Physiological regulation-deregulation and psychiatric disorders

This article discusses regulation-deregulation theory, a theory that integrates both old and new concepts to explain behavior-physiology interactions and changes in psychiatric disorder probability. The theory postulates: that specific types and frequencies of social interactions are essential to maintain normal physiological function; when essential interactions fail to occur, atypical physiological states (deregulation) develop; and deregulation is associated with the presence of unpleasant feelings and an increase in the frequency of psychiatric disorders. Implications of the theory are that certain types of social interactions are critical proximate mechanisms in determining the onset of psychiatric disorders, and that social interaction type and frequency, through affecting different physiological systems, alter the course of psychiatric disorders.     

Ethology and psychotherapy

During the last 25 years, ethology has developed systematic and quantitative methods for studying psychiatric patients' behavior, especially nonverbal behavior. Both research results as well as theoretical considerations may be of interest and value for psychiatric interviews and psychotherapy. Direct observations of endogenously depressed patients on the ward show significant behavior changes from admission to discharge. The depressive phase is characterized by withdrawal, nonspecific gaze, looking down, little self-activity, little motor activity, and a substantial reduction of social interaction. The recovery phase is characterized by verbal and nonverbal communication, that is , nod, smile, laughter, gesticulation, help, and others. Such behaviors are primarily useful for the assessment of a patient's mental state in the ward environment. In addition, they may also contribute to the psychiatric interview and future psychotherapeutic situations. These elements are related to four basic motivation categories: relaxation, assertion, contact, and flight. The theoretical considerations include evolutionary theory, ethological theory, and regulation-deregulation theory.     

The severity of psychiatric disorders

The issue of the severity of psychiatric disorders has great clinical importance. For example, severity influences decisions about level of care, and affects decisions to seek government assistance due to psychiatric disability. Controversy exists as to the efficacy of antidepressants across the spectrum of depression severity, and whether patients with severe depression should be preferentially treated with medication rather than psychotherapy. Measures of severity are used to evaluate outcome in treatment studies and may be used as meaningful endpoints in clinical practice. But, what does it mean to say that someone has a severe illness? Does severity refer to the number of symptoms a patient is experiencing? To the intensity of the symptoms? To symptom frequency or persistence? To the impact of symptoms on functioning or on quality of life? To the likelihood of the illness resulting in permanent disability or death? Putting aside the issue of how severity should be operationalized, another consideration is whether severity should be conceptualized similarly for all illnesses or be disorder specific. In this paper, we examine how severity is characterized in research and contemporary psychiatric diagnostic systems, with a special focus on depression and personality disorders. Our review shows that the DSM‐5 has defined the severity of various disorders in different ways, and that researchers have adopted a myriad of ways of defining severity for both depression and personality disorders, although the severity of the former was predominantly defined according to scores on symptom rating scales, whereas the severity of the latter was often linked with impairments in functioning. Because the functional impact of symptom‐defined disorders depends on factors extrinsic to those disorders, such as self‐efficacy, resilience, coping ability, social support, cultural and social expectations, as well as the responsibilities related to one's primary role function and the availability of others to assume those responsibilities, we argue that the severity of such disorders should be defined independently from functional impairment.     

Premenstrual mood changes in affective disorders.

Mood changes during the premenstrual phase have been the focus of considerable research in recent years. Although there has been significant progress in the diagnosis and etiology of major affective disorders, the relation between these disorders and menstrual changes remains controversial. There have been contradictory reports and speculations on women''s susceptibility to psychiatric disorders during the premenstrual phase. We describe three patients with a history of mood swings associated with menstruation in whom major affective disorders developed, necessitating intensive psychiatric treatment or admission to hospital. Among women who manifest menstrual mood changes, manic-depressive illness may develop only in a subgroup with genetic predisposition. In such cases the possibility of postpartum mania or depression should be kept in mind in follow-up.     

Stereotypes of autism

In their landmark papers, both Kanner and Asperger employed a series of case histories to shape clinical insight into autistic disorders. This way of introducing, assessing and representing disorders has disappeared from today''s psychiatric practice, yet it offers a convincing model of the way stereotypes may build up as a result of representations of autism. Considering that much of what society at large learns on disorders on the autism spectrum is produced by representations of autism in novels, TV-series, movies or autobiographies, it will be of vital importance to scrutinize these representations and to check whether or not they are, in fact, misrepresenting autism. In quite a few cases, media representations of talent and special abilities can be said to have contributed to a harmful divergence between the general image of autism and the clinical reality of the autistic condition.     

Heterozygosity of murine Crkl does not recapitulate behavioral dimensions of human 22q11.2 hemizygosity

Deletions in 22q11.2 human chromosome are known to be associated with psychiatric disorders, such as intellectual disability, schizophrenia, autism spectrum disorder, and anxiety disorders. This copy number variation includes a 3.0 Mb deletion and a nested proximal 1.5 Mb hemizygous deletion in the same region. Evidence indicates that the distal 22q11.2 region outside the nested 1.5 Mb deletion also might be contributory in humans. However, the precise genetic architecture within the distal region responsible for psychiatric disorders remains unclear, and this issue cannot be experimentally evaluated beyond the correlation in humans. As CRKL (CRK-like Proto-Oncogene, Adaptor Protein) is one of the genes encoded in the distal 22q11.2 segment and its homozygous deletion causes physical phenotypes of 22q11.2 hemizygous deletion, we tested the hypothesis that its murine homolog Crkl contributes to behavioral phenotypes relevant to psychiatric disorders in mice. Congenic Crkl heterozygosity reduced thigmotaxis, an anxiety-related behavior, in an inescapable open field, but had no apparent effect on social interaction, spontaneous alternation in a T-maze, anxiety-like behavior in an elevated plus maze, or motor activity in an open field. Our data indicate that the heterozygosity of murine Crkl does not recapitulate social deficits, working memory deficits, repetitive behavior traits or hyperactivity of human 22q11.2 hemizygous deletion. Moreover, while 22q11.2 hemizygous deletion is associated with high levels of phobia and anxiety in humans, our data suggest that Crkl heterozygosity rather acts as a protective factor for phobia-like behavior in an open field.     

Recruitment of both the mirror and the mentalizing networks when observing social interactions depicted by point-lights: a neuroimaging study

Background

Understanding social interactions requires the ability to accurately interpret conspecifics'' actions, sometimes only on the basis of subtle body language analysis. Here we address an important issue that has not yet received much attention in social neuroscience, that of an interaction between two agents. We attempted to isolate brain responses to two individuals interacting compared to two individuals acting independently.

Methodology/Principal Findings

We used minimalistic point-light displays to depict the characters, as they provide the most straightforward way to isolate mechanisms used to extract information from motion per se without any interference with other visual information. Functional magnetic resonance imaging (fMRI) method was used to determine which brain regions were recruited during the observation of two interacting agents, mimicking everyday social scenes. While the mirror and mentalizing networks are rarely concurrently active, we found that both of them might be needed to catch the social intentions carried by whole-body motion.

Conclusions/Significance

These findings shed light on how motor cognition contributes to social cognition when social information is embedded in whole-body motion only. Finally, the approach described here provides a valuable and original tool for investigating the brain networks responsible for social understanding, in particular in psychiatric disorders.     

DAT1 Polymorphism Determines L-DOPA Effects on Learning about Others’ Prosociality

Despite that a wealth of evidence links striatal dopamine to individualś reward learning performance in non-social environments, the neurochemical underpinnings of such learning during social interaction are unknown. Here, we show that the administration of 300 mg of the dopamine precursor L-DOPA to 200 healthy male subjects influences learning about a partners’ prosocial preferences in a novel social interaction task, which is akin to a repeated trust game. We found learning to be modulated by a well-established genetic marker of striatal dopamine levels, the 40-bp variable number tandem repeats polymorphism of the dopamine transporter (DAT1 polymorphism). In particular, we found that L-DOPA improves learning in 10/10R genoype subjects, who are assumed to have lower endogenous striatal dopamine levels and impairs learning in 9/10R genotype subjects, who are assumed to have higher endogenous dopamine levels. These findings provide first evidence for a critical role of dopamine in learning whether an interaction partner has a prosocial or a selfish personality. The applied pharmacogenetic approach may open doors to new ways of studying psychiatric disorders such as psychosis, which is characterized by distorted perceptions of others’ prosocial attitudes.     

Psychiatric Problems Affecting Dental Care of the Elderly1

The author reviews the major psychiatric disorders that can affect the dental care of the aged. Depression and dementia are the most common problems in the upper age groups. Other less frequent disorders include paranoid states, anxiety states, and alcohol abuse. All of these illnesses have both symptomatic and specific treatments so that a thorough evaluation and aggressive treatment plan should be pursued when psychiatric symptoms present in any elderly patient. Their treatment can have a considerable influence on the patient's dental care. Ageism, orality, preventive dentistry, xerostomia and periodontal disease are discussed in the context of these psychiatric illnesses of the aged.     

PSYCHIATRIC SERVICES IN GENERAL HOSPITALS—A Report of the Northern California Psychiatric Society's Committee on the Need for Psychiatric Services in General Hospitals

A study made by a special committee appointed for the purpose by the Northern California Psychiatric Society found that a real need exists for local psychiatric services in general hospitals of the Northern California area. Such services can be provided readily—and in some communities are already available. A broad segment of the population looks to the general hospital to provide diagnosis and care and so enable the patient''s prompt recovery from psychiatric disorders. The study further emphasizes the importance of such factors as a competent psychiatric chief, adequate staff and personnel and good planning in organizing inpatient and outpatient facilities and integrating treatment so that all the functions of the hospital are available to psychiatric patients. Granted these special considerations, the services can be provided more easily than many physicians, including some psychiatrists and administrators, suppose.     

Relationship of Psychiatric Diagnosis and Weight Loss Maintenance in Obese Breast Cancer Survivors

Objective: Obese breast cancer survivors are a unique population for weight loss counseling because both obesity and a diagnosis of breast cancer can increase the risk of depression. In this pilot study, weight loss maintenance was examined in obese breast cancer survivors with relationship to psychiatric diagnosis. Research Methods and Procedures: Forty‐eight subjects were enrolled. The intervention, which used individualized counseling for diet and exercise, lasted 24 months. After a 6‐month period of no contact with study subjects, a follow‐up body weight was obtained at 30 months. Results: The nine subjects who dropped out of the study before 12 months all failed to complete a structured psychiatric interview. Of the remaining 39 subjects, 9 had major depressive disorder, and 10 had a definable psychiatric disorder of lesser severity such as adjustment disorder. Subjects with any type of psychiatric diagnosis displayed significantly less weight loss at the 12‐month time‐point than those with no diagnosis (6.3% vs. 12.6% loss of baseline weight, respectively). At the 30‐month follow‐up visit, subjects with any psychiatric disorder had a mean weight loss of 1.2% of baseline weight compared with 7.8% weight loss in subjects with no diagnosis. Discussion: These results suggest that the presence of psychiatric disorders can interfere with weight loss. Therefore, recognition and treatment of psychiatric disorders may be important in attempts at weight reduction, and this will be especially important in populations such as cancer survivors, who seem to have higher rates of depression and other disorders than the general population.     

Preventive Psychiatry: The Psychiatric Team as Consultant to the Public Health Nurse

Various forms of collaboration between the disciplines of public health and psychiatry are briefly reviewed and the 25-year-old mental health program of the Vancouver Health Department is described. The public health nurse has prime responsibility in all children with emotional disorders. She is supported by a psychiatric team which provides active treatment and educational and consultative help for the nurse and the school. During the year 1963, six social workers had 2357 contacts with nurses and school personnel but only 1049 treatment interviews. Of 401 children referred to the psychiatric team, 138 received active clinic treatment, 141 remained under supervision by the public health nurse, and 122 were referred elsewhere. In addition, 1330 children were identified as “mental hygiene cases” in the caseload of the 170 public health nurses in the community. By close co-ordination, the public health nurse and the psychiatric team can enhance each other''s contributions to community mental health.     

Programming social behavior by the maternal fragile X protein

The developing fetus and neonate are highly sensitive to maternal environment. Besides the well‐documented effects of maternal stress, nutrition and infections, maternal mutations, by altering the fetal, perinatal and/or early postnatal environment, can impact the behavior of genetically normal offspring. Mutation/premutation in the X‐linked FMR1 (encoding the translational regulator FMRP) in females, although primarily responsible for causing fragile X syndrome (FXS) in their children, may also elicit such maternal effects. We showed that a deficit in maternal FMRP in mice results in hyperactivity in the genetically normal offspring. To test if maternal FMRP has a broader intergenerational effect, we measured social behavior, a core dimension of neurodevelopmental disorders, in offspring of FMRP‐deficient dams. We found that male offspring of Fmr1^+/? mothers, independent of their own Fmr1 genotype, exhibit increased approach and reduced avoidance toward conspecific strangers, reminiscent of ‘indiscriminate friendliness’ or the lack of stranger anxiety, diagnosed in neglected children and in patients with Asperger's and Williams syndrome. Furthermore, social interaction failed to activate mesolimbic/amygdala regions, encoding social aversion, in these mice, providing a neurobiological basis for the behavioral abnormality. This work identifies a novel role for FMRP that extends its function beyond the well‐established genetic function into intergenerational non‐genetic inheritance/programming of social behavior and the corresponding neuronal circuit. As FXS premutation and some psychiatric conditions that can be associated with reduced FMRP expression are more prevalent in mothers than full FMR1 mutation, our findings potentially broaden the significance of FMRP‐dependent programming of social behavior beyond the FXS population.     

Non-accidental injury in children: what we do in Derby.

A scheme for dealing with cases of non-accidental injury in children in the Derby clinical area has been operating since 1971. A stable team of doctors, policemen, and social workers deal with each case. The parents are told at once that battering is suspected, and the police and social services department co-operate closely in establishing the facts, supporting the family, and protecting the child. A psychiatric assessment of the parents may help social workers decide on the long-term care of the child, and the forensic physician is invaluable if the case has to go to court. The team has made three recommendations about prevention and management of these cases: a specialist social service team should be set up to deal with these children and regain the skills and knowledge lost when children''s departments were abolished in 1971; babies should be routinely weighed naked in infant welfare clinics; and juvenile courts should be able to order a psychiatric report on the parents in care proceedings.     

Psychiatric illness in inpatients with neurological disorders: patients' views on discussion of emotional problems with neurologists.

The prevalence of psychiatric morbidity in inpatients with neurological disorders and the extent to which it is detected by neurologists were measured by using a two stage model of psychiatric assessment and from information recorded in the patients'' medical notes. The prevalence of psychiatric morbidity was estimated as 39%, of which 72% was unrecognised by the neurologists. Only a minority of patients with an uncertain physical diagnosis had a psychiatric illness, showing the error in assuming that a patient''s physical symptoms arise from a psychological disturbance if an organic aetiology cannot be determined. When the patients were interviewed on their discharge from hospital they were divided on whether they had wished to discuss their mood with neurologists while they were in hospital. The reasons that they gave suggested that interactions between patients and doctors and the lack of ward facilities for private consultations with doctors are important determinants of hidden psychiatric morbidity in medical inpatients.     

Growth factors as clinical biomarkers of prognosis and diagnosis in psychiatric disorders

The psychiatric disorders are one of the most disabling illnesses in the world and represent a major problem for public health. These disorders are characterized by neuroanatomical or biochemical changes and it has been suggested that such changes may be due to inadequate neurodevelopment. Diverse alterations in the gene expression and/or serum level of specific growth factors have been implicated in the etiology, symptoms and progression of some psychiatric disorders. Herein, we summarize the latest information regarding the role of brain-derived neurotrophic factor (BDNF), epidermal growth factor (EGF), fibroblast growth factor (FGF), Insulin-like growth factor (IGF-1), neuroregulin-1 (NGR-1), erythropoietin (EPO), vascular growth factor (VEGF), transforming growth factor beta (TGF-β), nerve growth factor (NGF) and others cytokines in the pathogenesis of schizophrenia, depression, bipolar and anxiety disorders. Focusing on the role of these growth factors and their relationship with the main impairments (cognitive, emotional and social) of these pathologies. Some of these signaling molecules may be suitable biological markers for diagnosis and prognosis in cognitive, mood and social disabilities across different mental disorders.     

Childhood antecedents of schizophrenia and affective illness: social adjustment at ages 7 and 11.

OBJECTIVE--To investigate the social adjustment in childhood of people who as adults have psychiatric disorders. DESIGN--Subjects in a prospectively followed up cohort (the national child development study) who had been admitted as adults to psychiatric hospitals were compared with the rest of the cohort on ratings of social behaviour made by teachers at the ages of 7 and 11 years. SUBJECTS--40 adult patients with schizophrenic illnesses, 35 with affective psychoses, and 79 with neurotic illness who had been admitted for psychiatric reasons by the age of 28. 1914 randomly selected members of the cohort who had never been admitted for psychiatric treatment. MAIN OUTCOME MEASURES--Overall scores and scores for overreaction (externalising behaviour) and underreaction (internalising behaviour) with the Bristol social adjustment guide at ages 7 and 11. RESULTS--At the age of 7 children who developed schizophrenia were rated by their teachers as manifesting more social maladjustment than controls (overall score 4.3 (SD 2.4) v 3.1 (2.0); P < 0.01). This was more apparent in the boys (5 (2.6)) than the girls (3.4 (1.8)) and related to overreactive rather than underreactive behaviour. At both ages prepsychotic (affective) children differed little from normal controls. By the age of 11 preneurotic children, particularly the girls, had an increased rating of maladjustment (including overreactions and underreactions). CONCLUSION--Abnormalities of social adjustment are detectable in childhood in some people who develop psychotic illness. Sex and the rate of development of different components of the capacity for social interaction are important determinants of the risk of psychosis and other psychiatric disorders in adulthood.     

前额叶皮层在社交行为中的作用

社交行为对于个体身心健康和社会发展都极其重要。社交行为障碍已成为多种精神类疾病的典型临床表征,对个体的发展有严重不良影响。前额叶皮层作为调节社交行为的关键脑区之一,参与了社交、情绪、决策等高级功能,其内部神经元、神经胶质细胞的活动变化及相互作用对调节社交行为有着重要影响,而且前额叶皮层与其他脑区之间的协作也会影响不同的社会行为。本文回顾了前额叶皮层中神经元、神经胶质细胞以及脑区投射与社交行为关系的最新研究,系统综述了前额叶皮层在社交行为调节中的作用,以期为社交障碍的神经机制和有效诊疗提供参考。     

Unplanned cancer presentation in patients with psychiatric disorders: A nationwide register-based cohort study in Denmark

Unplanned presentation in the cancer pathway is more common in patients with psychiatric disorders than in patients without. More knowledge about the risk factors for unplanned presentation could help target interventions to ensure earlier diagnosis of cancer in patients with psychiatric disorders. This study aims to estimate the association between patient characteristics (social characteristics and coexisting physical morbidity) and cancer diagnosis following unplanned presentation among cancer patients with psychiatric disorders. We conducted a population-based register study including patients diagnosed with cancer in 2014–2018 and also registered with at least one psychiatric disorder in the included Danish registers (n = 26,005). We used logistic regression to assess patient characteristics associated with an unplanned presentation. Almost one in four symptomatic patients (23.6 %) with pre-existing psychiatric disorders presented unplanned in the cancer trajectory. Unplanned presentation was most common for severe psychiatric disorders, e.g. organic disorders and schizophrenia. Old age, male sex, living alone, low education, physical comorbidity, and non-attendance in primary care were associated with increased odds of unplanned presentation. In conclusion, several characteristics of patients with pre-existing psychiatric disorders were associated with unplanned presentation in the cancer trajectory; for some groups more than 40 % had an unplanned presentation. This information could be used to design targeted interventions for patients with pre-existing psychiatric disorders to ensure earlier diagnosis of cancer in this population.     

Aportaciones de los tests de supresión de cortisol al conocimiento de los trastornos psiquiátricos: revisión narrativa de la literatura

Activity of the hypothalamic-pituitary-adrenal axis had been studied for the past half century, when some researchers noted that some patients with Cushing's syndrome and severe mood disorders had high baseline cortisol levels, which resulted in an inhibited response in the 1 mg dexamethasone suppression test. Altered dexamethasone suppression test results were subsequently found in many psychiatric diseases, including anorexia nervosa, obsessive-compulsive disorder, degenerative dementia, bipolar disorders, and schizophrenia. The relationship between high baseline cortisol levels and stress has also been studied. Some researches on the genesis of borderline personality disorder focused on traumatic childhood backgrounds. Other investigations aimed at elucidating the relationship between traumatic backgrounds and some psychiatric disorders noted that patients with post-traumatic stress disorder and borderline personality disorder showed an enhanced cortisol suppression with low cortisol doses (0.5 mg). Recent studies showed that use of an ultra-low dose of cortisol during the dexamethasone suppression test may be helpful for deteting disorders with hyperactivity of the hypothalamic-pituitary-adrenal axis.Recent advances in neuroimaging support the existence of hyperactivity of the hypothalamic-pituitary-adrenal axis in patients with borderline personality disorder, relating a decreased pituitary gland volume to major traumatic backgrounds and suicidal attempts. The purpose of this paper is to make a narrative review of research using dexamethasone suppression test in psychiatric disorders, in order to ascertain its value as a supplemental diagnostic test or as a prognostic marker.