Biomedical subjects

Michael J Minzenberg

Publications and source records attributed to Michael J Minzenberg.

9 recordsLinked to original sources

PubMed2006

The effects of guanfacine on context processing abnormalities in schizotypal personality disorder.

BACKGROUND: The signature of impaired cognition in people with schizotypal personality disorder (SPD) may be centrally related to working memory impairments. Guanfacine, an alpha2A agonist that acts post-synaptically in the prefrontal cortex (PFC), has shown potential for reducing working memory limitations in other populations. This study examined the potential of guanfacine for improving context processing, a feature of working memory, in SPD. METHODS: 29 individuals with SPD entered into a 4-week, randomized parallel-design, double-blind, placebo-controlled trial of guanfacine treatment, followed by a 4-week open-label extension. A modified version of the AX-Continuous Performance Test (AX-CPT) was administered. On this task, evidence of intact context processing includes few BX errors (false cue, correct probe) and higher levels of AY errors (correct cue, false probe). RESULTS: At the end of double-blind treatment, participants treated with guanfacine demonstrated a significant reduction in BX errors and a small but significant increase in AY errors, a pattern that was not seen in the participants treated with placebo. CONCLUSIONS: SPD participants improved in their context processing toward a normal response bias, making fewer BX and more AY errors, after being treated with guanfacine.

Adrenergic alpha-Agonists↗

PubMed2006

Social-emotion recognition in borderline personality disorder.

Borderline personality disorder (BPD) is characterized by interpersonal disturbances, but the neurocognitive aspects of these symptoms are poorly understood. We hypothesized that patients with BPD have impaired perception of emotional expressions, which are related to symptoms of interpersonal dysfunction. To control potential confounding factors, this study excluded subjects with comorbid diagnoses known to be associated with impaired affect perception. We tested 43 outpatients with BPD and 26 healthy controls on emotion recognition tasks (facial, prosodic, and integrated facial/prosodic), nonemotional facial feature recognition, and interpersonal antagonism (Buss-Durkee Hostility Index). Patients with BPD showed normal ability to recognize isolated facial or prosodic emotions but had impaired recognition of emotions in integrated facial/prosodic stimuli, as well as impaired discrimination of nonemotional facial features. In patients with BPD, impaired recognition of integrated emotional stimuli was associated with interpersonal antagonism, particularly suspiciousness and assaultiveness. These results suggest that patients with BPD have deficits in higher order integration of social information, which may be related to some of the more serious symptoms of the disorder.

Adult↗

PubMed2006

Blunted hormone responses to Ipsapirone are associated with trait impulsivity in personality disorder patients.

Impulsive aggression is associated with central serotonergic dysfunction. Animal models particularly implicate the 5-HT(1A) receptor in this behavior. We tested the hypothesis that central 5-HT(1A) receptor function is impaired in impulsive aggressive personality disorder patients. A total of 52 individuals with DSM-III-R personality disorders, all medically healthy adult outpatients without concurrent psychiatric medication treatment, underwent serial plasma cortisol, prolactin, and temperature measurements before and after ipsapirone 20 mg oral administration. Subjects completed self-report measures of impulsivity, hostility, depression and anxiety, and childhood maltreatment. Stepwise regression analysis revealed impulsivity alone among symptom measures to be associated with significantly decreased peak cortisol and prolactin responses. Diagnoses of borderline personality disorder (BPD) and intermittent explosive disorder-revised (IED-R) were associated with significantly increased and decreased cortisol responses, respectively. However, post hoc analyses indicated that impulsivity was significantly negatively correlated with cortisol responses in the BPD group, and may mediate the association of both BPD and IED-R with altered cortisol responses. Temperature response was associated with neither diagnostic nor symptom measures. Neither diagnostic nor dimensional measures of depression or anxiety, nor severity of childhood maltreatment, were significantly associated with cortisol, prolactin, or temperature responses. Impulsivity is related to impaired function at (or downstream to) postsynaptic 5-HT(1A) receptors, and this relationship may be partly responsible for the association of impaired serotonergic function with diagnoses such as BPD and IED-R. In addition, D(2) receptor dysfunction may play a role in impulsivity, whereas 5-HT(1A) cell-body autoreceptor function may be spared in these disorders.

Adult↗

PubMed2006

Adult social attachment disturbance is related to childhood maltreatment and current symptoms in borderline personality disorder.

We characterized borderline personality disorder (BPD) along two fundamental dimensions of adult social attachment and evaluated attachment associations with childhood maltreatment and current symptoms using self-report measures in 40 outpatients with DSM-IV BPD. The BPD group had significantly greater dimensional attachment impairment and rate of fearful attachment type compared with a healthy control group. Among BPD subjects, dimensional attachment-anxiety was specifically associated with sexual abuse, whereas attachment-avoidance was associated with all five maltreatment types. The two attachment dimensions showed divergent associations with current interpersonal problems, impulsivity subtypes and mood symptoms. We conclude that (1) BPD is characterized by adult attachment disturbance; (2) these attachment problems are strongly related to childhood maltreatment, and to current interpersonal problems and clinical symptoms that are considered core features of BPD; and (3) the diverse problems of BPD patients may arise from two basic mechanisms, each tied to a different type of attachment disturbance, developmental history, and clinical outcome.

Adolescent↗

PubMed2006

Catechol-O-methyltransferase Val158Met genotype variation is associated with prefrontal-dependent task performance in schizotypal personality disorder patients and comparison groups.

OBJECTIVE: A single-nucleotide polymorphism of the gene coding for catechol-O-methyltransferase (COMT Val(158)Met) is associated with prefrontal-dependent task performance in schizophrenia. We evaluated the relationship of the COMT genotype with diagnostic status and cognitive performance in schizotypal personality disorder. METHODS: Unmedicated outpatients with schizotypal personality disorder (SPD; n = 67) and non-schizotypal personality disorder (NSPD; n = 154) by DSM-III-R, and normal control (NC; n = 60) participants were genotyped at the COMT Val(158)Met locus. Of these, 98 Caucasians (23 SPD, 52 NSPD and 23 NC) performed a brief neurocognitive battery: Wisconsin Card Sorting Test (WCST), Paced Auditory Serial Addition Test (PASAT), California Verbal Learning Test (CVLT), Visuospatial Working Memory (DOT) and Visual Delayed Recall (Wechsler Memory Scale Visual Reproduction, WMS-VR). RESULTS: Allele distribution was not significantly different in the full sample (by chi(2)) for the SPD group compared with either the NC or combined NC/NSPD groups. In analyses of variance of Caucasian individuals, the SPD group performance met or approached significantly worse performance than NC, NSPD or both groups, on the PASAT, CVLT and WMS-VR. In regression analyses of cognitive performance, the COMT genotype was significantly associated with performance on WCST and PASAT, independent of diagnosis, with the Val/Val genotype associated with the worse performance. CONCLUSIONS: (1) Allelic variation in COMT activity is unrelated to the diagnosis of SPD in this sample. (2) Individuals with SPD exhibit multiple deficits in prefrontal and temporal lobe-dependent tasks. (3) The COMT genotype is related to performance on prefrontal cortex-dependent tasks and may contribute to the deficit in prefrontal-dependent memory processes in SPD as it does in schizophrenia.

Adult↗

PubMed2006

Reduced Self-Referential Source Memory Performance is Associated with Interpersonal Dysfunction in Borderline Personality Disorder.

Source memory is impaired in schizophrenia, and this deficit is related to symptoms of interpersonal antagonism such as suspiciousness and hostility. The present study evaluated source memory in borderline personality disorder (BPD) and its relation to interpersonal antagonism. Forty-one noninpatient adults with BPD according to the DSM-IV and 26 healthy control subjects performed a verbal source memory test requiring completion of sentences with and without emotional content ("Hot" vs. "Cold" sentences). Subjects also completed self-report measures of suspiciousness and interpersonal antagonism (Buss-Durkee Hostility Inventory) and depression (Beck Depression Inventory). The BPD group showed no significant difference from the control group in self-referential source memory, recognition memory, response bias, and performance enhancement for items with emotion content. However, in the BPD group, poorer self-referential source memory was significantly related to Hostility measures including suspiciousness, but not with Depression scores. In contrast, generic item recognition memory was unrelated to Hostility. Heterogeneity in source memory function may be specifically related to some of the hallmark interpersonal disturbances of BPD, independent of the effects of general negative affect or general memory impairment.

Adult↗

PubMed2004

Association of anticholinergic load with impairment of complex attention and memory in schizophrenia.

OBJECTIVE: The authors' goals were 1) to establish a clinically useful standard index of the relative anticholinergic potency of psychiatric medications; 2) to determine which cognitive functions are most affected by the administration of anticholinergic medications to patients with schizophrenia; and 3) to compare in vitro and clinically derived indexes of anticholinergic load in predicting these cognitive impairments. METHOD: One hundred six clinically stable patients with schizophrenia were given a brief neuropsychological battery and evaluated on a standard symptom rating scale. The anticholinergic load associated with their psychiatric medications was estimated by using 1) a pharmacological index, calculated from a compilation of published studies reporting in vitro brain muscarinic receptor antagonism, and 2) a clinical index, based on clinician ratings of the anticholinergic side effects of medications. The authors analyzed the correlations of both indexes with the neuropsychological measures and with summary neuropsychological factor scores. RESULTS: The clinical and pharmacological anticholinergic indexes were highly correlated with each other and showed virtually identical associations with neuropsychological measures. Anticholinergic load was associated with lower scores on measures of attention and declarative memory, including several measures of auditory and visual memory and two tests of complex attention, but was unrelated to intelligence, simple attention, working memory, executive functions, conceptual fluency, or motor speed. CONCLUSIONS: This pattern of cognitive impairment with central cholinergic antagonism is consistent with emerging models of the functional anatomy of ascending forebrain cholinergic subsystems. Both pharmacological and clinical indexes show utility in predicting the effects of anticholinergic load on cognition in schizophrenia. Doses of psychiatric medication within the range of routine pharmacotherapy practice may have clinically significant effects on memory and complex attention in patients with schizophrenia; these effects may contribute as much as one-third to two-thirds of the memory deficit typically seen in patients with schizophrenia.

Adult↗

PubMed2003

Slowed lexical access is uniquely associated with positive and disorganised symptoms in schizophrenia.

INTRODUCTION: This study addressed the relationship of both semantic priming and slowed lexical access to the symptoms of schizophrenia, and evaluated their association with other neurocognitive deficits. METHODS: 57 outpatients with schizophrenia and 20 nonpsychiatric control subjects performed a lexical decision semantic priming task (LDT), and a brief neuropsychological battery. The schizophrenia group was also assessed with an extended Positive and Negative Symptom Scale. RESULTS: As expected, the schizophrenia group had significantly slower reaction times (RTs) than the control group, and poorer performance on most neuropsychological tasks. Both groups exhibited semantic priming effects in both automatic and controlled processing conditions; these effects were not significantly different between groups. RT was unrelated to age, illness duration, GAF scores, or neuroleptic dose; controlled semantic priming effects were related to illness duration only. RT to real word targets (but not to nonwords) on the LDT was significantly correlated with positive and disorganised, but not negative symptoms. The neurocognitive correlates of RT slowing were: full-scale IQ and verbal fluency, but not attention; working memory; episodic memory retrieval; executive function, or manual speed. Both controlled semantic priming effects as well as the difference between controlled and automatic priming effects were related to executive functions in general. Severity of symptoms in the three major symptom groups was generally unassociated with impairment on the neuropsychological battery. The associations of RT slowing to positive and disorganised symptoms remained even after controlling for each of the above clinical and neurocognitive measures. CONCLUSIONS: These findings suggest that in schizophrenia, slowed lexical access is uniquely related to positive and disorganised symptoms. This relationship is not accounted for by more general cognitive deficits, overall illness severity, or generalised effects of symptoms on cognitive function. This relationship may reflect a specific impairment in the access to semantic memory.

Journal Article↗

PubMed2002

Semantic priming in schizophrenia: a review and synthesis.

In this paper, we present a review of semantic priming experiments in schizophrenia. Semantic priming paradigms show utility in assessing the role of deficits in semantic memory network access in the pathology of schizophrenia. The studies are placed in the context of current models of information processing. In this review we include all English-language reports (from peer-reviewed journals) of single-word semantic priming studies involving participants with schizophrenia. The studies to date show schizophrenic patients to exhibit variable semantic priming effects under automatic processing conditions, and consistent impairments under controlled/attentional conditions. We also describe associations with other neurocognitive dysfunction, neurochemical and electrophysiological disturbances, and clinical manifestations (such as thought disorder).

Clinical Trials as Topic↗