Neuroendocrine effects of ovine corticotropin-releasing hormone in panic disorder patients

A number of neuroendocrine abnormalities have been reported in panic disorder patients: the most extensively studied being disturbances of hypothalamic-pituitary-adrenal function (Curtis et al. 1982; Leiberman et al. 1983; Uhde et al. 1988). The recent sequencing and synthesis of corticotropin-releasing hormone now allows direct testing of pituitary responsivity to this neuropeptide in affective and panic disorder patients (Holsboer et al. 1984; Gold et al. 1986; Roy-Byrne et al. 1986; Holsboer et al. 1987; Risch et al. 1988). We report the effects of intravenously administered ovine corticotropin-releasing hormone (0.03 micrograms/kg) on plasma concentrations of adrenocorticotropin hormone (ACTH) and cortisol in a small group of panic disorder patients and age- and sex-matched normal controls.     

When attention wanders: how uncontrolled fluctuations in attention affect performance

No matter how hard subjects concentrate on a task, their minds wander (Raichle et al., 2001; Buckner et al., 2008; Christoff et al., 2009; Killingsworth and Gilbert, 2010). Internal fluctuations cannot be measured behaviorally or from conventional neurophysiological measures, so their effects on performance have been difficult to study. Previously, we measured fluctuations in visual attention using the responses of populations of simultaneously recorded neurons in macaque visual cortex (Cohen and Maunsell, 2010). Here, we use this ability to investigate how attentional fluctuations affect performance. We found that attentional fluctuations have large and complex effects on performance, the sign of which depends on the difficulty of the perceptual judgment. As expected, attention greatly improves the detection of subtle changes in a stimulus. Surprisingly, we found that attending too strongly to a particular stimulus impairs the ability to notice when that stimulus changes dramatically. Our results suggest that all previously reported measures of behavioral performance should be viewed as amalgamations of different attentional states, whether or not those studies specifically addressed attention.     

Brief report: Open trial effects of beta-blockers on speech and social behaviors in 8 autistic adults

We began open trials of beta-blockers, as adjunctive medication, in eight consecutive autistic adults. The immediate result across all patients was a rapid diminution in aggressivity (Ratey et al., 1987). As time on the drug increased, subtler changes in speech and socialization emerged. While results of open trials must be interpreted with caution, these changes were significant and lasting. We speculate that these effects may be the result of a lessening of the autistic individual's state of hyperarousal. As the individual becomes less anxious, defensive and dearousing behaviors are relinquished and more social and adaptive behaviors appear. There is a concomitant improvement in language, though it is unclear whether lost skills are recouped or new ones developed. Further research is indicated.     

Head size in relation to schizophrenia and schizotypy

Cranial breadth and length on DSM-III schizophrenic probands (n = 16) and their nonpsychotic siblings (n = 34) were measured using standard anthropometric calipers. Siblings were divided into those with and those without DSM-III schizotypal personality disorder based on Baron et al.'s Schedule for Schizotypal Personalities interview (1981). These siblings provide controls for prenatal and childhood nutritional status, which could affect head size, and for genetic contributors to head size. Contrary to previous reports (Andreasen et al. 1986; and Pearlson et al. 1989), in the present sample schizophrenic patients did not have smaller heads. The relationship between height and head size for schizophrenic subjects, schizotypal siblings, and nonschizotypal siblings was also examined. As in Andreasen et al. (1986), the regression slope of head size on height was lower in schizophrenic patients than in their siblings, but here this difference was not significant. The data do not support a conjectured relationship between small or dysmorphic head size and schizophrenia or schizotypy.     

Conditioning and the kindling model of epilepsy

Since the development of the kindling preparation there has been much speculation on the contribution of conditioning mechanisms in accounting for the phenomenon. Two recent reports have described attempts to establish conditioned responses utilizing the kindling model. We suggest that the conclusion of uncondition-ability asserted by Wyler & Heavner (1979) is not warranted because of serious misunderstandings relating to the concepts and techniques that are central to both neurophysiological and conditioning theory. We further suggest that the results of their retardation effect can be better interpreted as positive evidence for the successful establishment of conditioning. With respect to the findings by Janowsky et al. (1980), we regard their sample size (2 animals undergoing simultaneous kindling and conditioning and one animal beginning conditioning following kindling) as inadequate for a conclusive demonstration of the success they report. Both studies, however, are seen as substantive contributions, insofar as they introduce this important perspective in kindling research, that can be expected to occupy a major role in the future developments of basic and clinical epileptology.     

Neurophysiological observations in diseased newborns.

The early statements that the EEG alone could correctly be used for the assessment of gestational age (cf., among others, Dreyfus-Brisac, 1964; Parmelee et al., 1968; and Nolte et al., 1969), even in pathological babies, need some restrictive qualifications. Likewise, the more recent statements that certain neurophysiological parameters, including nerve conduction velocity and basic EEG patterns are independent not only of gestational age and body weight, but also of various abnormal factors in the pre- and perinatal periods, appear also too rigid, at least as regards the EEG and the other parameters used in this study. As a matter of fact, some authors who had adhered rather strictly to these concepts have later on presented evidence suggesting some deviations in bioelectric brain maturation in some cases, as for example, in small-for-date newborns of toxemic mothers (Schulte et al., 1972). When more exact quantification by coding techniques was applied (Parmelee et al., 1968), the conclusion was also reached that extrauterine and intrauterine development of bioelectric brain activity developed according to the conceptional age, regardless of variable extrauterine experience, although it was recognized that other categories of behavioral and neurophysiological activities, for example, Moro reflex, states stability, crying, sucking, scores, etc., are more labile to environmental and pathological factors (Prechtl et al., 1972; Michaelis et al., 1973).     

Do panic disorder patients indiscriminately endorse somatic complaints?

Ehlers et al. (1986b) and Margraf et al. (1986) suggested that panic disorder patients indiscriminately endorse somatic complaints and that their responses to lactate infusion are nonspecific. Their Symptom Questionnaire was composed of anxiety/panic/lactate infusion relevant symptoms, while the Somatic Control Scale was composed of "irrelevant" symptoms. In an attempt to address and in part replicate the above findings among panic disorder patients, we adopted the SCS of Margraf et al. (1986) for use with our Acute Panic Inventory, an instrument similar to their Symptom Questionnaire. Contrary to their reports, we did not find a tendency for panic patients to indiscriminately endorse somatic complaints. Only Acute Panic Inventory scores differed significantly across assessment points.     

A new lead from genetic studies in depressed siblings: assessing studies of chromosome 3

Studies by Breen et al. and Pergadia et al. find evidence for genetic linkage between major depressive disorder and the same region on chromosome 3. The linked region contains the gene GRM7, which encodes a protein for the metabotropic glutamate receptor 7 (mGluR7). Both studies used affected sibling pairs, and neither was able to replicate its finding using association studies in individuals from larger population-based studies. Other family-based studies have also failed to find a signal in this region. Furthermore, there are some differences in how the phenotype was classified, with Breen et al. finding evidence only in the most severely affected patients. Nonetheless, the finding is not without other substantive support. A meta-analysis of 3,957 case subjects with major depressive disorder and 3,428 control subjects from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D), Genetics of Recurrent Early-onset Depression (GenRED), and the Genetic Association Information Network-MDD (GAIN-MDD) data sets demonstrated a region of association for major depressive disorder within GRM7. Thus, the significance of this finding remains uncertain, although it points to a gene that might hold significant promise for further developments in studying the pathophysiology and treatment of major depressive disorder.     

A new role for the community psychiatric nurse in working with families caring for a relative with schizophrenia

Over the last 20 years research has convincingly demonstrated that the illness, schizophrenia, is amenable to social and environmental influence (Leff et al. 1982; Falloon et al. 1985; Hogarty et al. 1986). The impetus for the research is the fact that, at best, genetic inheritance explains only 70% of the disorder's aetiology. The findings of the studies allow certain basic but important principles to be formulated. These are that some people inherit a genetic predisposition or "vulnerability" to schizophrenia which develops either in response to the acute stress of "life events" or the chronic stress encountered in some families. Originally the term "Expressed Emotion" was coined to describe emotional atmosphere at home which was thought to consist particularly of criticism, hostility or emotional over-involvement (Brown et al. 1962). Intervention strategies have arisen from the studies which demonstrates that stress in families caring for a relative with schizophrenia can be reduced, leading to not only a smaller risk of relapse in the relative with the illness, but also an improvement in the carer's own mental health status (Tarrier et al. 1988). Intervention consists of health education for carers and family stress management techniques which may help to lessen over-stimulation in family life. Community Psychiatric Nurses (CPNs) are a rapidly expanding sector of most mental health service provision in the United Kingdom but the evidence is that their role with the sufferer from schizophrenia consists largely of the administration of depot medication and very little else.(ABSTRACT TRUNCATED AT 250 WORDS)     

Behavioral flexibility in children with autism spectrum disorder and intellectual disability

Children with autism spectrum disorder (ASD) have particular difficulty with behavioral flexibility, but the knowledge base on behavioral flexibility in children with a diagnosis of ASD plus intellectual disability (ID) compared to children with ID only is still scarce. The aim of the present study was to assess behavioral flexibility in 111 children (84 boys) with ASD (87 autistic disorder; 24 PDD-NOS) plus ID (IQ range 10.59–72.67) and compare their scores to those of a control group consisting of 65 children with ID only (42 boys). Their age range was between 2:7 and 9:11 years/months. Behavior flexibility was measured using a Dutch version of the Behavioral Flexibility Rating Scale – Revised (Green et al., 2006, Peters-Scheffer et al., 2008). Results showed that behavioral flexibility in children with ASD plus ID was predicted by autism severity, developmental age, and initiating social interaction. A lack of behavioral flexibility seems to influence emotional and behavioral problems and maternal stress, but not adaptive behavior.     

The two major phosphoproteins in growth cones are probably identical to two protein kinase C substrates correlated with persistence of long-term potentiation

Regulation of neural protein kinase C (PKC) activity appears to directly affect the persistence of long-term potentiation (LTP; Akers and Routtenberg, 1985; Lovinger et al., 1985, 1986, 1987; Routtenberg et al., 1985, 1986; Akers et al., 1986; Linden et al., 1987), a model of neural plasticity (Bliss and Lomo, 1973). In addition, the in vitro phosphorylation of a brain-specific PKC substrate, protein F1 (Mr 47 kDa, pl 4.5), has been directly correlated with persistence of LTP (Lovinger et al., 1986). Because PKC has been implicated in neurite outgrowth and is present at high levels in growth cone-rich areas of fetal brain, we investigated and characterized PKC substrates in a preparation of isolated nerve growth cone fragments from fetal rat brain and compared them with PKC substrates found in adult rat hippocampus. Four major proteins in the growth cone preparation showed endogenous phosphorylation levels at least 10-fold greater than any other phosphoproteins. Three of these 4 phosphoproteins, termed pp40, pp46, and pp80 (Katz et al., 1985), were phosphorylated by exogenous PKC in a dose-dependent manner, indicating that PKC activity might be of particular importance relative to other kinases in growth cone function. The 2 most highly labeled PKC substrates, pp46 and pp80, comigrated on 2-dimensional gels with the adult hippocampal proteins F1 and "80k" (Mr 78-80 kDa, pl 4.0), respectively. In addition, similarities in charge heterogeneity, 2-dimensional phosphopeptide maps, and increased phosphorylation in the presence of exogenous PKC or PKC stimulators suggest that protein F1 and 80k are highly homologous to, if not identical to, pp46 and pp80, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modulation of calcium current and diverse K+ currents in identified Hermissenda neurons by small cardioactive peptide B

The molluscan neuropeptides, small cardioactive peptides A and B (SCPA,B), are known to modulate the responses of many molluscan central and peripheral target cells (see review by Lloyd, 1986), but their full range of physiological actions remains unknown. External application of SCPB (1-10 microM) modified diverse ionic conductances in a set of giant identifiable neurons in the brain of the marine mollusk Hermissenda crassicornis. SCPB caused a transient depolarization and increased input resistance that enhanced or promoted cell firing. Under voltage-clamp, SCPB reduced a "background" residual current (IR), reduced early transient K+ current (IA), reduced a delayed K+ current (IK(V], and enhanced ICa, IBa, and a Ca2+-activated K+ current, IK(Ca). In tetraethylammonium chloride (TEA) saline, SCPB enhanced the amplitude and duration and reduced the threshold of evoked Ca and Ba spikes. Immunocytochemical staining techniques have localized an endogenous SCPB-like peptide in numerous somata and their neurites in the nervous system of Hermissenda (Longley and Longley, 1985; Watson and Willows, 1986). These data are consistent with a role for SCPB as a neurotransmitter/neurohormone modulator of neuronal excitability in Hermissenda. A neurotransmitter role for endogenous SCPs has been proposed for a synaptic pair of cultured neurons in the Aplysia buccal ganglion (Lloyd et al., 1986). SCPB has been implicated in the control of feeding motor output in Aplysia (Sossin et al., 1986) and Tritonia (Willows and Watson, 1986), and in the presynaptic facilitation of sensory neurons mediating the gill and siphon defensive withdrawal reflex in Aplysia (Abrams et al., 1984).     

Allocentric neglect strongly associated with egocentric neglect

Following brain injury, many patients experience egocentric spatial neglect, where they fail to respond to stimuli on the contralesional side of their body. On the other hand, allocentric, object-based neglect refers to the symptom of ignoring the contralesional side of objects, regardless of the objects' egocentric position. There is an established tradition for considering these two phenomena as both behaviorally and anatomically dissociable. However, several studies and some theoretical work have suggested that these rather reflect two aspects of a unitary underlying disorder. Furthermore, in a recent large study Yue et al. [Archives of Physical Medicine and Rehabilitation 93 (2012) 156] reported that acute allocentric neglect is only observed in cases where substantial egocentric neglect is also present. In a new sample of right hemisphere stroke patients, we attempted to control for potential confounds by using a novel continuous measure for allocentric neglect (in addition to a recently developed continuous measure for egocentric neglect). Our findings suggest a strong association between egocentric and allocentric neglect. Consistent with the work of Yue et al. (2012), we found allocentric behavioral deficits only in conjunction with egocentric deficits as well as a large corresponding overlap for the anatomical regions associated with egocentric and with allocentric neglect. We discuss how different anatomical and behavioral findings can be explained in a unified physiologically plausible framework, whereby allocentric and egocentric effects interact.     

Expression of GAP-43, a rapidly transported growth-associated protein, and class II beta tubulin, a slowly transported cytoskeletal protein, are coordinated in regenerating neurons

GAP-43 is a membrane-associated phosphoprotein enriched in elongating axons (Meiri et al., 1986; Skene et al., 1986). After an axon has been interrupted by cutting or crushing a nerve (axotomy), the portion of the axon disconnected from the cell body (distal stump) degenerates and is replaced by the outgrowth (elongation) of regenerating sprouts arising from the proximal stump. Previous studies have shown that increased amounts of pulse-labeled GAP-43 undergo fast axonal transport in regenerating neurons (Benowitz et al., 1981; Skene and Willard, 1981 a, b). Using hybridization with a cloned cDNA probe, I now show that mRNA levels for GAP-43 increase in lumbar sensory neurons of rat after regeneration is initiated by crushing the sciatic nerve; the relatively high levels of GAP-43 mRNA in regenerating neurons are comparable to those in the developing neurons of 5-d-old animals. I further demonstrate that the induction of GAP-43 expression in regenerating neurons coincides temporally with an increase in mRNA levels for class II beta tubulin (Hoffman and Cleveland, 1988), suggesting that the expression of these proteins is closely coordinated during axonal elongation.     

Nicotinic acetylcholine receptor properties are modulated by surrounding lipids

In vitro studies carried out on liposomes of defined composition showed that nicotinic acetylcholine receptors (nAChRs) are fully functional when they are reconstituted in a heterogeneous lipid matrix, such as that provided by crude soybean (asolectin [R-Aso]) lipids. However, when they are reconstituted in plain phosphatidylcholine (R-PC) lipids, their functional activity is completely lost (Fong and McNamee, 1986). This kind of study also pointed out that phosphatidic acid (PA) and cholesterol (Chol) play an important role in preserving the ability of this protein to exhibit an optimal channel activity (Fong and McNamee, 1986). Furthermore, it has been shown recently that nAChR, itself, induces the formation of specific PA-rich lipid domains (Poveda et al., 2002). Because Xenopus oocytes incorporate functionally into their plasma membrane nAChRs after intracellular injection of liposomes bearing this protein (Morales et al., 1995), the aim of this work was to determine the effect of the reconstitution lipid matrix on the functional properties of the transplanted nAChRs.     

Assortative mating and affective disorders: psychopathology in offspring

Familial aggregation has been frequently observed among probands with depression, anxiety disorders, and alcoholism (Gershon et al. 1976; Goodwin et al. 1973; Crowe et al. 1983). Because of the familial nature of these disorders, offspring of such probands have been identified to be at high risk for developing these illnesses themselves (Tarter 1983). Information regarding such risk has come from several sources: retrospective studies of patients with psychiatric disorders; studies of children whose parents are being treated for these disorders; and longitudinal follow-up studies of children with symptoms of the disorder.     

Perspectives of zebrafish models of epilepsy: What,how and where next?

Epilepsy is a complex brain disorder with multiple underlying causes and poorly understood pathogenetic mechanisms. Animal models have been indispensable tools in experimental epilepsy research. Zebrafish (Danio rerio) are rapidly emerging as a promising model organism to study various brain disorders. Seizure-like behavioral and neurophysiological responses can be evoked in larval and adult zebrafish by various pharmacological and genetic manipulations, collectively emphasizing the growing utility of this model for studying epilepsy. Here, we discuss recent developments in using zebrafish models to study the seizure-like behavior involved in epilepsy, outlining current challenges and strategies for further translational research in this field.     

Turning behavior in rats with unilateral lesion of the subthalamic nucleus: synergism between D1 and D2 receptors

Summary Rats with unilateral kainic acid lesion of the subthalamic nucleus showed a dose dependent rotational response to the lesioned side (ipsilateral) after systemic administration of the non-selective dopaminergic agonist apomorphine. Both D2 and D1 selective antagonists ((–)sulpiride and SCH23390) inhibited the response to apomorphine in these rats. Selective D2 and D1 agonists (quinpirole and SKF38393) were unable to induce turning behavior. However, an ipsilateral circling response was obtained after the simultaneous application of both agonists. The interaction mechanism between dopaminergic receptor subtypes seems to be similar to that of other normosensitive models of turning previously studied (Barone et al, 1986; Robertson and Robertson, 1986; Arnt and Perregard, 1987; Asim et al., 1990; Pazo et al., 1993). It is proposed that the ipsilateral turning response to dopaminergic agonists in rats with subthalamic nucleus lesion results from an impaired behavioral expression of the action of dopaminergic agonists on one side, leading the rats to turn away from the intact hemisphere.     

Work and psychiatric illness: The significance of the posthospitalization occupational environment for the course of psychiatric illnesses

Summary The value of the reintegration and rehabilitation of inpatients vocationally was studied. Certain of the vocational experiences (unemployment and stressful working conditions) of former psychiatric inpatients were examined, with attention being paid to their stabilizing or destabilizing effect on symptomatic behaviour. A cohort of 230 first-time admissions for treatment of various disorders were interviewed while hospitalized and 1 year later. A 20-item list prepared by INFAS was used for indexing stressful working conditions. Psychopathological states were assessed with the help of the Present State Examination of Wing et al. (1973). The results indicate that mentally ill persons (especially those with organic or affective disorders), when confronted with unemployment after discharge from hospital, will usually respond by developing new or worse syndromes. Stressful working conditions appear to have very different effects in schizophrenia and affective disorders, viz. deterioration and amelioration of psychopathological syndromes respectively.This Study was supported by the Deutsche Forschungsgemeinschaft (German Research Association), as part of special program no. 129.This report is part of a prospective study of predictors, prognoses and the courses of first-time admissions for psychiatric disorders. Summary accounts of the study have appeared elsewhere (e.g. Aschoff-Pluta et al. 1984, 1985; Bell et al. 1986, 1988; Blumenthal et al. 1985, 1986; Vogel et al. 1985, 1986, 1987, 1988; Vogel 1988).     

Narcolepsy and emotional experience: a review of the literature

Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. This disease affects significantly the overall patient functioning, interfering with social, work, and affective life. Some symptoms of narcolepsy depend on emotional stimuli; for instance, cataplectic attacks can be triggered by emotional inputs such as laughing, joking, a pleasant surprise, and also anger. Neurophysiological and neurochemical findings suggest the involvement of emotional brain circuits in the physiopathology of cataplexy, which seems to depending on the dysfunctional interplay between the hypothalamus and the amygdala associated with an alteration of hypocretin levels. Furthermore, behavioral studies suggest an impairment of emotions processing in narcolepsy-cataplexy (NC), like a probable coping strategy to avoid or reduce the frequency of cataplexy attacks. Consistently, NC patients seem to use coping strategies even during their sleep, avoiding unpleasant mental sleep activity through lucid dreaming. Interestingly, NC patients, even during sleep, have a different emotional experience than healthy subjects, with more vivid, bizarre, and frightening dreams. Notwithstanding this evidence, the relationship between emotion and narcolepsy is poorly investigated. This review aims to provide a synthesis of behavioral, neurophysiological, and neurochemical evidence to discuss the complex relationship between NC and emotional experience and to direct future research.