-19-related trauma predicts PTSD symptom severity six to twelve months later. We conducted an online longitudinal survey using the PTSD Checklist for the DSM-5 (PCL-5) and the Tonic Immobility Scale to assess PTSD symptoms and the tonic immobility response, respectively. Multivariate regression models revealed a significant association between tonic immobility and PTSD symptoms. Each one-unit increase in the tonic immobility score was associated with a 1.5 % increase in the average PTSD symptom score six to twelve months after the traumatic event that triggered the tonic immobility. Furthermore, participants who showed significant or extreme levels of tonic immobility were 3.5 times or 7.3 times more likely to have a probable PTSD diagnosis, respectively. Hence, peritraumatic tonic immobility seems to have a lasting deleterious effect on mental health. Psychological treatment for health care professionals is urgent, and psychoeducation about the involuntary, biological nature of tonic immobility is essential to reduce suffering.

Delusional misidentification syndromes in obsessive-compulsive disorder.

Delusional misidentification syndromes (DMS) have been rarely reported in patients with conditions other than schizophrenia-related disorders, diffuse brain disease (dementia) and focal neurological illness. In this report, we describe DMS (i.e. Capgras and Fregoli syndromes) in two patients with severe and treatment resistant obsessive-compulsive disorder (OCD), one with paranoid personality disorder (PPD) and the other with a pervasive developmental disorder (PDD) not otherwise specified. While our findings highlight an interesting phenomenon (the occurrence of DMS in OCD), it is presently unclear whether this association is rare or underreported. Misidentification syndromes might be the ultimate result of a combination of obsessive fears and preexisting cognitive bias/deficits, such as mistrustfulness (in PPD) or poor theory of mind (in PDD).

Impaired Decision-Making Capacity in the Elderly King David (c. 1040-970 BCE): Was Hypothyroidism the Underlying Cause?

It has been suggested in the medical literature that in the last period of his life King David (c. 1040-970 BCE) suffered from dementia, osteoporosis, hyperparathyroidism, Parkinson's disease, autonomic neuropathy, major depression, and malignancy. The goal of this study was to identify, based on the "Succession Narrative (SN)," a historically objective section of the Old Testament, the clinical syndrome presented by King David and to determine whether an impaired decision making capacity may have been manipulated by his courtiers to influence his succession's politics. The "SN" indicates that besides forgetfulness and trouble in thinking, King David suffered from marked cold intolerance and sexual dysfunction. The symptom triad consisting of cognitive impairment, cold intolerance, and sexual dysfunction is more strongly suggestive of hypothyroidism than of any other diagnoses proposed in the medical literature so far. We hypothesized that hypothyroidism was the underlying cause of the elderly King David's clinical picture and that his sometimes troubled thinking was successfully manipulated by the courtiers to favor his son Solomon's accession to the throne, with profound historical consequences.