Validating the Alternative DSM-5 Criteria for Personality Disorders: A Study in the Basque Region of Spain.

In 2010, the Working Group of Personality and Personality Disorders of the DSM-5 task force proposed a thorough diagnostic reformulation of the category of personality disorders. After debates and negotiations, these alternative criteria ended in Section III of the DSM-5 manual (diagnoses in need of further testing). We tested these alternative criteria in a sample of Basque-speaking patients from the Basque region of Spain who had clinical diagnoses of personality disorder, using instruments that had been developed and used as part of the DSM-5 field trials in the United States for assessing the proposed new diagnostic category. All study instruments were translated and adapted for use in the Basque language. Interviews were done twice (time 1 and time 2) and were scheduled at least 1 month apart to assess test-retest reliability. The results demonstrated that the DSM-5 alternative criteria worked well in this clinical sample, with highly satisfactory levels of reliability being attained and a good level of clinician's satisfaction related to the use of the new criteria. The alternative criteria in personality disorders seemed to work well in this European sample with unique linguistic features.

Genetic contributions to circadian activity rhythm and sleep pattern phenotypes in pedigrees segregating for severe bipolar disorder.

Abnormalities in sleep and circadian rhythms are central features of bipolar disorder (BP), often persisting between episodes. We report here, to our knowledge, the first systematic analysis of circadian rhythm activity in pedigrees segregating severe BP (BP-I). By analyzing actigraphy data obtained from members of 26 Costa Rican and Colombian pedigrees [136 euthymic (i.e., interepisode) BP-I individuals and 422 non-BP-I relatives], we delineated 73 phenotypes, of which 49 demonstrated significant heritability and 13 showed significant trait-like association with BP-I. All BP-I-associated traits related to activity level, with BP-I individuals consistently demonstrating lower activity levels than their non-BP-I relatives. We analyzed all 49 heritable phenotypes using genetic linkage analysis, with special emphasis on phenotypes judged to have the strongest impact on the biology underlying BP. We identified a locus for interdaily stability of activity, at a threshold exceeding genome-wide significance, on chromosome 12pter, a region that also showed pleiotropic linkage to two additional activity phenotypes.

Rethinking funding priorities in mental health research.

Mental health research funding priorities in high-income countries must balance longer-term investment in identifying neurobiological mechanisms of disease with shorter-term funding of novel prevention and treatment strategies to alleviate the current burden of mental illness. Prioritising one area of science over others risks reduced returns on the entire scientific portfolio.

Brain structure-function associations in multi-generational families genetically enriched for bipolar disorder.

Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain-behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain-behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18-87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain-behaviour associations and test whether brain-behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain-behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non-bipolar disorder family members. Additionally, while age had a relatively strong impact on all neurocognitive traits, the effects of age on cognition did not differ between diagnostic groups. Most brain-behaviour associations were also similar across the age range, with the exception of cortical and ventricular volume and lingual gyrus thickness, which showed weak correlations with verbal fluency and inhibitory control at younger ages that increased in magnitude in older subjects, regardless of diagnosis. Findings indicate that neuroanatomical traits potentially impacted by bipolar disorder are significantly associated with multiple neurobehavioural domains. Structure-function relationships are generally preserved across diagnostic groups, with the notable exception of ventrolateral prefrontal and parietal association cortex, volumetric increases in which may be associated with cognitive resilience specifically in individuals with bipolar disorder. Although age impacted all neurobehavioural traits, we did not find any evidence of accelerated cognitive decline specific to bipolar disorder subjects. Regardless of diagnosis, greater global brain volume may represent a protective factor for the effects of ageing on executive functioning.

Geospatial investigations in Colombia reveal variations in the distribution of mood and psychotic disorders.

BACKGROUND: Geographical variations in mood and psychotic disorders have been found in upper-income countries. We looked for geographic variation in these disorders in Colombia, a middle-income country. We analyzed electronic health records from the Clínica San Juan de Dios Manizales (CSJDM), which provides comprehensive mental healthcare for the one million inhabitants of Caldas. METHODS: We constructed a friction surface map of Caldas and used it to calculate the travel-time to the CSJDM for 16,295 patients who had received an initial diagnosis of mood or psychotic disorder. Using a zero-inflated negative binomial regression model, we determined the relationship between travel-time and incidence, stratified by disease severity. We employed spatial scan statistics to look for patient clusters. RESULTS: We show that travel-times (for driving) to the CSJDM are less than 1 h for ~50% of the population and more than 4 h for ~10%. We find a distance-decay relationship for outpatients, but not for inpatients: for every hour increase in travel-time, the number of expected outpatient cases decreases by 20% (RR = 0.80, 95% confidence interval [0.71, 0.89], p = 5.67E-05). We find nine clusters/hotspots of inpatients. CONCLUSIONS: Our results reveal inequities in access to healthcare: many individuals requiring only outpatient treatment may live too far from the CSJDM to access healthcare. Targeting of resources to comprehensively identify severely ill individuals living in the observed hotspots could further address treatment inequities and enable investigations to determine factors generating these hotspots.

The frequencies of mental disorders vary by geographic region. Investigating such variations may lead to more equitable access to mental healthcare and to scientific discoveries that reveal specific localized factors that contribute to the causes of mental illness. This study examined the frequency of three disorders with a major impact on public health ­ schizophrenia, bipolar disorder, and major depressive disorder ­ by analyzing electronic health records from a hospital providing comprehensive mental health care for a large region in Colombia. We show that individuals receiving outpatient care mainly live relatively near the facility. Those receiving inpatient care live throughout the region, but cluster in a few scattered locations. Future research could lead to strategies for more equitable provision of mental healthcare in Colombia and identify environmental or genetic factors that affect the likelihood that someone will develop one of these disorders.

A randomized-controlled trial of an intervention to improve antidepressant adherence among Latinos with depression.

BACKGROUND: Studies have consistently shown that Latinos with depression have lower adherence to antidepressant medication. Given that low adherence is associated with poorer response to treatment, this is a likely source of unequal care. The current study examined the efficacy of a motivational interviewing intervention for improving antidepressant adherence among Latinos with a depressive disorder. METHODS: Participants were 50 Latinos with a DSM-IV diagnosis of major depression or dysthymia who were receiving treatment at a community mental health center. Participants were recruited from July 2007 to December 2009 and were randomized to receive usual care (UC) or Motivational Enhancement Therapy for Antidepressants (META). META participants received three sessions of motivational interviewing as an enhancement to their usual care. Participants were assessed as baseline (time 1), 5 weeks (time 2), and 5 months (time 3). Antidepressant adherence was measured with the Medication Event Monitoring System (MEMS®) and changes in depression were measured with the Beck Depression Inventory-II (BDI-II). RESULTS: After adjusting for covariates, META participants showed significantly higher antidepressant adherence than UC participants at time 2 (72% versus 42%, respectively, p < .01) and time 3 (60% versus 34%, p < .01). The groups did not differ on mean BDI-II score across time. However, after adjusting for covariates, META participants were significantly more likely to show symptom remission on the BDI-II, compared to UC participants (OR = 7.0, p < .05). CONCLUSIONS: This initial trial of META demonstrated feasibility and promising effects for improving antidepressant adherence. Some effects on depression were also observed.

Transcultural aspects of somatic symptoms in the context of depressive disorders.

Somatic symptoms are a common presentation of mental disorders or psychological distress worldwide, and may often coexist with depressive and anxiety symptoms, thus accounting for what might be the most frequent psychiatric syndrome in primary care. Indeed, physical symptoms accompanying the clinical presentations of a variety of mental disorders may be considered as universal 'idioms of distress' that may vary across cultures, depending on attitudes and explanations embedded in each one of them. These variations in symptom presentations are the result of various interacting factors that ultimately determine how individuals identify and classify bodily sensations, perceive illness, and seek medical attention. This chapter examines the impact of culture on the experiencing of somatic symptoms, based on an inclusive review of the topic from ethnic, nosological, clinical and social perspectives. Particular attention is paid to the association of somatic symptoms with mood symptoms, since depressive disorders appear to be the most common, costly and disabling psychiatric entities worldwide. The review shows that racial/ethnic variations in somatic symptoms in the context of depression are common, and seem to be related to depression severity. Sociocultural factors, particularly stigma, may influence the unique emphasis placed on somatic symptoms within depression, and may account for some racial/ethnic differences in somatic symptom reporting.

Non-affective psychosis in traditional Andean culture.

We report a case of non-affective psychosis with a brief discussion of the phenomenology and its characterization and treatment by traditional Inka healers and eventually by Western-trained psychiatrists. Traditional Inka psychopathology provided empirical support for the transcultural stability of the Kraepelinian dichotomy.

Psychophysiologic treatment for patients with medically unexplained symptoms: a randomized controlled trial.

BACKGROUND: Patients presenting with medically unexplained physical symptoms (MUPS) typically present with significant distress and marked impairment in functioning and pose a unique challenge to health care providers. The purpose of this study was to examine the efficacy of a psychophysiological treatment (PT) for MUPS. METHODS: Thirty-eight participants meeting criteria for subthreshold somatization disorder (abridged somatization) were randomly assigned to one of two conditions: (1) standard medical care augmented by a psychiatric consultation intervention (wait-list) or (2) a 10-session, manualized, individually-administered PT added to the psychiatric consultation intervention. Assessments were conducted at baseline, at midpoint (after four sessions), and after completing the last session. The primary outcome measure was the severity scale of the Clinical Global Impression Scale anchored for Somatic Symptoms (CGI-SD). Secondary outcome measures were responder status as determined by clinical ratings, self-report measures of mental and physical functioning. RESULTS: At the end of the trial, the severity (and frequency) of physical symptoms improved significantly more (p<0.05) in the intervention group. The average improvement in the CGI-SD was 0.80 points greater in the intervention group than in the wait-list group. PT was also associated with greater improvements in self-reported functioning and depressive symptomatology. The effect sizes at the final assessment point indicate that this intervention had a robust effect on complex somatic symptom presentations. CONCLUSION: For patients with high levels of MUPS (abridged somatization), PT produces significant improvements in symptoms and functional status.

Distinct and shared contributions of diagnosis and symptom domains to cognitive performance in severe mental illness in the Paisa population: a case-control study.

BACKGROUND: Severe mental illness diagnoses have overlapping symptomatology and shared genetic risk, motivating cross-diagnostic investigations of disease-relevant quantitative measures. We analysed relationships between neurocognitive performance, symptom domains, and diagnoses in a large sample of people with severe mental illness not ascertained for a specific diagnosis (cases), and people without mental illness (controls) from a single, homogeneous population. METHODS: In this case-control study, cases with severe mental illness were ascertained through electronic medical records at Clínica San Juan de Dios de Manizales (Manizales, Caldas, Colombia) and the Hospital Universitario San Vicente Fundación (Medellín, Antioquía, Colombia). Participants were assessed for speed and accuracy using the Penn Computerized Neurocognitive Battery (CNB). Cases had structured interview-based diagnoses of schizophrenia, bipolar 1, bipolar 2, or major depressive disorder. Linear mixed models, using CNB tests as repeated measures, modelled neurocognition as a function of diagnosis, sex, and all interactions. Follow-up analyses in cases included symptom factor scores obtained from exploratory factor analysis of symptom data as main effects. FINDINGS: Between Oct 1, 2017, and Nov 1, 2019, 2406 participants (1689 cases [schizophrenia n=160; bipolar 1 disorder n=519; bipolar 2 disorder n=204; and major depressive disorder n=806] and 717 controls; mean age 39 years (SD 14); and 1533 female) were assessed. Participants with bipolar 1 disorder and schizophrenia had similar impairments in accuracy and speed across cognitive domains. Participants with bipolar 2 disorder and major depressive disorder performed similarly to controls, with subtle deficits in executive and social cognition. A three-factor model (psychosis, mania, and depression) best represented symptom data. Controlling for diagnosis, premorbid IQ, and disease severity, high lifetime psychosis scores were associated with reduced accuracy and speed across cognitive domains, whereas high depression scores were associated with increased social cognition accuracy. INTERPRETATION: Cross-diagnostic investigations showed that neurocognitive function in severe mental illness is characterised by two distinct profiles (bipolar 1 disorder and schizophrenia, and bipolar 2 disorder and major depressive disorder), and is associated with specific symptom domains. These results suggest the utility of this design for elucidating severe mental illness causes and trajectories. FUNDING: US National Institute of Mental Health.

Contribution of common and rare variants to bipolar disorder susceptibility in extended pedigrees from population isolates.

Current evidence from case/control studies indicates that genetic risk for psychiatric disorders derives primarily from numerous common variants, each with a small phenotypic impact. The literature describing apparent segregation of bipolar disorder (BP) in numerous multigenerational pedigrees suggests that, in such families, large-effect inherited variants might play a greater role. To identify roles of rare and common variants on BP, we conducted genetic analyses in 26 Colombia and Costa Rica pedigrees ascertained for bipolar disorder 1 (BP1), the most severe and heritable form of BP. In these pedigrees, we performed microarray SNP genotyping of 838 individuals and high-coverage whole-genome sequencing of 449 individuals. We compared polygenic risk scores (PRS), estimated using the latest BP1 genome-wide association study (GWAS) summary statistics, between BP1 individuals and related controls. We also evaluated whether BP1 individuals had a higher burden of rare deleterious single-nucleotide variants (SNVs) and rare copy number variants (CNVs) in a set of genes related to BP1. We found that compared with unaffected relatives, BP1 individuals had higher PRS estimated from BP1 GWAS statistics (P = 0.001 ~ 0.007) and displayed modest increase in burdens of rare deleterious SNVs (P = 0.047) and rare CNVs (P = 0.002 ~ 0.033) in genes related to BP1. We did not observe rare variants segregating in the pedigrees. These results suggest that small-to-moderate effect rare and common variants are more likely to contribute to BP1 risk in these extended pedigrees than a few large-effect rare variants.

Influence of cultural and social factors on the epidemiology of idiopathic somatic complaints and syndromes.

OBJECTIVE: To review international research on somatic presentations often seen together with or attributed to psychopathology. For conceptual clarity, we refer to these presentations as "idiopathic somatic complaints and syndromes" (ISCS). This review will also pose specific questions on cultural issues affecting these somatic manifestations. METHOD: Selective review of the international literature dealing with the phenomenology, epidemiology, and cultural profile of ISCS focusing on papers published in refereed journals and written in English. RESULTS: Major problems with much of the previous research in this area are the use of different definitions and ascertainment procedures. As currently conceptualized in the literature, ISCS are universal and seem closely related to psychological issues (stress) and psychopathological conditions such as depression worldwide. Although there are many similarities regarding the form and content of these somatic presentations across cultures, there is some evidence for cultural patterning of symptoms. Unfortunately, current classifications for ISCS are unsatisfactory. CONCLUSIONS: We outline specific recommendations for conducting future research and for improving the classification of ISCS of presumed psychological origin or import in future nosologies.

Effectiveness of a time-limited cognitive behavior therapy type intervention among primary care patients with medically unexplained symptoms.

PURPOSE: Patients seeking care for medically unexplained physical symptoms pose a major challenge at primary care sites, and there are very few well-accepted and properly evaluated interventions to manage such patients. METHODS: We tested the effectiveness of a cognitive behavior therapy (CBT)-type intervention delivered in primary care for patients with medically unexplained physical symptoms. Patients were randomly assigned to receive either the intervention plus a consultation letter or usual clinical care plus a consultation letter. Physical and psychiatric symptoms were assessed at baseline, at the end of treatment, and at a 6-month follow-up. All treatments and assessments took place at the same primary care clinic where patients sought care. RESULTS: A significantly greater proportion of patients in the intervention group had physical symptoms rated by clinicians as "very much improved" or "much improved" compared with those in the usual care group (60% vs 25.8%; odds ratio = 4.1; 95% confidence interval, 1.9-8.8; P<.001). The intervention's effect on unexplained physical symptoms was greatest at treatment completion, led to relief of symptoms in more than one-half of the patients, and persisted months after the intervention, although its effectiveness gradually diminished. The intervention also led to significant improvements in patient-reported levels of physical symptoms, patient-rated severity of physical symptoms, and clinician-rated depression, but these effects were no longer noticeable at follow-up. CONCLUSIONS: This time-limited, CBT-type intervention significantly ameliorated unexplained physical complaints of patients seen in primary care and offers an alternative for managing these common and problematic complaints in primary care settings.

A qualitative analysis of the perception of stigma among Latinos receiving antidepressants.

OBJECTIVE: This study sought to describe the role of stigma in antidepressant adherence among Latinos. METHODS: The study utilized data generated from six focus groups of Latino outpatients receiving antidepressants (N=30). By using a grounded theory approach, qualitative analysis focused specifically on the role of stigma in antidepressant treatment, as well as salient Latino values. RESULTS: Perceptions of stigma were related to both the diagnosis of depression and use of antidepressant medication. Qualitative analyses showed that antidepressant use was seen as implying more severe illness, weakness or failure to cope with problems, and being under the effects of a drug. Reports of stigma were also related to social consequences. Also, the perceived negative attributes of antidepressant use were at odds with self-perceived cultural values. CONCLUSIONS: Stigma was a prominent concern among Latinos receiving antidepressants, and stigma often affected adherence. Furthermore, culture is likely to play an important role in the communication of stigma and its associated complications.

Cognitive-behavioral therapy for somatization disorder: a randomized controlled trial.

BACKGROUND: Patients diagnosed as having somatization disorder (SD) who present with a lifetime history of multiple, medically unexplained physical symptoms represent a significant challenge to health care providers. To date, no psychotherapeutic or pharmacologic intervention has been found to produce clinically meaningful improvement in symptoms or functioning of patients with SD. We examined the efficacy of cognitive-behavioral therapy (CBT) for SD. METHODS: Eighty-four participants meeting criteria for SD were randomly assigned to 1 of 2 conditions: (1) standard medical care augmented by a psychiatric consultation intervention or (2) a 10-session, manualized, individually administered CBT regimen added to the psychiatric consultation intervention. Assessments were conducted at baseline and 3, 9, and 15 months after baseline. The primary outcome measure was the severity scale of the Clinical Global Impression Scale for Somatization Disorder (CGI-SD). Secondary outcome measures were responder status as determined by clinical ratings, self-reported measures of physical functioning and somatic symptoms, and health care utilization assessed via medical records. RESULTS: Fifteen months after baseline, somatization symptoms were significantly less severe in the group treated with CBT (0.84 points on the CGI-SD 7-point scale) (P<.001). Patients treated with CBT also were significantly more likely to be rated as either very much improved or much improved than patients treated with only augmented standard medical care (40% [n = 17] vs 5% [n = 2]). Cognitive-behavioral therapy was associated with greater improvements in self-reported functioning and somatic symptoms and a greater decrease in health care costs. CONCLUSION: For patients diagnosed as having SD, CBT may produce clinical benefits beyond those that result from the current state-of-the-art treatment.

Parkinsonian motor impairment predicts personality domains related to genetic risk and treatment outcomes in schizophrenia.

Identifying endophenotypes of schizophrenia is of critical importance and has profound implications on clinical practice. Here we propose an innovative approach to clarify the mechanims through which temperament and character deviance relates to risk for schizophrenia and predict long-term treatment outcomes. We recruited 61 antipsychotic naïve subjects with chronic schizophrenia, 99 unaffected relatives, and 68 healthy controls from rural communities in the Central Andes. Diagnosis was ascertained with the Schedules of Clinical Assessment in Neuropsychiatry; parkinsonian motor impairment was measured with the Unified Parkinson's Disease Rating Scale; mesencephalic parenchyma was evaluated with transcranial ultrasound; and personality traits were assessed using the Temperament and Character Inventory. Ten-year outcome data was available for ~40% of the index cases. Patients with schizophrenia had higher harm avoidance and self-transcendence (ST), and lower reward dependence (RD), cooperativeness (CO), and self-directedness (SD). Unaffected relatives had higher ST and lower CO and SD. Parkinsonism reliably predicted RD, CO, and SD after correcting for age and sex. The average duration of untreated psychosis (DUP) was over 5 years. Further, SD was anticorrelated with DUP and antipsychotic dosing at follow-up. Baseline DUP was related to antipsychotic dose-years. Further, 'explosive/borderline', 'methodical/obsessive', and 'disorganized/schizotypal' personality profiles were associated with increased risk of schizophrenia. Parkinsonism predicts core personality features and treatment outcomes in schizophrenia. Our study suggests that RD, CO, and SD are endophenotypes of the disease that may, in part, be mediated by dopaminergic function. Further, SD is an important determinant of treatment course and outcome.

Cultural issues and psychiatric diagnosis: providing a general background for considering substance use diagnoses.

AIM: To establish a general context on the topic of cross-cultural diagnosis and suggest how it can be applied to substance use disorders. METHODS: Critical reviews of the literature on psychiatric diagnosis, cross-cultural issues and the concept of ethnicity were conducted to provide a framework for making specific recommendations for substance use diagnoses. RESULTS: Cross-cultural diagnosis remains in a state of flux. Key questions on ethnicity and psychopathology have not yet been fully answered by existing research. The broad use of the Diagnostic and Statistical Manual for Mental Disorders (DSM) system world-wide requires a careful look at its cross-cultural applicability. CONCLUSIONS: For DSM-V, cultural/ethnic issues have to be clearly defined in clear terms that lend themselves to operational definitions. Recommendations should be research-based and testable. Meaningful cultural annotations and a glossary of cultural terms that are applicable in daily clinical practice and not limited to less frequently encountered syndromes (culture-bound) would be highly desirable.

Idiopathic physical symptoms: a common manifestation of psychiatric disorders in primary care.

Worldwide, patients with common mental disorders, such as depression and anxiety, have a tendency to present first to primary care exhibiting idiopathic physical symptoms. Typically, these symptoms consist of pain and other physical complaints that remain medically unexplained. While in the past, traditional psychopathology emphasized the relevance of somatic presentations for disorders, such as depression, in the last few decades, the "somatic component" has been neglected in the assessment and treatment of psychiatric patients. Medical specialties have come up with a variety of "fashionable" labels to characterize these patients and the new psychiatric nomenclatures, such as the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, attempt to classify these patients into a separate "somatoform disorders" category. These efforts fall short, and revisionists are asking altogether for the elimination of "somatoform disorders" from future nomenclatures. This review emphasizes the importance of idiopathic physical symptoms to the clinical phenomenology of many psychiatric disorders, offers suggestions to the diagnostic conundrum, and provides some hints for the proper assessment and management of patients with these common syndromes.

Dialogues on depression management: the primary care and specialist perspectives.

Depression is a major public health problem in the United States and is responsible for an enormous economic burden and loss of productivity and quality of life. In many cases, PCPs are well situated to identify and treat unrecognized depression, but an optimal treatment program often comprises both medical and psychotherapeutic interventions. Many collaborative models that integrate the efforts of PCPs, psychiatrists, behavioral health organizations, and workplace assistance programs are being tested and may prove to be the best direction for improving care for patients with depression. Looking ahead, improvement in treatment of depression will depend on numerous factors, including educating health care practitioners to recognize silent depression, expanding current collaborative models to cover more of the population, involving MCOs and payers in the development of effective treatment systems, and improving workplace-support programs to encourage more patients to seek appropriate care.