The 10‐year course of psychosocial functioning among patients with borderline personality disorder and axis II comparison subjects

Zanarini MC, Frankenburg FR, Bradford Reich D, Fitzmaurice G. The 10‐year course of psychosocial functioning among patients with borderline personality disorder and axis II comparison subjects. Objective: The purpose of this study was to determine the 10‐year course of the psychosocial functioning of patients with borderline personality disorder (BPD). Method: The social and vocational functioning of 290 inpatients meeting both the Revised Diagnostic Interview for Borderlines (DIB‐R) and DSM‐III‐R criteria for BPD and 72 axis II comparison subjects were carefully assessed during their index admission. Psychosocial functioning was reassessed using similar methods at five contiguous 2‐year time periods. Results: Borderline patients without good psychosocial functioning at baseline reported difficulty attaining it for the first time. Those who had such functioning at baseline reported difficulty retaining and then regaining it. In addition, over 90% of their poor psychosocial functioning was due to poor vocational but not social performance. Conclusion: Good psychosocial functioning that involves both social and vocational competence is difficult for borderline patients to achieve and maintain over time. In addition, their vocational functioning is substantially more compromised than their social functioning.     

Enhancing the salience of dullness: behavioral and pharmacological strategies to facilitate extinction of drug-cue associations in adolescent rats

Extinction of drug-seeking is an integral part of addiction treatment, and can profoundly reverse or ameliorate the harmful consequences of drug use. These consequences may be the most deleterious during adolescence. The studies presented here build from recent evidence that adolescent rats are more resistant to extinction training than adults, and therefore may require unique treatment strategies. We used unbiased place-conditioning in male rats to show that passive, un-explicit extinction pairings resulted in delayed extinction in 40-day-old adolescents relative to 80-day-old adults. However, explicit-pairing of a previously cocaine-associated context with the absence of drug produces extinction in adolescents as rapidly as in adults. These data suggest that successful extinction of drug-paired associations in adolescents may be facilitated by stronger acquisition of a new (extinction) memory. Drug-paired associations are largely controlled by the prelimbic prefrontal cortex (plPFC) and its influence on the nucleus accumbens (NAc). This pathway mediates the motivational salience attributed to incoming stimuli through the D1 dopamine receptor. D1 receptors on plPFC outputs to the accumbens are transiently overproduced during adolescence. Since D1 receptors are selectively responsive to potent stimuli, we hypothesized that the adolescent plPFC hinders competition between potent drug-paired associations and the subtler, drug-free information necessary for extinction. To harness this unique profile of the adolescent plPFC, we aimed to increase the salience of unrewarded extinction memories by activating plPFC D1 receptors during extinction training. In a second study, extinction of drug-cue associations was facilitated in adolescents by elevating dopamine and norepinephrine in the PFC during extinction training with atomoxetine. In a third study, direct microinjection of the D1 receptor agonist SKF38393 mimicked this effect, also facilitating extinction in adolescent subjects. Furthermore, pharmacological intervention attenuated subsequent drug-primed reinstatement of cocaine-conditioned preferences. We establish a potential direction for distinct strategies to treat this vulnerable population.     

Subtypes of major depression in substance dependence

Aims   This study evaluated features that differentiate subtypes of major depressive episode (MDE) in the context of substance dependence (SD).
Design   Secondary data analysis using pooled data from family-based and case–control genetic studies of SD.
Setting   Community recruitment through academic medical centers.
Participants   A total of 1929 unrelated subjects with alcohol and/or drug dependence.
Measurements   Demographics, diagnostic criteria for psychiatric and substance use disorders and related clinical features were obtained using the Semi-Structured Assessment for Drug Dependence and Alcoholism. We compared four groups: no life-time MDE (no MDE), independent MDE only (I-MDE), substance-induced MDE only (SI-MDE) and both types of MDE.
Findings   Psychiatric measures were better predictors of MDE subtype than substance-related or socio-demographic ones. Subjects with both types of MDE reported more life-time depressive symptoms and comorbid anxiety disorders and were more likely to have attempted suicide than subjects with I-MDE or SI-MDE. Subjects with both types of MDE, like those with I-MDE, were also more likely than subjects with SI-MDE to be alcohol-dependent only than either drug-dependent only or both alcohol- and drug-dependent.
Conclusions   SD individuals with both types of MDE have greater psychiatric severity than those with I-MDE only or SI-MDE only. These and other features that distinguish among the MDE subtypes have important diagnostic and potential therapeutic implications.     

D-serine added to clozapine for the treatment of schizophrenia.

OBJECTIVE: D-Serine is a full agonist at the glycine site on the N-methyl-D-aspartate (NMDA) receptor. Previous administration of D-serine to schizophrenic patients taking nonclozapine antipsychotics improved positive, negative, and cognitive symptoms, whereas the partial agonist D-cycloserine improved negative symptoms of patients taking conventional antipsychotics but worsened symptoms in clozapine-treated patients. To study the difference between full and partial agonists at the NMDA receptor glycine site, the clinical effects of adding D-serine to clozapine were assessed. METHOD: In a 6-week double-blind trial, 20 schizophrenic patients received placebo or D-serine (30 mg/kg per day) in addition to clozapine. Clinical efficacy, side effects, and serum levels of D-serine were determined every other week. RESULTS: The patients exhibited no improvement with D-serine, nor did their symptoms worsen, as previously reported with D-cycloserine. CONCLUSIONS: The results suggest either that clozapine may have an agonistic effect on the NMDA system or that clozapine-treated patients do not respond to D-serine.