TBMaLT, a flexible toolkit for combining tight-binding and machine learning.

Tight-binding approaches, especially the Density Functional Tight-Binding (DFTB) and the extended tight-binding schemes, allow for efficient quantum mechanical simulations of large systems and long-time scales. They are derived from ab initio density functional theory using pragmatic approximations and some empirical terms, ensuring a fine balance between speed and accuracy. Their accuracy can be improved by tuning the empirical parameters using machine learning techniques, especially when information about the local environment of the atoms is incorporated. As the significant quantum mechanical contributions are still provided by the tight-binding models, and only short-ranged corrections are fitted, the learning procedure is typically shorter and more transferable as it were with predicting the quantum mechanical properties directly with machine learning without an underlying physically motivated model. As a further advantage, derived quantum mechanical quantities can be calculated based on the tight-binding model without the need for additional learning. We have developed the open-source framework-Tight-Binding Machine Learning Toolkit-which allows the easy implementation of such combined approaches. The toolkit currently contains layers for the DFTB method and an interface to the GFN1-xTB Hamiltonian, but due to its modular structure and its well-defined interfaces, additional atom-based schemes can be implemented easily. We are discussing the general structure of the framework, some essential implementation details, and several proof-of-concept applications demonstrating the perspectives of the combined methods and the functionality of the toolkit.

Interrater reliability of the Psychiatric Research Interview for Substance and Mental Disorders in an HIV-infected cohort: experience of the National NeuroAIDS Tissue Consortium.

The interrater reliability of the Psychiatric Research Interview for Substance and Mental Disorders (PRISM) was assessed in a multicentre study. Four sites of the National NeuroAIDS Tissue Consortium performed blinded reratings of audiotaped PRISM interviews of 63 HIV-infected patients. Diagnostic modules for substance-use disorders and major depression were evaluated. Seventy-six per cent of the patient sample displayed one or more substance-use disorder diagnoses and 54% had major depression. Kappa coefficients for lifetime histories of substance abuse or dependence (cocaine, opiates, alcohol, cannabis, sedative, stimulant, hallucinogen) and major depression ranged from 0.66 to 1.00. Overall the PRISM was reliable in assessing both past and current disorders except for current cannabis disorders when patients had concomitant cannabinoid prescriptions for medical therapy. The reliability of substance-induced depression was poor to fair although there was a low prevalence of this diagnosis in our group. We conclude that the PRISM yields reliable diagnoses in a multicentre study of substance-experienced, HIV-infected individuals.

Mortality and community mental health. The Alachua County, Florida, mortality study.

This study reports the results of a household survey and search of death certificates that show a relationship between depression, anxiety, and subsequent mortality. It is part of an effort to develop practical epidemiologic techniques for continuous assessment of community mental health. Use is made of the population attributable mortality rate, estimated from a comparison of the prevalence of a given factor in life and at death. The study estimated attributable mortality prospectively by following up participants in a mental health survey of Alachua County, Florida, for up to four years. Of eight mental scales examined, five (mood, depression, somatic symptoms of anxiety, the Health Opinion Survey, and selected psychopathologic symptoms) showed significant association of scores with community mortality. The data suggest linkages of mental factors to mortality of an order of magnitude sufficient to warrant consideration of these factors as leading causes of death.

Exclusion criteria of DSM-III. A study of co-occurrence of hierarchy-free syndromes.

The diagnostic criteria of the third edition of the DSM-III often state that one diagnosis cannot be made if it is "due to" another disorder. Using data from the National Institute of Mental Health Diagnostic Interview Schedule, with a sample of 11,519 subjects from a community population, we found that if two disorders were related to each other according to the DSM-III exclusion criteria, then the presence of a dominant disorder greatly increased the odds of having the excluded disorder. We also found that disorders, which DSM-III says are related to each other, were more strongly associated than disorders, which DSM-III says are unrelated. However, we also found there was a general tendency toward co-occurrence, so that the presence of any disorder increased the odds of having almost any other disorder, even if DSM-III does not list it as a related disorder. We concluded that empirical studies are needed to study the assumptions underlying the use of a diagnostic hierarchy.

Six-month prevalence of psychiatric disorders in three communities 1980 to 1982.

Six-month prevalence rates for selected DSM-III psychiatric disorders are reported based on community surveys in New Haven, Conn, Baltimore, and St Louis. As part of the Epidemiologic Catchment Area program, data were gathered on more than 9,000 adults, employing the Diagnostic Interview Schedule to collect information to make a diagnosis. The most common disorders found were phobias, alcohol abuse and/or dependence, dysthymia, and major depression. The most common diagnoses for women were phobias and major depression, whereas for men, the most predominant disorder was alcohol abuse and/or dependence. Rates of psychiatric disorders dropped sharply after age 45 years.

The design of the Epidemiologic Catchment Area surveys. The control and measurement of error.

Several methods are used to minimize and measure error in the NIMH Epidemiologic Catchment Area program. Sampling methods involve the inclusion of group quarters such as prisons, nursing homes, and mental hospitals in the sample frame and the use of probability sampling throughout. Interviewing, methods include use of identical diagnostic interview protocols, centralized training of interview supervisors, standard instructions to interviewers, and reinterview of a subsample by clinicians. In the area of completion, the methods include a 75% to 80% respondent completion rate, a 95% or greater completion rate for individual questions, use of informant interviews where necessary, and statistical adjustments to correct for low completion rates in some subgroups. Analytic methods include use of a computerized diagnostic algorithm, common estimation formulas on identically formatted data files, and estimation of exact variances that take account of the multistage sample design.

Results of the DSM-IV mood disorders field trial.

OBJECTIVE: The DSM-IV mood disorders field trial, a multisite collaborative study, was designed to explore the reliability of a course-based diagnostic classification system for major depression, evaluate the symptom criteria for dysthymia, and explore the need for additional diagnostic categories for milder forms of mood disorder (e.g., minor and recurrent brief depression). METHOD: Five hundred twenty-four depressed subjects were recruited from inpatient, outpatient, and community settings at five sites and evaluated with structured interviews according to DSM-III and DSM-III-R criteria, with careful attention to longitudinal course. Within- and across-site interrater reliability studies and 6-month test-retest reliability studies were also conducted on subsets of the sample. RESULTS: For evaluations of major depression and dysthymia, intrasite reliability was good to excellent and intersite reliability was fair to good; 6-month test-retest reliability was fair for dysthymia and poor to fair for major depression. Interrater reliability for six course of illness specifiers was fair to good, and almost all subjects could be assigned to a specific type of course. CONCLUSIONS: The results supported the use of a course-based classification system for major depression. They also suggested that the content validity of the DSM-III-R symptom criteria for dysthymia could be improved by emphasizing cognitive and social/motivational symptoms, although such changes are unlikely to sharpen the distinction between dysthymia and major depression. Finally, 91% of the subjects met the criteria for current or lifetime major depression or dysthymia, suggesting that additional categories for milder forms of depression are not needed.

Depressive personality disorder: clinical implications.

Although the concept of a depressive personality has a long and rich tradition in psychiatry, it has only recently been included in any official nomenclature. Those afflicted with depressive personality have been subsumed under a variety of mood disorders and other personality disorders. This article presents criteria for depressive personality disorder that were developed for the DSM-IV Task Force. A framework for validating a personality disorder, including that of depressive personality disorder, is presented. Results of the DSM-IV Mood Disorders Field Trial relevant to this issue are reported in the article. Results show that DSM-IV depressive personality disorder identifies a group of patients whose diagnosis does not overlap substantially with major depression, dysthymia, or early-onset dysthymia; the patients have significant social and occupational morbidity. These results provide significant evidence to justify the validity of depressive personality disorder.

Alcoholism, life events, and psychiatric impairmant.

A sample of 122 DPs was compared to a "normative" sample of CSRs. The presentation of psychiatric disorder scores and numbers and kind of stressful life events was detailed. Results of this comparative analysis suggest that research that focuses on high psychiatric disorder-controlling for life events is in order. Furthermore, therapeutic intervention must obviously take into account the iterative nature of alcohol and stressful life events. Also, these findings suggest and support the role of life stress in the possible formation of alcoholism.

National distribution of child and adolescent psychiatrists.

OBJECTIVE: To describe the national distribution of child and adolescent psychiatrists by state, community, and youth population. METHOD: Data on child and adolescent psychiatrists were compiled for states and counties and compared by state, county characteristics, number of youth, percentage of youth living in poverty, and child and adolescent psychiatry residents. RESULTS: The number of child and adolescent psychiatrists per 100,000 youth varied greatly by state and county. Child and adolescent psychiatrists were significantly more likely to be located in metropolitan counties and counties with a low percentage of children living in poverty. The distribution of child and adolescent psychiatrists was not significantly related to the distribution of child and adolescent psychiatry residency training programs. CONCLUSIONS: The shortage of child and adolescent psychiatrists is accentuated for nonmetropolitan areas and youth at greatest risk for mental disorders by the current pattern of distribution.

A binational school survey of depressive symptoms, drug use, and suicidal ideation.

New findings are presented from a survey of depressive symptoms, illicit drug use, and suicidality among 4,157 adolescents attending school in six border cities in Texas and neighboring Tamaulipas, Mexico. Among the Texas youth, 48.08% scored above 16 on the Center for Epidemiologic Studies' Depression Scale (CES-D); 21% reported illicit drug use in the past month; and 23.43% said they had thought about killing themselves during the past week. Rates were lower among the Mexican youth: 39.41% had high CES-D scores; 4.95% reported drug use and 11.57% reported current suicidal ideation. Multivariate models are presented to show the linkage between psychological distress, drug use, and suicidality in this sample of border youth.

The Alcohol Use Disorders Identification Test (AUDIT) as a screen for at-risk drinking in primary care patients of different racial/ethnic backgrounds.

This study examined the operating characteristics of the Alcohol Use Disorders Identification Test (AUDIT) as a screen for "at-risk" drinking in a multi-ethnic sample of primary care patients, from a family practice center located in the southwestern United States. A probability sample of 1,333 family medicine patients, stratified by gender and racial/ethnic background (white, African-American and Mexican-American) completed the AUDIT, followed by the Alcohol Use Disorders and Associated Disabilities Interview Schedule (AUDADIS) to determine ICD-10 diagnoses. Indicators of hazardous alcohol use and alcohol-related problems were included as measures of "at-risk" drinking. Despite differences in the spectrum of alcohol problems across patient subgroups, there was no evidence of gender or racial/ethnic bias in the AUDIT as indicated by Receiver Operating Characteristic Curve analysis. Excluding abstainers from the analysis and little impact on screening efficacy. In this population, the AUDIT appears to be an unbiased measure of "at-risk" drinking.

Comparison of DSM-III-R chronic major depression and major depression superimposed on dysthymia (double depression): validity of the distinction.

The nosology of chronic depression has become increasingly complex since the publication of the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R; American Psychiatric Association, 1987), but there are few data available to evaluate the validity of the distinctions between the subtypes of chronic depression. The validity of the distinction between DSM-III-R chronic major depression (CMD) and major depression superimposed on dysthymia (double depression, DD) was examined. Participants were 635 patients with chronic depression in a 12-week trial of antidepressant medications. Patients with CMD, DD, and a 3rd group with a chronic major depressive episode superimposed on dysthymia (DD/CMD) were compared on demographic and clinical characteristics, family history, and response to treatment. Few differences were evident, although the depression of patients with DD/CMD tended to be more severe.

Reliability of diagnosis in mood disorders.

The reliability of diagnosing mood disorders is reviewed for previous and current versions of the American Psychiatric Association's DMS. Reliability is shown to improve with the increasing specificity of diagnostic criteria. The new specifiers for the course of major depression in relation to dysthymia also are shown to be reliable.

Symptomatology in dysthymic and major depressive disorder.

The lists of associated symptoms included in the DSM-III, DSM-III-R, and DSM-IV criteria for dysthymic disorder have been criticized for lacking content and discriminant validity. The literature on the content and discriminant validity of dysthymic symptoms was reviewed and relevant data from the DSM-IV Mood Disorders Field Trial were presented. These data indicate that cognitive and social-motivational symptoms are much more characteristic of dysthymic disorder than are vegetative and psychomotor symptoms. In addition, subjects with major depressive disorder exhibit higher rates of most depressive symptoms than do subjects with dysthymic disorder, but there is little evidence of qualitative distinctions in symptomatology between these conditions. Finally, after taking course and exclusion criteria into account, variations in the symptom criteria do not have a major effect on case definition.

Social-vocational adjustment in unipolar mood disorders: results of the DSM-IV field trial.

430 patients participating in the DSM-IV field trial receiving a DSM-III-R SCID-derived diagnosis of episodic major depression (n = 131), dysthymic disorder (n = 37) and double depression (n = 262) completed the social adjustment scale-self-report (Weissman and Bothwell, 1976). Patients with double depression demonstrated greater social morbidity than those suffering from episodic major depression or dysthymic disorder (P < 0.05). Significant predictors of high social morbidity in double depressives included severity of symptoms (P < 0.0001), followed by age of onset of first major depression (P < 0.04). Subscale analysis revealed that double depressives were significantly more impaired in work outside the home and in terms of their financial status (P < 0.05).

The epidemiology of depression. An update on sex differences in rates.

Data from the New Haven, CT, Standard Metropolitan Statistical Area, site of the NIMH Epidemiologic Catchment Area (ECA) study, a multi-site collaborative community survey of psychiatric disorders is presented. The 6-month prevalence rates based on the Diagnostic Interview Schedule (DIS) interview and the DSM-III found that major depression was more frequent in women than men (2.4:1). The sex ratios for bipolar disorder were about equal. The sex ratios for major depression were fairly consistent at different time periods retrospectively assessed. There appeared to be a birth cohort effect with cohort's born after 1936 having an earlier age of onset and higher rates of major depression but not a change in sex ratios. These findings must be considered in light of the methodologic limitations of retrospective recall.

Hispanic Americans and the state mental hospitals in Texas: ethnic parity as a latent function of a fiscal incentive policy.

This paper examines patterns of utilization of the state mental hospitals in Texas by Hispanics compared to Anglos over a 5-year period from FY 1984 to FY 1988. Historically, Hispanics have been underrepresented in public mental health client populations in the United States. In the mid-1980s in Texas, the ethnic gap in use of psychiatric facilities was expected to widen as Hispanic population growth outpaced the capacity of the public system to provide accessible mental health services for persons with serious and persistent psychiatric illnesses. But in the inpatient sector, the gap narrowed significantly in the second half of the decade, due to a policy-driven sharp reduction in the overall census of the state mental hospitals. A fiscal incentive program to stimulate the development of community-based mental health services had a markedly different effect on subsequent inpatient utilization by Anglos compared to Hispanics, most notably in counties that were less urban and less affluent and counties with a relatively high proportion of Hispanic residents. The context and mixed implications of these developments are explored.

DNA and protein contents of hepatocytes in primary cultures monitored by flow cytometry: Effect of phenobarbital and dimethylsulphoxide.

Primary rat hepatocyte cultures were analysed by two-parameter flow cytometry (FCM) analysis. The simultaneous highly reproducible measurements of DNA and protein contents of hepatocytes showed a high resolution and allowed individual ploidy classes to be monitored during culture. Among both the 2N- and 4N-cell populations of freshly isolated hepatocytes two subpopulations were detectable by their different protein contents. From day 1 to day 7 in culture, the relative contributions of the 2N-, 4N- and 8N-cell populations remained more or less unchanged. The protein content decreased with prolonged culture time to 30% of the original level at day 7. The subpopulations within the 2N- and 4N-cells were no longer detectable. After chronic treatment with phenobarbital (PB, 3 mm), cell detachment was reduced. The contributions of the 2N- and 8N-cell populations decreased whereas that of the 4N-cell population increased. Furthermore, compared to untreated cultures, the cellular protein content was enhanced in all ploidy classes. These PB-induced effects in vitro reflect the hyperplastic and hypertrophic activities of PB that have been observed in vivo. FCM data are compatible with the hypothesis that phenobarbital exerts its tumour promoting activity in vivo by an inhibition of apoptosis. After chronic exposure to dimethylsulphoxide (DMSO, 2%, v/v), a reduction only in the 2N-cell population but an increase in the 8N-cell population was found. The protein content of individual hepatocytes was not enhanced. It seemed that DMSO stabilizes liver cells in vitro at a level that corresponds to the adult stage in vivo. DNA/protein FCM analysis was an efficient tool which was suitable to describe the dynamics of the reactions of hepatocytes in culture after nontoxic, chronic exposure to the growth and differentiation modifying drugs PB and DMSO.

Training health professionals in the recognition and treatment of depression.

A total of 423 health professionals, including physicians, psychologists, counselors, social workers, and nurses, attended a two-day program to increase awareness, recognition, and treatment of depression. In a preprogram opinion survey, nurses and social workers reported less perceived ability to recognize mood disorders compared with physicians and psychologists. In a group of 274 respondents who took a 20-item test of their knowledge about depression before and after attending the program, scores for all professions increased after the program and pretest differences in scores between professions decreased. The results suggest that training was successful in increasing knowledge about depression among a diverse group of health professionals.