CLINICAL CHALLENGE

Editor: Joseph B. Stoklosa, MD

Idiom Use in a Young Man with Schizophrenia and Prominent Sexual Delusions Sarah K. Fineberg, MD, PhD, Adam Mecca, MD, PhD, Benjamin A. Lerner, AB, Oscar F. Hills, MD, Philip R. Corlett, PhD, and Mark Viron, MD Keywords: delusions, language, metaphor, psychosis, social cognition

CASE HISTORY Presenting Problem Mr. L is a 25-year-old single, obese, Caucasian man who presented to our state psychiatric hospital from the outpatient early psychosis service. His family and treatment team had become increasingly concerned about him over the prior few weeks as he had increased both his seemingly indiscriminant sexual propositions to others and his wandering away from home. History of Present Illness Mr. L first came to psychiatric attention at age 19 when he was hospitalized for disorganized and threatening behavior toward his family, including destruction of property at home. He was hospitalized twice that month, and symptoms improved with risperidone (oral, then long-acting injectable), valproate (500 mg daily), and lorazepam (1 mg twice daily). He returned home and was well enough to continue career training. He had a second episode of acute psychosis two years later in the context of a change back to oral medication (and likely decreased adherence to medication regimen). Symptoms included religious and persecutory delusions, disorganized behavior, and auditory hallucinations. He reported ideas of reference, such as God playing songs for him on the radio. He was quite agitated, threatening his mother and breaking a glass door. He was hospitalized twice in six months. A four-month trial of 25 mg fluphenazine From the Department of Psychiatry (Drs. Fineberg, Mecca, Hills, and Corlett), Yale School of Medicine (Mr. Lerner); Western New England Institute of Psychoanalysis, New Haven, CT (Dr. Hills); Harvard Medical School and Massachusetts Mental Health Center, Boston, MA (Dr. Viron). Supported by National Institute of Mental Health grant no. 5T32MH019961 (Dr. Fineberg), Connecticut State Department of Mental Health and Addiction Services (Drs. Fineberg and Corlett), International Mental Health Research Organization/Janssen Rising Star Translational Research Award (Dr. Corlett), and Clinical and Translational Science Award grant no. UL1 TR000142 from the National Center for Research Resources and the National Center for Advancing Translational Science (Dr. Corlett). Correspondence: Sarah K. Fineberg, MD, Clinical Neuroscience Research Unit, 3rd floor CMHC, 34 Park St., New Haven CT 06511. © 2014 President and Fellows of Harvard College DOI: 10.1097/HRP.0000000000000053

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decanoate was of little benefit, but clozapine 200 mg daily did reduce symptoms. His third episode occurred two years later with unclear precipitant. Mr. L became agitated and paranoid, shouting “I’m being tricked!” in the streets, leading to police involvement. He began wearing ear plugs to reduce distress from voices. Clozapine was increased to 375 mg, and visiting nurse services were added to help with treatment adherence (one suspected reason for worsening symptoms). Clozapine was decreased to 200 mg, however, after he developed severe constipation. At this point, Mr. L began to report to family and the clinical team that he believed all his current problems stemmed from an unconsummated sexual encounter with another boy when Mr. L was 14: “that was the cause of my problems.” He began to make sexual propositions (requests for specific sex acts) to various people he knew, including his outpatient clinician and his sister’s boyfriend. He would at times kneel down in front of someone as he made a suggestion, but he never touched or tried to get too close to anyone. Many of these propositions were made to men, but he also approached women. He told us he was engaging in this behavior in an effort to solve his “problems.” Both his family and outpatient team agreed that he needed to return to the hospital for medication change and safety. He had now begun to proposition strangers, and family feared that in their neighborhood an indiscriminant proposition could result in an assault or in harassment charges. Past Psychiatric History Mr. L’s mother reported that he met developmental milestones on time, though nocturnal enuresis did persist into elementary school, and he had a brief psychiatric treatment, after which symptoms resolved. He did well in school until high school, when his grades declined and he became more withdrawn. His mother initially attributed these changes to school bullying and marijuana use. He graduated from a trade high school carpentry program, aiming to join a trade union as his father had. Hospital Course Mr. L has spent the last year on our inpatient unit and has had a complicated course of illness. He spent time playing pool, pacing the unit, and making trips with staff to the Volume 22 • Number 5 • September/October 2014

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Idiom Use in a Young Man with Schizophrenia

Chinese restaurant across the street. Though his clinicians fell into these routines with him, many of us were left with a feeling of persistent distance over his long inpatient stay—with a sense that we were not coming to know him much better. He was continued on clozapine, valproate, and lorazepam. Clozapine levels were initially low due to nonadherence (Mr. L had been spitting out the medication; in discussion, he seemed unable to describe his motivation in doing so). When he began swallowing the clozapine, levels rose (to nearly 1000 ng/mL), and he seemed to gradually but slowly improve, with fewer episodes of agitation, disorganization, and sexual invitations to staff and strangers. After a couple of months, however, his improvement plateaued, with many residual symptoms. Mr. L continued to be isolative, and conversation was frequently interrupted by thought blocking and by his perseverative focus on delusional content (still almost singly focused on the need for sexual experience with another person to solve his psychiatric problems). He continued to report intermittent auditory hallucinations but did not elaborate on their content. Also, his overall level of function seemed to have declined, with little independent initiative and the return of nocturnal (and sometimes daytime) enuresis. He would often not change clothes or bed sheets after these episodes unless prompted. It now seemed unlikely that he would work independently, and it was hard to imagine him even minimally managing things that he had been able to do in the past, such as attending high school. Nonliteral Language It was at this point that we began to notice that at quiet times on the unit, especially in the early evening, Mr. L would seek out nurse and physician staff members to talk. He would ask about discharge planning and express distress about his lengthy hospital stay. When we engaged him on this or other topics, however, we often noticed that, after a few minutes of linear, logical back-and-forth, he would respond by suddenly blurting out nonliteral language (often proverbs or idioms). In response to a question or request for elaboration, he would say, for example, “Puzzles, they’re puzzling,” “My life is going down the drain,” “Why did the chicken cross the road?” He would seem unable to elaborate, often walking away if we asked for clarification. Sometimes, we would make an effort to explain: when asked about having said “Who’s on first?” he responded, “It’s a joke. It’s America’s pastime.” We wondered if some of these phrases were attempts at sexual innuendo. He would only infrequently—and only when especially distressed—refer to literal sexual acts in conversation; instead, he would use phrases like, “performing a ritual” or “going to the movies.” Nursing staff also noticed that he would sometimes approach them blurting out something urgent-sounding in a whisper, and then claim he had not said anything at all. These episodes, in particular, were remarkable to us, as despite appearing to be efforts on Mr. L’s part to communicate and connect, staff were often left feeling confused and alienated.* Harvard Review of Psychiatry

QUESTIONS TO THE CONSULTANTS 1. This patient was held in hospital for many months due to concerns about his safety once he was discharged back to the early psychosis service, which does some case management but does not include outreach care or assertive community treatment. How do you go about addressing inappropriate sexual behavior in the context of delusions? Also, what are some issues when balancing patient autonomy and safety for self/others as we plan for discharge? 2. This patient would blurt out nonliteral language to staff most days in the early evening. By the end of his hospital stay, he would also sometimes (every one or two weeks) become quite disorganized around 5 p.m.—but not at other times of day. How might we think about the use of nonliteral language, such as metaphor, in people with schizophrenia? Is this an effort to facilitate or block communication? Is it simply a case of loosening associations? Does the time of day or association with increased disorganization in the afternoon give any clue to the process at work? 3. It seems that nonliteral speech could function in various ways for this patient. Used as a way to discuss difficult material in veiled form (a euphemism), it may serve as a coping mechanism (balancing pressure to talk about his delusion versus social norms). That could suggest that he has some insight into the way that other people think or feel about his delusion. Alternatively, perhaps what is happening is simply the loosening of associations: not holding onto the literal forms in most linear discourse, or grasping for a familiar phrase (a conventional metaphor or word association) when feeling unmoored. We also have wondered if these nonliteral expressions are simply stop signs. It was difficult for us to persist in the conversation when faced with a sudden, unexplained, blurted idiom—which may have been a way of saying he had had enough. How might nonliteral language (in particular, familiar sayings) interact with social isolation or social dysfunction in schizophrenia? Oscar F. Hills, MD These days, consulting a psychoanalyst in a case of treatmentresistant schizophrenia is seldom a clinician’s first thought.1 Stereotypes of patients, clinicians, and psychoanalysts themselves increase reluctance, as does the current move of health care practices away from the psychodynamic framework for treating severe mental illness. Further, no one, not even a psychoanalyst, believes that either psychoanalysis or the dynamic therapies are effective primary treatments for schizophrenia. * The case history was prepared by Sarah K. Fineberg, MD, PhD, Adam Mecca, MD, PhD, and Benjamin A. Lerner, AB.

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Most mental health care providers are aware, however, that a small number of people suffering from schizophrenia have been able to make advantageous use of these therapies to help themselves participate in clozapine treatment, clarify their own motivations and conflicts, and develop autonomous solutions to living.2 The odds that Mr. L is one of these people are low, of course, based on numbers alone. But Mr. L’s yearlong hospitalization reminds us that our patients do not always take easily to the methods of quotidian behavioral health care and that under such conditions a consultation with the local psychoanalyst, especially concerning the complexities of a patient’s affect and thought content—our stock in trade—might help free up a potentially stagnating treatment. In conducting a classical psychoanalysis, we ask the analysand to “free associate” without censorship, and we often use the couch, aiming to make the procedure all about utterances.3 We focus our attention on such questions as the following: What is the analysand saying? What does the analysand mean? And why is the analysand saying that, of all things? Extensive thinking about these types of questions is embedded in almost twelve decades of clinical wisdom in the psychoanalytic literature. And, of course, pondering the “use of idiom” in particular—which is part of the title of this Clinical Challenge—raises similar questions as to what Mr. L might be trying to get across to his caregivers, in his own way. Why his own way is what it is, is of immense neurobiologic and psycholinguistic interest, by the way, and not only because of its amenability to the psychoanalytic exploration of the more abstract phenomena of psychic continuity, meaning, and forms of relatedness. In order to mitigate unhelpful stereotypes, we might recall that the psychoanalytic model has at its core the unconscious.4,5 Over as many as eight million years of hominin evolution, consciousness, if present at all, bore little resemblance to the capacity for representation and situational awareness that we saw emerge forty to seventy thousand years ago and that has since then accompanied our capacity to change the face of the world in a staggeringly short period.6 In spite of our explosive evolutionary cognitive gains, one might say that eight million years’ worth of what it is to be human remains nonconscious.7 Freud’s unconscious, the dynamic unconscious, bears a striking resemblance to the evolutionary nonconscious, but its contents can find their way into consciousness, at which point they bear a more striking resemblance to thoughts. Psychoanalysis, with its psychodynamics, is the communicative-level science of the unconscious,8 fraught with epistemological peril as it may be, and it is human motivation that lies outside of awareness that we seek to address effectively through its techniques.9 One tenet is that conflict-laden thought content is held unconscious dynamically by defense mechanisms, sacrificing the recognition of some portion of reality in favor of 308

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fantasy that allows for the mobilization of less painful affects.10,11 One common defensive cluster gives rise to “onecause” or “one-solution” forms of thought about one’s own development or lack thereof. In Mr. L’s case, a boyhood sexual encounter of some kind is the “cause” of his “problems,” and another sexual encounter will be the “solution.” To simplify the defensive makeup of these ideas, we can call them a product of splitting—that is, of unconsciously dividing the world into discrete and easily identifiable black and white parts, in this case devoid of logical or psychic coherence. Such ideas, because they are thoughts in the direction of behavior, have not only an internal, representational dimension, but also a relational one. For example, it is common for these utterances and related behaviors to frustrate clinicians since this carrying on seems both to foreclose further thinking—often with a sharp paranoid edge—and to signal potentially maladaptive and undesirable action. As we know, some theorists focus on the patient’s development of a theory of mind as a desideratum for improved mental health and social functioning. Many sufferers, when at their best, maintain an adequate theory of the minds of others, but they find that the model deteriorates under psychic stress.12 A robust theory of mind is a later acquisition in psychic development13 and, as such, finds itself having fallen by the wayside on a last-in-first-out basis under stress, almost always attachment related. This mechanism could be simplified to the term regression.14 When Mr. L begins to speak of his sexual solution to his problems, he is not only regressively blunting his cognition but also pushing away human connection and withdrawing from it. These motivations are outside of his awareness—that is, they are unconscious15—but they are reinforced by their own results. The result on the side of comfort is a simplification of overwhelming stimulation and a reduction of social demand, but on the side of displeasure, a distortion of reality and an alienation from interpersonal connection. Helping the patient re-recruit logic is a fine place to begin a therapeutic encounter, but failing that (the yearlong hospitalization probably points to a certain regularity of that failure in this case), we might seek to hypothesize about a more coherent overall meaning of the patient’s clinical state in the hope of securing some greater purchase in the struggle for progress. We might try to make some interpretation that could contextualize Mr. L’s conundrum for him and that could, if accurate, produce a deepening of rapport, an acknowledgment of what we have said, and a generalized decrease in chaos. Perhaps it would help to make a statement regarding attachment and ambivalence such as, “When you say oversimplified and provocative things like sex with a stranger is the cure, it is off-putting, and it also undermines your discharge because we worry about you. I think you want very much to be close to people, myself included, and to join with the world, but you feel at the same time that your illness makes that impossible. And because that feeling scares, frustrates, and disappoints you so much, you push Volume 22 • Number 5 • September/October 2014

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Idiom Use in a Young Man with Schizophrenia

us all away and yet cling at the same time, stuck in the hospital. I think you are telling me that I will never be able to help you if I cannot even understand that.” Why might I make that interpretation, of all that are possible? It helps to think developmentally. From an evolutionary or phylogenetic perspective, the development of all life is characterized by internalization—that is, the progressive ability to meet demands from within.16 The mind, itself an abstraction layer of the central nervous system, might be viewed as an extensively internalized descendent of the reflex arc. A stimulus is subjected to complex internal, mental processes before external action is initiated. Development allows for the internal management of increasingly complex tasks. In the ontogeny of representational mental life, the infant’s hands and mouth are the end organs of attachment and sensory gratification, enlisted in order to gain nutrition and protection in the service of survival, but also later in life for purposes of finding pleasure. One might say that oral sexuality, later in the life cycle, remains at the root of the far more complex tasks of forging relationships—enduring and emotionally significant ones—outside of the family of origin.17 At the most highly evolved levels of human organization such as groups, and even nations, civilization has largely transcended conscious sexuality altogether in its synthetic complexity.18 It is not uncommon in severely ill psychiatric patients— who have difficulty distinguishing their own thoughts from external reality, and thus their internal world from the external one—to struggle with making emotional connections with others. The very identification that leads them to feel merged with “the other” also prevents the other from feeling merged with them. We often feel that we are mere extensions of the idiosyncratic worlds of very ill patients; as such, we are allowed very little room to be ourselves. Further, the patients’ infantile longings for love and care are often frustrated by their inability to accept such care, or even to elicit it. As they get older, these longings feel increasingly childish, and people frequently hide them and express them in terms of more adult-seeming sexual longings.7,19 While the sexualization of infantile wishes renders them more tolerable to the patient, their retained infantile quality makes them even less likely to be fulfilled when expressed in predominately this way. When Mr. L drops to his knees and makes an “inappropriate” sexual proposition, he expresses the need of a small person for attachment, love, and caring—but in terms that sound adult, except for their peculiar context. In a sense, a summation of this bizarre communication by action is the following: “keep this unruly infant in the hospital forever and take loving care of him.” Of course, Mr. L also hates feeling reduced to this behavior, and manages to turn the entire transaction into a fight. This is another show of strength and defiance in an attempt to compensate for infantile need. His “who’s on first” types of riddles and puzzles are, by the way, of a similar nature. The well-known baseball metaphor for sexual activity puts Harvard Review of Psychiatry

the person “on first” at the oral level of kissing, suckling, and infantile attachment. Mr. L wishes to be on “first.” Because this wish is an infantile one, so utterly frustrated, it is embarrassing and thus it must be disguised as sexualized, like a wish to round the bases, and also as defiant, a nod to Abbott and Costello’s crowning version of the vaudeville “Who’s on First” act. Here Costello, the precocious manchild, hopelessly confuses Abbott, the straight man, with utterly accurate, yet preposterous information. This is the man being brought to his knees by the power of childish negativism at its best.20 The thinking I have outlined above is a sampling of the kinds of ideas that subtend the interpretation I imagined. Our goal in making an interpretation is to increase rapport with the patient by decreasing his defensiveness.21 We do so by understanding what he is trying to tell us at a higher level of abstraction than the concrete. If his response to my statement is negative and distancing, then I revise my theory in whatever direction his response takes me. If his response is positive and fosters a closer engagement with me, then we are off and running, discussing matters that seem real and important to him, while respecting his humanity, his adulthood, and the magnitude of his struggle with this tragic illness. To answer the questions put to the consultants in terms of the above: 1. After appropriate antipsychotic pharmacotherapy when possible, I would address the patient’s profound wish for human emotional connection as it is expressed in his sexualized, “adultomorphized” delusions, as well in as his fear and ambivalence. I would expect his problematic behavior to begin to outlive its usefulness in this light and to fade into a more manageable constellation of affect, thought, and behavior facilitating discharge planning over time. 2. “Simple” loosening of associations is not possible from the perspective of verbal communication. Our logical associations are looser than we like to think they are under the best of circumstances, and all associations point to fundamental abstract classes of mental events, of which the associations themselves are instantiations, whether loose or not. 3. The social dimension of loose associations, puns, puzzles, riddles, and obscure references is seen in its less pathological form in precocious, but fearful, adolescents. A high school student might respond to my suggestion that he try to do his homework on time with, “Yeah, that’ll get me about as far as trying to quantize gravity.” It demonstrates his intelligence at the same time as it pushes me, the feared and envied guardian of the adult world, away by rejecting my offering and by making me feel unintelligent. In schizophrenia, those needs are amplified by the ravages of the patient’s dysfunction, chiefly paranoia and “Capital A” ambivalence22 at the psychoanalytic level, with the consequence that the

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obscurity of the language, coupled with its thinly veiled derision, is all the more intense. In the spirit of psychoanalytic thought, a description of the psychology of schizophrenic social isolation might be that it is thus the projective identificatory result of a profoundly ambivalent attachment struggle.23

Philip R. Corlett, PhD I should like to focus my discussion on questions 2 and 3, which I paraphrase as follows: Do these utterances mean anything? Is there significance to their content and timing? Are they indicative of underlying pathophysiology? Given the communicative function of language, what is the relationship between these dysfunctions and the social problems afflicting this young man? What is the direction of causality here? I do not pretend to have definitive answers to any of these questions. I shall attempt, however, to apply some of what we know from cognitive neuroscience and neuropsychiatry to these issues and to present my perspective on them. Language, by which I mean the words uttered in combination to communicate particular ideas to others, is disrupted in patients with schizophrenia.24–26 This disruption is reflected perhaps most obviously in thought disorder, a symptom dimension involving changes in both speech production and coherence, with extreme forms ranging from tangential word salad to completely impoverished speech.24–26 The relationships between speech disruptions and a patient’s inner mental life are complex. It is unclear whether thought-disordered speech reflects a person’s distorted thoughts or whether it reflects a person’s difficulties with speech itself—that is, that they are not saying what they are thinking.27 Beyond thought disorder, patients’ speech has been discussed in the context of their delusions, hallucinations, and negative symptoms. Berrios28 has argued that delusions are “empty speech acts,” things that patients say aloud that signify nothing, that are distinct from beliefs, and that lack the manifest conviction of beliefs. Some models suggest that hallucinations are engendered when patients perceive their own inner speech as external voices. The same brain regions are engaged during auditory hallucinations as during inner speech production, and electromyogram studies reveal that hallucinations are associated with subvocal speech articulation.29 Furthermore, impoverished speech is a key component of negative symptoms.24 Finally, in the absence of objective diagnostic tests based on underlying pathophysiology, patients’ spoken descriptions of their lives and difficulties are the basis for diagnosis. What they say and how they say it is a key signifier of the problems that they have been having—a signpost toward diagnosis.30 It is possible that speech disruptions reflect the welldocumented deficits in the fundamental cognitive-control processes that characterize schizophrenia.31 For example, 310

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word salad may be explicable via the dysfunction of context processing and working-memory maintenance that attends patients with schizophrenia; speech jumps from topic to topic because the constraining effect of context is absent. People with thought disorder forget where they were going with their utterance, and hence their speech “clangs” to a semantically associated concept. Functional-imaging studies of context-dependent working memory tasks (such as the AX-CPT, in which subjects must respond to a letter X only when it is preceded by a letter A) show inappropriate engagement of dorsolateral prefrontal cortex that correlates with the severity of thought disorder.32 The point here is that the task appears to engage the same process. Patients with thought-disordered speech have trouble appreciating and maintaining context in order to respond appropriately to the context-dependent task.31 It is also possible, however, that the Mr. L’s inappropriate use of metaphor represents an attempt at establishing some intersubjective meaning, albeit ineffectively.33 Some of his utterances do seem to have some delusion-relevant meaning. Metaphors involve conceptualizing one mental domain in terms of another.34 In that way they are like explanatory or causal models, schemes through which psychotic experiences might be explained. The model for Mr. L is that his difficulties “growing up” are a result of his sexual inexperience and that the difficulties will resolve if he can gain sexual experience. His sexual problem became a metaphor for his psychosis. Causal models are a way that we reason about data using prior beliefs.35,36 In brief, causal models are representational structures that guide how we form and use beliefs.37 Like metaphors, causal models contain a propositional logic, and they (and perhaps also metaphors) allow us to reason bidirectionally between causes and effects so that we can make diagnostic and prognostic predictions.37 Delusions may be aberrant causal models—inappropriate metaphors, formed based on inappropriate learning and memory processes.38 The aberrant application of metaphor is particularly pertinent to delusion formation.33 Delusions do not always emerge fully formed; rather, they develop during a prodromal period characterized by oddly salient experiences.39–41 While delusions are fermenting, sufferers search for explanations for their odd experiences.39–41 During this period—the delusional mood—the world takes on a new quality.42 Important things feel different, and different things feel important.39–41,43,44 Sufferers use relative terms to describe their experiences; for example, “It is as if people are actors, walking down the street wearing masks.”45 Healthy subjects administered psychotomimetic drugs use similar language to describe their experiences.46 As these experiences persist, the relative terms subside (people are wearing masks; they are in disguise); the simile becomes a metaphor as the delusion develops.33 Both similes and metaphors are rhetorical devices intended to describe a set of circumstances by comparison to some unrelated object. In the present context, they are intended to Volume 22 • Number 5 • September/October 2014

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communicate meaning in order to render the inexplicable experiences of the delusional mood understandable to the patient. An interesting corollary of this theory—that delusions are explanatory schemes and that some of Mr. L’s metaphoric language represents an attempt at explanation—is that delusions may hold a kernel of truth.47 By tracing from the patient’s expressed beliefs, it may be possible to find the kernel of truth that they are attempting to explain. In one early observation, a patient claiming to have bowel disease despite no obvious obstruction was found at post mortem to indeed have physical illness (in the small intestine and lung).48 Similar early observations were made in other patients with somatic delusions.49 The point is, despite the audacious nature of delusional utterances and their apparent impossibility, they may signal something with which you can work if you listen carefully. For example, with his bizarre utterances, Mr. L is trying to tell us about his problems with unrequited sexual and romantic interactions. As a scientist who studies delusions, I find it interesting to consider his utterances within the context of erotic delusions like Othello syndrome or delusional jealousy. These can occur following closed head injury or normal pressure hydrocephalus associated with right hemisphere damage,50 left frontal hyperactivity,51 and midline damage.52 More practically, by listening to Mr. L’s metaphorical utterances and trying to empathize, we learn what he is finding a challenge (e.g., knowing when it is appropriate to talk about sex and relationships), and we can make these challenges the basis for our treatment goals. Mr. L’s attempt at shared meaning fails. Perhaps it fails because psychotic symptoms are fundamentally ununderstandable.53 Alternatively, shared meaning may fail due to shortcomings in the patient’s ability to represent and use a theory of mind for the person with whom the patient is interacting.54,55 It appears, from some of the verbal exchanges described, that Mr. L believed his use of metaphor would be understandable to others. His use of metaphors assumes (and requires) a shared set of representations and how those representations can be meaningfully juxtaposed to make the point—creating numerous junctures through which metaphor use may be disrupted. For example, a deficit in semantic memory may result in the activation of fewer or inappropriate representations.25 In addition, the impaired cognitive-control processes described above may preclude the appropriate manipulation of those representations. It is also possible, instead, that a theory of mind deficit—a problem in representing others’ mental states—might underpin the deficit in metaphor use. People with schizophrenia fail second-order false-belief tasks; they find it difficult to know what someone with different experiences might know about a certain set of circumstances. These patients’ second-order belief-evaluation deficit correlates with their inability to comprehend metaphors.54 This failure regarding second-order false beliefs is perhaps reflective of a more basic disruption in prospective cognition or modelbased inference.56,57 As we fractionate cognition more Harvard Review of Psychiatry

completely, we will perhaps be able to clarify the role of specific cognitive processes in speech disruption and symptomatology in psychotic illness.58,59 One complexity that was raised in the description of Mr. L is the role of other people in his communication problems. This is a difficult question. Does social disconnection cause deficits in speech production, or vice versa? It is clear that patients with psychotic illnesses experience social isolation. Some writers have argued that social isolation engenders psychotic symptoms; for example, hallucinations may arise when people impose others’ voices top-down, in the absence of other people to interact with.60 Hallucinations can occur in conditions of both extreme social isolation and sensory deprivation.61 In Mr. L’s case, it is possible that the combination of his social isolation, the pressure he perceives during social interactions, and his cognitive deficits may induce his unusual speech patterns. It is also clear, however, that this patient’s specific difficulties, including his idiosyncratic use of metaphor, may further alienate other people. I turn finally to the timing of the patient’s utterances—for which there may also be a social explanation. At the time of his utterances, in the late afternoon and evenings, the clinical research unit on which Mr. L was being cared for becomes quieter, much of the research staff leaves for the day, and the social milieu is reduced. Such calm conditions are possibly easier to handle and more inviting to a person who lacks confidence in social interactions (due to bad prior experiences). This young man has learned that the things he says often have punitive consequences. Perhaps he timed his utterances to minimize the number of people who might be bothered by them. This type of learning is typical of patients with delusions. They experience extended hospital stays predicated on their verbal endorsement of their delusions. Over time, they learn to deny their delusions in order to leave the hospital.62 Perhaps the timing of Mr. L’s confusing utterances reflects a degree of insight into his situation and the problems that attend it. It is also possible that a neuroendocrine explanation may account for the timing of Mr. L’s utterances. In brief, hormones (e.g., testosterone and estrogen) influence our cognitive abilities.63 They fluctuate throughout the day.64 Particularly relevant to Mr. L’s presentation, the ratio of testosterone to estrogen correlates with working memory performance,65 and testosterone level is negatively correlated with the severity of negative symptoms such as social withdrawal.66 Testosterone levels also correlate with the frequencies of verbal utterances.67 In a small clinical study in female patients with schizophrenia, the application of exogenous estrogen improved the patients’ ability to interpret metaphors.68 Testosterone levels decrease in men throughout the day64 and may already be lower in patients with psychotic illnesses.69 Against this background, it is possible that Mr. L’s speech disruptions are a product of his neuroendocrine milieu. In sum, Mr. L’s challenges are complicated. My speculations from the point of view of cognitive neuroscience and

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neuropsychiatry highlight how far away we are from an explanation of his difficulties in terms of pathophysiological cognitive or neural mechanisms. Nevertheless, his presentation provides clues as to the potential causes of his problems. The neuroendocrine connection is particularly intriguing from a scientific standpoint, although not yet a standard part of evaluation or treatment. At a psychological level, it is possible that training in metacognition and social skills might help Mr. L; some evidence suggests that theory of mind deficits can be ameliorated with social-cognition training in people recovering from psychosis.70 More fundamentally, Mr. L reminds us of the pervasive and labyrinthine manifestations of psychosis. As we work toward a better understanding of the neural and cognitive basis of psychosis, we would do well to remember that patients are trying to tell us something. We will learn more if we listen to them. Mark Viron, MD The ultimate goal of discharge planning for this 25-yearold gentleman with treatment-resistant schizophrenia and illness-related problematic sexual behaviors is to facilitate a successful and enduring return to the community so that he may pursue his vision of recovery. Despite a lengthy hospitalization and an adequate dose and duration of clozapine, Mr. L continues to have delusional thought content, disorganized speech, and auditory hallucinations. Addressing these symptoms is of primary importance, particularly given that his delusion of needing a “sexual experience with another person to solve his psychiatric problems” may jeopardize his safety and that of others in the community. Ongoing effective treatment of his schizophrenia can mitigate these risks. Treatment should balance the risks and benefits of psychopharmacologic interventions, address medication nonadherence and substance use, and utilize evidence-based psychosocial treatments to assist with medication-resistant symptoms and to support his family and recovery goals. MEDICATION CONSIDERATIONS Although clozapine is the most effective antipsychotic agent for treatment-resistant schizophrenia, partial response to clozapine is unfortunately common,71 and medication augmentation strategies with robust evidence of significant efficacy are lacking. A couple of interventions, however, are worth considering. The addition of lamotrigine to clozapine may ameliorate residual positive symptoms72 and, except for the minimal risk of StevensJohnson syndrome, is usually well tolerated. Alternatively, adding risperidone may provide some limited clinical benefit, but additional side effects are common.73 Given Mr. L’s historically favorable response to risperidone, one might predict a more substantial benefit than that seen in risperidone augmentation studies, though no available literature supports such a hypothesis. The long-term necessity of Mr. L’s current medications and dosages should be evaluated prior to discharge. Occasionally, certain medications and doses are needed (or effective) only in acute situations, and side effects and 312

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cumbersome medication-administration schedules may undermine adherence in the community. The ongoing need for valproate, prescribed here for psychotic agitation, should be carefully considered, as it has limited evidence of utility in schizophrenia outside of acute agitation,74,75 and it may worsen cardiometabolic parameters,76 an important concern for Mr. L, who is already obese. Clozapine, by contrast, has superior anti-aggressive efficacy compared to other medications,77 so clozapine monotherapy may be sufficient for Mr. L. Mr. L’s clozapine levels are currently near 1000 ng/mL. While levels between 300 and 400 ng/mL are known to be optimal for treatment-resistant illness, the existence of an “upper limit” beyond which efficacy plateaus and toxicity emerges is debated. Clozapine doses greater than 500– 600 mg/day can increase the risk of seizure substantially, but available evidence does not allow conclusions as to a safety-related upper threshold for plasma levels with respect to seizure risk, agranulocytosis, myocarditis, gastrointestinal hypomotility, or overall tolerability.78 Plasma levels greater than 600–800 ng/mL, however, may not provide improved efficacy,78 so the risks and benefits of maintaining a clozapine level near 1000 ng/mL should be weighed cautiously. NONADHERENCE AND SUBSTANCE USE Nonadherence is common in schizophrenia, and Mr. L’s history strongly suggests that nonadherence may recur in the future. Analyzing reasons for past episodes of nonadherence, planning for future barriers to adherence, and discussing how Mr. L feels his medication may or may not play a role in his life and his treatment will help his clinicians establish a meaningful plan to support adherence. Periodic clozapine plasma levels may aid in monitoring adherence, though intermittent adherence is difficult to detect through such a practice and may result in unreliable information on which to base dosing changes. If clozapine nonadherence returns in the community, temporary use of orally disintegrating tablets or the newly available oral suspension may assist with adherence when used in conjunction with supervised medication administration, although health insurance coverage of these formulations may be limited. As insurance issues have served as an external obstacle to optimal treatment in Mr. L’s past, the inpatient team should verify outpatient coverage of his medications and obtain any necessary prior authorizations before discharge. Substance use can precipitate psychotic decompensation and increase the risk of violence. Mr. L’s history of marijuana use should be addressed in his treatment plan in order to reduce these associated risks. Even if substance use is not recent, historical usage patterns and triggers should be noted, and a relapse prevention plan developed. Treaters and family members should remain vigilant for signs of relapse, and evidence-based treatments should be offered in the event of recurrence. PSYCHOTHERAPEUTIC INTERVENTIONS FOR MEDICATION-RESISTANT Cognitive-behavioral therapy is a valuable evidencebased intervention for the treatment of medication-resistant

PSYCHOSIS

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psychotic symptoms.79 Mr. L’s delusional beliefs, auditory hallucinations, and disorganized speech are all potential targets for CBT.80 The foundation of the CBT approach to delusions is a systematic and thorough assessment and formulation of delusional beliefs and related behaviors. Mr. L identifies a specific “unconsummated sexual encounter” as the cause of his “problems,” and in pursuit of a “solution” to these problems, he has made sexual propositions to a variety of people. Over the course of his inpatient admission, he has reduced his frequency of “sexual invitations” to staff and strangers, but he still speaks of his need for a “sexual experience with another person to solve his psychiatric problems.” The assessment of his delusional beliefs entails gentle, judgment-free, guided discovery:80 to search for the origins of his delusions, to define the “problems” he is trying to solve, and to explore how and why he feels a sexual encounter will provide a solution. Modifying his delusions will require asking Mr. L to examine the evidence for and against his beliefs and to take a different perspective in considering the beliefs (e.g., “If someone said this to you, how would you respond? What does your family think of this belief?”). The clinician should listen for logical inconsistencies or instances where Mr. L is uncertain about his ideas, as these occasions signify beliefs that may be amenable to change through the exploration of alternative hypotheses or perspectives. With resistant delusions, delusion-related behaviors or preoccupation with delusional content may decrease in frequency long before the delusions disappear entirely. In addition to cognitive techniques, CBT can directly target behaviors driven by delusional beliefs. Even if a patient is resistant to discussing his delusions, attention can be drawn to the negative aspects and potential consequences of problematic behaviors. Working from a patient-centered, goal-oriented approach, the clinician can explore how such behaviors may be detrimental to Mr. L’s vision of recovery (e.g., discharge from the hospital, remaining in the community and free of legal charges, obtaining a job, having friends). A collaborative objective of eliminating the problematic behavior should be set, and the behavior should be monitored. Further occurrences should be followed by immediate feedback that helps define and shape the problematic behaviors. The delusions may persist, but extinguishing these associated behaviors is a vital initial step, one that will keep Mr. L and others safe. Mr. L’s auditory hallucinations can also be addressed with CBT. Insofar as they may be command in nature and associated with his problematic sexual behaviors, they may represent an important treatment target. While Mr. L’s guardedness may at times limit the extent of the assessment, CBT for voices involves detailed exploration of auditory hallucinations, including frequency, content and character, precipitating factors, the patient’s explanatory model for the voices, and any associated maladaptive beliefs, such as omnipotence of the voices and feeling powerless to take action to ameliorate them. Treatment should aim to reduce related Harvard Review of Psychiatry

distress by counteracting cognitive distortions with more rational beliefs and promoting active coping skills that involve distracting or focusing techniques. Patients often have developed their own coping strategies, as Mr. L has in this case (wearing ear plugs). Patient-identified approaches should be evaluated for efficacy and either reinforced if helpful or used to inform selection of alternative strategies if not. Mr. L’s disorganized speech, characterized by moderate loosening of associations/derailment and poverty of content, is not uncommon in schizophrenia. Stress or fatigue can exacerbate such symptoms. The CBT approach to thought disorder has less empirical support than approaches for delusions, hallucinations, and negative symptoms, but it provides useful techniques that can facilitate effective communication. All of the following strategies may be useful when dealing with significant thought disorder: summarizing and reflecting what seem to be the pertinent points or main underlying themes; persisting in a topic of conversation despite disruptive interjections; having a patient link seemingly unconnected thoughts (“You started off telling me that you ‘have come to a realization’ and then asked ‘why did the chicken cross the road?’ How do these things relate to one another?”); identifying and reducing intense affective states associated with the onset of disorganized speech; and setting clear communication as a shared goal and providing feedback to the patient when linearity and comprehensibility are lost. PSYCHOSOCIAL INTERVENTIONS TO SUPPORT RECOVERY AND FAMILY Mr. L’s vision of recovery includes learning a trade, securing gainful employment, and socializing with friends. Supported employment, especially when combined with cognitive remediation, is successful in returning to work even those with serious mental illness and significant cognitive dysfunction.81 Mr. L’s family remains involved and helpful to him. To encourage their ongoing and productive support, they should be empowered, educated, and aided by evidence-based family interventions, if not already engaged in such activities. Multifamily group therapy82 and the family-to-family program available through the National Alliance on Mental Illness83 are two such interventions. When available, these broad-based community supports that augment psychiatric treatment will provide the optimal system of care for Mr. L, allowing him the best chance not only for remaining safe but also for thriving in the community. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article. REFERENCES 1. Frese FJ 3rd, Knight EL, Saks E. Recovery from schizophrenia: with views of psychiatrists, psychologists, and others diagnosed with this disorder. Schizophr Bull 2009;35:370–80.

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