Shoaling in zebrafish: what we don't know

Zebrafish have been gaining increasing popularity in behavioral neuroscience. However, the number of behavioral test paradigms specifically designed for zebrafish, and in general the amount of information available on the behavior of this species, is relatively small when compared with classical laboratory model organisms such as the mouse, the rat, and the fruit fly. A particularly typical behavioral feature of zebrafish is shoaling, i.e., group formation. Given the importance of social behavior in our own species and the fact that zebrafish possess several characteristics similar to those of other vertebrates, including humans, at many levels of biological organization (e.g., neuroanatomy, neurochemistry, biochemical processes, and amino acid sequence of proteins or nucleotide sequence of genes), the zebrafish is expected to be an excellent tool not only for basic research but perhaps also for translational research. Briefly, we propose that once social behavior of the zebrafish is better characterized and once appropriate behavioral methods have been developed, this species can be utilized for the analysis of the mechanisms of social behavior of other vertebrates including our own. In this review, we discuss general principles of shoaling and highlight what we know and what we do not know about this behavior as it pertains to zebrafish.     

Sleep and epilepsy: what we know, don't know, and need to know.

Long-term video-EEG and, more recently, video-polysomnography, have provided the means to confirm and expand on the interconnections between sleep and epilepsy. Some of these relationships have become firmly established. When one of the authors (N.F.S.) presented part of this paper at a symposium on the Future of Sleep in Neurology at an American Clinical Neurophysiology Society annual meeting in 2004, the purpose was to summarize what we know, don't know, and need to know about the effects of sleep on epilepsy and epilepsy on sleep. Here we seek to summarize some of the more firmly established relationships between sleep and epilepsy and identify intriguing associations that require further elucidation.     

Patent foramen ovale and stroke: what we do and don't know

Paradoxical embolism through a patent foramen ovale (PFO) is a commonly identified mechanism of ischemic stroke, especially in young patients. The ability to detect PFOs in life improved dramatically with the development of aerated ultrasound contrast, transesophageal echocardiography, and transcranial Doppler ultrasound. Similarly, the ability to detect source venous thromboemboli is improving with pelvic magnetic resonance venography. Coexisting atrial septal aneurysm is the only definite potentiator of stroke risk in patients with PFO. PFO size and degree of functional shunting may be additional risk factors. Currently, PFOs are treated variably with antiplatelet agents, anticoagulants, surgical closure, or, increasingly, percutaneous closure devices. Completion of randomized clinical trials is urgently needed to clarify if the risks of invasive endovascular device placement are outweighed by a long-term reduction in recurrent vascular events.     

Stress-linked cortisol concentrations in hair: what we know and what we need to know

Cortisol has major impacts upon a range of physiological homeostatic mechanisms and plays an important role in stress, anxiety and depression. Although traditionally described as being solely synthesised via the hypothalamic-pituitary-adrenal (HPA) axis, recent animal and human studies indicate that cortisol may also be synthesised via a functionally-equivalent 'peripheral' HPA-like process within the skin, principally within hair follicles, melanocytes, epidermal melanocytes and dermal fibroblasts. Current data indicate that basal levels of cortisol within hair vary across body regions, show diurnal variation effects, respond to the onset and cessation of environmental stressors, and may demonstrate some degree of localisation in those responses. There are conflicting data regarding the presence of variability in cortisol concentrations across the length of the hair shaft, thus challenging the suggestion that hair cortisol may be used as a historical biomarker of stress and questioning the primary origin of cortisol in hair. The need to comprehensively 'map' the hair cortisol response for age, gender, diurnal rhythm and responsivity to stressor type is discussed, plus the major issue of if, and how, the peripheral and central HPA systems communicate.     

Cytokines and the aging brain - what we don't know might help us

Cognitive aspects of aging represent a grave challenge for our societal circumstances as members of the baby-boom generation spiral toward a collective 'senior moment'. In addition, age-related changes in the CNS can contribute to motor deficits and other somatic aberrations. Inflammation and its regulation by cytokines have been connected to many aspects of aging, and mechanisms addressed here provide a rationale for this. Nevertheless, a role for cytokines in normal aging of the human brain has not been confirmed, and it seems to be possible to ameliorate both cognitive decline and cytokine elevation via lifestyle choices. So ignorance of the brain should not prohibit development of successful strategies for delaying or avoiding neurological deficits.     

Memory and cognition in preclinical dementia: what we know and what we do not know

This overview focuses on the cognitive transition between normal aging and dementia. Numerous studies indicate that individuals who will go on to develop dementia show cognitive deficits many years before the time at which a clinical diagnosis could be rendered. The degree of preclinical impairment is remarkably similar for tasks assessing episodic memory, executive functioning, and perceptual speed, consistent with the view that multiple brain alterations occur prior to clinical disease onset. Although most research in this area has dealt with Alzheimer disease (AD), several recent reports indicate that the pattern of preclinical impairment is very similar in the second largest dementia disorder, vascular dementia (VaD). This is important because currently the possibility for interventions to postpone disease onset is greater in VaD than in AD. Despite pronounced preclinical cognitive deficits in dementia, the performance distributions between cases and controls are largely overlapping, hampering the ability to identify high-risk individuals. To alleviate this problem, future research should evaluate hybrid models for the prediction of dementia. In such models, multiple indicators of cognitive functioning should be included along with markers from other domains that have been linked to subsequent dementia (such as brain imaging, genetics, and lifestyle variables). To the extent that these categories of variables add unique variance, classification accuracy will increase and the overlap in performance scores between incident cases and controls will decrease, thereby enhancing clinical usefulness. This approach would also facilitate the examination of interactive effects among classes of preclinical markers.     

HIV in adolescents: What we know and what we need to know

HIV, the cause of AIDS, has infected more than 65 million people worldwide, including 1 million children. An estimated 39.5 million people are living with HIV. As of 2006, 4.3 million were newly infected, with 2.8 million occurring in sub-Saharan Africa. Rates of infection have risen more than 50% in Eastern Europe and Central Asia. Mother-to-child transmission occurs rarely with antiretroviral treatments in the United States, and congenitally infected children are living to adulthood. HIV is now a “youth-driven disease” worldwide. In the United States, 40% of new HIV infections occur in individuals less than 25 years old, and HIV is the sixth-leading cause of death among adolescents. Young people with HIV/AIDS live with this chronic condition and its associated medical and psychological morbidities while coping with identity and maturation issues. In this paper, we review what we know about HIV and psychiatric disorders among adolescents.     

Depression in patients with chronic renal disease: what we know and what we need to know

Depression is a common, but underdiagnosed and understudied problem in patients with renal disease. The overlap between symptoms of chronic medical illness and those of depression make for a particularly challenging diagnosis in this illness. The prevalence of depression varies with the diagnostic tool employed. The gold standard for the psychiatric diagnosis is the interview, using DSM-IV TR criteria. Researchers in the field of renal disease have often not distinguished between the diagnosis of major depression and high levels of depressive affect in studies. There are almost no data regarding the magnitude of depression in patients with chronic renal insufficiency, patients treated with peritoneal dialysis, and children with renal disease, compared with adults with end-stage renal disease treated with hemodialysis. The relationships between age, ethnicity, marital status and satisfaction, and perception of quality of life and level of depressive affect and diagnosis of depression, and medical outcomes have not been determined in patients with renal disease. The mediators which may underlie the deleterious effects of depression in patients with renal disease, and their relationship with stage of renal dysfunction have not been delineated. More emphasis must be placed on well-designed treatment studies and survival analyses in these populations, using longitudinal techniques.     

Epidemiology of insomnia: what we know and what we still need to learn

Epidemiologists have published more than 50 studies of insomnia based on data collected in various representative community-dwelling samples or populations. These surveys provide estimates of the prevalence of insomnia according to four definitions: insomnia symptoms, insomnia symptoms with daytime consequences, sleep dissatisfaction and insomnia diagnoses. The first definition, based on insomnia criteria as defined by the DSM-IV, recognizes that about one-third of a general population presents at least one of them. The second definition shows that, when daytime consequences of insomnia are taken into account, the prevalence is between 9% and 15%. The third definition represents 8-18% of the general population. The last definition, more precise and corresponding to a decision-making diagnosis, sets the prevalence at 6% of insomnia diagnoses according to the DSM-IV classification. These four definitions of insomnia have higher prevalence rates in women than in men. The prevalence of insomnia symptoms generally increases with age, while the rates of sleep dissatisfaction and diagnoses have little variation with age. Numerous factors can initiate or maintain insomnia. Mental disorders and organic diseases are the factors that have been the most frequently studied. The association between insomnia and major depressive episodes has been constantly reported: individuals with insomnia are more likely to have a major depressive illness. Longitudinal studies have shown that the persistence of insomnia is associated with the appearance of a new depressive episode. Future epidemiological studies should focus on the natural evolution of insomnia. Epidemiological genetic links of insomnia are yet to be studied.     

Child maltreatment: what we know in the year 2000.

This paper provides an overview of child maltreatment within a public health framework, based on the Closing Plenary Address presented at the 1999 Joint Meeting of the American Academy of Child and Adolescent Psychiatry and the Canadian Academy of Child Psychiatry. A brief historical perspective is followed by a discussion of the burden of suffering associated with child maltreatment. Evidence about the prevention and treatment of child abuse and neglect is reviewed. Evidence supports a program of nurse home visits as effective in preventing abuse and neglect among first-time, at-risk mothers. Sexual abuse education programs improve children's knowledge and prevention skills; whether such programs reduce the occurrence of child sexual abuse remains to be established. In the area of treatment, therapeutic day-care programs improve cognitive skills among physically abused and neglected children. Abuse-specific cognitive-behaviour therapy has been shown to be effective in reducing symptoms among sexually abused children in both preschool and older age groups. Further research is necessary across all subcategories of child maltreatment, particularly neglect and emotional abuse.