Modulation of transmitter release by action potential duration at the hippocampal CA3-CA1 synapse

Presynaptic Ca2+ influx through voltage-dependent Ca2+ channels triggers neurotransmitter release. Action potential duration plays a determinant role in the dynamics of presynaptic Ca2+ influx. In this study, the presynaptic Ca2+ influx was optically measured with a low-affinity Ca2+ indicator (Furaptra). The effect of action potential duration on Ca2+ influx and transmitter release was investigated. The K+ channel blocker 4-aminopyridine (4-AP) was applied to broaden the action potential and thereby increase presynaptic Ca2+ influx. This increase of Ca2+ influx appeared to be much less effective in enhancing transmitter release than raising the extracellular Ca2+ concentration. 4-AP did not change the Ca2+ dependence of transmitter release but instead shifted the synaptic transmission curve toward larger total Ca2+ influx. These results suggest that changing the duration of Ca2+ influx is not equivalent to changing its amplitude in locally building up an effective Ca2+ concentration near the Ca2+ sensor of the release machinery. Furthermore, in the presence of 4-AP, the N-type Ca2+ channel blocker omegaCgTx GVIA was much less effective in blocking transmitter release. This phenomenon was not simply due to a saturation of the release machinery by the increased overall Ca2+ influx because a similar reduction of Ca2+ influx by application of the nonspecific Ca2+ channel blocker Cd2+ resulted in much more inhibition of transmitter release. Rather, the different potencies of omega-CgTx GVIA and Cd2+ in inhibiting transmitter release suggest that the Ca2+ sensor is possibly located at a distance from a cluster of Ca2+ channels such that it is sensitive to the location of Ca2+ channels within the cluster.     

Dendritic properties of hippocampal CA1 pyramidal neurons in the rat: intracellular staining in vivo and in vitro

Dendritic morphology and passive cable properties determine many aspects of synaptic integration in complex neurons, together with voltage-dependent membrane conductances. We investigated dendritic properties of CA1 pyramidal neurons intracellularly labeled during in vivo and in vitro physiologic recordings, by using similar intracellular staining and three-dimensional reconstruction techniques. Total dendritic length of the in vivo neurons was similar to that of the in vitro cells. After correction for shrinkage, cell extent in three-dimensional representation was not different between the two groups. Both in vivo and in vitro neurons demonstrated a variable degree of symmetry, with some neurons showing more cylindrical symmetry around the main apical axis, whereas other neurons were more elliptical, with the variation likely due to preparation and preservation conditions. Branch order analysis revealed no difference in the number of branch orders or dendritic complexity. Passive conduction of dendritic signals to the soma in these neurons shows considerable attenuation, particularly with higher frequency signals (such as synaptic potentials compared with steady-state signals), despite a relatively short electrotonic length. Essential aspects of morphometric appearance and complex dendritic integration critical to CA1 pyramidal cell functioning are preserved across neurons defined from the two different hippocampal preparations used in this study.     

In vivo chronoamperometric measures of extracellular serotonin clearance in rat dorsal hippocampus: contribution of serotonin and norepinephrine transporters

The effects of blockade of serotonin (5-HT) and norepinephrine (NE) transporters (SERT and NET, respectively) on the removal of locally applied 5-HT from extracellular fluid (ECF) were examined using in vivo chronoamperometry. Male Sprague-Dawley rats were anesthetized with chloralose/urethane, and a Nafion-coated, carbon fiber electrode attached to a multibarrel micropipette was positioned into either the dentate gyrus or CA3 region of the dorsal hippocampus. Pressure ejection of 5-HT elicited reproducible electrochemical signals of similar peak amplitude and time course in both structures. Local application of the selective serotonin reuptake inhibitors (SSRI) fluvoxamine and citalopram prolonged the clearance of 5-HT in both brain regions and also increased signal amplitude in the CA3 region. These effects were abolished in rats pretreated with 5, 7-dihydroxytryptamine (5,7-DHT), a selective 5-HT neurotoxin. The NE uptake inhibitors desipramine (DMI) and protriptyline did not alter the 5-HT signal in the CA3 region but prolonged the clearance of 5-HT in the dentate gyrus; this effect was absent in rats pretreated with 6-hydroxydopamine (6-OHDA), a selective catecholamine neurotoxin. The prolongation of the removal of 5-HT from the ECF in the dentate gyrus caused by fluvoxamine or desipramine was of comparable magnitude and was dose dependent. Furthermore, per picomole of 5-HT applied, the signal amplitude and clearance time were significantly increased in the dentate gyrus of rats lesioned with either 5,7-DHT or 6-OHDA. Only 5,7-DHT treatment caused this effect in the CA3 region. From these data, it is inferred that in certain regions of brain (dentate gyrus), both the SERT and NET contribute to the active clearance of exogenously applied 5-HT.     

NMDA receptor-dependent and metabotropic glutamate receptor-dependent forms of long-term depression coexist in CA1 hippocampal pyramidal cells

The development and maturation of the endolymphatic sac (ES) and duct (ED) were studied in the newt Cynops pyrrhogaster. The ES first appears as an oval capsule at the dorsal-medial tip of the otic vesicle at stage 39, about 11 days after oviposition. The ES consists of polymorphous epithelial cells with a minimum of cytoplasm. The intercellular space (IS) between the epithelial cells is narrow and has a smooth surface. At stage 44, the size of the ES increases as many vacuoles in the IS become filled. At stage 46, 18 days after oviposition, the ES elongates markedly and a slit-like lumen is found in the ES. The epithelium contains a few cell organelles which are scattered in the cytoplasm. The vacuoles in the IS are fused, which expands the IS. Two days later (stage 48), floccular material (endolymph) is present in the expanded lumen. The IS dilates and has a wide and irregular appearance. At stage 50, approximately 26 days after oviposition, the ES extends and expands significantly and crystals (otoconia) can now be seen in the widened lumen of the ES. The cytoplasm of the cuboidal epithelial cells contains an abundance of vesicles surrounded by ribosomes and Golgi complexes. Intercellular digitations are formed in the expanded IS. At stage 54, the ES forms a large bellow-like pouch. Numerous otoconia accumulate in the lumen. Free floating cells and cell debris can be seen in the lumen at this stage. The epithelial cells contain numerous cytoplasmic organelles which are evenly distributed in the cytoplasm. Granules are found in the apical and lateral cytoplasm. The IS is loose and displays a labyrinthine appearance. The primitive ED first appears as a connection between the ES and the saccule but no lumen is present inside at stage 39. At stage 46, a narrow lumen is formed in the ED, which corresponds to the formation of the ES lumen. At stage 50, as the ED extends, floccular material is seen in the lumen. At stage 54, the ED bears numerous microvilli on its luminal surface. Otoconia and endolymph are present in the ED. Tight junctions between the epithelial cells are formed at stage 46. A fully developed intercellular junctional complex is produced at stage 54. Based on the development of the ES and ED, the maturation of function of the ES and ED are discussed.     

Hypoxia-tolerant neonatal CA1 neurons: relationship of survival to evoked glutamate release and glutamate receptor-mediated calcium changes in hippocampal slices

Neurons in the neonatal mammalian brain survive greater degrees of hypoxic stress than those in the mature brain. To investigate how developmental changes in glutamate receptor-mediated neurotoxicity contribute to this difference, we measured hypoxia-evoked glutamate release, glutamate receptor contribution to hypoxia-evoked intracellular calcium changes, and survival of hypoxia-/ischemia-sensitive CA1 neurons in rat hippocampus. Glutamate release was measured by a fluorescence assay, calcium changes in CA1 neurons with fura-2, and cell viability using Nissl and fluorescence staining with calcein-AM/ethidium homodimer, all in 300-micron thick hippocampal slices from 3-30 post-natal day (PND) rats. Glutamate released from PND 3-7 slices during hypoxia (PO2 = 5 mmHg) was only one third that of PND 18-22 slices. In PND 3-7 slices, survival of CA1 neurons after 5 min of hypoxia and 6 h of recovery was significantly greater than in PND 18-22 slices (viability indices 0.60 and 0.28, respectively, (p < 0.05). Five min of anoxia significantly altered Nissl staining pattern and morphology of CA1 neurons in PND 18-22 but not PND 3-7 slices. Hypoxia (PO2 = 5 mm Hg) caused three to five times greater increases in [Ca2+]i in PND 18-22 slices than in PND 3-7 slices (p < 0.001). During re-oxygenation, [Ca2+]i returned to baseline in PND 3-7 slices, but remained elevated in PND 18-22 slices. Glutamate receptor-mediated calcium changes in CA1 during hypoxia were 33% and 62% of the total calcium change in PND 3-7 and PND 18-22 CA1, respectively. We conclude that survival of CA1 neurons in PND 3-7 slices following hypoxic stress is associated with smaller increases and enhanced recovery of [Ca2+]i, less accumulation of glutamate, and less glutamate receptor-mediated calcium influx than in PND 18-22 slices.     

Mechanism of steroid action in inflammation: inhibition of prostaglandin synthesis and release

Acute arthritis was induced by injection of cell-free extract of group A Streptococci into the knee joints of mature male rats. Slices of control and inflamed synovia were incubated for 30 to 240 minutes and the rate of prostaglandin E (PGE) released into the medium was measured by radioimmunoassay. PGE release from inflamed synovia was 5-8 fold higher than that in normal tissue. Incubation of inflamed synovia with corticosterone acetate, dexamethasone or prednisone (100 mug/ml) for one or four hours reduced PGE release by 33% and 55% respectively. Lower concentrations of corticosterone (10 - 30 mug/ml) were ineffective. Aldosterone and progesterone (100 mug/ml) had no effect on PGE release throughout the incubation period. Chloroquine (10 mug/ml) inhibited PGE release from inflamed synovia by 50%. Indomethacin (1 mug/ml) abolished PGE release by 90%. Corticosterone, dexamethasone and prednisone reduced PGE content of inflamed synovia by approximately 45% during a 4-h incubation period. Aldosterone and progesterone were ineffective, while indomethacin reduced PGE content by 70%. The suppressive action of corticosterone on PGE release was prevented by addition to the medium of arachidonic acid (2 mug/ml). By contrast, the inhibitory action of indomethacin was not affected by provision of exogenous substrate. We suggest that glucocorticosteroids reduce PGE release by limiting the availability of the substrate for prostaglandin biosynthesis, and this may well explain some of their anti-inflammatory properties.     

Prolonged enhancement and depression of synaptic transmission in CA1 pyramidal neurons induced by transient forebrain ischemia in vivo

Evoked postsynaptic potentials of CA1 pyramidal neurons in rat hippocampus were studied during 48 h after severe ischemic insult using in vivo intracellular recording and staining techniques. Postischemic CA1 neurons displayed one of three distinct response patterns following contralateral commissural stimulation. At early recirculation times (0-12 h) approximately 50% of neurons exhibited, in addition to the initial excitatory postsynaptic potential, a late depolarizing postsynaptic potential lasting for more than 100 ms. Application of dizocilpine maleate reduced the amplitude of late depolarizing postsynaptic potential by 60%. Other CA1 neurons recorded in this interval failed to develop late depolarizing postsynaptic potentials but showed a modest blunting of initial excitatory postsynaptic potentials (non-late depolarizing postsynaptic potential neuron). The proportion of recorded neurons with late depolarizing postsynaptic potential characteristics increased to more than 70% during 13-24 h after reperfusion. Beyond 24 h reperfusion, approximately 20% of CA neurons exhibited very small excitatory postsynaptic potentials even with maximal stimulus intensity. The slope of the initial excitatory postsynaptic potentials in late depolarizing postsynaptic potential neurons increased to approximately 150% of control values up to 12 h after reperfusion indicating a prolonged enhancement of synaptic transmission. In contrast, the slope of the initial excitatory postsynaptic potentials in non-late depolarizing postsynaptic potential neurons decreased to less than 50% of preischemic values up to 24 h after reperfusion indicating a prolonged depression of synaptic transmission. More late depolarizing postsynaptic potential neurons were located in the medial portion of CA1 zone where neurons are more vulnerable to ischemia whereas more non-late depolarizing postsynaptic potential neurons were located in the lateral portion of CA1 zone where neurons are more resistant to ischemia. The result from the present study suggests that late depolarizing postsynaptic potential and small excitatory postsynaptic potential neurons may be irreversibly injured while non-late depolarizing postsynaptic potential neurons may be those that survive the ischemic insult. Alterations of synaptic transmission may be associated with the pathogenesis of postischemic neuronal injury.     

Long-term and short-term plasticity in the CA1, CA3, and dentate regions of the rat hippocampal slice

Subregions of the rat hippocampal slice were investigated in relation to (a) the presence of long-term potentiation and (b) responsiveness to low-frequency stimulation. Long-term potentiation was observed in CA1, CA3 and dentate. The effect occasionally lasted up to 6 h, developed gradually, and depended upon repeated low-frequency tetani for maximal effect. To low-frequency monosynaptic stimulation, areas CA3 and CA1 exhibit response facilitation whereas the dentate gyrus exhibits response depression. Reponsiveness in all areas was influenced by stimulus frequency. Recovery was rapid in all areas.     

Stimulation of benzodiazepine receptors in the dorsal hippocampus and median raphé reveals differential GABAergic control in two animal tests of anxiety

The effects of pharmacological challenges to the benzodiazepine receptors in the dorsal hippocampus and median raphé nucleus were investigated in the social interaction and the elevated plus-maze tests of anxiety in rats. In the social interaction test, bilateral administration of midazolam (1 and 2 micrograms), into the dorsal hippocampus had anxiolytic effects; flumazenil (500 ng) was silent, but was able to antagonize the anxiolytic effects of midazolam (2 micrograms). In the social interaction test, midazolam was also anxiolytic when infused into the median raphé nucleus; flumazenil (100 and 500 ng) increased locomotor activity, but did not change anxiety measures. As an anatomical control, midazolam (1 and 2 micrograms) was infused into the adjacent pontine reticular nucleus, and was without effect. In contrast to the social interaction test, local infusion of midazolam (1 and 2 micrograms) and flumazenil (100 and 500 ng) into either the dorsal hippocampus or the median raphé nucleus failed to change anxiety measures in the elevated plus-maze (trials 1 and 2). These results show that stimulation of the benzodiazepine receptors in the hippocampus or the median raphé nucleus leads to anxiolytic effects in the social interaction test, but not in the elevated plus-maze. It would therefore appear that the two tests detect different types of anxiety that are differentially modulated by GABAA-benzodiazepine receptors in the dorsal hippocampus and the median raphé nucleus.     

In vivo voltammetric studies of the effects of intrathecal morphine on noxious heat stimuli-induced serotonin release in the nucleus raphe magnus of anesthetized rats

MOTIVATION: The principal motivation was to design an environment for the development of image-analysis applications which would allow the integration of independent modules into one frame and make available tools for their build-up, running, management and mutual communication. RESULTS: The system was designed as modular, consisting of the core and work modules. The system core focuses on overall management and provides a library of classes for build-up of the work modules, their user interface and data communication. The work modules carry practical implementation of algorithms and data structures for the solution of a particular problem, and were implemented as dynamic-link libraries. They are mutually independent and run as individual threads, communicating with each other via a unified mechanism. The environment was designed to simplify the development and testing of new algorithms or applications. An example of implementation for the particular problem of the analysis of two-dimensional (2D) gel electrophoretograms is presented. The environment was designed for the Windows NT operating system with the use of Microsoft Foundation Class Library employing the possibilities of C++ programming language. AVAILABILITY: Available on request from the authors.     

Biodegradable polyesters for controlled release of trypanocidal drugs: in vitro and in vivo studies

Copolymers of epsilon-caprolactone and L-lactide P(CL-LLA), epsilon-caprolactone and D,L-lactide P(CL-DLLA) and epsilon-caprolactone and trimethylene carbonate P(CL-TMC) were synthesized. The composition of comonomers and their sequence lengths were determined by means of 1H and 13C NMR measurements. The effect of the comonomer on the thermal properties was investigated by differential scanning calorimetry (DSC) analysis. The in vitro degradation of the rods obtained by melt extrusion of the synthesized copolymers and the commercial homopolymers poly(epsilon-caprolactone) P(CL) and poly(D,L-lactide) P(DLLA) was carried out in phosphate buffer (PB) pH 7.4 at 37 degrees C. The rate of degradation depends on comonomers and polymer composition. The in vitro release of the selected drugs, isometamidium chloride (IMM) and ethidium bromide (EtBr), from such devices was carried out under the same conditions as used for the in vitro degradation. The release experiments show that the release of IMM is faster than for EtBr. During the first stage, for IMM the release is governed by osmotic pressure whereas for EtBr the release is mainly diffusion-controlled. The in vitro release of these drugs is governed by polymer matrix degradation at the later stage of the release process. Comparative in vitro release study from the different polymers showed that the release depends mainly on the physical properties of the polymer. The in vivo experiments carried out in the field on cattle and in the laboratory on rabbits using the classical treatment (intramuscular injection) and the sustained release devices (SRD) subcutaneously implanted, showed that the prophylactic period is significantly enhanced in the case of SRD as compared to intramuscular injection. The comparative efficacy of SRD containing IMM and EtBr evaluated in the case of rabbits showed that, the SRD (IMM) prophylactic period is much longer than for SRD (EtBr).     

The selective neuronal NO synthase inhibitor 7-nitro-indazole blocks both long-term potentiation and depotentiation of field EPSPs in rat hippocampal CA1 in vivo

The membrane-permeant gas NO is a putative intercellular messenger that has been proposed on the basis of previous in vitro studies to be involved in synaptic plasticity, especially the induction of long-term potentiation (LTP) of excitatory synaptic transmission in the hippocampus and cortex. In the present study, the role of NO in synaptic plasticity has been investigated in vivo. In particular, the action of the novel and selective neuronal NO synthase (nNOS) inhibitor 7-nitro-indazole (7-NI) has been investigated on the induction of LTP and depotentiation (DP) of field EPSPs in CA1 of the hippocampus in vivo. Unlike previously studied nonselective NOS inhibitors, 7-NI does not increase arterial blood pressure. In vehicle-injected rats, high-frequency stimulation consisting of a series of trains at 200 Hz induced LTP. However, LTP induction was strongly inhibited in 7-NI (30 mg/kg, i.p.)-treated animals. The inhibitory effect of 7-NI on the induction of LTP was prevented by pretreatment with L-arginine, the substrate amino acid used by NOS. In control animals, low-frequency stimulation consisting of 900 stimuli at 10 Hz induced DP of previously established LTP, whereas in 7-HI-treated animals only a short-term depression was induced. This effect of 7-NI also was prevented by D-arginine. The LTP and DP induced in control animals in this study were NMDA receptor-dependent, the NMDA receptor antagonist 3-(R,S)-2-carboxypiperazin-4-yl-propyl-1- phosphonic acid inhibiting the induction of both forms of synaptic plasticity. The present experiments are the first to demonstrate that an NOS inhibitor blocks the induction of the synaptic component of LTP and DP in vivo and, therefore, these results strengthen evidence that the production of NO is necessary for the induction of LTP and DP.     

Tolerance and sensitization to the behavioral effects of cocaine in rats: relationship to benzodiazepine receptors

Tolerance and sensitization to the behavioral effects of cocaine were investigated in rats responding under a fixed-consecutive-number eight schedule of food reinforcement. The development of tolerance or sensitization was induced by delivering the drug either immediately before or after each behavioral session during chronic administration. Chronic cocaine administered before each session resulted in tolerance, as indicated by the shift to the right in the cocaine dose response curve. This tolerance was more likely to develop in the presence of an external discriminative stimulus. On the other hand, when cocaine was delivered after each session, the injections did not disrupt responding and sensitization or increased sensitivity rather than tolerance developed. This sensitization was more likely to occur when the external discriminative stimulus was not present. These data suggest that either tolerance or sensitization to the behavioral effects of cocaine can occur following the same number of chronic injections, with the effect dependent on the context under which the drug is delivered. Significant differences in benzodiazepine receptor binding measured autoradiographically using [3H]flumazenil were observed between rats that received cocaine before or after each session, suggesting that the development of tolerance and sensitization may be mediated through changes in benzodiazepine receptors in discrete brain regions.     

Endogenous adenosine attenuates long-term depression and depotentiation in the CA1 region of the rat hippocampus

We describe a series of 144 cases of leptospirosis diagnosed in 1989 in New Caledonia. The incidence rate was 90 per 100,000 person-years, with a specific mortality rate of 4% patients. Those affected (100 males, 44 females) were mainly aged 20 to 40 years. Incidence in rural areas (112 per 100,000 person-years) was seven times higher than in urban settlements. Two periods with higher incidence were noticed corresponding to highest rainfall. Twenty-nine of the cases occurred in individuals with professions commonly associated with leptospirosis. Contacts with rats, dogs and ditch or river water were the most frequently mentioned. The clinical expression of the disease was polymorphic: 60% of the patients had mild symptoms, 40% were acute forms including Weil's disease. Of 57 hospitalized, 23% were admitted with an initial diagnosis of dengue, and 37% with leptospirosis. Main clinical syndromes were: icterus and/or renal syndrome in 50% of patients, cardiac syndrome in 65%, acute myalgies in 58% and pulmonary syndrome in 50%. Although hemorrhages were uncommon (17%), 40% of the cases demonstrated thrombocytopenia (< 50,000/m3). Pancreatic involvement with hyperamylasemia was evidenced in 50% of cases. Twelve serogroups of Leptospira were implicated, Icterohaemorragiae predominated (41%), but was not associated with severe forms. In New Caledonia, like in all tropics, leptospirosis must be considered as an environmental diseases, professional activities being just an additional risk factor. Use of serology as a reliable tool for confirmation of cases in areas of high environmental contamination is discussed.     

Mechanism of chaperonin action: GroES binding and release can drive GroEL-mediated protein folding in the absence of ATP hydrolysis

As a basic principle, assisted protein folding by GroEL has been proposed to involve the disruption of misfolded protein structures through ATP hydrolysis and interaction with the cofactor GroES. Here, we describe chaperonin subreactions that prompt a re-examination of this view. We find that GroEL-bound substrate polypeptide can induce GroES cycling on and off GroEL in the presence of ADP. This mechanism promotes efficient folding of the model protein rhodanese, although at a slower rate than in the presence of ATP. Folding occurs when GroES displaces the bound protein into the sequestered volume of the GroEL cavity. Resulting native protein leaves GroEL upon GroES release. A single-ring variant of GroEL is also fully functional in supporting this reaction cycle. We conclude that neither the energy of ATP hydrolysis nor the allosteric coupling of the two GroEL rings is directly required for GroEL/GroES-mediated protein folding. The minimal mechanism of the reaction is the binding and release of GroES to a polypeptide-containing ring of GroEL, thereby closing and opening the GroEL folding cage. The role of ATP hydrolysis is mainly to induce conformational changes in GroEL that result in GroES cycling at a physiologically relevant rate.     

Stimulation on the positive phase of hippocampal theta rhythm induces long-term potentiation that can Be depotentiated by stimulation on the negative phase in area CA1 in vivo

Long-term potentiation (LTP) of synaptic transmission induced by high-frequency stimulation (HFS) is considered to be a model for learning processes; however, standard HFS protocols consisting of long trains of HFS are very different from the patterns of spike firing in freely behaving animals. We have investigated the ability of brief bursts of HFS triggered at different phases of background theta rhythm to mimic more natural activity patterns. We show that a single burst of five pulses at 200 Hz given on the positive phase of tail pinch-triggered theta rhythm reliably induced LTP in the stratum radiatum of the hippocampus of urethane-anesthetized rats. Three of these bursts saturated LTP, and 10 bursts occluded the induction of LTP by long trains of HFS. Burst stimulation on the negative phase or at zero phase of theta did not induce LTP or long-term depression. In addition, stimulation with 10 bursts on the negative phase of theta reversed previously established LTP. The results show that the phase of sensory-evoked theta rhythm powerfully regulates the ability of brief HFS bursts to elicit either LTP or depotentiation of synaptic transmission. Furthermore, because complex spike activity of approximately five pulses on the positive phase of theta rhythm can be observed in freely moving rats, LTP induced by the present theta-triggered stimulation protocol might model putative synaptic plastic changes during learning more closely than standard HFS-induced LTP.     

Indicators of anxiety and depression in subjects with different kinds of diet: vegetarians and omnivores

The following study, one of the first done in Puerto Rico, investigate the different kinds of diet and the level of anxiety and depression that the subjects present. The sample consists of 80 subjects between 25 and 70 years age divided into two main groups (vegetarian versus no vegetarian) depending their diet consumption. The basic findings in the three psychological tests given (IDARE-1, IDARE-2 and CES-D) to the subjects demonstrate significant differences in anxiety and depression between groups. More anxiety and depression where reported in the no vegetarian groups in comparison with the vegetarian groups. In addition, diet analysis found more nutritional antioxidant agents levels in the vegetarian group in comparison with the no-vegetarian group.     

Analyzing true change in longitudinal multitrait-multimethod studies: Application of a multimethod change model to depression and anxiety in children.

The authors show how structural equation modeling can be applied to analyze change in longitudinal multitrait-multimethod (MTMM) studies. For this purpose, an extension of latent difference models (McArdle, 1988; Steyer, Eid, & Schwenkmezger, 1997) to multiple constructs and multiple methods is presented. The model allows investigators to separate true change from measurement error and to analyze change simultaneously for different methods. The authors also show how Campbell and Fiske’s (1959) guidelines for analyzing convergent and discriminant validity can be applied to the measurement of latent change. The practical application of the multimethod change model is illustrated in a reanalysis of child depression and anxiety scores (N = 906 American children) that were assessed by self- and parent reports on three measurement occasions. The analyses revealed that (a) the convergent validity of change was low for both constructs and (b) sex was a significant predictor of self-reported, but not of parent reported, anxiety states. Finally, the authors discuss advantages and limitations and compare the model with other approaches for analyzing longitudinal MTMM data. (PsycINFO Database Record (c) 2010 APA, all rights reserved)