A Psychobiological

Perspective J.

Larry

A preliminary substrates sonality vide

but growing

ofpersonality, disorders. The

an empirical

chological

point ality

Each

ego

to explore The

from which disorders.

J

Psychiatry

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propose

1991;

from

the

between

and

biological

a psychobiological

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ofgenetic

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model affective I and axis

evidence

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of the

development

to each

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instability, II disorders.

in relation

heuristic,

investigation

M.D.

the existence

impulsivity/aggression, the DSM-III-R axis

an approach

L. Davis,

Disorders

of a psychobiological perspective on the percorrelates ofpersonality disorders can pro-

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authors

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suggesting investigation

base

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Siever,

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a promising

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anxiety/inThe authors

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dimenvantage person-

148:1647-1658)

first

with

and trends, though it is true that nature or what determines them.

individual we can not

-

disspec-

F reu d ( 1 )

F

reud’s observation more than SO years ago reflected his increasing appreciation that innate or “constitutional” differences may bias the character and plasticity of an individual’s adaptational capacities. Such vanations may provide the substrates for the enduring and characteristic patterns of thinking, feeling, and behaving termed “personality” or, if these patterns are sufficiently maladaptive, personality disorders.” The identification of the specific biological mechanisms underlying these predispositions is now increasingly feasible and represents an important step toward developing a more valid nosology and more effective treatments for the personality disorders. In this article, we present a specific heuristic model of psychobiologically based dimensions of personality disorder and evidence pertaining to this model. This model offers a starting point for biological investigation of the personality disorders and is not intended to accommodate all

the complexities of our knowledge of personality disordens from either a biological or a psychological perspective. It offers an opportunity to integrate clinical observations from psychoanalysis

suchand seemingly behaviorism. divergentWe

perspectives will propose

asa

number of implications of this model for the development and clinical treatment of personality disorders. Although some of the proposed implications are speculative, new investigative strategies generated by this model are suggested to test specific hypotheses.

HISTORICAL

BACKGROUND

“

Received July 13, 1990; revision received Feb. March 20, 1991. From the Bronx VA Medical School Service,

of Medicine.

1 16A,

Bronx

Address

reprint

VA Medical

requests

Center,

to Dr.

Bronx,

1 1, 1991; accepted Center, Mt. Sinai Siever,

Psychiatry

NY 10468.

The authors acknowledge the collaborative research efforts of Emil Coccaro, M.D., Robert Trestman, M.D., Jeremy Silverman, Ph.D., Howard Klar, M.D., Andrew Aronson, M.D., Oren Kalus, M.D., Timothy Lawrence, M.D., and many others, which stimulated the writing of this paper. They also thank John Gunderson, M.D., Philip Holzman, Ph.D., S. Charles Schulz, M.D., Marjorie Klein, Ph.D., and Beatrice Hamburg, M.D., for their helpful comments.

Am

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148:12,

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1991

Biological approaches to personality are not new; they date back to the time of Hippocrates (2, 3). Psychoanalysts have long perceived individual differences in the strength of the “drives” and the choice of defense mechanisms. Psychologists such as Eysenck have documented psychometric dimensional factors in normal personality; these factors have been hypothesized to reflect a genetic/biological basis (4-7). Recent developments in the clinical neurosciences as well as in the diagnosis of the personality disorders now enable the direct study of biological factors in the personality disorders. Advances in basic neurobiology have stimulated the development of powerful tools to understand the pathophysiology of the axis I disorders, which are now being applied to the DSM-III-R axis II disorders with promising results. Operationalized diagnostic interviews based on specific diagnostic criteria permit the reliable assessment of the personality disorders and have made them a more accessible target of investigation. Interest in the biology of the personality disorders has

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PSYCHOBIOLOGICAL

PERSPECTIVE

ON

PERSONALITY

also been bolstered by recent developments in our understanding of child development and genetics. Not only does there appear to be a substantial degree of continuity of temperament from infancy through childhood (8, 9), but studies of twins, including twins reared apart, demonstrate a major genetic influence on personality development, greater than has previously been appreciated (1 0, 1 1 ). Although these studies are based on samples unselected for pathology, personality disorder traits also show familial aggregation (12-17) and, in some cases, have been shown to be significantly heritable (18, 19). The demonstration of robust genetic contributions to personality suggests that biological factors mediating these genetic susceptibilities in the context of ongoing environmental influences may be identified.

CORE

PSYCHOBIOLOGICAL

PREDISPOSITION

The psychobiology of personality disorder can be formulated as a dimensional model grounded in the major axis I syndromes. This model affords an opportunity to build on several decades of intensive research into the biology and genetics of the major psychiatric disorders and incorporates the advantages of a dimensional rather than categorical approach to the personality disorders (20). The major classes of the DSM-III-R axis I disorders include the schizophrenic disorders, affective disorders, impulse control disorders, and anxiety disorders. The core features of the schizophrenic, affective, impulse, and anxiety disorders can be conceptualized as reflecting disturbances in fundamental psychobiological dimensions of cognitive/perceptual organization, affective regulation, impulse control, and anxiety modulation. Abnormalities in these dimensions can occur on a continuum on which extreme, discrete symptoms manifest as an axis I disorder. At the other end of the continuum, milder persistent disturbances on one or more of these dimensions might contribute to the development of specific defense mechanisms and adaptational strategies. If these susceptibilities crystallize to define the pervasive, characteristic ways in which an individual behaves across occupational and interpersonal situations, then that individual can be considered to have an axis II disorder. For example, the schizophrenic disorders are characterized by disturbances in cognitive/perceptual organization, which are manifest in thought disorder, psychotic symptoms, and social isolation. More subtle disturbances in cognitive controls may be expressed not only as persistent symptoms reflecting cognitive/perceptual distortions but also as traits of eccentricity, peculiar speech, and social detachment, as observed in schizotypal personality disorder, the prototype of the “odd cluster” diagnoses. The affective disorders are characterized by alterations in the regulation and intensity of mood. The major affective disorders are characterized by relatively sustained, autonomous episodes of mood disturbance. In contrast, more transient, environmentally responsive

1648

affective shifts may interfere with the development of stable relationships and self-image, as in borderline personality disorder. The impulse control disorders are characterized by a diminished capacity to delay or inhibit action, particularly aggressive action. Poor impulse control may result in episodic impulsive/aggressive behaviors associated with axis I disorders such as intermittent explosive disorder, pathological gambling, or kleptomania. When chronic and pervasive, a predisposition to impulsive/aggressive behaviors may result in persistent self-destructive and antisocial behaviors, as in borderline and antisocial personality disorders. A dimension of anxiety/inhibition can be defined as a low threshold for subjective fear and autonomic arousal in anticipation of aversive consequences, often associated with behavioral inhibition. Although discrete episodes of anxiety, compulsive rituals, or phobias can be observed in the axis I anxiety disorders, attempts to cope with a pervasively low threshold for anxiety might contribute to the avoidant, compulsive, and dependent behaviors of the “anxious cluster” diagnoses. Thus, dimensions of personality disorder such as cognitive/perceptual organization, affective instability, impulsivity/aggression, and anxiety/inhibition may be represented as occurring on continua with the phenomenologically corresponding axis I and axis II disorders, and characteristic symptoms, traits, and defenses may be associated with each dimension (table 1). Vanations in severity along each dimension and interactions between dimensions can provide a rich biological vocabulary contributing to the many temperamental styles characteristic of the personality disorders. For cxample, criteria for the “dramatic cluster” disorders indude those which reflect both impulsivity/aggression and affective instability. Impulsivity/aggression without prominent affective instability is more characteristic of antisocial personality disorder, and affective instability without impulsivity/aggression can be observed in cyclothymia and some “anxious cluster” diagnoses. Severe personality disorders such as borderline personality disorder are likely to demonstrate disturbances along several of these dimensions. Although this framework is a heuristic one to facilitate psychobiological investigation, it is congruent with other classification schemata based on psychometric and genetic considerations in defining three to four pnimary dimensions of personality along similar lines (47, 21). For example, anxiety/inhibition, which is also a dimension in Gray’s schema (7), might be expected to correlate with high harm avoidance in Cloninger’s tridimensional system (21 ), and impulsivity/aggression, also identified in Gray’s schema, might be mapped into low harm avoidance and high novelty seeking. Affective instability may be related to high reward dependence in Cloninger’s schema. These other systems, however, represent attempts to define a comprehensive schema of normal personality derived from psychometric studies of nonclinical populations rather than a schema of abnormal personality

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LARRY J. SIEVER AND KENNETH

TABLE 1. Phenomenologically Corresponding Axis I and Axis II Disorders, Vulnerabilities), Defenses, and Coping Strategies of Dimensions of Personality Axis I Disorder

Dimension Cognitive! perceptual

Odd cluster (schizotypal personality disorder)

Impulse

Dramatic

disorders

cluster

derline

and

personality Affective

Major

instability

tive

affecdisor-

ders Anxiety! inhibition

Biological

Schizophrenia

organization

Impulsivity/ aggression

Axis II Disorder

Anxiety disorders

Dramatic

(bor-

antisocial

disorders) cluster

derline

and

(bor-

cholinergic

personality

ing

Preliminary

data

are available

in patients

with personality

ORGANIZATION

Definition The reflects

AmJ

dimension of cognitive/perceptual an individual’s capacity to perceive

Psychiatry

148:12,

December

1991

responses

and Chara cteristic

to

(Core

Defenses and Coping Strategies

Disorganization, psychotic-like symptoms

Social isolation, detachment, guardedness

Readiness to action, irritability/aggression

Externalization, dissociation, enactment, repression Exaggerated

Environmentally responsive,

and yohimbine

Traits

tran-

sient affective shifts Autonomic arous-

tivity,

affec-

“manipu-

lativeness,” “splitting” Avoidant, compul-

al, fearfulness,

sive,

inhibition

ent behaviors

and

depend-

disorder.

derived from studies of patients with severe personality disorders or axis I disorders. Accordingly, these approaches emphasize schizophrenia-related or affectivedisorder-related symptoms less than variations in normal personality. In contrast, the model presented here is designed as a heuristic framework for psychobiological research of the personality disorders using clinical constructs with face validity. The extent of convergence of dimensions of normal and pathological personality disorders remains to be determined. External validity studies in both normal subjects and patients with personality disorders will be required to determine the cxact character of dimensions of personality. The model proposed here represents only a starting point for future studies. The framework proposed here builds on the base of knowledge of the biology of the axis I disorders. Biological measures that have proved useful in investigating the axis I disorders may be evaluated for the corresponding axis II disorders by using both dimensional and categorical assessments of personality disorder. In most cases, the hypotheses generated by such a paradigm remain untested and further research is required to evaluate the commonalities and differences between the axis I and axis II disorders along each dimension. We will review here the available evidence implicating an association of specific biological factors with each of these dimensions and will also discuss the clinical implications of these findings and suggest hypotheses for further research.

COGNITIVE/PERCEPTUAL

challenges,a

responses,

lactate

Indexes,

Characteristic Traits

Indexes

responses to catecholaminergic challengesa Heart rate variability,a orient-

disorder) a

Biological

Eye movement dysfunction,a continuous performance task, backward masking test,a plasma HVA,a CSF HVA,a evoked potential response, VBR CSF SHIAA,a responses to serotonergic challenge, galvanic skin response,a continuous performance task REM latency, responses to

possibly

histrionic personality disorders) Anxious cluster (avoidant

Potential Disorders

L. DAVIS

organization and attend

to important incoming stimuli, process this information in relation to previous experience, and select appropriate response strategies. Disturbances in this dimension will be apparent in defects in the attention/selection processes that organize an individual’s cognitive/perceptual evaluation of and relatedness to his or her environment. The result may be impairment and discomfort in social interactions and a misunderstanding or suspiciousness of others’ motivations. Social isolation may represent the major strategy to cope with defective information processing of social cues. In more severe cases, such individuals may be prone to cognitive/perceptual distortions, amplified by social detachment, which forestalls the possibility of potentially corrective input for reality testing.

Biological

Correlates

The

inclusion of schizotypal personality disorder in was based in part on the demonstrated genetic association between schizophrenia and schizophreniarelated personality traits (22). This relationship has stimulated the biological investigation of schizotypal personality disorder using measures that have been used extensively in investigations of patients with chronic schizophrenia. Tests of attention/information processing have demonstrated abnormalities similar to those of patients with schizophrenia in subjects with schizotypal disordens (23). Eye movement dysfunction has been demonstrated not only in patients with chronic schizophrenia and their relatives (24) but also in schizotypal patients and volunteers (25-27) and has been particularly associated with deficit symptoms in schizotypal patients (23, 26-28). Performance on other tests of visual or auditory attention, such as the backward masking test (23, 29), the continuous performance task (23, 30, 31), and sensory gating tests (23, 32, 33), have also been DSM-III

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reported to be impaired in schizotypal subjects (patients, volunteers, and/or relatives of schizophrenic probands) as well as in schizophrenic patients. These measures also have been associated with deficit symptoms and social withdrawal in schizophrenic patients. Although information processing deficits on some of these tasks have been reported in some studies of patients with affective disorders as well, these abnormalities are more likely to be state-dependent and may be different in character in subjects with affective disorders than they are in schizophrenic subjects (23, 24, 29, 32, 34, 35). These results suggest that schizotypal individuals share an impairment in attention/information processing with patients with chronic schizophrenia which may be associated particularly with the enduring deficit symptoms of the schizophrenia spectrum. Further investigation of this possibility and the specificity of such a relationship is required. In contrast, indexes of dopamine metabolism, such as plasma homovanillic acid (HVA) (36, 37), are associated with psychotic symptoms in schizophrenic patients. Similarly, higher levels of plasma (38) and CSF (34, 39) HVA in preliminary studies of patients with schizotypal personality disorder than in control subjects are correlated specifically with the psychotic-like symptoms of schizotypal personality disorder. Thus, dopaminergic activity could modulate the expression of an underlying genotype for the schizophrenia-related disorders toward or away from severe psychotic symptoms. Given the greater prevalence of schizophrenia-related personality disorders than of chronic schizophrenia itself in the relatives of schizophrenic patients, chronic schizophrenia may represent only the tip of the iceberg of the schizophrenia-related disorders. The cognitive disorganization underlying these disorders might be more likely to manifest itself as schizotypal or even milder, related personality disorder traits. Determination of the exact boundaries of the schizophrenia-related spectrum and whether they extend to include individuals with schizoid and paranoid traits in clinical settings or families of patients with schizophrenia requires further investigation. Treatment

Implications

The implications of a psychobiological model for patients with schizotypal personality disorder are twofold. First, neuroleptics would be expected to benefit the schizotypal patient with psychotic-like symptoms, particularly in periods of decompensation. Indeed, schizotypal psychotic-like symptoms improve with neuroleptic treatment (40, 41 ). Second, the need of schizotypal subjects for “distance,” as a means of managing their limited capacity for interpersonal relatedness and vulnerability to stress, needs to be respected. Such an approach does not preclude acknowledgment and encouragement of the schizotypal individual’s desires for more comfortable social interactions through interpersonal learning in individual psychotherapy or social skills training (42).

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IMPULSIVITY/AGGRESSION

Definition Impulsivity/aggression can be formulated as a low threshold for active responses to internal or external stimuli, i.e., motor disinhibition, manifest as a tendency toward action-oriented and aggressive behavioral strategies. Impulsive/aggressive individuals have difficulty anticipating the effects of their behavior, learning from undesirable consequences of their previous behaviors, and inhibiting or delaying action appropriately. They tend to externalize the source of their difficulties, are prone to the excessive expression of aggression and frustration, and may be less likely to experience guilt or anxiety. A number of the personality disorders of the “dramatic cluster” and borderline personality disorder in particular manifest at least some characteristics related to impulsivity/aggression, although each emphasizes different features of this dimension. For example, in antisocial personality disorder, impulsivity/aggression is manifest in a lack of suppression of aggressive behaviors that defy normal social constraints, such as stealing or lying. In borderline personality disorders, impulsivity/ aggression may be expressed as suicide attempts, angry outbursts, fights, and substance abuse, often in response to a disappointment or frustration in an important relationship. Impulsivity/aggression may also contribute to the exaggerated displays of emotion and lack of tolerance to frustration of the histrionic patient and to the disinhibited rage in response to criticism of the narcissistic patient. Impulsive patients tend to use defenses of repression, dissociation, or enactment to avoid the cxpenience of anxiety. Impulsivity/aggression does not define a single personality disorder but, rather, a dimension of behavior and related defenses that can occur in a range of personality disorders. Indeed, genetic and family history studies suggest a genetic component to antisocial personality disorder, borderline personality disorder, and other “dramatic cluster” diagnoses (1 3, 1 5-1 8). Moreover, these disorders cluster together in families, and the familial aggregation may be better accommodated by a dimension of impulsivity/aggression than by discrete heritable categories (1 5). Further research will be required to determine whether this dimension is best restricted to disinhibited aggression or to a more encompassing motor disinhibition and its relationship to disinhibition in the cognitive domain (e.g., obsessivecompulsive disorder).

Biological

Correlates

A predisposition to impulsive behaviors implies dysfunction of brain systems modulating and inhibiting action and aggressive behaviors in response to environmental stimuli. Studies before the advent of DSM-III posited that greater EEG slow-wave activity and a low threshold for sedation discriminate sociopathic mdi-

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LARRY

viduals from dysthymic individuals, suggesting lower cortical inhibitory function and reduced arousal in the sociopath (5, 43). Impulsive or sociopathic individuals also show less inhibition of motor responses, weaker sympathetic responsiveness, and more rapid habituation in their skin conductance response than other patient groups (5, 44). These psychophysiological and psychomotor differences between impulsive and nonimpulsive personality disorders are consistent with the proposition that impulsive or sociopathic individuals are more likely to respond to important environmental stimuli by motor responses than by an evaluative delay characterized by cortical activation, sympathetic arousal, and an inhibition of motor output. Preclinical studies suggest that the serotonergic system mediates behavioral inhibition. Lesions of the serotonergic system result in a diminished capacity to suppress punished behaviors. The deficit seems to reside in a loss of the capacity to translate the anticipation of punishment into appropriate behavioral inhibition (7, 45). A concomitant of behavioral disinhibition is a pronounced increase in unmodulated aggressive behaviors, e.g., the unrestrained killing of mice in serotonergically lesioned rats (46). A similar diminution of serotonergic function appears to be associated with a disinhibition of impulsive and aggressive behaviors in patients with personality disorders. Indeed, reduced concentrations of the serotonm metabolite S-hydroxyindoleacetic acid (S-HIAA) have been reported in both depressed patients and patients with personality disorders who have attempted suicide (47, 48), in patients with personality disorders displaying violent and aggressive behavior (48), and in violent offenders (49). The prolactin response to the serotonergic releasing agent fenfluramine is lower in patients with borderline personality disorder, suggesting diminished serotonergic function (SO). Diminished serotonergically mediated responses in patients with personality disorders are specifically associated with impulsive/aggressive behaviors, both self-directed (suicide attempts) and other-directed (fights), but not depression, anxiety, or other behavioral traits. In depressed patients, in contrast, diminished prolactin responses to fenfluramine have been reported (SO, 51 but, similar to findings in studies of CSF S-HIAA in depression, have been more specifically associated with suicide attempts than externally directed aggression (SO). Pharmacological agents that enhance serotonergic function may attenuate aggressive acts and suicidal behavior in criminal offenders and psychiatric patients (52, 53). The noradrenergic system may also be involved in the control of impulsive/aggressive behaviors. Higher levels of noradrenergic metabolites have been found in gamblers and are associated with extroversion in gamblers (54) and with sensation-seeking in volunteer subjects (SS). Greater growth hormone responses to the noradrenergic agonist clonidine have also been positively correlated with measures of irritable aggression in a preliminary study of patients with personality disorders (56). Since the noradrenergic system mediates arousal

)

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AND

KENNETH

L. DAVIS

and orientation to the environment, enhanced noradrenergic activity might be expected to increase the likelihood of externally directed aggression. Impaired noradrenergic transmission, on the other hand, would block other-directed aggression. In fact, in animal studies, concomitant lesions of the noradrenergic system prevent the aggression usually associated with serotonergic lesions (57). In clinical studies, reduced noradrenergic function, as for example in major depressive disorders (58), may contribute to the lack of an association between blunted serotonergic activity and externally directed aggression in depressed patients, while the association with self-directed aggression remains intact (SO). The interaction of serotonergic abnormalities with abnormalities in other biological systems may contribute to the differential behavioral correlations with serotonergic abnormalities across the affective, anxiety, schizophrenic, and personality disorders. In the personality disorders, both the noradrenergic and serotonergic systems may be important determinants of impulsive and aggressive behaviors directed toward the self and others.

Treatment

Implications

The concept of an underlying biological contribution to impulsive behaviors raises the possibility that pharmacological interventions might have an impact on the treatment of these disorders. Lithium, which enhances postsynaptic serotonergic receptor function, has indeed been reported to reduce aggressive behaviors in criminal offenders (53). Preliminary trials have found that the serotonin reuptake blocker fluoxetine reduces impulsive behaviors and borderline traits (59). Enhancement of nonadrenergic activity (e.g., by stimulants or antidepressant treatment) may have a negative impact on impulsivity/aggression, while antiadrenergic agents such as propranolol have been reported to reduce aggressive behaviors (60). Pharmacological intervention, by reducing impulsive behaviors, may also facilitate psychological change in psychosocial treatment modalities. If such intervention decreased the tendency of patients with “dramatic clusten” personality disorders to enact their conflicts, they might facilitate insight-oriented psychotherapy. An appreciation by the therapist of the action-oriented proclivities of these patients might enhance an empathic but limit-setting approach to them.

AFFECTIVE

INSTABILITY

Definition Affective instability can be defined as a predisposition to marked, rapidly reversible shifts in affective state that are extremely sensitive to meaningful environmental events which might induce more modest emotional responses in other people, such as separation, frustration of expectations, or criticism. Because the de-

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veloping representations of self and others may be influenced by affective state, an instability in mood may impair an individual’s capacity to maintain a stable selfesteem. Such individuals may develop coping and defense mechanisms to minimize the impact of their affective sensitivity. The character of these defenses may depend on variations in other dimensions. Inhibited, anxious individuals will tend to avoid potentially painful involvements with others. Disinhibited, impulsive individuals may exaggerate their affective responses, using their emotionality to control the behavior of others in order to modulate their own mood and self-esteem. Such individuals often do not perceive their behavior as manipulative but as essential to the maintenance of their affective well-being. Biological

oid dysphonic” patients, who are defined by their pronounced emotional reactivity to losses, respond to the monoamine oxidase inhibitors (MAOIs), which serve to stabilize catecholaminergic function (67). In contrast, neuroendocnine and behavioral responses to noradrenergic challenges in major depressive disorder tend to be blunted (58). These results raise the possibility that instability and hyperresponsiveness of catecholamine function, in contrast to the hyporesponsive catecholamine function associated with the classical affective disorders, may contribute to the affective instability of patients with borderline personality disorder. It is unclear to what extent affective instability might occur in attenuated form in other “dramatic cluster” diagnoses; investigation using biological correlates of affective disorders across personality disorders is called for.

Correlates Treatment

Affective instability is a central criterion for borderline personality disorder. Many patients with borderline personality disorder develop depressive episodes (15-17). Probands with borderline personality disorder and a comorbid major depressive disorder have been reported to have a higher prevalence of affective disorders in their relatives (15, 16). In contrast, affectively unstable personality disorders are more prevalent in the relatives of patients with borderline personality disorden whether or not they carry a comorbid depressive diagnosis (15). These results raise the possibility of a heritable, biologically based trait of affective instability that may be partially related to the major affective disorders. The precise relationship of this trait to the classical affective disorders requires further investigation. Biological data also point to the possibility of a relationship between major depressive disorder and the affective instability of borderline personality disorder (61 ). Although shorter REM latency is characteristic of major depressive disorder, patients with borderline personality disorder also have been reported to demonstrate shorter and more variable REM latencies (61, 62). Enhanced reduction in REM latency in response to the muscaninic agonist arecoline, which has been demonstrated in patients with acute and remitted depression (63), was observed in a preliminary study of patients with borderline personality disorder as well (64), raising the possibility that greater cholinergic responsiveness may also contribute to affective symptoms in affectively unstable personality disorders. In contrast, classic state-dependent correlates of major depressive disorder, such as the dexamethasone suppression test, have failed to consistently distinguish patients with borderline personality disorder from patients with other personality disorders (65). Hyperresponsiveness of the noradrenergic system also may be associated with affective instability. Patients with borderline personality disorder, particularly those with comorbid schizotypal personality disorder, may demonstrate greater behavioral responses to the catecholamine-releasing agent amphetamine (66). The affective sensitivity and addictive behaviors of “hyster-

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Implications

Agents that stabilize catecholaminergic function and possibly those which antagonize cholinergic function may be helpful for both the discrete depressive episodes as well as the affective instability of the patient with borderline personality disorder. MAOIs such as phenelzine have been demonstrated to be effective for borderline personality disorder (68), for atypical depressive episodes often observed in patients with personality disorders, and for the rejection sensitivity of hysteroid dysphonia (67). The emotional instability of affectively unstable personality disorders has also been reported to be responsive to lithium carbonate (69) and carbamazepine (70), both of which may stabilize neurotransmitter function. Since no mechanism has yet been convincingly established for the affective instability of the personality disorders, more informed pharmacological treatments await further investigation. Affective lability may have long-term consequences for self-esteem and the capacity to relate to others that are not easily reversed by pharmacological intervention. Psychotherapeutic strategies (71 ) might permit modification of deeply ingrained, maladaptive interactional patterns, originally developed as strategies to modulate unstable affective states.

ANXIETY/INHIBITION

Definition Anxiety/inhibition may be defined as the subjective and physiological concomitants of anticipation of future danger or aversive consequences of current behavior, e.g., punishment (7). Pathological anxiety may be based on an excessive sensitivity to punishment. The anxious individual is thus more ready to interpret environmental events as threatening and manifests an excessive reaction to stimuli that others might find relatively innocuous. The reaction to the perceived threatening events is characterized by heightened arousal and a transient inhibition of motor responsiveness. When the anxious individual acts, it is

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LARRY

often in the direction of avoidance of or withdrawal from the environment. A number of the DSM-III-R personality disorders, particularly those of the “anxious” cluster, are characterized by behaviors that may be related to maladaptive attempts to ward off anxiety. For example, in avoidant personality disorder the anxiety associated with the anticipation of rejection is forestalled by avoiding relationships that might culminate in the experience of disappointment. Obsessive-compulsive personality disorder is marked by an excessive need for order to reduce anxiety related to uncertainty regarding future consequences of behavior. Dependent personality disorder is characterized by a pervasive pattern of submissive behavior associated with anxiety regarding initiating activity and fear of disapproval and abandonment. Anxiety regarding the direct cxpression of anger is considered central to the passive resistance and procrastination of passive-aggressive personality disorder. Individuals with any of these disorders can be viewed as having developed behavioral patterns determined in part by a need to manage exaggerated anxiety responses, although the empirical justification for each of these disorders and their association with an underlying dimension of anxiety/inhibition require further investigation. Biological

Correlates

The “anxious cluster” of personality disorders has perhaps the least well-documented relationship to the axis I anxiety disorders. Family studies have yet to be undertaken in patients with “anxious cluster” personality disorders to determine whether they demonstrate familial aggregation and whether they are familially related to the anxiety disorders. However, biological factors have been implicated in the pathophysiology of anxiety symptoms in the personality disorders. Anxious/inhibited individuals demonstrate higher tonic 1evels of cortical arousal and sympathetic arousal, lower sedation thresholds, and diminished habituation to novel stimuli (5, 7, 9, 43). Hypotheses of altered noradrenergic, ‘y-aminobutynic acid (GABA)-minergic, or chemoreceptor function have been suggested for the axis I disorders but have not yet been actively investigated in the “anxious cluster” disorders Clinical

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OF THE

AND

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L. DAVIS

KENNETH

BETWEEN

AXIS

I

There has been a tendency for psychiatrists to regard biological factors as key determinants of the pathogenesis of the axis I disorders and psychosocial developmental factors as key determinants of the pathogenesis of the axis II disorders (65, 72). Both axis I and axis II disorders, however, may represent manifestations of the interaction between the environment and underlying genetic predispositions. Genetic studies of the axis I disorders raise the possibility that corresponding axis I and II disorders may be related along a continuum, as, for example, in the schizophrenia spectrum disorders. Although less evidence exists for anxiety/inhibition, affective, and impulsiviry/aggression spectrum disorders, these possibilities invite systematic investigation. Genetic susceptibilities to, for example, cognitive disorganization can be expressed in enduring personality traits that either directly reflect the “core” predisposition (e.g., eccentric appearance, odd speech) or represent adaptations to the “core” vulnerability (e.g., social isolation) to forestall emergence of psychotic symptoms. When these adaptations fail, the genetic vulnerability can be expressed as symptomatic episodes (e.g., a schizophreniform episode) in response to stress, accounting for the high comorbidiry of axis I and axis II disorders (65). This model has an important nosological implication, namely, that although the division between axis I and axis II may be valuable from a clinical point of view, the pathophysiology of psychiatric disorders may transcend this division. Current controversies in the formulation of DSM-IV revolve around the appropriate placement of disorders (such as schizotypal personality disorder, dysthymia, and social phobia/avoidant personality disorder) that represent enduring characteristics, compatible with the axis II disorders, but are phenomenologically and biologically linked with their corresponding axis I disorders. These nosological ambiguities may reflect the fact that disorders with a similan underlying pathophysiology may present as axis I and/or axis II conditions. A dimensional or “spectrum” approach that transcends the two axes should be considered when sufficient data are available for future psychiatric diagnostic systems.

IMPLICATIONS OF A DIMENSIONAL FOR DEVELOPMENT

Implications

Lacking a specific biology for anxiety-related personality disorders, there can be no specific implications for psychopharmacological intervention, although antianxiety medications may aid in the management of the more anxiety-related symptoms of these patients. These patients may be more amenable than impulsive or schizotypal patients with personality disorders to psychodynamic psychotherapy aimed at examination of conflicts underlying defensive behavioral patterns or behavior therapy aimed at reducing overt anxiety.

Am

IMPLICATIONS AND AXIS II

J. SIEVER

APPROACH

A dimensional

psychobiological approach to personalbe useful in generating testable hypotheses on the ways innate differences influence the developing child’s experience of and strategies to cope with his or her environment. For example, the impulsive child might tend toward action as a response to internal needs or distress, while the anxious/inhibited child will more likely take a cautious approach to initiating activity. The ways in which these strategies are molded into the enduring copity may

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ing patterns of adult personality will depend in part on the responses of important caretaking figures. Often parents focus on and identify with characteristics of the child that represent either unwanted vulnerabilities (e.g., impulsivity/aggression, anxiety/inhibition) or strengths (e.g., motor skills, intelligence). The nature of the parents’ attnibutions ofand/or identification with the child as a function of both parents’ and child’s predispositions and defensive styles may be important in determining how the child’s vulnerabilities unfold (3, 73). For example, a mother struggling with her own vulnerability to cognitive disorganization may find it particularly difficult to interact with an infant with impaired psychomotor coordination and may thus experience the child as difficult, while an unusually empathic mother may help to compensate for an underlying neurointegrative impairment. An anxious parent with a strong need to deny or control aggression may react to an active, impulsive infant by excessively constraining the child’s activity and labeling the child as destructive or “out of control.” In contrast, a more action-oriented parent may indulge the aggressiveness of the developing child, who, if the parent is too permissive, may fail to internalize social norms appropriately. Thus, the ultimate adaptiveness of the adult personality may depend on the “goodness of fit” between the child’s predispositions and vulnerabilities and the caretakers’ resources and demands. Individual differences along these dimensions may also influence the way in which the developing child expeniences and begins to internally represent his or her environment. By the age of 2 months infants may be able to retain representations oftheir environment; by 10 months they can react to “mismatches” from expectations of the mother. These prototypical representations form the basis for more differentiated internal representations of self and others that provide the expectational set the individual brings to interpersonal interactions (74). Individual psychobiological differences in intensity and regulation of affects, impulsivity/aggression, anxiety/inhibition, and cognitive/perceptual organization might influence the developing child’s mode of representing the world around him or her. The following examples of the emergence of specific personality traits and defenses associated with the proposed core dimensions are presented to illustrate the utility of the psychobiological perspective for development. These examples are presented in the context of established processes of normal development that may be influenced by variations along each psychobiological dimension. Although some of these considerations are speculative, each generates testable hypotheses that stimulate the investigation of the relationship between the biology underlying these dimensions and personality psychopathology. Cognitive/Perceptual

the

What might dimension

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of a vulnerability organization?

in In

the earliest stages of development, infants must learn to organize their experience and engage caretakers in dyadic relationships (74-76). Their interactions are grounded in rhythmic reciprocal facial expressions, head and body movements, and vocalizations; these become entrained or temporally matched between the mother and the child. Frame-by-frame film analyses of these interactions reveal “interlocking” behaviors between mother and child that are synchronized on the order of fractions of a second (76, 77). This reciprocal engagement appears to form the template for later empathy and interpersonal rapport. The successful mutual engagement of mother and infant depends on the developing child’s capacity to screen and respond appropniately to the mother’s signals as well as the mother’s capacity to attune to the infant’s expressive behavior. An altered capacity to respond smoothly and appropriately to maternal cues grounded in an underlying disturbance in cognitive/perceptual organization could easily impair the development of synchronous, mutually satisfying relationships, as has been documented for preterm infants (77). Impaired information processing and ensuing misrepresentation of the environment might also result in less coherent representations of the environment, less empathy and rapport, and erratically inappropriate or “odd” behavior, as observed in schizoid children and the offspring of schizophrenic parents (31,78). Indeed, neurological dysfunction and psychomotor incoordination have been documented to be greater in the high-risk infant offspring of schizophrenic parents, a higher than expected proportion of whom later develop schizotypal personality disorder (79). Attentional abnormalities have also been demonstrated in the offspring of schizophrenic patients and are associated with social detachment (3 1 ). The impact of the neurointegrative impairment requires more explicit investigation in longitudinal “high-risk” studies, but these observations suggest that interpersonal as well as cognitive development may be sensitively affected. Affective

Instability

Individual differences in affective responsiveness can be observed in children (8) and have been associated with at least one biological variable-greater adrenocortical responsiveness-in both adults and newborns (80, 81 ). In primates, marked individual differences in both behavioral and psychobiological reactions to maternal separation that appear to have a substantial genetic component have been demonstrated in longitudinal studies of the rhesus monkey and have been associated with altered adrenocortical and catecholaminergic functioning (82). How might a propensity for less modulation or instability of affective states influence the process of affective differentiation in the developing child? The progressive differentiation and regulation of affective states is an important concomitant of personality development. Even in beginning infancy, individual differences be-

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tween infants can be observed in the discreteness and organization of sleep states (REM and non-REM) and waking states of alert arousal (83). The infant’s affective states, signaled by crying, smiling, etc., provide cues to the mother of changes in the infant’s internal or cxternal milieu, and their recurrence provides an organizing framework for the interaction between child and caretaker. As the child matures, the regulation and cxpression of affective states continue to play a major role in shaping interactions with parents. Affective states may also powerfully color the way in which the world is experienced, encoded internally, and retrieved from memory. Thus, the way in which developing children perceive themselves in relation to others may depend in part on their affective state, analogous to “state-dependent” learning (84). For example, when frustrated and angry, children may perceive themselves and/or their caretakers as bad, while euphoric, excited states may be associated with feelings of omnipotence. Affectively unstable children might be expected to be more sensitive to transient frustrations and separations throughout their development, thus impairing their mastery of these inevitable concomitants of normal development and distorting their self-image and affective perception of others. They may attempt to avoid the dysphoria of separation by clinging to the mother, interfening with the normal development of autonomy, or attempting to secure her continued presence by displays of distress or “tantrums” that take on a “manipulative” quality. Their appraisal of themselves and others may be powerfully influenced by intense, recurrent dysphoric feelings, so that they may tend to experience themselves in the context of the negative feelings of separation as “defective” and their caretakers as abandoning or frustrating (71 ). Wide oscillations in affect might impair continuity in the sense of self and others. Highly polarized dissociated affective states may promote “splitting”-the defensive separation of aggressively charged representations from more idealized, positively charged images (85). The underlying affective lability and ensuing alterations in representations of self and others may ultimately manifest themselves as the affective and relational instability of the adult patient with borderline or histrionic personality disorder. Impulsivity/Aggression Marked individual differences in aggression that cxhibit longitudinal stability are present by the age of 3 (86). Children also show variation along a dimension of reflectiveness versus impulsivity/aggression in their approach to problem solving and their ability to moniton their own behaviors (87), particularly those behavions which are prohibited. How might the capacity to inhibit impulsivity/aggression influence growing children’s mastery of their motor responses to their environment as well as their evolving experience of self in relation to others? Increased motor activity and aggression in response to frustration in the child may engender anxiety and disapproval in parents,

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contributing to a negative self-perception. A relative insensitivity to the prospect of punishment and an associated failure to inhibit aggressive behaviors that result in punishment might also be expected to interfere with the normal internalization of prohibitions against such behaviors. Impairment of the conscience or “superego” would be a likely consequence of the impulsive diathesis that might be expressed as “superego lacunae” (88) (as in the sociopath) or as primitive, harsh forerunners of the mature superego (as in the patient with borderline personality disorder) (85). Anxiety/Inhibition Stable, individual differences between children have been clearly documented for the dimension of anxiety/ inhibition. Psychobiological correlates of this dimension include the greater sympathetic nervous system activity and adrenocortical responsiveness associated with anxiety disorders. These differences may be detected even in infancy in regulation of heart rate and arousal (9). Offspring of patients with panic disorder and/or agoraphobia are more likely to manifest inhibition than offspring of control subjects (89). Longitudinal studies could be designed to test the hypothesis that these inhibited children will develop personality disorders of the “anxious cluster” with higher than expected frequency. Mastery of anxiety is required for the child to venture out beyond familiar and comfortable surroundings and explore the environment. How would children with a very low threshold for anxiety meet this challenge? Such children would tend to be shy, inhibited, and fearful and would experience difficulty in forming new relationships or mastering new situations. As a result, they may be more dependent on familiar caretakers and avoid novel situations. They might also be more apprehensive of potential negative consequences of their behaviors and be less able to arrive at action-oriented solutions to interpersonal conflicts on dilemmas. The inhibition could interfere with their learning the more realistic and often beneficial outcomes of more assertive behaviors. Fearful children may be more likely to expenience anxiety and inhibition in potentially conflictual situations involving the expression of aggression such as competitive activities with peers. Accordingly, they could tend to develop avoidant, dependent, or compulsive traits as long-term strategies to forestall the dysphonic experience of anxiety.

IMPLICATIONS

FOR

FUTURE

INVESTIGATION

Although this psychobiological dimensional model of personality disorders includes some speculative considerations, such a schema nevertheless suggests a number of useful strategies that might test the following hypotheses. Hypothesis 1 : A dimensional schema cuts across the personality disorders but provides a superior organiz-

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ing principle and closer association with external validators than a simple categorical approach. It provides a link between the axis I disorders and their related axis II disorders. This hypothesis could be tested in patients with DSM-III-R personality disorders by evaluating specific dimensions of psychopathology; specific external validators such as family history, biological comelates, treatment response, and clinical course; and the relationship of these disorders to the analogous axis I disorders. Hypothesis 2: Cognitive/perceptual organization is a dimension that spans a continuum from schizophrenia to milder forms of schizoid personality disorder. These disorders are genetically related and characterized by alterations in biological tests of higher cortical organization or information processing. Psychotic-like symptoms are associated with abnormalities in dopaminergic function. These hypotheses can be tested by using both genetic and biological strategies in schizophrenic and schizotypal patients, their relatives, and “high risk” subjects. Hypothesis 3: Impulsivity/aggression is a genetically transmitted dimension associated with reductions in senotonergic activity. It may be associated with the impulsive personality disorders or the axis I impulse disordens. If this hypothesis is proved correct, family studies should demonstrate a coaggregation of impulsiviry/aggression and indexes of reduced senotonengic function. Impulsive/aggressive individuals should show reductions in symptoms with serotonergic agents. Hypothesis 4: Affective instability is a genetically transmitted dimension that may be related to abnonmalities in cholinergic and catecholaminengic function. This hypothesis predicts that patients with personality disorders and their relatives with affective instability will show greater responses to cholinergic and adnenengic challenges. Hypothesis 5: Anxiety/inhibition is a dimension of personality disorder genetically related to the axis I anxiety disorders. As yet, no biological correlates are clear candidates for abnormalities in this system, but the GABAminergic and nonadnenergic systems deserve exploration. Investigations of these hypotheses will undoubtedly generate more specific hypotheses regarding the relationship of these dimensions to specific constellations of behaviors and defenses and their underlying biological mechanisms. The psychobiological approach, without being reductionistic, may provide a heuristic bridge between observable behavioral and psychological phenomena and the molecular mechanisms that are increasingly implicated as substrates of psychopathology.

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