Effects of cocaine and withdrawal on the mouse nucleus accumbens transcriptome.

Genetic association studies, pharmacological investigations and analysis of mice-lacking individual genes have made it clear that Cocaine administration and Withdrawal have a profound impact on multiple neurotransmitter systems. The GABAergic medium spiny neurons of the nucleus accumbens (NAc) exhibit changes in the expression of genes encoding receptors for glutamate and in the signaling pathways triggered by dopamine binding to G-protein-coupled dopamine receptors. Deep sequence analysis provides a sensitive, quantitative and global analysis of the effects of Cocaine on the NAc transcriptome. RNA prepared from the NAc of adult male mice receiving daily injections of Saline or Cocaine, or Cocaine followed by a period of Withdrawal, was used for high-throughput sequence analysis. Changes were validated by quantitative polymerase chain reaction or Western blot. On the basis of pathway analysis, a preponderance of the genes affected by Cocaine and Withdrawal was involved in the cadherin, heterotrimeric G-protein and Wnt signaling pathways. Distinct subsets of cadherins and protocadherins exhibited a sustained increase or decrease in expression. Sustained down-regulation of several heterotrimeric G-protein ß- and γ-subunits was observed. In addition to altered expression of receptors for small molecule neurotransmitters, neuropeptides and endocannabinoids, changes in the expression of plasma membrane transporters and vesicular neurotransmitter transporters were also observed. The effects of chronic Cocaine and Withdrawal on the expression of genes essential to cholinergic, glutamatergic, GABAergic, peptidergic and endocannabinoid signaling are as profound as their effects on dopaminergic transmission. Simultaneous targeting of multiple Withdrawal-specific changes in gene expression may facilitate development of new therapeutic approaches that are better able to prevent relapse.

Psychological impact of news of genetic risk for Huntington disease.

A one-year longitudinal study was conducted investigating the psychological effects of the news of genetic testing for the Huntington disease (HD) gene. Participants were assessed at baseline (before obtaining news of test results) and at three, six, and 12 months after test results on stress-specific symptom measures. Among carriers of the HD gene, a considerable number (55%) showed evidence of neurological impairment at baseline, indicative of HD. Also noteworthy, these individuals had significantly higher psychological symptom scores at baseline than carriers without neurological impairment or noncarriers. Despite this, these individuals were no more aware of their carrier status at baseline than carriers without HD symptoms or noncarriers. Furthermore, the psychological symptom levels of HD carriers with neurological impairment remained elevated across the follow-up assessments. Results for noncarriers and carriers without HD neurological symptoms were consistent with the findings of previous studies indicating that news of genetic testing for the HD gene had limited detrimental impact. The clinical implications of the results are discussed.

Object relations as a predictor of adjustment in conjugal bereavement.

The impact of object relations on adjustment in conjugal bereavement was examined. At approximately 6 months postbereavement, 46 midlife bereaved participants engaged in a narrative interview in which they were asked to discuss their past relationship with their deceased spouse. The Westen et al. object relations scoring system was applied to these narratives. Participants also completed depression and grief-specific symptom measures at 6 months and again at 14 and 25 months postbereavement. Object relations correlated differently with grief-specific symptoms and depression: it was more strongly negatively associated with 6 month postloss grief-specific symptoms while more strongly negatively correlated with depression at 25 month postloss. In a growth curve analysis, more mature object relations was also predictive of a faster rate of decrease in depression over time. The results were discussed in terms of current theoretical perspectives on what is required in successful adaptation to conjugal bereavement.

The relation of continuing attachment to adjustment in conjugal bereavement.

The role of continuing attachment in adjustment to conjugal loss was examined. At 6 months postloss, 70 midlife bereaved participants were interviewed to assess different forms of continuing attachment. They also engaged in a monologue role-play with their deceased spouse, providing a behavioral measure of grief-related distress. In addition, they completed general and grief-specific symptom inventories at 6 months and again at 14 and 25 months postloss. The results indicated that use of the deceased's possessions to gain comfort was positively correlated with concurrent distress in the role-play and predictive to less of a decrease in grief-specific symptoms over time in a growth curve analysis. In contrast, attachment through fond memories was related to less distress in the role-play. The results, therefore, suggest that whether continuing attachment is adaptive or not depends on its form.

Sequential consequences of therapists' interventions.

Using sequential analysis, the authors examined how therapists' actions related to the verbal disclosure and defensive patterns that followed therapists' interventions within a single therapy hour for 20 patients. At the same time, a new measure, the Psychodynamic Intervention Rating Scale (PIRS), was tested for reliability and construct validity. Results indicated that therapists fit their styles of intervention to patients' levels of distress and functioning. Within the session, patient's emotional elaboration was followed by therapist's defense interpretation, followed by more patient emotional elaboration. Patient elaboration of significance was followed by more transference interpretation, followed by more patient elaboration of significance. Noninterpretive interventions were followed by patient's disclosure of facts, not emotion. Both interpretive intervention process sequences and therapist's use of support predicted posttreatment symptom reduction. The PIRS was shown to have satisfactory reliability and construct validity.

Prediction of complicated grief by positive and negative themes in narratives.

A narrative coding system was employed to investigate the thematic parameters of complicated grief among participants who had recently experienced spousal loss. Two goals guided the research. First, we investigated the prevalence of and interrelationship between positive and negative themes in a narrative interview conducted 6 months into bereavement. The coding system was modeled after Erikson's (1982) scheme of crises solutions across the life span. Second, we examined the relationship of these themes to various symptom measures obtained at 6- and 14 months postloss. Results revealed no systematic relationship between corresponding positive and negative themes. Aggregated positive and negative themes showed significant correlations with 6-month measures of intrusion and avoidance and, as predicted, with various 14-month symptom levels. Regression analyses revealed that positive themes explained significant portions of 14-month symptom variance, even when 6-month symptom scores were controlled. Findings are discussed with regard to conceptualizations of grief as a stress response syndrome, where intrusive processes (e.g., in narration) are of importance.

Interpersonal ambivalence, perceived relationship adjustment, and conjugal loss.

Ambivalence is widely assumed to prolong grief. To examine this hypothesis, the authors developed a measure of ambivalence based on an algorithmic combination of separate positive and negative evaluations of one's spouse. Preliminary construct validity was evidenced in relation to emotional difficulties and to facial expressions of emotion. Bereaved participants, relative to a nonbereaved comparison sample, recollected their relationships as better adjusted but were more ambivalent. Ambivalence about spouses was generally associated with increased distress and poorer perceived health but did not predict long-term grief outcome once initial outcome was controlled. In contrast, initial grief and distress predicted increased ambivalence and decreased Dyadic Adjustment Scale scores at 14 months postloss, regardless of initial scores on these measures. Limitations and implications of the findings are discussed.

Applying an empty-chair monologue paradigm to examine unresolved grief.

In this study the Gestalt empty-chair technique was applied in a research context to assess unresolved grief and its relation to later adjustment. Bereaved individuals who experienced the death of a spouse on average 6 months ago participated in an empty-chair monologue task in which they were instructed to speak to their deceased spouse, imagining that they had one last opportunity to do so. They completed a questionnaire at the end of their monologue speech assessing their affective experience during the monologue. It contained items associated with unresolved grief (e.g., anger, guilt, helplessness, nonacceptance). Near the time of the monologue session, bereaved participants also completed the Beck Depression Inventory (BDI) (Beck and Steer 1987) and the Impact of Event Scale (IES) (Horowitz, Wilner, and Alvarez 1979). At 14 months postloss, bereaved participants again were administered the BDI and IES. As hypothesized, the extent of unresolved grief as assessed by the monologue questionnaire at 6 months postloss was predictive of 14-month postloss symptoms, even when statistically controlling for 6-month postloss symptoms in hierarchical regression analyses.

Diagnostic criteria for complicated grief disorder.

OBJECTIVE: Some prolonged and turbulent grief reactions include symptoms that differ from the DSM-IV criteria for major depressive disorder. The authors investigated a new diagnosis that would include these symptoms. METHOD: They developed observer-based definitions of 30 symptoms noted clinically in previous longitudinal interviews of bereaved persons and then designed a plan to investigate whether any combination of these would serve as criteria for a possible new diagnosis of complicated grief disorder. Using a structured diagnostic interview, they assessed 70 subjects whose spouses had died. Latent class model analyses and signal detection procedures were used to calibrate the data against global clinical ratings and self-report measures of grief-specific distress. RESULTS: Complicated grief disorder was found to be characterized by a smaller set of the assessed symptoms. Subjects elected by an algorithm for these symptoms patterns did not significantly overlap with subjects who received a diagnosis of major depressive disorder. CONCLUSIONS: A new diagnosis of complicated grief disorder may be indicated. Its criteria would include the current experience (more than a year after a loss) of intense intrusive thoughts, pangs of severe emotion, distressing yearnings, feeling excessively alone and empty, excessively avoiding tasks reminiscent of the deceased, unusual sleep disturbances, and maladaptive levels of loss of interest in personal activities.

Configurational analysis for case formulation.

Diagnosis by DSM-IV is seldom sufficient to the task of planning and conducting treatment by psychotherapy. Formulation is vital for the task. I have developed a formulation approach called configurational analysis, and usually employ this tool in my work with individual adult cases. However, in this paper, I have also applied it to an evaluation session of a small, three-person family.

Psychotherapy for histrionic personality disorder.

The author uses a configurational analysis method for case formulation and to establish links between individualized formulation and treatment techniques. A prototype of formulation for the histrionic personality disorder is presented, using theories for formulation about states of mind, defensive control processes, and person schemas. A phase-oriented prototype of a treatment plan is linked to these levels of formulation. The result can provide a guideline for clinicians and a teaching document for trainees.

States of emotional control during psychotherapy.

The authors' objective was to develop a simple and reliable descriptive method for categorizing patient states during psychotherapy. The categories would be based on the degree of apparent control over emotional expressions. Methods involved scoring videotapes of psychotherapy for 5 patients with neurotic-level Axis I disorders. Three judges rated each 30-second segment as predominantly one of these four states: well modulated, overmodulated, undermodulated, or shimmering. Shimmering states combine emotional display with efforts to stifle that expression. The results showed that judges could reliably rate states by the definitions used in this study. This technique can provide a simplified and general approach to observation of degrees of defensive control of emotion of patients in psychotherapy.

Signs of defensive control locate conflicted topics in discourse.

BACKGROUND: Psychodynamic clinicians cite defensive actions observed in evaluation and treatment as a source of important information. Empirical support for such assertions has seldom been based on objective study of recorded psychotherapy. A quantitative study of the association of signs of defensive control with disclosure of conflicted beliefs was undertaken. METHODS: Brief dynamic psychotherapies of two patients with pathological grief reactions were recorded and reviewed by independent judges. Periods of heightened defensive control of verbal and nonverbal communication were quantified using operational definitions. Reliably scored defensive episodes were algorithmically selected by computer programs. The people and topics discussed by patients were independently scored. RESULTS: Highly defensive periods contained disproportionately more frequent instances of patient discourse about people involved in conflict and unresolved topics. CONCLUSIONS: The findings support the psychodynamic hypothesis that observation of defensive behaviors may locate times of communication about conflicted themes.

When avoiding unpleasant emotions might not be such a bad thing: verbal-autonomic response dissociation and midlife conjugal bereavement.

It has been widely assumed that emotional avoidance during bereavement leads to either prolonged grief, delayed grief, or delayed somatic symptoms. To test this view, as well as a contrasting adaptive hypothesis, emotional avoidance was measured 6 months after a conjugal loss as negative verbal-autonomic response dissociation (low self-rated negative emotion coupled with heightened cardiovascular activity) and compared with grief measured at 6 and 14 months. The negative dissociation score evidenced reliability and validity but did not evidence the assumed link to severe grief. Rather, consistent with the adaptive hypothesis, negative dissociation at 6 months was associated with minimal grief symptoms across 14 months. Negative dissociation scores were also linked to initially high levels of somatic symptoms, which dropped to a low level by 14 months. Possible explanations for the initial cost and long-term adaptive quality of emotional avoidance during bereavement, as well as implications and limitations of the findings, are discussed.

Role-relationship models for case formulation.

BACKGROUND: Personality disorders are important because they occur frequently and often complicate psychiatric symptom disorders. They are difficult to diagnose and formulate because unitary core traits and themes are hard to define for individual patients. A multiple-selves approach helps clinicians define core contradictions in belief that are frequently present. METHOD: A configurational system for case formulation was used with an approach of states and person schemas. Transactions and stories involving self and others were observed for recurrent elements of identity, attribution, and action. These elements were systematically arranged as role relationship models for each important state of behavior. Cyclic repetitions of maladaptive interpersonal behavior patterns were then explained in terms of motivations and social events that activate enduring, but erroneous, beliefs. RESULTS: Reliable and valid individualized formulations were derived by means of configurations of role relationship models. Inferring several levels of diverse self and other beliefs clarified the complexity usually found in disorders of personality. CONCLUSIONS: The role relationship models method of formulation is compatible with integrative approaches to treatment planning.

Dysfluency and topic orientation in bereaved individuals: bridging individual and group studies.

Discourse of bereaved individuals talking about the deceased and other topics was examined using computer-based text analyses and judged ratings of verbal behavior for patterns indicating dysfluency and orientation toward topics. Using factor analysis, the discourse structure of low-distress bereaved individuals was compared with that of high-distress bereaved individuals and with that of single bereaved individual both early and late in psychotherapy. Meaningful differences were observed for the distress groups and for the single individual early and late in therapy, and these findings indicate possible quantitative and qualitative means for detecting maladaptive responses to stressors.

Cyclical patterns of states of mind in psychotherapy.

OBJECTIVE: A quantitative study of shifts in states of mind was conducted to demonstrate a clinically useful mode of observation. This mode categorizes observations of a patient's mental state into well-modulated, overmodulated, undermodulated, and shimmering patterns. METHOD: The authors used reliable systems for scoring a patient's state of mind on videotapes of all sessions of her brief psychotherapy and, using separate procedures, scored the topics of discourse. These data were then examined by means of a lagged log-linear sequential analysis for patterns of shifts from one state to another and for concurrent shifts in topics. RESULTS: The findings indicated nonrandom shifts in state. Patterns of shifting from a well-modulated state to alternative states and back again were overrepresented. Such shifts were related to conflictual topics of discourse. CONCLUSIONS: Observing such shifts in mental state may help psychotherapists to formulate the contents of conflict and also to make technical interventions to stabilize optimal states for doing the work of psychotherapy.

Expressive and defensive behavior during discourse on unresolved topics: a single case study of pathological grief.

Both psychodynamic and social-cognitive theoretical domains have control process models of behavior but with different ideas about the purpose and loci of control. This study examines expressive and defensive behaviors associated with different topics of discourse in the time-limited psychotherapy of a woman treated for pathological grief. Conceptually the study is based on a model of defensive control processes that integrates states of mind and person schemas. Theoretically derived measures of discourse topics, verbal and nonverbal defensive behaviors, emotional disclosure, and states of mind were applied to transcripts and videotapes of the entire therapy. Evidence from combined cluster and factor analyses supported the existence of recurring emotionally significant states. Two of these are particularly interesting from a clinical perspective: One, a "shimmering" state of intense emotional expression with concurrent signs of avoidance, was associated with topics identified clinically as stressful, unresolved, and conflictual. The other, a state of more uniformly stifled emotionality, was characteristic of discourse thought of clinically as resistance.