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Trace amines have been implicated in a number of neuropsychiatric disorders including depression and schizophrenia. Although long known to modulate neurotransmission indirectly through the release of catecholamines, the identification of the Trace Amine 1 receptor (TA1) offers a mechanism by which trace amines can influence synaptic activity directly. TA1 binds and is activated by trace amines such as β-phenylethylamine and tyramine. Our pharmacological characterization of mouse TA1 showed that, as in rat and primate, amphetamine is an agonist at this receptor but with surprisingly high potency. Without selective ligands for TA1 that do not also possess catecholamine-releasing properties, however, it has not been possible to study its physiological role in the central nervous system. To that end, a line of mice lacking the TA1 receptor was generated to characterize its contribution to the regulation of behavior. Compared with wild-type littermates, TA1 knockout (KO) mice displayed a deficit in prepulse inhibition. Knockout animals, in which the TA1-agonist influence of amphetamine was absent, showed enhanced sensitivity to the psychomotor-stimulating effect of this drug, which was temporally correlated with significantly larger increases in the release of both dopamine and norepinephrine in the dorsal striatum and associated with a 262% increase in the proportion of striatal high-affinity D2 receptors. TA1 therefore appears to play a modulatory role in catecholaminergic function and represents a potentially novel mechanism for the treatment of neuropsychiatric disorders. Furthermore, the TA1 KO mouse may provide a useful model for the development of treatments for some positive symptoms of schizophrenia. [ABSTRACT FROM AUTHOR]

Both physiological and environmental constraints can be important selective factors on behaviors. The results of the present study showed that fecundity is significantly reduced if copulation is delayed for as short a time as 6 ± 6h in the amphipod crustacean Gammarus palustris (Bousfield, 1969). This led to the prediction that selection would favor behaviors which minimize the likelihood of delays. In amphipods of this genus, amplexus occurs before the female molts and copulation occurs within minutes afterwards. The results of field observations support the prediction; it is estimated that 99% of the females are in amplexus when they molt. However, while the physiological constraints that were demonstrated show the advantages of pairing before copulation, it is speculated that amplexus as the specific pairing behavior evolved in response to the selective pressures of the free‐roaming habits of G. palustris. [ABSTRACT FROM PUBLISHER]

Elasmopus levis is commonly found among shallow subtidal and intertidal macrofaunal assemblages along western Atlantic coasts, yet virtually nothing is known about its life history. The present study reports the results of laboratory observations of the key features of its pattern of reproduction. The observations show that the reproductive physiology of this species is similar to that of most amphipods studied to date, but it seems to spend much less energy on reproductive behaviors than others. No courtship or pair‐bonding behaviors were observed, and, although the male and female of heterosexual pairs were found in proximity more often at the time of the female molt than at other times, the frequency of these associations was lower than that of other species observed. It is hypothesized that the principal reproductive stimulus for this species may be an environmental factor, rather than a stimulus produced by the receptive female, as is the case in other species. [ABSTRACT FROM PUBLISHER]

The use of a choice test apparatus has shown that receptive females of the tube-building amphipod crustacean Microdeutopus gryllotalpa (Costa) secrete a waterborne substance which attracts males. This substance (1) increases the level of activity of males, and (2) orients the males' movements towards its source. Males do not secrete this substance. In this species, females tend to remain inside their residential tubes, and males generally travel from receptive female to receptive female. Thus, in the field, the attractant may stimulate the male to accelerate his movements toward, and guide him directly to a receptive female. On the other hand, at the concentration tested, the substance alone does not elicit 'intermittent pleopod beats', a male-specific behavior that only occurs in a reproductive context. The expression of 'intermittent pleopod beats' is shown to require the presence of a female plus its tube. [ABSTRACT FROM AUTHOR]

Background Identifying sensitive, specific, and reliable indicators of disease progression in Huntington's disease (HD) is key to selecting the appropriate population for clinical trials that assess novel treatments that may slow or delay the onset of HD's debilitating symptoms. The PREDICT-HD study is an NIH and CHDI-funded study that began in 2001, with the goal of documenting the neurobiological and neurobehavioral changes that occur in HD-gene carriers in the period leading up to the diagnosis of HD. The PREDICT-HD study provides a rich source of data that can be mined to identify HD-gene carriers who show rapid progression in the early stages of the disease, prior to diagnosis based on their motor symptoms. Aims To identify a population of PREDICT-HD participants who show rapid progression in motor symptoms over the course of the first four years of the PREDICT-HD study, and to determine if there are specific measures that classify participants a priori. Methods The change in the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor score between Baseline and Year 4 was calculated for all PREDICT-HD participants who had completed four annual visits. A model was generated to distinguish rapid progressors from gene-carriers not showing progression utilizing the baseline motor, cognitive, and imaging data from PREDICT-HD participants. Results Examination of the inter-quartile ranges of change-from-baseline total motor scores showed that PREDICT-HD participants in the top (fourth) quartile had a change in score of approximately 14 points; the average change in the third quartile was only 5 points. The classification model that was developed included disease burden score, striatal volume, motor and cognitive variables. The model was 82.4% accurate in identifying HD-gene carriers in PREDICT-HD who showed rapid progression in their UHDRS motor scores; the model was 91.9% accurate in identifying HD-gene carriers in PREDICT-HD who did not show a substantial increase in their motor scores. Conclusions There is a population of HD-gene carriers in the PREDICT-HD study that show a rapid progression in their motor symptoms as assessed by the UHDRS Motor Subscale. We have developed a model that is highly accurate in identifying these patients. This model needs to be further refined and validated. This model may be useful in identifying HD-gene carriers for recruitment in therapeutic clinical trials. [ABSTRACT FROM PUBLISHER]

Background The earliest clinical manifestations of Huntington's (HD) disease are poorly characterized, and there is a need for clinical scales designed specifically to measure early signs and symptoms in individuals with the huntingtin gene mutation. Aims The Functional Rating Scale Taskforce for pre-Huntington's Disease (FuRST-pHD) is comprised of a multidisciplinary team of clinical experts, drug developers, and psychometricians that work in close association with advocacy groups and HD gene carriers to develop a valid functional rating scale to assess changes in symptom severity in pre- and early-HD. Such a measurement tool is essential in order to assess the efficacy of early intervention treatments. Methods FuRST-pHD has established a data-driven, iterative, and collaborative process to develop a clinical scale to assess symptoms and their functional impact in pre- and early-HD. The process involves input from numerous sources to identify relevant symptom domains, including gene expansion carriers, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing observational studies in HD (PREDICT-HD and REGISTRY) using existing clinical scales. Clinical scale interview questions were developed by expert teams of clinicians and psychometricians in order to gather data about the identified symptom domains through field testing in pre-HD individuals. We report here the progress of the FuRST-pHD initiative. Results At present, more than 60 structured interview questions aimed at determining the presence and extent of severity in a number of symptom domains have been developed, including motor, cognitive and psychiatric symptoms. The interview questions have undergone, or are undergoing, testing at various clinical centres involved with FuRST-pHD and PREDICT-HD. We present data supporting the development of items to assess a number of symptoms in pre-HD, including Anger and Irritability, Obsessions and Compulsions, and Depression and Anxiety. Conclusions Many CAG expanded individuals clearly exhibit a range of motor, cognitive and psychiatric signs years prior to clinical diagnosis. The present data suggest a number of behavioural/psychiatric symptom clusters that should be assessed in order to capture fully the scope of dysfunction in pre-HD individuals. [ABSTRACT FROM PUBLISHER]

Historically, the diagnosis of HD has been based on the presence of motor-related symptoms. There is emerging evidence, however, that prior to the manifestation of motor symptoms sufficient to warrant clinical diagnosis, many patients exhibit subtle motor, cognitive, and psychiatric signs, suggesting that people with HD may experience detectable changes before clinical diagnosis (i.e., pre-HD). There is currently a need for a rating scale that is sensitive enough to detect early symptomatic changes and disease progression in pre-HD. The Functional Rating Scale Taskforce for pre-HD (FuRST-pHD) has been established to develop such a measure. In the initial phase of this program, FuRST-pHD will identify which symptoms should be addressed in a clinical scale, and how best to measure those symptoms. Depression is thought to be a component of HD that may be present prior to clinical diagnosis. In the present study, FuRST-pHD examined the expression of signs and symptoms associated with depression using data obtained from PREDICT-HD, utilizing a non-parametric item response analysis of depression ratings (UHDRS-III, BDI-II). Item response modeling can be used to evaluate the performance of individual items (or symptoms) on rating scales, assessing the relationship between a score assigned to a particular item and overall severity of the disease. The results show that pre-HD CAG-expanded subjects (≥37 repeats, n = 752) reported greater depressive symptomatology compared to the comparison group (<30 repeats, n = 181). Depression-related symptoms generally increased as a function of overall depressive severity, with six UHDRS-III items (Depressed Mood, Guilt/Self-Esteem, Apathy, Anxiety, Irritability and Anger) and seven BDI items (Sadness, Loss of Pleasure, Guilt, Loss of Energy, Irritability, Concentration, and Fatigue) showing good relation between item score and overall severity. These depression-related signs and symptoms warrant further assessment as items to include on a scale to assess pre-HD symptoms. FuRST-pHD is sponsored by CHDI Foundation. [Copyright &y& Elsevier]

There is an unmet need for the development of treatments for Huntington''s disease (HD). The ideal goal would be to develop drugs that can be administered sufficiently early (i.e., pre-HD), such that the full manifestations never develop or are at least delayed. Unfortunately, there is currently no sensitive validated tool capable of measuring symptomatic changes in pre-HD that can be used in clinical trials. The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal to develop a data-driven, comprehensive, psychometrically sound, sensitive, functional rating scale to be utilized in clinical trials to measure symptoms in patients at the pre-HD stage of the disease. The Taskforce will first identify signs and symptom clusters that should be assessed in pre-HD patients, based on input from a variety of sources, including clinical experts, patients, caregivers, and regulatory agencies. The Taskforce will then develop clinical measures of these signs and symptoms using an iterative processes involving field testing and psychometric analyses. The Taskforce will also rely on the analyses of existing datasets to identify items that may have utility in measuring pre-HD symptomatology. The Taskforce is currently analyzing data from PREDICT-HD, using item response theory (IRT), an approach that has been shown to be a powerful method for evaluating the performance of individual items of rating scales by assessing the relationship between item scores and severity. The development of a new data-driven, reliable, valid, and easily administered instrument would be valuable in the assessment of pre-HD symptoms in clinical trials. This collaborative effort welcomes input from HD researchers. FuRST-pHD is sponsored by CHDI Foundation. [Copyright &y& Elsevier]

Presents a correction to the article 'Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist,' published in the September 2002 issue of the journal 'Nature Medicine.'