An empirical and theoretical investigation of psychodynamic psychotherapy and neuroleptic medication for the treatment of schizophrenia

Since the early 1950s, biopsychiatric conceptualizations have dominated empirical, theoretical and therapeutic efforts to understand the treatment of schizophrenia. The contemporary preeminence of biopsychiatric conceptualizations of schizophrenia have overshadowed other perspectives that might contribute fruitfully to our capacity to understand and aid individuals suffering with this devastating emotional disorder. The origin of modern biopsychiatric conceptualizations is deconstructed by illuminating the non-epistemic underpinnings of Emil Kraeplin\u27s dementia praecox concept, which is the forerunner of the modern schizophrenia construct. Two widely held assumptions of the biomedical model, namely: 1) that schizophrenia is a degenerative, organic brain disease; and 2) that neuroleptic medications are the most effective and safest treatment of schizophrenia are empirically reviewed. Psychodynamic theory and therapy alternatives are also reviewed empirically and theoretically.The comparative effectiveness of Psychodynamic Psychotherapy-only (n = 9) and Medication-only (n = 12) was investigated using an experimental design (Karon & VandenBos, 1981). All patients were administered the Thematic Apperception Test (TAT) at pre- and post-treatment (20 months). Westen\u27s (1995; Hilsenroth, Stein, & Pinsker, 2004) Social Cognition and Object Relations Scale (SCORS) was used to rate pre- and post-treatment TAT narratives in order to assess changes in the cognitive and affective aspects of patients\u27 object relations throughout treatment. Jacobson and Truax\u27 (1991) Clinical Significance methodology was used to detect clinically significant change for each individual patient. Results show the SCORS is a reliable and valid instrument for use with a schizophrenia sample.Treatment outcome results suggest that patients receiving psychodynamic psycotherapy exhibit clinically significant change in a variety of object relations domains when assessed at the group and individual levels. Comparative analyses indicated that Psychodynamic Psychotherapy-only patients outperformed Medication-only patients in regard to changes in a variety of object relations domains. Medication-only patients did not outperform Psychodynamic Psychotherapy-only patients in any domain of object relations. Significantly more Medication-only patients exhibited clinical regression compared to patients receiving psychodynamic psychotherapy. (Dr. Leonard Handler served as the chairperson of this dissertation committee.

The ABCB1 transporter gene and antidepressant response

P-glycoprotein, encoded by the ABCB1 gene, may modulate the brain concentration of several antidepressants. Functional genetic variation is thought to exist in this gene, and here we review several studies that have attempted to associate this variation with clinical response to antidepressant treatment

Classifying the metal dependence of uncharacterized nitrogenases

Nitrogenase enzymes have evolved complex iron–sulfur (Fe–S) containing cofactors that most commonly contain molybdenum (MoFe, Nif) as a heterometal but also exist as vanadium (VFe, Vnf) and heterometal-independent (Fe-only, Anf) forms. All three varieties are capable of the reduction of dinitrogen (N_2) to ammonia (NH_3) but exhibit differences in catalytic rates and substrate specificity unique to metal type. Recently, N_2 reduction activity was observed in archaeal methanotrophs and methanogens that encode for nitrogenase homologs which do not cluster phylogenetically with previously characterized nitrogenases. To gain insight into the metal cofactors of these uncharacterized nitrogenase homologs, predicted three-dimensional structures of the nitrogenase active site metal-cofactor binding subunits NifD, VnfD, and AnfD were generated and compared. Dendrograms based on structural similarity indicate nitrogenase homologs cluster based on heterometal content and that uncharacterized nitrogenase D homologs cluster with NifD, providing evidence that the structure of the enzyme has evolved in response to metal utilization. Characterization of the structural environment of the nitrogenase active site revealed amino acid variations that are unique to each class of nitrogenase as defined by heterometal cofactor content; uncharacterized nitrogenases contain amino acids near the active site most similar to NifD. Together, these results suggest that uncharacterized nitrogenase homologs present in numerous anaerobic methanogens, archaeal methanotrophs, and firmicutes bind FeMo-co in their active site, and add to growing evidence that diversification of metal utilization likely occurred in an anoxic habitat

A Deep ROSAT HRI Observation of NGC 1313

We describe a series of observations of NGC 1313 using the ROSAT HRI with a combined exposure time of 183.5 ksec. The observations span an interval between 1992 and 1998; the purpose of observations since 1994 was to monitor the X-ray flux of SN1978K, one of several luminous sources in the galaxy. No diffuse emission is detected in the galaxy to a level of ~1-2x10^37 ergs/s/arcmin^-2. A total of eight sources are detected in the summed image within the D_25 diameter of the galaxy. The luminosities of five of the eight range from \~6x10^37 to ~6x10^38 erg/s; these sources are most likely accreting X-ray binaries, similar to sources obseved in M31 and M33. The remaining three sources all emit above 10^39 erg/s. We present light curves of the five brightest sources. Variability is detected at the 99.9% level from four of these. We identify one of the sources as an NGC 1313 counterpart of a Galactic X-ray source. The light curve, though crudely sampled, most closely resembles that of a Galactic black hole candidate such as GX339-4, but with considerably higher peak X-ray luminosity. An additional seven sources lie outside of the D_25 diameter and are either foreground stars or background AGN.Comment: 18 pages, 9 figures; accepted AJ, scheduled for November 200

FAR and NEAR Target Dynamic Visual Acuity: A Functional Assessment of Canal and Otolith Performance

Upon their return to earth, astronauts experience the effects of vestibular adaptation to microgravity. The postflight changes in vestibular information processing can affect postural and locomotor stability and may lead to oscillopsia during activities of daily living. However, it is likely that time spent in microgravity affects canal and otolith function differently. As a result, the isolated rotational stimuli used in traditional tests of canal function may fail to identify vestibular deficits after spaceflight. Also, the functional consequences of deficits that are identified often remain unknown. In a gaze control task, the relative contributions of the canal and otolith organs are modulated with viewing distance. The ability to stabilize gaze during a perturbation, on visual targets placed at different distances from the head may therefore provide independent insight into the function of this systems. Our goal was to develop a functional measure of gaze control that can also offer independent information about the function of the canal and otolith organs

Temporal decline in defibrillation thresholds with an active pectoral lead system

AbstractOBJECTIVESThe objective of this study was to characterize temporal changes in defibrillation thresholds (DFTs) after implantation with an active pectoral, dual-coil transvenous lead system.BACKGROUNDVentricular DFTs rise over time when monophasic waveforms are used with non-thoracotomy lead systems. This effect is attenuated when biphasic waveforms are used with transvenous lead systems; however, significant increases in DFT still occur in a minority of patients. The long-term stability of DFTs with contemporary active pectoral lead systems is unknown.METHODSThis study was a prospective assessment of temporal changes in DFT using a uniform testing algorithm, shock polarity and dual-coil active pectoral lead system. Thresholds were measured at implantation, before discharge and at long-term follow-up (70 ± 40 weeks) in 50 patients.RESULTSThe DFTs were 9.2 ± 5.4 J at implantation, 8.3 ± 5.8 J before discharge and 6.9 ± 3.6 J at long-term follow-up (p < 0.01 by analysis of variance; p < 0.05 for long-term follow-up vs. at implantation or before discharge). The effect was most marked in a prespecified subgroup with high implant DFTs (≥15 J). No patient developed an inadequate safety margin (<9 J) during follow-up.CONCLUSIONSThe DFTs declined significantly after implantation with an active pectoral, dual-coil transvenous lead system, and no clinically significant increases in DFT were observed. Therefore, routine defibrillation testing may not be required during the first two years after implantation with this lead system, in the absence of a change in the cardiac substrate or treatment with antiarrhythmic drugs

A sulfated carbohydrate epitope inhibits axon regeneration after injury

Chondroitin sulfate proteoglycans (CSPGs) represent a major barrier to regenerating axons in the central nervous system (CNS), but the structural diversity of their polysaccharides has hampered efforts to dissect the structure-activity relationships underlying their physiological activity. By taking advantage of our ability to chemically synthesize specific oligosaccharides, we demonstrate that a sugar epitope on CSPGs, chondroitin sulfate-E (CS-E), potently inhibits axon growth. Removal of the CS-E motif significantly attenuates the inhibitory activity of CSPGs on axon growth. Furthermore, CS-E functions as a protein recognition element to engage receptors including the transmembrane protein tyrosine phosphatase PTPσ, thereby triggering downstream pathways that inhibit axon growth. Finally, masking the CS-E motif using a CS-E-specific antibody reversed the inhibitory activity of CSPGs and stimulated axon regeneration in vivo. These results demonstrate that a specific sugar epitope within chondroitin sulfate polysaccharides can direct important physiological processes and provide new therapeutic strategies to regenerate axons after CNS injury