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Previous research has suggested that schizotypal personality disorder (SPD), a condition that shares clinical and cognitive features with schizophrenia, may be associated with elevated striatal dopamine functioning; however, there are no published studies of dopamine release within subregions of the striatum in SPD. To characterize dopamine release capacity in striatal subregions and its relation to clinical and cognitive features in SPD. We used positron emission tomography with [11C]raclopride and an amphetamine challenge to measure dopamine D2-receptor availability (binding potential, BPND), and its percent change post-amphetamine (∆BPND) to index amphetamine-induced dopamine release, in subregions of the striatum in 16 SPD and 16 healthy control participants. SPD participants were evaluated with measures of schizotypal symptom severity and working memory. There were no significant group differences in BPND or ∆BPND in any striatal subregion or whole striatum. Among SPD participants, cognitive-perceptual symptoms were associated at trend level with ∆BPND in the ventral striatum, and disorganized symptoms were significantly negatively related to ∆BPND in several striatal subregions. In contrast to previous findings, SPD was not associated with elevated striatal dopamine release. However, in SPD, there was a moderate positive association between ventral striatal dopamine release and severity of cognitive-perceptual symptoms, and negative associations between striatal dopamine release and severity of disorganized symptoms. Future larger scale investigations that allow for the separate examination of subgroups of participants based on clinical presentation will be valuable in further elucidating striatal DA functioning in SPD.

Impaired interpersonal functioning is a core feature of borderline, schizotypal, and avoidant personality disorders characterized by abnormal social information processing; however, pharmacologic treatments targeting social cognition are currently lacking. Oxytocin is a novel treatment for social cognitive abnormalities that has yielded promising preliminary results in the autism spectrum, social anxiety disorders, and schizophrenia. Here, we describe the main components of social cognition and review the biology of the oxytocinergic system and the hypothesized models and mechanisms through which exogenous oxytocin modulates social cognition. We then review the studies on the effect of oxytocin administration on social cognition and their application to the treatment of personality disorders. We also review the preliminary evidence supporting the use of oxytocin as an adjunct to non-pharmacologic interventions. Finally, we describe the main challenges that need to be addressed to be able to use oxytocin effectively in clinical populations.

Abnormal fronto-amygdala circuitry has been implicated in impulsive aggression, a core symptom of borderline personality disorder (BPD). We examined relative glucose metabolic rate (rGMR) at rest and after m-CPP (meta-chloropiperazine) with (18)fluorodeoxyglucose (FDG) with positron emission tomography (PET) in 26 impulsive aggressive (IED)-BPD patients and 24 controls. Brain edges/amygdala were visually traced on MRI scans co-registered to PET scans; rGMR was obtained for ventral and dorsal regions of the amygdala and Brodmann areas within the prefrontal cortex (PFC). Correlation coefficients were calculated between rGMR for dorsal/ventral amygdala regions and PFC. Additionally, amygdala volumes and rGMR were examined in BPD and controls. Correlations PFC/amygdala Placebo: Controls showed significant positive correlations between right orbitofrontal (OFC) and ventral, but not dorsal, amygdala. Patients showed only weak correlations between amygdala and the anterior PFC, with no distinction between dorsal and ventral amygdala. Correlations PFC/amygdala: m-CPP response: Controls showed positive correlations between OFC and amygdala regions, whereas patients showed positive correlations between dorsolateral PFC and amygdala. Group differences between interregional correlational matrices were highly significant. Amygdala volume/metabolism: No group differences were found for amygdala volume, or metabolism in the placebo condition or in response to meta-chloropiperazine (m-CPP). We demonstrated a tight coupling of metabolic activity between right OFC and ventral amygdala in healthy subjects with dorsoventral differences in amygdala circuitry, not present in IED-BPD. We demonstrated no significant differences in amygdala volumes or metabolism between BPD patients and controls.

We previously reported that subjects with a schizophrenia spectrum personality disorder (ie, an odd cluster personality disorder), of which the prototype is schizotypal personality disorder, show cognitive impairment in circumscribed areas (working memory) compared with healthy control subjects, and that amphetamine administration improves working memory in subjects with schizotypal personality disorder. In this larger series, we wanted to determine whether amphetamine treatment ameliorates working memory impairment using three groups: subjects with a schizophrenia spectrum personality disorder (ie, schizotypal, paranoid, or schizoid personality disorder), other (subjects with nonschizophrenia spectrum) personality disorder, and healthy volunteers. We hypothesized that amphetamine treatment would improve cognitive function in domains in which subjects with schizophrenia spectrum personality disorder show impairment compared with healthy volunteers and the other personality disorder group. Overall, amphetamine treatment did not improve performance in any task compared with placebo, and there was no group by drug interaction in the total sample. However, when the sample was restricted to the subjects who showed impairment at baseline, amphetamine treatment improved visuospatial working memory. In the total patient sample, amphetamine treatment reduced negative symptoms, whereas positive symptoms remained unchanged. Amphetamine treatment improves working memory in those subjects with cognitive impairment at baseline, most of whom meet criteria for a schizophrenia spectrum disorder.

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.

Reduced serotonergic activity has been associated with impulsive aggression in personality disordered patients in metabolite and pharmacologic challenge studies. This study used positron emission tomography to explore whether reduced serotonergic function occurs in critical brain regions such as orbital frontal and cingulate cortex that, may play a role in modulating aggression. Six impulsive-aggressive patients and five healthy volunteers were evaluated for changes in regional glucose metabolism after administration of the serotonergic releasing agent d,l-fenfluramine (60 mg, p.o.) or placebo. Volunteers demonstrated increases in orbital frontal and adjacent ventral medial frontal cortex, cingulate, and inferior parietal cortex, whereas impulsive-aggressive patients showed no significant increases in glucose metabolism after fenfluramine in any region. Compared with volunteers, patients showed significantly blunted metabolic responses in orbital frontal, adjacent ventral medial and cingulate cortex, but not in inferior parietal lobe. These results are consistent with reduced serotonergic modulation of orbital frontal, ventral medial frontal, and cingulate cortex in patients with impulsive-aggressive personality disorders.

Pharmacotherapy is used increasingly as a helpful adjunct to psychotherapeutic interventions in the treatment of borderline personality disorder. Clinical trials have been performed to investigate drug treatment of the 3 symptom clusters associated with borderline personality disorder — impulsivity, affective lability and psychotic-like symptoms. Although no single agent ameliorates all the symptoms of this diagnosis, and patients vary considerably in their response to medication, pharmacological strategies for each symptom can be delineated. Impulsivity and aggression can be treated with selective serotonin (5-hydroxy-tryptamine; 5-HT) reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), lithium, β-adrenoceptor blockers or antipsychotics. Affective symptomology has also been found to respond to MAOIs, SSRIs and lithium. Interestingly, patients with borderline personality disorder do not seem to respond to tricyclic antidepressants. As would be expected, antipsychotics are the most effective medications for the treatment of the psychotic symptoms of borderline personality disorder. Various techniques to improve compliance and enhance the treatment alliance with the patient can be suggested, including patient education about the role of the pharmacologist (and therapist) in treatment and about the nature of agents prescribed. In addition, if possible, patients should be allowed to play an active part in the selection of drugs.

Top of pageAbstract To determine if serum TRAb measurements are useful in diagnosis and management of JGD, we studied 48 pts with JGD & 113 controls: 41 adults; 41 children & 31 with Hashimoto's Disease (HD), 9 with ↑ TSH levels. We tested 3 groups of JGD pts, I: active and untreated disease; II: recurrent disease; III: in remission on no therapy. TRAb was measured by displacement of labeled bTSH from porcine thyroid membranes (C1. Endocr. 20:539,1984), and values expressed as % inhibition of tracer TSH binding. No antiidiotypic antibodies were detected. There was no correlation between TRAb and TSH in HD with ↑ elevated TSH. False negative TRAb results occurred in 2 JGD-I (7%) pts and 1 JGD-II (6%) pt; false positive TRAb results occurred in 6 JGD-III (17%) pts, and were not associated with relapse of the disease. In conclusion: Abnormal TRAb values will confirm the diagnosis of JGD in > 90% of pts with hyperthyroidism, and are found in > 90% of JGD pts in relapse. TRAb values are greater at initial diagnosis than during relapse, probably reflecting a shorter duration and less severity of disease during relapse. Abnormal TRAb values during remission may result from TRAb without thyroid stimulation, or the development of co-existing HD.