Autonomic reactivity and clinical severity in children with sickle cell disease

Abstract Individual differences in autonomic nervous system reactivity have been studied in relation to physical and mental health outcomes, but rarely among children with chronic disease. The purpose of this study was to examine the associations among autonomic reactivity, clinical severity, family stressors, and mental health symptoms in children with homozygous sickle cell disease. Nineteen children with homozygous sickle cell disease participated in a cross-sectional study involving parent-completed measures, medical record reviews and laboratory-based measures of autonomic nervous system responses to social, cognitive, physical and emotional challenges. Autonomic reactivity was significantly associated with both clinical severity and externalizing behavior symptoms. Children with greater parasympathetic withdrawal during challenges compared to rest had significantly more severe disease (r=–0.45, p<0.05); greater sympathetic activation during challenges compared to rest was associated with more externalizing behavior symptoms (r=0.44, p<0.05). Children experiencing major family stressors had internalizing behavior symptoms but no difference in autonomic reactivity or clinical severity compared to children experiencing fewer family stressors. Individual differences in autonomic reactivity may offer a new, biologically plausible account for observed variation in painful episodes, other physical complications and behavioral symptoms among children with sickle cell disease.     

Age disorientation in schizophrenia: an indicator of progressive and severe psychopathology, not institutional isolation

The authors investigated age disorientation in chronic schizophrenia to determine whether specific symptomatic, neurologic, and cognitive disturbances were linked to its presentation. Disorientation to their age was detected in 30% (16/54) of the schizophrenic patients in a chronic care facility. In matched comparisons, age-disoriented patients showed lower educational achievement, poorer mental state performance, and a greater severity of symptoms, as well as more severe motor and sensory impairments. Levels of social withdrawal did not differentiate the two groups. A two-hit model consistent with neurodevelopmental and neurodegenerative processes is proposed to explain the data.     

Prevalence of mental disorders in young adults with chronic physical diseases since childhood as identified by the Present State Examination and the CATEGO program

To find out whether long-term physical disorders in childhood increase the risk for mental disorder, we interviewed 407 young adults and compared their findings to a control group of 123 age-matched controls. The overall prevalence of mental disorders according to ICD-8 classification exceeded 20% in both groups. Depression and phobic disorders were the most common diagnostic syndromes, being most prevalent in women with motor handicaps or short stature. Only 7 patients had received psychotherapy, 5 for psychotic symptoms. In conclusion, only a severe physical disease, visible and disabling for years in everyday life, seems to increase the risk for mental problems. The results demonstrate the need to improve the approach towards psychological problems in the somatic clinics treating patients with long-term physical diseases.     

Diagnosing genetic anomalies by inspection.

Several readily identifiable syndromes that have a genetic basis consist of mental retardation, hyperactivity or other abnormal behaviors, and characteristic physical signs. These disorders are not only an opportunity for clinical diagnosis, but they reflect the neurologic underpinning of intellect and behavior. Moreover, the wide variations in their phenotypes suggests that genetic testing be considered in children with abnormal appearance and mental retardation.     

Clinical use of CT and MR scans in psychiatric patients.

During a three-year period, 337 CT or MR scans were ordered for psychiatric patients in a teaching hospital. Scans were normal in 185 instances, equivocal in 34, and abnormal in 118 instances. When a history of neurologic disorder and/or the presence of abnormal neurologic/organic mental signs was positive, scans were abnormal in 74% of cases; when these indicators were negative, scans were normal in 72% of cases. In all, only 4 new diagnoses were made. Two patients, both with markedly abnormal neurological findings, were shown to have brain tumors, which changed their management. Two others showed abnormalities which would have been missed, both of which were of no clinical consequence. The following are suggested as sound indications for ordering CT or MR brain imaging among psychiatric patients: 1) positive history of head injury, stroke or other neurologic disease, as well as suspected Alzheimer disease or multi-infarct dementia; 2) presence of abnormal neurologic signs or organic mental signs, such as confusion or cognitive decline; and, 3) a first psychotic break or personality change after the age of 50 years.     

重型颅脑损伤患者精神障碍的临床分析

目的 探讨重型颅脑损伤后精神障碍的发生率、表现形式及影响因素。方法 以深圳市1999年10月1日至2000年9月30日因交通事故所致重型颅脑损伤的183例幸存者为研究对象,在颅脑损伤治疗后（平均6个月）,由2名精神科副主任医师根据中国精神疾病分类方案与诊断标准第2版修订本对这些伤者的精神状态进行评估。结果 （1）在183例中,罹患各类精神障碍者共165例,发生率为90．2％,其中智能障碍者为142例（77．6％）。（2）在183例,中度及其以上智力损伤者为29例（15．8％）。（3）有智力损伤组的脑干损伤、颅内血肿及≥3个脑叶损伤的比例高于无智力损伤组（P＜0．01）;伴有精神障碍组的平均年龄（P＜0．05）、脑干损伤（P＜0．05）及≥3个脑中损伤（P＜0．01）的比例高于无精神病性障碍组;有人格改变组额叶损伤、开颅清除血肿并减压治疗的比例高于无人格改变组（P＜0．01）。结论 重型颅脑损伤后精神障碍的发生率较高,应引起有关临床学科的重视。     

Brain disorders and the biological role of music

Despite its evident universality and high social value, the ultimate biological role of music and its connection to brain disorders remain poorly understood. Recent findings from basic neuroscience have shed fresh light on these old problems. New insights provided by clinical neuroscience concerning the effects of brain disorders promise to be particularly valuable in uncovering the underlying cognitive and neural architecture of music and for assessing candidate accounts of the biological role of music. Here we advance a new model of the biological role of music in human evolution and the link to brain disorders, drawing on diverse lines of evidence derived from comparative ethology, cognitive neuropsychology and neuroimaging studies in the normal and the disordered brain. We propose that music evolved from the call signals of our hominid ancestors as a means mentally to rehearse and predict potentially costly, affectively laden social routines in surrogate, coded, low-cost form: essentially, a mechanism for transforming emotional mental states efficiently and adaptively into social signals. This biological role of music has its legacy today in the disordered processing of music and mental states that characterizes certain developmental and acquired clinical syndromes of brain network disintegration.     

Child physical abuse: Risk for psychopathology and efficacy of interventions

The emerging research on child physical abuse (CPA) is reviewed herewith. Incidence of CPA may be as high as 11% for adolescents in the US. Child physical abuse survivors vary in their symptom picture of severity and type. Children who have been physically abused may experience symptoms of post-traumatic stress disorder, anxiety disorders, depressive disorders, or disruptive behavior disorders. Additionally, developmental disturbances include problems with attachment, social skills, and affect regulation. Chronic abuse is associated with more severe psychopathology. Cognitive processing of the abuse may mediate the impact of CPA on development. Service delivery studies indicate that as many as half of children with substantiated cases of CPA do not receive mental health services. Emerging treatment outcome research reveals the potential efficacy of cognitive behavioral treatment for CPA. Reactions to existing literature and recommendations for future work are presented.     

Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges

Increasing evidence suggests that disrupted temporal organization impairs behavior, cognition, and affect; further, disruption of circadian clock genes impairs sleep-wake cycle and social rhythms which may be implicated in mental disorders. Despite this strong evidence, a gap in understanding the neural mechanisms of this interaction obscures whether biological rhythms disturbances are the underlying causes or merely symptoms of mental disorder. Here, we review current understanding, emerging concepts, gaps, and opportunities pertinent to (1) the neurobiology of the interactions between circadian oscillators and the neural circuits subserving higher brain function and behaviors of relevance to mental health, (2) the most promising approaches to determine how biological rhythms regulate brain function and behavior under normal and pathological conditions, (3) the gaps and challenges to advancing knowledge on the link between disrupted circadian rhythms/sleep and psychiatric disorders, and (4) the novel strategies for translation of basic science discoveries in circadian biology to clinical settings to define risk, prevent or delay onset of mental illnesses, design diagnostic tools, and propose new therapeutic strategies. The review is organized around five themes pertinent to (1) the impact of molecular clocks on physiology and behavior, (2) the interactions between circadian signals and cognitive functions, (3) the interface of circadian rhythms with sleep, (4) a clinical perspective on the relationship between circadian rhythm abnormalities and affective disorders, and (5) the pre-clinical models of circadian rhythm abnormalities and mood disorders.     

Psychiatric manifestations of neurocysticercosis: a study of 38 patients from a neurology clinic in Brazil.

OBJECTIVE: To determine the frequency and features of psychiatric morbidity in a cross section of 38 outpatients with neurocysticercosis. METHODS: Diagnosis of neurocysticercosis was established by CT, MRI, and CSF analysis. Psychiatric diagnoses were made by using the present state examination and the schedule for affective disorders and schizophrenia-lifetime version; cognitive state was assessed by mini mental state examination and Strub and Black's mental status examination. RESULTS: Signs of psychiatric disease and cognitive decline were found in 65.8 and 87.5% of the cases respectively. Depression was the most frequent psychiatric diagnosis (52.6%) and 14.2% of the patients were psychotic. Active disease and intracranial hypertension were associated with higher psychiatric morbidity, and previous history of mood disorders was strongly related to current depression. Other variables, such as number and type of brain lesions, severity of neuropsychological deficits, epilepsy, and use of steroids did not correlate with mental disturbances in this sample. CONCLUSIONS: Psychiatric abnormalities, particularly depression syndromes, are frequent in patients with neurocysticercosis. Although regarded as a rare cause of dementia, mild cognitive impairment may be a much more prevalent neuropsychological feature of patients with neurocysticercosis. The extent to which organic mechanisms related to brain lesions may underlie the mental changes is yet unclear, although the similar sex distribution of patients with and without depression, as well as the above mentioned correlations, provide further evidence of the part played by organic factors in the cause of these syndromes.     

Organic brain syndromes: new classification, concepts and prospects

The concept, definitions and classification of organic mental disorders have been radically revised in DSM-III, the new American classification. Seven organic brain syndromes have been included and their diagnostic criteria explicitly formulated. The boundary between so-called functional and organic mental disorders has been blurred. The author discusses these changes in the light of growing importance of organic psychiatry due to aging of the population and the high incidence and prevalence of organic mental disorders in the elderly.     

Neurologic complications of systemic cancer

Patients with cancer commonly suffer neurologic disabilities. These neurologic disorders can be either metastatic to the brain, spinal cord, leptomeninges, or peripheral nerves or nonmetastatic including infections, vascular problems, metabolic abnormalities, side effects of therapy, or paraneoplastic syndromes. Careful diagnostic evaluation of patients with cancer and neurologic symptoms often indicates effective therapy.     

Small-world brain networks in schizophrenia

Summary

Over the last decade the combination of brain neuroimaging techniques and graph theoretical analysis of the complex anatomical and functional networks in the brain have provided an exciting new platform for exploring the etiology of mental disorders such as schizophrenia. This review introduces the current status of this work, focusing on the topological properties of human brain networks – called ‘small-world brain networks’ – and on the disruptions in these networks in schizophrenia. The evidence supporting the findings of reduced efficiency of information exchange in schizophrenia both within local brain regions and globally throughout the brain is reviewed and the potential relationship of these changes to cognitive and clinical symptoms is discussed. Finally we propose some suggestions for future research.Schizophrenia is a severe mental disorder characterized by positive symptoms (delusions, hallucinations and other thought disturbances), negative symptoms (apathy, social withdrawal and other behaviors), cognitive impairments, and emotional dysregulation. Despite more than a century of research, the pathophysiological mechanisms that result in schizophrenia remain unknown, presumably because of the incredible complexity of the human brain.[1] The intensive study of the structure and function of complex systems in nature – ‘network science’[2] – may provide insights that can be applied to the study of the brain and, thus, improve our understanding of mental disorders like schizophrenia. Network science describes the topological properties of complex networks in terms of the characteristics of ‘small-world architecture’, ‘centrality,’ ‘hierarchy,’ ‘modularity,’ and ‘distribution of network hubs’. When applied to the brain, these hypothesized small-world properties may enable the cortical network to process information globally and locally with maximal efficiency. This article briefly reviews the current understanding of the small-world network of the brain and then focuses on recent studies about the relationship between disruptions of the small-world brain network and schizophrenia.     

Infantile epileptic syndromes and metabolic etiologies

Inherited metabolic disorders can cause onset of epilepsy in the first year of life. Epilepsy rarely dominates the clinical presentation, which is more frequently associated with other neurologic symptoms, such as mental retardation, hypotonia and/or dystonia, or vigilance disturbances. The pathogenesis of seizures is multifaceted; inherited metabolic disorder can affect the balance between excitatory and inhibitory chemical mediators, eliminate an energetic substrate at the cerebral level, cause in utero brain malformation, or provoke acute brain lesions. Some clinical disorders that strongly suggest particular metabolic etiologies can be identified. For example, specific clinical signs and findings on electroencephalogram (EEG) are characteristic of pyridoxine-dependent seizures, and inherited metabolic disorders associated with early myoclonic encephalopathy are well defined. In most cases, however, epilepsy secondary to inherited metabolic disorders presents with polymorphic clinical and EEG features that are difficult to classify into precise epileptic syndromes. Common characteristics of these seizures include onset in the first months of life; usually partial, multifocal; simple partial motor semiology; successive appearance of tonic seizures, spasms, and massive myoclonus; and resistance to antiepilepsy drugs. Inherited metabolic disorders must be considered in patients presenting with epilepsy and progressive neurologic worsening.     

Epidemiology of early-onset schizophrenia

A total of 232 (84%) first episodes of schizophrenia from our epidemiologically defined ABC sample (Age, Beginning and Course) were retrospectively assessed with regard to the onset and early course of the disorder. In a follow-up study a representative subgroup (n=133) was prospectively examined in five cross sections over 3 years from first admission on. Population-based incidence rates for 5-year age groups comprising a range of <10-<60 years were calculated on the basis of two definitions of onset: first sign of disorder and first psychotic symptom. In 40% of adult patients who had been admitted with a first schizophrenic episode after age 20 years the prodromal phase, in 11% the psychotic prephase, began before that age. This demonstrates that schizophrenia often begins in an age period in which the social and cognitive development and brain maturation are still unfinished. Early-onset schizophrenias (<-20 years) were compared with a medium-onset group (21<35 years) and a late-onset group (35-<60 years) with regard to age and type of onset, early symptom-related course, social development and social course. The number of schizophrenia-specific positive and negative syndromes in early-onset schizophrenia is comparable to that of higher age groups. However, neurotic syndromes, emotional disorders and conduct disorders are most frequent in younger patients, especially in young men. Paranoid syndromes seem to prevail in late-onset schizophrenia, whereas less differentiated positive syndromes, such as delusional mood, are more frequent in the youngest age group. An earlier onset of schizophrenia has more severe social consequences than onset in adults, because it interrupts the cognitive and social development at an earlier stage. The worse social course of schizophrenia in men compared with women cannot be related to a more severe symtomatology, but to the earlier age at onset and the impairment or stagnation of social ascent at an earlier stage of social and cognitive development. Social disability in the sense of an adaptation to the expectations of the social environment, as well as symtomatology during the further course of schizophrenia, show no major differences between the genders nor between the age groups.     

Now is the time to retire the term "organic mental disorders".

The organic/nonorganic distinction in contemporary classifications of mental disorders such as DSM-III and DSM-III-R has important prognostic and treatment implications, because it directs the clinician to pay special attention to the possibility of an underlying "physical" disorder as the cause of the mental disturbance. However, the term "organic" raises serious and intractable problems, since the connotative meaning of the term always returns to its historical roots, which imply an outmoded functional/structural, psychological/biological, and mind/body dualism. The authors present a proposal being considered for DSM-IV that would eliminate the term "organic" and reorganize the classification of organic mental disorders. Disorders previously referred to as "organic mental disorders" would be renamed as either "secondary disorders" (if they are due to "physical" disorders) or "substance-induced disorders." The entire classification of mental disorders would be reorganized to distribute the secondary and substance-induced disorders into the major groups with which they share phenomenology. The traditional organic mental disorders--delirium, dementia, and amnestic disorder--would be grouped together under the rubric of "cognitive impairment disorders." While acknowledging problems with the suggested new terminology and reorganization of the classification, the authors argue that the potential benefits of the proposal for clarity and for facilitating differential diagnosis justify putting to rest the familiar but now anachronistic term "organic mental disorders."     

Neurobiological mechanisms in addictive and psychiatric disorders.

The studies reviewed indicate that brain stress system play an important role in the acquisition and maintenance of drugs of abuse that target the brain's reward centers. In doing so, they may destabilize these areas, making the perception of pleasure more elusive and difficult to attain. Withdrawal from drugs of abuse leads to the activation of brain CRF systems that may produce the anxiogenic response associated with drug withdrawal. More research, however, is needed to investigate the role of brain stress systems and neuropeptides in other drug withdrawal symptoms such as anhedonia. A better understanding of the brain systems underlying drug withdrawal may help in the development of improved pharmacotherapies that can alleviate drug withdrawal symptoms. The second part of the article indicated that there is a very high comorbidity between depression and drug dependence. The reviewed studies suggest that depressed patients initiate drug-taking behavior to self-medicate the symptoms associated with their psychiatric disorder. Chronic use of drugs of abuse, however, may exacerbate the symptoms of pre-existing mental disorders and subsequently increase drug-taking behavior. Conversely, professional treatment of pre-existing psychiatric disorders may decrease the use of illicit substances.     

Predictors of delayed social maturation and mental health disorders in young adults chronically ill since childhood

To ascertain the influence of juvenile-onset chronic physical diseases and associating factors of social environment on delayed social maturation and mental health disorders in young adults, we analysed a group of 407 (184 female, 223 male) subjects with these conditions and compared the results with those of 123 (63 female, 60 male) healthy controls studied at the age of 19-25 years. The social maturation index was formed on the basis of a demographic interview, which also reviewed the state of social development and the family situation during childhood. Mental health disorders were assessed with a Present State Examination (PSE) interview analysed with the CATEGO program. With regard to social maturation at least half of the patients and controls were doing well, whereas for 29% (CI(95), 25%-33%) of the patients and 17% (CI(95), 10%-24%) of the controls the index showed delayed maturation. Subjects with poor social maturation were found most often among the disabled patients but also among the patients without severe diseases. The prevalence of PSE-CATEGO-identified psychiatric syndromes was equal in the patients and the controls (22% versus 20%). However, the patients with severe or disabling diseases had more severe psychiatric syndromes. The prevalences of depressive syndromes were also equal, but the depression of the patients was more often a profound affective disorder. Male sex, poor scholastic and vocational success, and social problems in the family during childhood were significantly associated with poor social maturation. On the other hand, the most significant predictors of mental health problems in young adults were female sex, family distress during childhood, and a severe disease. Juvenile-onset physical disease was considered to delay social maturation in some subjects and to deepen or modulate the clinical picture of mental health disorders. It is concluded that juvenile-onset physical diseases combined with family-related factors affect in different ways the social growth and psychiatric well-being. The results suggest that the subjects with chronic diseases during childhood should be thoroughly assessed by a child psychiatrist to evaluate the orientation of psychological development and the impact of the child's disease on the family and to ensure balanced psychological and social growth.     

Paraneoplastic Neurologic Disorders in Children

Paraneoplastic neurologic syndromes are rare disorders that have potentially devastating effects on the developing brain. Recently, there has been increased interest in possible immunotherapy for these disorders. Recognition of paraneoplastic syndromes in children may lead to early detection and treatment of the pediatric cancer and may diminish the neurologic damage that is the major source of morbidity in children with successfully treated tumors. This article reviews the presenting symptoms, immunology, long-term sequelae, and management options for paraneoplastic neurologic syndromes, focusing on those most commonly reported in children: opsoclonus-myoclonus ataxia, limbic encephalitis, and anti-NMDAR encephalitis. The child neurologist plays an important role in recognizing these disorders, initiating a tumor search, and directing ongoing treatment and management of neurologic symptoms after oncologic treatment is complete. Given the rarity of these conditions, multisite collaborative efforts are needed to develop standardized approaches to characterization and treatment.