Abstract
Chief Complaint and Presenting Problem
History of Present Illness
Mother reported that A. was a “hyperactive” and excessively impulsive child who ran to family friends and bit their legs in a show of affection. Mother reports that he was treated in preschool with dextroamphetamine; at age three years, the medication was changed to methylphenidate and risperidone, presumably to more effectively address both hyperactivity and impulsivity. Subsequently, A. was treated with risperidone alone, on which he remained compliant and stable until about the age of 15.
Mother reports that A. had had a history of suicidal ideation and scratching himself at times for years in early adolescence, but he had no history of suicide attempts.
At age 15, A. experienced an increase of suicidal ideation and began to threaten violence against his mother and was first hospitalized. During this admission, A. was tapered off risperidone and discharged on quetiapine 600 mg and valproate 500 mg daily, presumably for lack of efficacy of risperidone and the development of mood symptoms.
A.'s mother described him as “very smart” but a “loner” whose contacts with peers were rare and usually quite odd and inappropriate. Reportedly, A. attempted to impress peers with dramatic presentation of his rigid and bizarre thoughts, which usually backfired, resulting in further alienation. Mother reported that while A. had always had circumscribed interests, few friends, poor socialization and impaired academic functioning, when he began to perseverate on demons and black magic, A. became increasingly disheveled, disorganized in speech and behavior, had increasing difficulty initiating tasks, and had significant academic difficulties above and beyond his prior cognitive deficits.
A. reportedly brought a knife to church, saying that “the curve of the blade followed the natural curve of his arm.” He was described as being “enthralled by black magic and demons,” and stated that he himself was “a demon who deserved to be sacrificed.” His mother described an incident prior to admission during which A. grabbed a knife, which she then removed to prevent A. from “punishing himself for the evil inside him.” A. believed that he had a special power to perform black magic, and that he had the power to kill others if he chose.
Despite compliance with medications corroborated by laboratory studies, A. was referred for the most recent acute admission 6 months later, after making multiple remarks that he wanted to rape and kill his mother. During this admission, quetiapine and valproate were discontinued, and olanzapine 20 mg and lithium 650 mg were initiated, after elevated transaminases were noted on quetiapine.
A. was subsequently transferred to a state hospital for stabilization. A.'s medications at the time of transfer to the state unit included lithium 650 mg and olanzapine 20 mg. However, at the time of admission to the state hospital, A. continued to express a desire to inflict self-harm, believing he was worthless and hopeless. He denied any intent to hurt his mother, stating that he actually loved her and regretted saying previously that he hated her. Moreover, A. reportedly said that, as his mother was a Christian, it was wrong for him to practice black magic and that he would have to resist the desire to use his gifts. He denied hallucinations at the time of the current admission, but records of the previous acute admission reported auditory and visual hallucinations of demons prior to the initiation of olanzapine. On this admission, A. stated he heard only two voices, one of his mother's and another of a woman's voice, calling out his name.
Mother denied A. had any history of sleep disturbance, consistent irritable or elevated mood, pressured speech, or excessive goal directed behavior prior to or after onset of the current symptoms.
Past Psychiatric History
A. was initially evaluated in preschool for developmental delays, hyperactivity and impulsivity and received early intervention. A. received outpatient psychopharmacological treatment starting in preschool. A. had been hospitalized twice prior to the current admission, and most recently had been receiving day treatment.
Past Psychometric Testing
Psychometric testing at age 10 revealed full scale intelligence quotient (IQ) as 78. Testing performed at age 13 indicated a full scale IQ of 81. Neuropsychological testing conducted at age 16, after onset of psychosis during a period in which psychotic symptoms were stable, revealed full scale IQ of 70, verbal comprehension index 81, perceptual reasoning index 90, working memory index 56, and processing speed index 68. These results indicated a precipitous drop of 24 points on working memory, as well as relative drops in verbal comprehension and perceptual reasoning of 8 and 10 points, respectively, with stable processing speed from most recent testing at age 13, indicating that the patient experienced a significant cognitive decline by the age of 16.
Developmental History
A. was born full term via Caesarean section due to a breech position; birth weight was 7 lbs 14 oz. A. met his early milestones on time, but began experiencing delays at 18 months in areas of speech, and fine and gross motor skills. Early intervention services were initiated by age 2 years.
Educational History
A. has required special education services throughout his school history, including early intervention services prior to the age of 2 years.
Social History
A.'s biological father abandoned the family prior to A.'s birth, and as a result A. was raised solely by his mother. A. was reportedly very sheltered by his mother, who accompanied him to most places in addition to school, created social outings for both of them, and reportedly deterred him from socializing with children who she felt might tease or bully him.
A. has one friend, age 21, who lives in his neighborhood and is reportedly cognitively impaired, and also living with his mother. This friend is reported to come to A.'s home to play video games.
A. denies any history of drug or alcohol use.
Family History
A.'s paternal history is unknown, and maternal psychiatric or medical illnesses are denied.
Medical History
A. was anemic at birth and required iron for 6 months. A. had recurrent ear infections for the first year of life. Hearing was reported to be normal. He received all appropriate vaccinations.
Medication History
A. was treated with dextroamphetamine and methylphenidate in preschool, and risperidone in the past. He had also received quetiapine and valproate in the past year, but experienced adverse effects to quetiapine as elevated transaminases. He currently receives lithium 650 mg (serum level 0.60) and olanzapine 20 mg at bedtime.
Mental Status Exam on Admission
A. was a well-nourished adolescent boy who appeared older than his stated age. He had long, disheveled hair that fell sloppily in front of his face as he pushed it back repeatedly in a disorganized fashion. He had fair eye contact for a period of time and then frequently averted his gaze. He was cooperative on exam but related coldly and would engage only by perseverating on his rigid and bizarre interests with a concomitant inappropriate affect. His speech was slightly dysarthric, and he mumbled unless redirected to speak clearly. His thought process was mostly linear and logical in short responses but was frequently tangential and disorganized on further discussion. He denied suicidal or homicidal ideation but spoke passionately about his powers in black magic and his association with demons and the grim reaper.
A. knew the time, day, place, and situation. His ability to abstract was quite limited, but his remote and immediate memory were intact. His insight was fair, in that he knew he had a mental illness but had a simplistic understanding of it as an “anger” problem. His judgment was also fair, in that he accepted medication and treatment but continued to verbalize that he might have to participate in black magic in the hospital.
Hospital Course
On transfer to the state facility, A. was taking olanzapine 20 mg and lithium 650 mg at bedtime. Physical and neurological examinations and laboratory assessments, including magnetic resonance imaging, were within normal limits. As there was no clear indication of hypomania or mania, lithium was slowly tapered without adverse effects. On further evaluation, initial “depressive” symptoms were more accurately described as negative symptoms, and fluoxetine 10 mg was added at week two to target both the negative symptoms and intrusive and obsessive symptoms. The working diagnosis was both a psychosis and an autism spectrum disorder. Olanzapine 20 mg was continued from admission.
One month after admission on this regimen, although A. denied intent to harm self or others, he described persistent egodystonic, intrusive thoughts of violent as well as sexual nature directed toward older women, which caused him significant anxiety. Yale Brown Obsessive Compulsive Scale (YBOCS) at this time was 22, which was in the clinically significant range. Over the next month, fluoxetine was gradually titrated up to 40 mg and olanzapine was increased gradually to 25 mg to further target psychotic symptoms. At month three, the YBOCS was 12, and patient reported significant relief from intrusive thoughts of death, gore, and black magic. Significant improvement of disorganized communication was also noted. At this time, as A. had gained 17 pounds since admission, and as he improved after increasing both fluoxetine and olanzapine, olanzapine was decreased to 20 mg. Within two weeks of this adjustment, A. began reporting daily, persistent, intrusive thoughts about death and harming others. Within three weeks, he began perseverating on his powers to use black magic and literally described a demon who lived inside his body. Olanzapine was increased again to 25 mg with resolution of delusions and intrusive thoughts within three days.
Over the following month, the patient remained on fluoxetine 40 mg and olanzapine 25mg, which seemed to decrease expression and degree of conviction regarding his thoughts of black magic, as well as prevented recurrence of auditory or visual hallucinations.
Once psychotic symptoms were better controlled, the Autism Diagnostic Observation Schedule and Autism Diagnostic Interview-Revised were administered to A. and his mother, respectively, in order to clarify the autism spectrum diagnosis. The results of both assessments were consistent with pervasive developmental disorder PDD.
Brief Formulation
In summary, A. is a 16-year-old adolescent boy with PDD-NOS with a one-year history of psychotic symptoms that have emerged in the context of a prodromal period of worsening social and cognitive function. A.'s psychotic symptoms emerged acutely and at later onset than the early-onset autistic symptoms, and corresponded to neuropsychological deficits illustrated on testing. A.'s significant decline in working memory performance compared to more relative decline in verbal comprehension and perceptual reasoning occurring after the onset of current symptoms are suggestive of neurobiological changes consistent with schizophrenia. Additionally, from a biological perspective, there was no medical illness or substance use that could account for the given symptoms. Family history is incomplete but does not appear to suggest a diathesis for psychotic illness or autism spectrum disorders.
From a psychological perspective, A.'s delusions and hallucinations surrounding death, black magic, and demons stand in sharp contrast to the Christian beliefs held by his mother and may be conceptualized as a representation of A.'s conflicts regarding separation-individuation; these conflicts may be over-determined by his significant emotional dependency on his mother and his resulting ambivalence as he transitioned into adolescence. From a social perspective, A. was extremely isolated from peers, which may have only fostered more dependence on his mother.
A.'s strengths include a supportive mother and school community and his willingness to accept treatment.
Multi-Axial Diagnoses On Admission
Schizophrenia, undifferentiated type PDD-NOS
Borderline intellectual functioning
Anemia, past, resolved Serous otitis media, past, resolved
Mild: educational, social
Current Global Assessment of Functioning (GAF) Score = 40
Discussion
This case is a rich illustration of the challenges of both diagnosis and treatment of new-onset psychotic symptoms in an adolescent with PDD-NOS and borderline intellectual functioning. Although older literature has established predictive validity of autism as a distinct diagnosis from early-onset schizophrenia, it may be difficult to differentiate the two, as there can be overlapping symptoms (Rutter 1972; Dosseter 2007). As autism spectrum disorders may present with social impairments, disorganized communication, perseveration and rigidity, it can be difficult to tease out the presence of an independent psychotic disorder. Disorganization of thought and speech, and negative symptoms such as flattened affect and abulia can be observed in both the autism spectrum and early onset schizophrenia. DSM-IV-TR (American Psychiatric Association 2000) notes that although PDD and schizophrenia share disturbances in language, affect and social relatedness, PDD is usually recognized in early childhood. PDD is also notable for an absence of prominent delusions and hallucinations, with more abnormal affect and speech characterized by perseveration or abnormalities in prosody. A diagnosis of schizophrenia is made only if prominent hallucinations or delusions have been present for at least a month (American Psychiatric Association 2000). The differential diagnosis is also made more complicated in cognitively delayed individuals.
Another interesting aspect of this case is the development of obsessive-compulsive or perseverative symptoms in the course of onset of the psychotic illness. A. was reported to have persistent egodystonic, intrusive violent and sexual thoughts early on in his admission while on litihium 650 mg and olanzapine 20 mg. Although it appears that the content may have been over-determined by the emotional dependency on his mother, it seems there was nevertheless persistence and intrusiveness, quantified by his YBOCS score of 22, which is well within the clinical range for obsessive-compulsive disorder (OCD). Obsessive-compulsive symptoms (OCS) and even OCD are not unusual in schizophrenia in youth and may indicated a poorer prognosis (Niendam et al. 2008). OCS has been reported to be associated with poorer cognitive function, which is suggested in this case, mood symptoms, more severe negative symptoms, and higher rates of hospitalization (Nechmad et al. 2003; Samuel et al. 1993). Some authors have suggested that OCS symptoms in medicated patients with schizophrenia may result from effects of antipsychotic medication on serotonergic tracts in the basal ganglia (Tibbo and Warneke 1999).
A recent study of 64 adolescents with ultra high risk (UHR) for psychosis compared to 26 non-prodomal (NPC) youth reported that UHR had higher rates of OCS and had higher positive symptom severity, self-reported depression, and a trend toward more suicidal ideation than the NPC youth (Niendam et al. 2008). However, on the other hand, clinical diagnosis of OCD was associated with lower risk of conversion to psychosis over the mean 11-month follow up period (Niendam et al 2008).
Clearly, A. had a beneficial response to the addition of fluoxetine to his medication regimen, corroborated by the reduction of YBOCS to below clinical threshold at 40 mg. However, attempts to reduce the olanzapine from 25 mg to 20 mg for 17 pound weight gain resulted in recurrence of persistent intrusive thoughts of death, harm, and delusions of black magic and demons. It is interesting to note that A. needed the addition of a selective serotonin reuptake inhibitor to the antipsychotic, which appeared to target both the OCS and the psychotic symptoms, perhaps a reflection of a need for targeted combined pharmacotherapy to address the comorbid clinical pictures.
Another issue that is interesting about this case is A.'s apparent lack of response and/or intolerability to antipsychotic medication. Interestingly, it appears that A. may have benefited from a long-term treatment with risperidone, presumably for aggressive behavior in early childhood, without reports of significant adverse effects. This is fortunate, given the greater likelihood of adverse metabolic effects to antipsychotics in children and adolescents compared to adults (Correll and Carlson 2006), although details of the history that would support or negate this hypothesis are missing. Observation regarding efficacy and response in adolescents must take into account their propensity for becoming non-adherent over time, but there are indications that A. had developed psychotic symptoms while on antipsychotic medication despite adherence to his regimen. It is well established that there is significant variability between patients in response to individual medications. The fact that A. responded to a higher dose of olanzapine than is generally recommended is not at all unusual; there are both pharmacokinetic and perhaps pharmacodynamic explanations for such variability. It is also possible that A.'s “dual diagnosis” or comorbidity with both PDD and psychotic illness may have rendered him more likely to be relatively treatment resistant to monotherapy with one antipsychotic or even combination therapy.
Disclosures
Drs. Kaur, Dobroshi, and McCarthy have no conflicts of interest or financial ties to disclose. Dr. Coffey has received research support from Boehringer Ingelheim, Bristol Myers Squibb, Lilly Pharmaceutical, NIMH, NINDS, Otsuka, Shire and the Tourette Syndrome Association.
Footnotes
Acknowledgment
We would also like to acknowledge and thank Stephanie Samar, M.A. and Amanda Zwilling, B.A. for their assistance in review and preparation of the manuscript.