Apathy predicts rate of cognitive decline over 24 months in premanifest Huntington's disease.

BACKGROUND: Cognitive impairment is a core feature of Huntington's disease (HD), however, the onset and rate of cognitive decline is highly variable. Apathy is the most common neuropsychiatric symptom of HD, and is associated with cognitive impairment. The aim of this study was to investigate apathy as a predictor of subsequent cognitive decline over 2 years in premanifest and early HD, using a prospective, longitudinal design. METHODS: A total of 118 premanifest HD gene carriers, 111 early HD and 118 healthy control participants from the multi-centre TRACK-HD study were included. Apathy symptoms were assessed at baseline using the apathy severity rating from the Short Problem Behaviours Assessment. A composite of 12 outcome measures from nine cognitive tasks was used to assess cognitive function at baseline and after 24 months. RESULTS: In the premanifest group, after controlling for age, depression and motor signs, more apathy symptoms predicted faster cognitive decline over 2 years. In contrast, in the early HD group, more motor signs, but not apathy, predicted faster subsequent cognitive decline. In the control group, only older age predicted cognitive decline. CONCLUSIONS: Our findings indicate that in premanifest HD, apathy is a harbinger for cognitive decline. In contrast, after motor onset, in early diagnosed HD, motor symptom severity more strongly predicts the rate of cognitive decline.

Detection of Huntington's disease decades before diagnosis: the Predict-HD study.

OBJECTIVE: The objective of the Predict-HD study is to use genetic, neurobiological and refined clinical markers to understand the early progression of Huntington's disease (HD), prior to the point of traditional diagnosis, in persons with a known gene mutation. Here we estimate the approximate onset and initial course of various measurable aspects of HD relative to the time of eventual diagnosis. METHODS: We studied 438 participants who were positive for the HD gene mutation, but did not yet meet the diagnostic criteria for HD and had no functional decline. Predictability of baseline cognitive, motor, psychiatric and imaging measures was modelled non-linearly using estimated time until diagnosis (based on CAG repeat length and current age) as the predictor. RESULTS: Estimated time to diagnosis was related to most clinical and neuroimaging markers. The patterns of association suggested the commencement of detectable changes one to two decades prior to the predicted time of clinical diagnosis. The patterns were highly robust and consistent, despite the varied types of markers and diverse measurement methodologies. CONCLUSIONS: These findings from the Predict-HD study suggest the approximate time scale of measurable disease development, and suggest candidate disease markers for use in preventive HD trials.

The Iowa Personality Disorder Screen: A validation study in a psychiatric population that receives long-term group psychotherapy for personality related problems.

Personality disorder (PD) is common among psychiatric patients, and diagnosing such disorders is of great importance for the choice of treatment. Diagnosing PD is a demanding and time-consuming process. The utilities of several PD screening instruments have been studied in different populations, but not in a population who receives long-term group psychotherapy. In the current study, we investigate the predictive properties of the Iowa Personality Disorder Screen (IPDS) in a sample of 694 psychiatric outpatients with and without PD who were admitted for psychodynamic long-term group therapy from 2012 to 2014. The definitive, reference diagnoses were defined according to the SCID-II, by which 484 patients (68%) warranted a PD diagnosis. The IPDS correctly classified 67.4 percent of all participants. Sensitivity (0.75) and specificity (0.51) were lower than in previous validation studies of IPDS. We discuss possible explanations related to the general concept of PD and, more specifically, to our study sample. Because of the weaker predictive properties of IPDS, we advise caution in use of the IPDS in similar clinical settings. Copyright © 2018 John Wiley & Sons, Ltd.

Distinct contributions of conduct and oppositional defiant symptoms to adult antisocial behavior: evidence from an adoption study.

BACKGROUND: We conducted an exploratory multivariate analysis of juvenile behavior symptoms in an adoption data set. One goal was to see if a few DSM-interpretable symptom dimensions economically captured information within the data. A second goal was to study the relationships between any such dimensions, biological and environmental background, and eventual adult antisocial behavior. METHODS: The data originated from a retrospective adoption study. Probands with a biological background for parental antisocial personality or alcoholism were heavily oversampled. Symptoms were ascertained by proband and adoptive parent interview. We performed, by gender, orthogonal rotated principal component analyses of juvenile behavior disturbance symptoms (females, n = 87; males, n = 88). We used structural equation modeling to examine the relationships hypothesized above. RESULTS: For both genders, an oppositional defiant disorder (ODD) component and at least 1 conduct component emerged. Regardless of the conduct component scores, the ODD components were significant predictors of adult antisocial behavior. For males, the ODD component was predicted by an antisocial biological background, but not by scores on the Adverse Adoptive Environment Scale. The conduct components were predicted by adoptive environment alone. For females, biological background or biological-environmental interactions predicted each of the components. CONCLUSIONS: There has been little previous distinction between conduct disorder and ODD in studies of genetic and environmental influences on juvenile behavior. The study suggests that adolescent ODD symptoms may be a distinct antecedent of adult antisocial personality. In males, adolescent ODD symptoms may represent early expression of genetic sociopathic personality traits.

Depression spectrum disease, I: The role of gene-environment interaction.

OBJECTIVE: This study used an adoption study design to separate genetic from environmental factors in the etiology of depression spectrum disease, a type of major depression characterized by families in which male relatives are alcoholic and females are depressed. The genetic etiology hypothesis of depression spectrum disease proposes that an alcoholic genetic diathesis predisposes to depression in females but alcoholism, not depression, in males. METHOD: The study examined 197 adult offspring (95 male and 102 female) of alcoholic biological parents and used logistic regression models to determine the contribution to major depression in male and female adoptees that could be explained by the genetic alcoholic diathesis combined with an environmental factor that was characterized by psychiatrically or behaviorally disturbed adoptive parents. RESULTS: Major depression in females was predicted by an alcoholic diathesis only when combined with the disturbed adoptive parent variable. The same regression model failed to predict depression in males. Other possible environmental confounding factors contributing to an increased chance of depression were found in females: fetal alcohol exposure, age at the time of adoption, and a family with an adopted sibling who had a psychiatric problem. These variables did not diminish the significance of the prediction of depression with the alcohol genetic diathesis and disturbed parent model. CONCLUSIONS: The results show that a genetic factor is present for which alcoholism is at least a marker, and which exerts its effect in women as a gene-environment interaction leading to major depression. This finding suggests that an important etiologic factor in depression spectrum disease is gene-environment interaction.

The Iowa Personality Disorder Screen: development and preliminary validation of a brief screening interview.

The length and expense of comprehensive personality disorder interviews makes them unwieldy for routine use. A brief but sensitive screen could eliminate administration of longer instruments in many instances. We describe the development of the Iowa Personality Disorder Screen (IPDS)--a mini-structured interview which can be completed in less than 5 minutes. Retrospective analyses using 1,203 SIDP-R interviews suggested that the IPDS items should provide good sensitivity and specificity. We present results from a prospective validation study, using a mixed group of 52 nonpsychotic inpatients and outpatients who were diagnosed using the SIDP-IV. Blind administration of the IPDS yielded excellent sensitivity (92%) and good specificity (79%), using a subset of five screening items. Addition of two more items leads to an estimated sensitivity of 79% and specificity of 86%. The IPDS shows promise as a quick personality disorder screen for use in research settings or standard clinical interviews.

Relationship between service effectiveness and satisfaction among persons receiving Medicaid mental health services.

Relationships between service satisfaction, life satisfaction, and self-reported mental health status were examined for Iowa Medicaid mental health service recipients. Of the 16,579 persons who received services in 1993, a mail-out survey was sent to 2,520 persons and returned by 815 (32.3 percent). Persons with schizophrenia reported greater service satisfaction and life satisfaction than persons with other diagnoses, and their ratings of their mental health were higher. A relationship between service satisfaction and current life satisfaction was observed for persons with schizophrenia, affective disorder and adjustment disorder, but not for persons with anxiety disorder.

Mild cognitive impairment in prediagnosed Huntington disease.

BACKGROUND: Cognitive decline has been reported in Huntington disease (HD), as well as in the period before diagnosis of motor symptoms (i.e., pre-HD). However, the severity, frequency, and characterization of cognitive difficulties have not been well-described. Applying similar cutoffs to those used in mild cognitive impairment (MCI) research, the current study examined the rates of subtle cognitive dysfunction (e.g., dysfunction that does not meet criteria for dementia) in pre-HD. METHODS: Using baseline data from 160 non-gene-expanded comparison participants, normative data were established for cognitive tests of episodic memory, processing speed, executive functioning, and visuospatial perception. Cutoff scores at 1.5 standard deviations below the mean of the comparison group were then applied to 575 gene-expanded pre-HD participants from the observational study, PREDICT-HD, who were stratified by motor signs and genetic risk for HD. RESULTS: Nearly 40% of pre-HD individuals met criteria for MCI, and individuals closer to HD diagnosis had higher rates of MCI. Nonamnestic MCI was more common than amnestic MCI. Single-domain MCI was more common than multiple-domain MCI. Within the nonamnestic single-domain subtype, impairments in processing speed were most frequent. CONCLUSIONS: Consistent with the Alzheimer disease literature, MCI as a prodromal period is a valid concept in pre-HD, with nearly 40% of individuals showing this level of impairment before diagnosis. Future studies should examine the utility of MCI as a marker of cognitive decline in pre-HD.

Tapping linked to function and structure in premanifest and symptomatic Huntington disease.

OBJECTIVE: Motor signs are functionally disabling features of Huntington disease. Characteristic motor signs define disease manifestation. Their severity and onset are assessed by the Total Motor Score of the Unified Huntington's Disease Rating Scale, a categorical scale limited by interrater variability and insensitivity in premanifest subjects. More objective, reliable, and precise measures are needed which permit clinical trials in premanifest populations. We hypothesized that motor deficits can be objectively quantified by force-transducer-based tapping and correlate with disease burden and brain atrophy. METHODS: A total of 123 controls, 120 premanifest, and 123 early symptomatic gene carriers performed a speeded and a metronome tapping task in the multicenter study TRACK-HD. Total Motor Score, CAG repeat length, and MRIs were obtained. The premanifest group was subdivided into A and B, based on the proximity to estimated disease onset, the manifest group into stages 1 and 2, according to their Total Functional Capacity scores. Analyses were performed centrally and blinded. RESULTS: Tapping variability distinguished between all groups and subgroups in both tasks and correlated with 1) disease burden, 2) clinical motor phenotype, 3) gray and white matter atrophy, and 4) cortical thinning. Speeded tapping was more sensitive to the detection of early changes. CONCLUSION: Tapping deficits are evident throughout manifest and premanifest stages. Deficits are more pronounced in later stages and correlate with clinical scores as well as regional brain atrophy, which implies a link between structure and function. The ability to track motor phenotype progression with force-transducer-based tapping measures will be tested prospectively in the TRACK-HD study.

The adult antisocial syndrome with and without antecedent conduct disorder: comparisons from an adoption study.

DSM antisocial personality disorder (ASPD) requires a retrospective diagnosis of conduct disorder-historical behavior not present in everyone with adult ASPD criteria. Using adoption study data, we examined the impact of this requirement on biological and environmental risk associations. We also compared clinical correlates of adult antisocial behavior with and without prior conduct disorder. We defined three subgroups: DSM-III ASPD (n = 30), adult antisocials without conduct disorder (n = 25), and controls (n = 142). By design, the sample had a high incidence of biological parent ASPD, which was partially confounded with fetal alcohol exposure. We compared the associations of both of these putative risk factors with subgroup membership after controlling for gender and adverse adoptive environment. We also examined differences in two sociopathy scales and the incidence of co-occurring affective, alcohol, and other substance use disorders. Finally, we explored differences in individual antisocial symptoms. Having an antisocial biological parent was a specific risk factor for ASPD. In contrast, fetal alcohol exposure, male gender, and adverse environment were associated with the adult antisocial syndrome, regardless of conduct disorder history. The two antisocial groups were similar with respect to sociopathy scales, co-occurring diagnoses, and the incidence of most individual symptoms. However, several adult and conduct disorder symptoms had significant specific associations with biological or environmental background or their interaction. Phenotypic expression of the biological-possibly genetic-risk for ASPD appears to be manifest before adulthood. The influence of other risk factors may not depend on antecedent conduct disorder. Despite this, we could not detect clinically important differences between the two sociopathic groups. The conduct disorder requirement therefore may be more relevant to etiological than clinical understanding of adult antisocial behavior.

Discriminant analysis using the unweighted sum of binary variables: a comparison of model selection methods.

Many clinical decision-making rules are equivalent to linear discriminant functions that involve the unweighted sum of binary variables (SBV). We briefly consider the geometry of this restriction and then propose a number of methods for forward stepwise selection of SBV models. Using a simulation study, we compare the performance of these methods under a wide range of plausible conditions and show that no single method is uniformly superior for selecting models of a fixed size. Factors of general importance in relative method performance are the ratio of sample size to the number of candidate variables and the class-conditional moment structure of the data. We conclude by offering some practical strategies for SBV model construction.

Clinical correlates of self-mutilation among psychiatric inpatients.

The charts of 660 consecutive admissions to a university psychiatric hospital were examined. After excluding those with mental retardation, 32 patients who had mutilated themselves and 88 patients admitted for unsuccessful suicide attempts were identified. Women were significantly overrepresented among the mutilators, but the groups did not differ with respect to age. Most analyses were restricted to women, of whom 27 were self-mutilators and 51 were nonmutilating suicide attempters. Mutilators were less likely to receive diagnoses of major depression or adjustment disorder but were more likely to have a history of substance abuse and receive Axis II diagnoses. The mutilative behavior was generally repetitive. The most common form was superficial cutting of the arms and wrists. Reports of lifetime sexual or physical abuse were more common among mutilators. Mutilators also had frequent histories of suicide attempts distinct from their mutilation behavior, multiple hospitalizations, and transfer to state hospitals for longer-term care. These findings suggest a chronic course with significant morbidity and associated features which may be of clinical significance.

Health Attitude Survey. A scale for assessing somatizing patients.

The authors designed an instrument, the Health Attitude Survey, to assess somatization, and administered it to over 1,000 patients attending a general medicine clinic. Within this population, a series of somatizing patients and control patients were identified for purposes of developing and testing the instrument. The 27-item scale was rapidly administered and acceptable to the patients. Based on comparisons with other measures of somatization, the instrument appeared to be a valid measure of the attitudes and perceptions of somatizing patients, and it distinguished these patients from the control subjects. The measure showed acceptable predictive value and may prove useful in clinical settings, where rapid screening is desired.

A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length.

Huntington's disease (HD) is a neurodegenerative disorder caused by an unstable CAG repeat. For patients at risk, participating in predictive testing and learning of having CAG expansion, a major unanswered question shifts from "Will I get HD?" to "When will it manifest?" Using the largest cohort of HD patients analyzed to date (2913 individuals from 40 centers worldwide), we developed a parametric survival model based on CAG repeat length to predict the probability of neurological disease onset (based on motor neurological symptoms rather than psychiatric onset) at different ages for individual patients. We provide estimated probabilities of onset associated with CAG repeats between 36 and 56 for individuals of any age with narrow confidence intervals. For example, our model predicts a 91% chance that a 40-year-old individual with 42 repeats will have onset by the age of 65, with a 95% confidence interval from 90 to 93%. This model also defines the variability in HD onset that is not attributable to CAG length and provides information concerning CAG-related penetrance rates.

Personality dysfunction among somatizing patients.

To examine the nature and extent of personality dysfunction related to somatization, the authors administered the Structured Interview for DSM-IV Personality and the NEO Five-Factor Inventory to a series of somatizing and nonsomatizing patients in a general medicine clinic. A greater percentage of somatizers met criteria for one or more DSM-IV personality disorders, especially obsessive-compulsive disorder, than did control patients. Somatizers also differed from control patients with respect to self-defeating, depressive, and negativistic personality traits and scored higher on the dimension of neuroticism and lower on the dimension of agreeableness. In addition, initial and facultative somatizers showed more personality pathology than true somatizers. These findings suggest that certain personality disorders and traits contribute to somatization by way of increased symptom reporting and care-seeking behavior.