BAX inhibitor-1 is a Ca(2+) channel critically important for immune cell function and survival.

The endoplasmic reticulum (ER) serves as the major intracellular Ca(2+) store and has a role in the synthesis and folding of proteins. BAX (BCL2-associated X protein) inhibitor-1 (BI-1) is a Ca(2+) leak channel also implicated in the response against protein misfolding, thereby connecting the Ca(2+) store and protein-folding functions of the ER. We found that BI-1-deficient mice suffer from leukopenia and erythrocytosis, have an increased number of splenic marginal zone B cells and higher abundance and nuclear translocation of NF-κB (nuclear factor-κ light-chain enhancer of activated B cells) proteins, correlating with increased cytosolic and ER Ca(2+) levels. When put into culture, purified knockout T cells and even more so B cells die spontaneously. This is preceded by increased activity of the mitochondrial initiator caspase-9 and correlated with a significant surge in mitochondrial Ca(2+) levels, suggesting an exhausted mitochondrial Ca(2+) buffer capacity as the underlying cause for cell death in vitro. In vivo, T-cell-dependent experimental autoimmune encephalomyelitis and B-cell-dependent antibody production are attenuated, corroborating the ex vivo results. These results suggest that BI-1 has a major role in the functioning of the adaptive immune system by regulating intracellular Ca(2+) homeostasis in lymphocytes.

The effects of training in time-limited dynamic psychotherapy: changes in therapeutic outcome.

The present study explored the effects on therapeutic outcomes of training therapists in brief manualized therapy. As part of the Vanderbilt II project, each of 16 therapists (8 psychiatrists and 8 clinical psychologists) treated 2 moderately disturbed adult patients using his or her customary short-term treatment methods; they then received a year of training in a manualized form of brief dynamic therapy, Time-Limited Dynamic Psychotherapy (TLDP); finally, they administered TLDP to 2 additional patients. It was hypothesized that training would result in improved outcomes generally and that differentially greater improvement would be seen in patients commonly considered less suitable for brief dynamic therapy. Outcome data obtained at termination failed to support either hypothesis. Measurements of interpersonal dependency obtained at a one-year follow-up were consistent with the first hypothesis, but the follow-up data were inconsistent with the second. A systematic review of the 32 posttraining cases suggested that the majority of the therapists had not achieved basic competence at TLDP. Die hier beschriebene Studie untersucht die Wirkungen eines Trainings in manualisierter Kurzzeitherapie auf das Therapierergebnis. Als Teil des Vanderbilt II Projektes behandelten jeweils 16 Therapeuten (8 Psychiater und 8 klinische Psychologen) zwei mittelgradig beeinrächtigte erwachsene Patienten mit den ihnen vertrauten Kurzzeitbehandlungsmethoden. Danach wurden sie über ein Jahr in einer manualisierten Form psychodynamischer Kurzzeittherapie ausgebildet und wandten diese Therapie auf zwei weitere Patienten an. Es wurde angenommen, dass die Ausbildung in besseren Ergebnisdaten, die bei Ende der Therapie erhoben wurden, konnten diese Hypothese nicht bestätigen. Maße für die interpersonale Abhängigkeit zu einem Einjahreskatamnesezeitpunkt waren mit der ersten Hypothese konform, aber inkonsistent mit der zweiten. Eine systematische Untersuchung der 32 nach der Ausbildung behandelten Fälle legt nahe, dass die Mehrzahl der Therapeuten keine grundlegende Kompetenz in zeitlich limitierter dynamischer Psychotherapie erworben hatte. Cette éude explore les effets sur les résultats thérapeutiques de la formation des thérapeutes dans une thérapie brève, manualissée. Dans le cadre du projet Vanderbilt II, chacun des 16 thérapeutes (8 psychiatrs et 8 psychologues cliniciens) a traité deux patients adultes modérément perturbés, chacun par sa méthode habituelle de thérapie brève; ensuite ils ont reçu une formation d'une année dans une méthode manualisée de thérapie brève, la Psychothérapie Dynamique Limitée dans le Temps (TLDP); pour finir, ils ont appliqué la TLDP à de meilleurs résultats en général, et qu'une amélioration comparativement plus importante sera observée chez des patients habituellement considérés comme moins adaptés à une thérapie dynamique brè. Les résultats obtenus à la terminaison n'ont pu confirmer aucune de ces hypothèses. Des mesures de la dépendance interpersonnelle une année après étaient consistantes avec la première hypothèse, mais les données catamnestiques étaient inconsistantes avec la deuxième. Une revue systématique des 32 cas après formation a suggéré que la majorité des thérapeutes n'avait pas acquis une compétence de base en TLDP. Este estudio exploró la efectividad del entrenamiento de terapeutas en una terapia breve manualizada. Como parte del proyecto Vanderbilt II, dieciséis terapeutas (ocho psiquiatras y ocho psicólogos clínicos) trataron dos pacientes adultos mooderadamente perturbados con sus métodos habituales de tratamiento a corto plazo. Estos terapeutas recibieron luego un año de entrenamiento en terapia dinámica breve manualizada que se Ilamó Psicoterapia Dinámica de Tiempo limitado (TLDP). Finalmente, administraron esta TLDP a dos pacientes más. La hipótesis fue que el entrenamiento ilevaría, en general, a resultados mejores y que habría mayor mejoramiento en pacientes menos aptos para una terapia dinámica breve. Los resultados a la terminación no apoyaron ninguna de las dos hipótesis. Las mediciones de dependencia interpersonal al año de seguimiento resultaron consistentes con la primera hipótesis, mientras que los resultados de seguimiento fueron inconsistentes con la segunda. Una revisión sistemática de los treinta y dos casos luego del entrenamiento sugiere que la mayoría de los terapeutas no había l.

Effects of training in time-limited dynamic psychotherapy: changes in therapist behavior.

Sixteen therapists participated in a year-long manualized training program as part of the Vanderbilt II study of time-limited dynamic psychotherapy. Changes in therapist behavior were measured with the Vanderbilt Therapeutic Strategies Scale (an adherence measure), the Vanderbilt Psychotherapy Process Scale (VPPS), and interpersonal process codings using the Structural Analysis of Social Behavior (SASB). The training program successfully changed therapists' technical interventions in line with the manualized protocol. After training, there was increased emphasis on the expression of in-session affect, exploration of the therapeutic relationship, an improved participant-observer stance, and greater use of open-ended questions. There was also an indication of unexpected deterioration in certain interpersonal and interactional aspects of therapy as measured by the VPPS and SASB ratings. These results question the assumption that greater control of the therapy variable is straightforwardly achieved with manuals and adherence scales. Changing or dictating specific therapist behaviors to achieve technical adherence may alter other therapeutic variables in unexpected and even counterproductive ways.

Effects of training in time-limited dynamic psychotherapy: mediators of therapists' responses to training.

Sixteen therapists were enrolled in a year-long manualized training program as part of the Vanderbilt II study of time-limited dynamic psychotherapy (TLDP). The training program successfully changed therapists' interventions in line with prescriptions of the TLDP manual, but some unanticipated changes ran counter to the intent of the training, including increased negative interpersonal transactions as indicated by process measures such as the Structural Analysis of Social Behavior (SASB). We examined therapist variables, patient variables, and training variables that appeared to mediate therapist responses to the training program. Results indicate that patient difficulty may mediate certain aspects of therapists' responses to training. Therapists with self-reported hostile and controlling introjects showed the greatest technical adherence, which was intriguing because prior research has linked hostile therapist introject to greater frequency of counter-therapeutic interpersonal process. Of special interest were differences in effects of training associated with individual training faculty. This finding, if generalizable, has important implications for manualized therapy research, especially multisite trials.

Patient and therapist introject, interpersonal process, and differential psychotherapy outcome.

The Structural Analysis of Social Behavior (SASB; Benjamin, 1974, 1982, 1984) system was used to study the interpersonal process between patient and therapist in the 3rd session of 14 therapeutic dyads. Dyads were grouped into good and poor outcomes cases (n = 7) on the basis of the amount of change in the patients' introject as measured by the INTREX Introject Questionnaire (Benjamin, 1983). Strong support was found for the following hypotheses based on interpersonal theory, linking therapists' introject state, interpersonal process in therapy, and outcome: (a) Poor outcome cases (no introject change) were typified by interpersonal behaviors by the therapist that confirmed a negative patient introject; (b) the number of therapists' statements that were subtly hostile and controlling was highly correlated with the number of self-blaming statements by the patients; (c) therapists with disaffiliative introjects tended to engage in a much higher level of problematic interpersonal processes that have been associated with poor outcome. Implications for future research and therapist training are discussed.

Converging evidence for identification of recurrent relationship themes: comparison of two methods.

The therapeutic process is complex, and researchers and clinicians alike search for organizing principles or underlying structures that will reduce this complexity and thereby augment the efficacy of their respective endeavors. As other papers in this issue indicate, one such organizing principle is the concept of a recurring relationship theme that can be identified in the patient's descriptions of current and past relationships, as well as observed in the patient's interaction with the therapist. This concept has its origins in Freud's discovery of the transference phenomenon (1912), wherein the patient reenacts early relationships with significant others in the relationship with the analyst, and in Sullivan's interpersonal theory of psychiatry, with its central tenet that "personality is the relatively enduring pattern of recurrent interpersonal situations which characterize a human life" (1953, pp. 110-11). In the psychoanalytic and interpersonal therapies, these recurrent interpersonal themes, associated with the patient's difficulty in living and characterized as self-defeating and self-perpetuating, can potentially serve three main purposes: diagnosing and describing patients' difficulties, focusing therapeutic interventions, and measuring change on an individual basis. However, until recently, research on transference and rigidity of interpersonal style has been hampered by the lack of objective and clinically relevant measures for quantifying this clinical phenomenon (Kiesler 1986; Luborsky and Spence 1978). Luborsky (1977) developed the first reliable method for operationalizing the transference concept. Since then, as the companion papers in this issue point out, several different methods have been developed (e.g., Gill and Hoffman 1982; Horowitz 1979; Schacht et al. 1984). Although these methods differ in the postulated structural composition or components of the transference theme or recurrent relationship theme, they operate from similar methods of assessment. This paper presents the results of an initial investigation into convergent validity (Cronbach and Meehl 1955) of two of the major relationship theme methods--the Core Conflictual Relationship Theme (CCRT) of Luborsky and colleagues (Luborsky 1977), and the Cyclical Maladaptive Pattern (CMP: formerly called the "dynamic focus") of the Vanderbilt group (Schacht et al. 1984; Schacht and Henry, in press). In our investigation, developers of the approaches independently applied their methods to the same interview with a depressed patient. It was hypothesized that aside from differences due to the structural composition, the two methods would identify a similar relationship theme.