Impulsivity, suicidal behavior, and major depression in the personality disorders: Differential correlates with noradrenergic and serotonergic function

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Schizophrenia Spectrum and Personality Disorders

protein and 75.2 pmol/m~ .... a cells in the controls (n = 24) (F = 11.9, p = 0.001; F = 5.2; p = 0.027, respectively). In patients, beta receptor density increased towards the level seen in controls following 4 weeks of adinazolam treatment (n = 10) but was unchanged by placebo (n = 11; F = 3.4, p = 0.08). Isoproterenol-stimulated cAMP production was unchanged in both treatment groups. Other clinical correlations with receptor function will be presented. The results will be discussed with regard to the hypothesis that changes in beta adrenoreceptor function in patients with panic disorder represent adaptive, homeostatic respor.~e to the illness:_

SCHIZOPHRENIA SPECTRUM AND PERSONALITY DISORDERS T h u r s d a y , A p r i l 30, 2 : 0 0 - 4 : 0 0 aM

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16 CHARACTERISTICS OF SCHIZOTYPAL SUBJECTS RELATED TO SCHIZOPHRENIC VERSUS AFFECTIVE PROBANDS: SYMPTOMATOLOGY, CO-MORBIDITY, AND FAMILIAL PSYCHOPATHOLOGY Michael Lyons, Ming Tsuang, Stephen Faraone, William Kremen Boston University, Boston, MA 02115. The diagnosis of schizotypal personality disorder (SPD) originated in genetic studies of schizophrenia. However, since its inception, there have been questions about whether it identifies a heterogenous group, with only some schizotypals having a disorder genetically related to schizophrenia. Related to this issue is a flurly consistent linding that the relatives of affective probands have an elevated risk for ]~PD that is comparable to the risk in the relatives of schizophrenics, in this family study, the rate of defi~,lite SPD did not differ between the interviewed first-degree relatives of schizophrenics (9 of 161) versus affectives (7 of 126) or for deiinite plus probable SPD (23 of 161 versus 22 of 126). There was a trend for $PD relatives of schizophrenics to have more inadequate rapport and fewer illusions than those related to affective probands. Am~,ng definite plus probable SPDs, relatives of schizophrenics had more odd speech and a trend for fewer illusions. Definite SPDs related to schizophrenics had a signilicantly lower rate of co-morbid personality disorders (18% versus 86%); definite plus probable SPDs also differed significantly (32% versus 64%). First-degree relatives (excluding the schizophrenic probands) of the schizophrenia-related SPDs had a significantly lower rate of personality disorders (6.6%) than the SPD relatives (excluding the affective probanti~) of the affective SPDs (43%).

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IMPULSIVITY, SUICIDAL BEHAVIOR, AND MAJOR DEPRESSION IN THE PERSONALITY DISORDERS: DIFFERENTIAL CORRELATES WITH NORADRENERGIC AND SEROTONERGIC FUNCTION Robert L. Trestman, Emil F. Coccaro, Susan Weston, Vivian Mitropoulou, Felice Ramella, Steven Gabriel, Larry J. Siever Mr. Sinai School of Medicine, New York, NY 10029. On the basis of prior work, we hypothesized that (I) central noradrenergic (NA) dysfunction is associated with irritability or overreactivity to the environment, but not with violence per se, and that (2) central serotonergic (5-HT) dysfunction is associated with motoric impulsivity, assaultiveness, and suicidal behavior in personality disorder (PD) patients. Thirty nine patients with DSM-Iil PD from two medical centers

Schizophrenia Spectrum a:.d Personality Disorders

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participated in this extension of a previous study (Coccaro et al, AGP 1989). The growth hormone (GH) response to IV clonidine, a measure of central or-2 NA function, correlated with self-rated measures of irritability in all PD patients: Buss-Durkee Hostiht~ Inventory (BDHI)--lrritability: r := 0.28, p < 0.G7; (BDHI--Verbal Hostility: r = 0.37~ p < 0.03) but not overt violence. (BDHI--Assault: ns) or history of suicidal behavier; and in the male :,:,ubgroup (n = 18). Peripheral plasma NE levels also correlated with these measures in the whole sample of PD patients and in the male subsample. Central 5-HT function was assessed with plasma prolactin response (delta PRL) to fenfluramine (FEN; 60 mg orally), a 5-HT releasing/uptake-inhibiting agent. The delta PRL was inversely correlated in males with several self-rated measures of impulsivity and aggression (n = 32; Barratt Impulsivity Scale (BIS)--Motor Impulsivity: r = - 0. 34, p < 0.03; BDHlwAssault: r = - 0.56, p < 0.001), and both with history of suicide attempts (r = - 0.27, p < 0.07) and the medical lethality of the attempts (r = -0.33, p < 0.03). Present or past history of major depression neither altered nor correlated with any of the above findings. The NA and 5-HT systems may therefore each contribute differentially to aspects of impulsivity and aggression. These findings are discussed in terms of hypothesized dimensions underlying PD diagaos=s.

18 BLUNTED PROLACTIN RESPONSE TO FENFLURAMINE IN BORDERLINE PERSONALITY DISORDER APPEARS INDEPENDENT OF DEPRESSION J.E. Myers, K.M. Malone, G.L. Haas, T.M. Kelly, T. Mieczkowski, D. Abbondanza, J.A. Sweeney, J.J. Mann University of Pittsburgh, Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213. Borderline personality disorder (BPD) has been theorized by some to be an affective spectrum disorder given the high comorbidity with major depression (MDD). This study was designed to distinguish features of BPD from MDD using biologic and clinical variables. We evaluated the prolactin (PRL) response to 5HT indirect agonist (fenfluramine) on 17 inpatients with BPD, I1 of whom had concurrent MDD, and compared them with 24 inpatients with MDD alone. Clinical variables included GAS, age, BPRS scores, history of suicide attempts, suicide lethality rating, Suicide Intent Scale (degree of planning), HAM-D scores, and total lifetime aggression score (Brown-Goodwin Scale). Patients with BPD alone had .~ignificantly lower max PRL (3.2 - 2.1) than BPD with MDD (9.9 ± 7.0) or MDD alone (8.2 - 8.1)', p = 0.04. BPD alone patients were not distinguished from BPD plus MDD on demographic, nr clinic~d variables. These findings support the relationship between decreased 5-tIT function and borderline personality disorder which may be independent of that seen in MDD alone. Supported by MH46745.

19 CORRELATES OF SENSORIMOTOR GATING FAILURES IN SCHIZOPHRENIC SPECTRUM PATIENTS David L. Braff, Mark A. Geyer UCSD School of Medicine, La Jolla CA 92093. Schizophrenic spectrum patients and their family members show deficient CNS mediated gating or inhibition in a number of paradigms. For example, when a weak prepulse slimulus precedes a startling stimulus by 100 msec, the startle response is inhibited or gated in normal subjects and other mammals. This probe of inhibitory function is useful in schizophrenic spectrum patients where neural gating/inhibition is lost. Animal experiments have identified a cascade of cortico-striatai-pallidal-thalamic (CSPT) neurons that modulate startle gating. This finding is escecially useful as the CSPT circuit disruptions that cause a loss of gating include abnormalities (e.g., increased nucleus accumbens dopamine D2 tone) that are observed in some schizophrenic patients. We have now identified a number of factors that are associated with gating failures in schizophrenic spectrum patients. We have tested over 100 schizophrenic spectrum patients and can now report "risk factors" or markers of vulnerability to gating deficits. Specifically, gating, deficits are a~ociated with (I) increased Wisconsin card sort ]~rseverative responses; (2) impairments in thought disorder and deficits in Perry's Rorshach-derived Ego Impairment Index; (3) abnormalities in reaction time set and visual