Word use in first-person accounts of schizophrenia.

BACKGROUND: Language use is often disrupted in patients with schizophrenia; novel computational approaches may provide new insights. AIMS: To test word use patterns as markers of the perceptual, cognitive and social experiences characteristic of schizophrenia. METHOD: Word counting software was applied to first-person accounts of schizophrenia and mood disorder. RESULTS: More third-person plural pronouns ('they') and fewer first-person singular pronouns ('I') were used in schizophrenia than mood disorder accounts. Schizophrenia accounts included fewer words related to the body and ingestion, and more related to religion. Perceptual and causal language were negatively correlated in schizophrenia accounts but positively correlated in mood disorder accounts. CONCLUSIONS: Differences in pronouns suggest decreased self-focus or perhaps even an understanding of self as other in schizophrenia. Differences in how perceptual and causal words are correlated suggest that long-held delusions represent a decreased coupling of explanations with sensory experience over time.

A multifunctional calmodulin-dependent protein kinase. Similarities between skeletal muscle glycogen synthase kinase and a brain synapsin I kinase.

Calmodulin-dependent glycogen synthase kinase isolated from skeletal muscle and synapsin I kinase II isolated from brain have several properties that are very similar. These properties include: substrate and site-specificities, immunological cross-reactivity, and phosphopeptide maps following limited proteolysis. Both enzymes phosphorylate a wide variety of substrate proteins. The two kinases may represent different isozymes of a multifunctional calmodulin-dependent protein kinase that mediates many of the actions of Ca2+ in various tissues. Therefore, we propose the name 'calmodulin-dependent multi-protein kinase' for this broad specificity enzyme.

Conservative surgical management of placental implantation site hemorrhage.

BACKGROUND: Our purpose is to show that a simple, conservative, fertility-preserving surgical technique can be used to control postpartum hemorrhage from a hypotonic placental implantation site. CASE: Postpartum hemorrhage from a hypotonic placental implantation site at cesarean delivery was treated with surgical excision of the hypotonic segment, resulting in immediate cessation of the bleeding when other measures had failed. The patient's postoperative course was uneventful. The uterus and adjacent vascular structures were evaluated with magnetic resonance imaging studies at 4 weeks postpartum and were free of abnormality. CONCLUSION: Simple excision of a hypotonic bleeding site may be desirable and practical when fertility preservation is desired.

Synapsin I, a phosphoprotein associated with synaptic vesicles: possible role in regulation of neurotransmitter release.

The data presented here provide evidence that the study of neuronal phosphoproteins can lead to the identification of previously unknown proteins and that these proteins may play important roles in neuronal communication. Specifically, in the case of synapsin I, direct evidence has been obtained that this phosphoprotein is involved in regulating neurotransmitter release. A tentative explanation of the results obtained in the micro-injection studies is as follows: synapsin I, in the dephosphostate, is bound to the cytoplasmic surface of synaptic vesicles and inhibits the ability of the vesicle to interact with the plasma membrane; increases in intracellular calcium activate calmodulin kinase II which in turn phosphorylates synapsin I and the phosphorylated synapsin I dissociates from the synaptic vesicle thus removing a constraint on the release of neurotransmitter. Clearly, more studies need to be done to rigorously test this hypothesis. Nevertheless these studies of synapsin I suggest that the study of previously unknown phosphoproteins will lead to the elucidation of previously unknown regulatory processes in neurons.

Preliminary research on plasma oxytocin in normal cycling women: investigating emotion and interpersonal distress.

The neurohormone oxytocin is responsible for initiating childbirth and the let-down reflex in lactating women and is released during sexual orgasm. Oxytocin has been thought of as an affiliation hormone because research on nonhuman mammals has demonstrated that it plays a key role in the initiation of maternal behavior and the formation of adult pair bonds. It has been speculated that social stimuli may induce oxytocin release and that oxytocin may make positive social contact more rewarding. Data are presented from an initial study to examine change in plasma oxytocin in response to a standard imagery task that elicits emotion related to attachment. Twenty-five normal cycling, healthy women underwent imagery tasks and completed questionnaires on attachment and interpersonal problems. Blood draws (5 ml) were bone via an indwelling catheter before, during, and after three interventions (massage, positive emotion, and negative emotion) and to establish baselines. Overall, the data showed a tendency for oxytocin levels to be elevated in response to relaxation massage and decreased in response to sad emotion. There were individual differences in response to the interventions. Those who showed evidence of increased oxytocin levels for positive emotion and massage and who maintained oxytocin levels during negative emotion were less likely to report interpersonal problems associated with intrusiveness. Maintaining oxytocin levels during sadness was also correlated with lower anxiety in close relationships. Women who were in a couple relationship had greater increases in oxytocin in response to positive emotion. In contrast, higher basal levels of oxytocin were associated with greater interpersonal distress. These data suggest that peripheral secretion of oxytocin in response to emotional stimuli is associated with the individual's interpersonal characteristics.

Affect, attachment, memory: contributions toward psychobiologic integration.

Recent decades have seen a marked expansion in knowledge regarding human neurophysiology, and psychiatry is currently challenged with the task of integrating this information with a psychodynamic understanding of emotional life. In this paper we review portions of the relevant literature regarding the basic brain functions of affect, memory, and attachment, and we consider the implications of these data for integrated psychobiologic conceptualizations of emotional dysfunction and its treatment. In particular, data from these three areas of study point to the possibility that implicit memory of the early attachment relationship, communicated via the language of affect, is an enduring neural structure that influences both emotional self-regulation and behavior related to relatedness. Finally, we consider the implications of this proposition for the nature of psychotherapy, which from a psychobiologic view might be profitably conceptualized as a directed attachment relationship whose purpose is the revision of the implicit emotional memory of attachment.

Risk and protective factors in children adopted from the former Soviet Union.

INTRODUCTION: The former Soviet Union (including the present independent republics of Russia, Ukraine, Latvia, Belarus, Lithuania, and Georgia) is the leading source of children adopted from overseas by persons in the United States (US Department of State, 1998). This study sought to (a) characterize the current social, academic, and conduct competencies of 6- to 9-year-old children adopted from the former Soviet Union who have resided in the United States for at least 2 years and (b) evaluate both risks and protective influences of adoptive families and their relationships to competence via a structural equation model. METHOD: Telephone interviews and a postal survey of children were drawn from a US community sample of 105 children. Measures included (a) Child Behavior Checklist, (b) Teacher Report Form, (c) Vineland Adaptive Behavior Scales, (c) Family Environment Scale, and (d) demographic information. RESULTS: Many children had experienced abuse, abandonment, or neglect between birth and entry to the institution. Their mean birth weight was 2637 g, and alcohol abuse by the birth mother was common (41%). Although the children scored below average in competence, adoptive family environments were positive and served as buffers between the risks experienced by the children and the subsequent development of competence within the adoptive family. CONCLUSION: Children's abilities ranged from severely challenged to developmentally normal. The high rate of fetal alcohol exposure in the children may portend future challenges for families.

The art of therapeutic drawing. Helping chronic trauma survivors.

1. Survivors of chronic trauma, who may have survived hundreds of episodes of battering and abuse, have no gauge of what is normal and continue to live in the same emotional climate. 2. The coping patterns that are a result of chronic trauma are below the level of awareness and prevent healthy adaptation. 3. The inclusion of expressive techniques, such as therapeutic drawing, can be used to facilitate the emotional work of chronic trauma issues.

A quiet migration: cultural influences impacting children adopted from the former Soviet Union.

When children immigrate to another culture, a variety of salient variables influence their adaptation. Among internationally adopted children, these variables include early history, changes in socioeconomic status, awareness of multiple issues impacting the child post-adoption, availability of social networks, and anti-immigration sentiments in the host culture. The change in socioeconomic status of children adopted from the former Soviet Union is a positive influence with the concomitant improvement in the child's nutrition and health care. Many internationally adopted children have spent time in institutional environments that constitute a culture in and of itself. The orphanages are microenvironments which may be closed to the influences of the larger culture. The environmental components of the orphanage transmit a collection of traits and values which, taken as a whole, constitute the orphanage culture. Adoptive parents must facilitate the children's adjustment to a new cultural milieu with different language, food, and customs. Further, children must adapt to the culture of the family, a culture that may have been previously unknown. Nurses can promote the adaptation of these families by increasing awareness of the multitude of issues that impact internationally adoptive families.

Alcohol taxation: EC approximation and its UK effects.

The paper reviews the European Commission's (EC's) latest proposals for the approximation of indirect taxes on alcohol. In them, the Commission publicly and unequivocally accepts the connection between alcohol taxes and health. The paper compares the proposed target rates with existing alcohol taxes in the UK, and presents some simulated estimates of their effect on UK consumption. The estimates are preliminary, but are published now rather than risk delaying until the EC has taken irreversible decisions. They relate to 1988, the latest year for which simulations could be run, and suggest that, if the target rates had applied then in the UK, consumption per adult would have been more than two litres of pure alcohol higher than otherwise. The paper also reviews the objectives of a Single Internal Market in the EC and argues that indirect tax approximation is not necessary to achieve them. The current EC proposals are a serious threat to alcohol control policy in the UK, but are unnecessary to attaining the basic goals of a Single Internal Market and contain an open invitation for Member States to argue for national sovereignty, on health grounds, in choosing rates of alcohol excise duty. The paper suggests that this should be the UK argument in continuing discussions at the Community level.

Resilience: analysis of the concept.

Resilience describes a process whereby people bounce back from adversity and go on with their lives. It is a dynamic process highly influenced by protective factors. Protective factors are specific competencies that are necessary for the process of resilience to occur. Competencies are those healthy skills and abilities that the individual can access and may occur within the individual or the interpersonal or family environment. Psychiatric-mental health nursing has always focused on mental-health promotion and attempted to discern positive outcomes from adversity and states of wellness amidst difficult circumstances or severe illness. Defining specific protective factors that facilitate mental health in high-risk groups would enhance our position in today's health care climate.

A calcium/calmodulin-dependent protein kinase from mammalian brain that phosphorylates Synapsin I: partial purification and characterization.

A calcium/calmodulin-dependent protein kinase, which phosphorylates a synaptic vesicle-associated protein designated Synapsin I, has been shown to be present in both soluble and particulate fractions of rat brain homogenates. In the present study, the particulate activity was solubilized by washing with a low ionic strength solution, and the enzymes from the two fractions were partially purified by ion exchange chromatography and calmodulin-Sepharose affinity chromatography. By each of several criteria, the partially purified enzymes from the two sources were indistinguishable. These criteria included specificity for various substrate proteins, concentration dependence of activation by calcium and calmodulin, pH dependence, and apparent affinities for the substrates Synapsin I and ATP. The mild conditions that released the particulate enzyme indicated that it was not tightly bound to the membrane and suggested that it may exist in a dynamic equilibrium between soluble and particulate-bound states. The partially purified enzyme preparations from both the soluble and particulate fractions contained three proteins that were phosphorylated in the presence of calcium and calmodulin, a 50-kilodalton (Kd) protein and two proteins in the 60-Kd region. When compared by phosphopeptide mapping and two-dimensional gel electrophoresis, the proteins were indistinguishable from three proteins of corresponding molecular weights that were shown by Schulman and Greengard (Schulman, H., and P. Greengard (1978) Nature 271: 478-479) to be prominent substrates for calcium/calmodulin-dependent protein kinase in a crude particulate preparation from rat brain. The 50-Kd substrate was the major Coomassie blue staining protein in both partially purified enzyme preparations. The peak of this protein coincided with that of enzyme activity during DEAE-cellulose and calmodulin-Sepharose chromatography. These results suggest that the 50-Kd phosphoprotein may be an autophosphorylatable subunit of the Synapsin I Kinase or may exist in a complex with it.

Immunocytochemical localization of calcium/calmodulin-dependent protein kinase II in rat brain.

Calcium/calmodulin-dependent protein kinase II (CaM kinase II) is a prominent enzyme in mammalian brain capable of phosphorylating a variety of substrate proteins. In the present investigation, the subcellular and regional distribution of CaM kinase II has been studied by light and electron microscopic immunocytochemistry using an antibody that recognizes the Mr 50,000 and 60,000/58,000 subunits of the enzyme. Light microscopy demonstrates strong immunoreactivity in neuronal somata and dendrites and weak immunoreactivity in axons. Electron microscopy, in addition to confirming light microscopic observations, reveals moderate immunoreactivity in spines and weak immunoreactivity in nerve terminals. An accumulation of immunoreaction product is also present on postsynaptic densities. The presence of CaM kinase II in diverse structures throughout the neuron supports the view that this enzyme may be involved in mediating a variety of calcium-dependent physiological processes. CaM kinase II immunoreactivity is present in neurons throughout the brain, but a marked regional variation in the strength of the immunoreactivity exists. Overall, there is a gradient of staining intensity with the strongest immunoreactivity in the telencephalon and the weakest in the myelencephalon. The most heavily labeled regions of the telencephalon are the hippocampal formation, lateral septum, cortical regions, neostriatum, and amygdaloid complex.

Ca2+/calmodulin-dependent protein kinase II. Isozymic forms from rat forebrain and cerebellum.

Ca2+/calmodulin-dependent protein kinase II, an abundant brain protein proposed to mediate a number of Ca2+-regulated processes in neuronal tissue, is composed of autophosphorylatable subunits of Mr 50,000 and 60,000/58,000. A recent study (McGuinness, T. L., Lai, Y., Greengard, P., Woodgett, J.R., and Cohen, P. (1983) FEBS Lett. 163, 329-334) suggested that this kinase exists as isozymes which vary in the relative ratio of these subunits in different tissues or species. Other studies (Walaas, S. I., Nairn, A. C., and Greengard, P. (1983) J. Neurosci. 3, 291-301, 302-311) provided evidence which suggested that the ratio of these phosphopeptides might vary in different brain regions. In the present investigation, we have tested this possibility by comparing Ca2+/calmodulin-dependent protein kinase II purified from rat forebrain and cerebellum. The two kinases had similar purification characteristics, subunit compositions, physical properties, and substrate specificities. Gel filtration and sucrose density gradient centrifugation provided an estimated molecular weight of 550,000 for the forebrain kinase and 615,000 for the cerebellar kinase. The kinases from the two regions clearly differed in the relative proportions of the Mr 50,000 and 60,000/58,000 subunits. Three independent methods indicated that the forebrain kinase contained the Mr 50,000/(60,000/58,000) subunits in approximately a 3:1 ratio, while the cerebellar kinase contained the Mr 50,000/(60,000/58,000) subunits in approximately a 1:4 ratio. The forebrain kinase subunits were shown to be identical to the corresponding subunits of the cerebellar kinase by several criteria. The data are consistent with the existence in various brain regions of isozymic forms of Ca2+/calmodulin-dependent protein kinase II which differ in their relative subunit ratios.

Evidence that the major postsynaptic density protein is a component of a Ca2+/calmodulin-dependent protein kinase.

Polypeptides of Mr 50,000 and 60,000 in isolated synaptic junctions have been compared to polypeptides of corresponding molecular weight in Ca2+/calmodulin-dependent protein kinase II. The polypeptides of corresponding molecular weight from the two preparations were shown by several criteria to be indistinguishable. These criteria included 125I-labeled tryptic/chymotryptic peptide patterns, 32P-labeled proteolytic peptide maps, and crossreactivity on immunoblots using polyclonal and monoclonal antibodies. Furthermore, studies examining the phosphorylation of substrate proteins, by the endogenous synaptic junction kinase and by Ca2+/calmodulin-dependent protein kinase II, indicated that the two enzymes have similar substrate specificities. Since the Mr 50,000 polypeptide present in synaptic junctions is known to be the major postsynaptic density protein, the present results indicate that the major postsynaptic density protein is a component of Ca2+/calmodulin-dependent protein kinase II.

Effects of synapsin I and calcium/calmodulin-dependent protein kinase II on spontaneous neurotransmitter release in the squid giant synapse.

The molecular events that control synaptic vesicle availability in chemical synaptic junctions have not been fully clarified. Among the protein molecules specifically located in presynaptic terminals, synapsin I and calcium/calmodulin-dependent protein kinase II (CaM kinase II) have been shown to modulate evoked transmitter release in the squid giant synapse. In the present study, analysis of synaptic noise in this chemical junction was used to determine whether these proteins also play a role in the control of spontaneous and enhanced spontaneous transmitter release. Injections of dephosphorylated synapsin I into the presynaptic terminal reduced the rate of spontaneous and enhanced quantal release, whereas injection of phosphorylated synapsin I did not modify such release. By contrast CaM kinase II injection increased enhanced miniature release without affecting spontaneous miniature frequency. These results support the view that dephosphorylated synapsin I "cages" synaptic vesicles while CaM kinase II, by phosphorylating synapsin I, "decages" these organelles and increases their availability for release without affecting the release mechanism itself.

Intraterminal injection of synapsin I or calcium/calmodulin-dependent protein kinase II alters neurotransmitter release at the squid giant synapse.

Synapsin I and calcium/calmodulin-dependent protein kinase II were pressure-injected into the preterminal digit of the squid giant synapse to test directly the possible regulation of neurotransmitter release by these substances. Neurotransmitter release was determined by measuring the amplitude, rate of rise, and latency of the postsynaptic potential generated in response to presynaptic depolarizing steps under voltage clamp conditions. Injection of dephosphosynapsin I decreased the amplitude and rate of rise of the postsynaptic potential, whereas injection of either phosphosynapsin I or heat-treated dephosphosynapsin I was without effect. Conversely, injection of calcium/calmodulin-dependent protein kinase II, which phosphorylates synapsin I on site II, increased the rate of rise and amplitude and decreased the latency of the postsynaptic potential. The effects of these proteins were observed without any detectable change in the initial phase of the presynaptic calcium current. A synapsin I-like protein and calcium/calmodulin-dependent protein kinase II were demonstrated by biochemical and immunochemical techniques to be present in squid nervous tissue. The data support the hypothesis that synapsin I regulates the availability of synaptic vesicles for release; we propose that calcium entry into the nerve terminal activates calcium/calmodulin-dependent protein kinase II, which phosphorylates synapsin I on site II, dissociating it from the vesicles and thereby removing a constraint in the release process.