SCHIZOPHRENIA/SEASONAL AFFECTIVE DISORDER
from Golden Gleanings from Gracious, Galvanizing Gurus, sponsored by the University of Wisconsin Medical School and the
Madison Institute of Medicine, Inc.
| COGNITIVE DYSFUNCTION IN SCHIZOPHRENIA: ASSESSMENT AND TREATMENT —Rona J. Hu,
MD, Assistant Professor of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, and
Medical Director, Acute Psychiatric Inpatient Unit, Stanford Hospital, Stanford, California
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| Cognitive dysfunction: characteristics—schizophrenic patients exhibit cognitive deficits in executive function (processes
related to planning, problem solving, attention allocation, motivation, self-regulation, concept formation,
and working memory), verbal fluency, verbal and visual learning, memory, and attention; prevalence—
schizophrenia affects ≈2.5 million people in United States; cognitive dysfunction seen in ≤95% of patients
with schizophrenia; economic losses estimated at $65 billion per year; cognitive dysfunction responsible for
largest proportion of economic cost (eg, from lost wages or underemployment of individuals); natural
history—can appear early in course of disease, precede development of psychosis, persist after resolution of
acute psychotic symptoms, be found in treatment-naive patients, and predict disease course; cognitive function
declines before first psychotic episode and may continue to decline, remain the same, or improve, but
tends not to return to baseline
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 | Functional outcome: cognitive dysfunction can negatively affect medication compliance, awareness of illness,
social functioning, occupational functioning (10% of patients with schizophrenia work full-time and
20% part-time; patients often underemployed), independent living and self-care (high rate of homelessness
among schizophrenic population), and capacity for making decisions (affects informed consent and ability
to participate in research projects); increases risk for psychotic relapse, rehospitalization, and dependence
on others
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| Evaluation: Wisconsin Card Sort Test (WCST)—consists of cards with various shapes, colors, and numbers that can
be sorted according to these attributes; assesses ability to perform strategic planning and set shifting; patients
with schizophrenia unable to shift from sorting method to sorting method as determined by examiner; Stroop
Color-Word test—words representing colors illustrated in different color than that represented by word; subject
must read color and not word; Tower of London test—subject given 3 upright dowels and rings of various sizes
and must place rings according to size, with larger rings on bottom and smaller on top, creating pyramid
structure; tests strategic planning and problem-solving ability; Trail Making Test—numbers and letters scattered
across page; patient must connect numbers and letters in alternating pattern; clinical questioning—Diagnostic
and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria (eg, disorganized speech, grossly disorganized
or catatonic behavior) and negative symptoms (eg, affective flattening, alogia, avolition) related directly
to cognitive functioning; ask patient and family or caregivers about daytime activities of patient, amount of
help needed preparing food or handling money, and when patient last worked
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| Improving cognitive dysfunction: focus of treatment; consider traditional neuroleptic drugs (improve positive
symptoms), atypical antipsychotic agents (improve positive, negative, and cognitive symptoms), or off-label
therapies, which include central nervous system (CNS) stimulants (methylphenidate and amphetamine),
proglutamatergic agents (glycine and cycloserine), serotonin agonists (tandospirone), and agents that decrease
sedation (modafinil [Provigil])
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| Atypical antipsychotic agents: functional improvement spread inconsistently among different aspects of cognitive
functioning; clozapine improves attention and verbal fluency; risperidone and olanzapine improve cognitive
functioning in different areas with little overlap; ziprasidone improves functioning without much
sedation; quetiapine sedating and not as effective; partial dopamine agonist aripiprazole (Abilify) may preserve
cognitive function without as much sedation (dopamine key neurotransmitter in neurotransmission of attention;
stimulants increase amount of dopamine in synapse); study data—Bilder et al found haloperidol
(Haldol) improved cognitive functioning, clozapine produced more improvement than haloperidol, risperidone
more effective than clozapine, and olanzapine more effective than clozapine in improving cognition
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| Adjunct treatment: modafinil—approved by Food and Drug Administration (FDA) to promote wakefulness in
narcoleptic patients; does not act directly on dopaminergic neurons; can be used to reduce sedation and improve
cognitive functioning in patients with schizophrenia; associated with low incidence of side effects and
risk for abuse; not associated with increase in psychotic symptoms; decreases antipsychotic-induced sedation;
improves set shifting in patients with schizophrenia; study data—Rosenthal et al performed open-label
study using modafinil in patients with schizophrenia; patients and examiners reported improvements in patients’
clinical condition, fatigue, and quality of life scores; improvement of cognitive function on Wechsler
Adult Intelligence Scale (WAIS) not significant because of small number of patients in study; Turner et al
found modafinil improved set shifting, especially in extradimensional shifting and extradimensional reversal,
in patients with schizophrenia
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| OVERCOMING SEASONAL AFFECTIVE DISORDER —Norman E. Rosenthal, MD, Clinical Professor of
Psychiatry, Georgetown University Medical School, Washington, DC, and Medical Director, Capital Clinical
Research Associates, and practicing psychiatrist, Rockville, Maryland
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| Rosenthal et al: described correlation between seasonal changes in length of photoperiod and depression that occurs
in some individuals
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| Diagnostic criteria: regularly recurring depression during fall and winter with full remission in spring and summer
and at least one previous episode of depression that meets criteria for major depressive disorder; DSM-IV
refers to seasonal affective disorder (SAD) as major depressive disorder with seasonal pattern
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| Demographic and clinical features: National Institutes of Mental Health (NIMH) study of 662 patients showed average
age of patient late 30s, with average age of onset in early 20s; female-to-male ratio 3:1; average length
of depression ≈5 mo; mixed psychiatric diagnosis between bipolar and unipolar disorder, with small number
of patients diagnosed with bipolar I disorder; patients often describe family history of depression and seasonal
depression
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| Patient characteristics: Modell et al found strong female preponderance with average age of onset in 20s; on average,
patients had 13 previous episodes of depression, and 60% had not received treatment before study; majority
of patients who had undergone previous treatment received drug therapy
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| Evaluation: symptoms—slow and insidious onset that corresponds to shortening photoperiod; patients complain of
difficulty awakening, decreased energy, carbohydrate craving, increased appetite, weight gain, difficulty concentrating,
and decreased libido; affective elements often manifest late in progression of symptoms, often
around holidays, with symptoms relenting around April; screening—use Seasonal Pattern Assessment Questionnaire
(SPAQ); SPAQ used to determine Global Seasonality Scale (GSS); patients score between 0 and 24; patients
diagnosed with SAD have average GSS score of 16 to 17
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| Subsyndromal SAD: diagnosis consistent with SAD if patient has GSS ≥11 and describes at least moderate problem
during December to February; distinguishing “winter blues” (subsyndromal SAD) from SAD can be
problematic; “winter blues” can develop into SAD if patient experiences shorter photoperiod in their environment
(eg, moving to higher latitude or to home with less natural light); patients with subsyndromal SAD also
respond to light therapy
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| Risk factors: latitude—prevalence of SAD and subsyndromal SAD increases with latitude; sex and age—women
in early reproductive years have higher GSS scores than men, but scores decline toward those of men as they
age; relatively low prevalence in children until 9th grade; prevalence triples in girls of postpubertal age, but
shows only modest increase in boys after puberty; female sex hormones thought to play role in sensitizing
brain to changes in light during fall and winter
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| Phototherapy: study showed mood improved within 2 to 3 days after initiation of bright light therapy and worsened
within 2 to 3 days after cessation of light therapy in patients with SAD (much quicker effect than antidepressants);
parameters—consider intensity of light, timing and duration of therapy (depends on time of year;
may need less in autumn than in middle of winter), patient’s sensitivity to light, and amount of time patient
can spend receiving therapy; timing of therapy—studies comparing efficacy of morning to evening light therapy
found greater clinical response rate after morning exposure than after evening exposure; study found
morning exposure to phototherapy can double response rate; speaker recommends exposing patients to morning
and evening light treatment in clinical practice; wavelength—ordinary white light sufficient (avoid using
blue light); anatomic route—study found phototherapy effect occurs within eye and not skin; intensity—home
lighting equals 100 lux, office light ranges from 300 to 500 lux; light therapy uses light source of 10 000 lux;
effective light source requires box with surface area of 1 ft by 1.5 ft (larger surface area of light stimulates
more receptors on retina); side effects—headache, feeling “wired,” eyestrain, nausea or dizziness, and hypomania;
almost all can be treated by reducing exposure (eg, sitting further away or decreasing duration of therapy);
nausea best predictor of positive response to light therapy; no evidence of toxicity or damage to eye
with light therapy; dawn simulation—study found dawn simulation effective as light therapy; consider having
patients use dawn simulators (eg, sunUp dawn simulator); consider recommending timer to turn bedside lamp
on for 45 min before awakening to help patients get out of bed on winter morning; efficacy—Golden et al
found light therapy and dawn simulation effective for SAD, and light therapy effective for nonseasonal depression;
obtain baseline eye examination before treatment if patient had previous retinal injury or disease,
cataract surgery, or systemic disease, and in elderly patients; negative-ion generators found to have antidepressant
effect (may counteract positive ions in air)
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| Drug therapy: can use light and drug therapy to treat patients with SAD; Lam et al showed fluoxetine (Prozac)
has equivalent efficacy as light therapy; consider drug therapy if patient has typical melancholic symptoms;
consider light therapy if patient has atypical symptoms (eg, overeating, oversleeping); studies show fluoxetine,
sertraline, and bupropion effective
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| Pathophysiology of SAD: involves multiple neurotransmitters, particularly serotonin; greater concentration of serotonin
in brain on sunny day than on winter day; in humans, serotonin concentrations drop during winter;
also involves norepinephrine and dopamine; melatonin involved in regulating seasonal behavior in animals
and fertility behavior in sheep; melatonin occurs as nighttime pulse at night in animals; Wehr et al found that
melatonin response lengthened in winter in patients with SAD but not in normal control group
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Educational Objectives
| The goal of this activity is to provide the clinician with an understanding of the assessment and treatment of
cognitive dysfunction in patients with schizophrenia and of patients with seasonal affective disorder (SAD). After
hearing and assimilating this program, the clinician will be better able to:
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| 1. Describe the characteristics of cognitive dysfunction.
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| 2. Discuss the tests used to evaluate cognitive dysfunction in patients with schizophrenia.
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| 3. Select the most appropriate method of treating cognitive dysfunction in patients with schizophrenia.
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| 4. Screen patients for SAD.
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| 5. Choose an effective method of treatment for a patient with SAD.
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Discussed on This Program
Amphetamine and dextroamphetamine [Adderall, Adderall XR]
Aripiprazole [Abilify]
Bupropion HCl [Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban]
Clozapine [Clozaril, FazaClo]
Cycloserine [Seromycin Pulvules]
Fluoxetine HCl [Prozac, Prozac Pulvules, Prozac Weekly, Sarafem, Sarafem Pulvules]
Glycine (aminoacetic acid)
Haloperidol [Haldol, Haldol Decanoate 50, Haldol Decanoate 100]
Methylphenidate HCl [Concerta, Metadate CD, Metadate ER, Methylin, Methylin ER, Ritalin, Ritalin LA,
Ritalin–SR]
Modafinil [Provigil]
Olanzapine [Zyprexa, Zyprexa Intramuscular, Zyprexa Zydis]
Quetiapine fumarate [Seroquel]
Risperidone [Risperdal, Risperdal Consta, Risperdal M-TAB]
Sertraline HCl [Zoloft]
Tandospirone citrate
Ziprasidone HCl [Geodon]
Suggested Reading
Flashman LA: Review of cognition and brain structure in schizophrenia: profiles,longitudinal course, and effects of
treatment.Psychiatr Clin North Am 27:1, 2004; Goel N et al: Controlled trial of bright light and negative air ions for
chronic depression. Psychol Med 35:945, 2005; Golden RN et al: The efficacy of light therapy in the treatment of
mood disorders: a review and meta-analysis of the evidence. Am J Psychiatry 162:656, 2005; Levitt AJ et al: The impact
of latitude on the prevalence of seasonal depression. Can J Psychiatry 47:361, 2002; Lewine RR et al: Comparative
effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: a
randomized, double-blind trial of olanzapine versus low doses of haloperidol.Am J Psychiatry 161:985, 2004; Meltzer
HY et al: The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia.Schizophr Bull
25:233, 1999; Meltzer HY: Cognitive factors in schizophrenia: causes, impact, and treatment. CNS Spectr 9(Suppl
11):15, 2004; Miller AL: Epidemiology, etiology, and natural treatment of seasonal affective disorder. Altern Med Rev
10:5, 2005; Peuskens J et al: Treatment of cognitive dysfunction in schizophrenia. Clin Ther 27(Suppl A):25, 2005;
Sharma T et al: Cognitive function in schizophrenia. Deficits, functional consequences, and future treatment. Psychiatr
Clin North Am 26:25, 2003. Sharma T: Impact on cognition of the use of antipsychotics.Curr Med Res Opin
18(Suppl 3):13, 2002; Velligan DT eat al: Cognitive dysfunction in schizophrenia and its importance to outcome: the
place of atypical antipsychotics in treatment. J Clin Psychiatry 60 (Suppl 23);25, 1999.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant
financial relationship with the manufacturer or provider of any commercial product or service discussed.
The following has been disclosed: Dr. Hu receives research support from Astra Zeneca, Bristol-Myers Squibb,
Janssen Pharmaceutica, and Forest Laboratories, is a consultant for Abbott Laboratories, Astra Zeneca, Bristol-
Myers Squibb, Ely Lilly and Co., Janssen Pharmaceutica, Pfizer, Inc., and is on the Speakers’ Bureau of Abbott
Laboratories, AstraZeneca, Bristol-Myers Squibb, Cephalon, Inc., Eli Lilly and Co., GlaxoSmithKline, Janssen
Pharmaceutica, and Pfizer Inc. Dr. Rosenthal is a consultant for GlaxoSmithKline.
Drs. Hu and Rosenthal were recorded at Golden Gleanings from Gracious, Galvanizing Gurus, sponsored by the University
of Wisconsin Medical School and the Madison Institute of Medicine, Inc. The Audio-Digest Foundation
thanks the speakers and the sponsors for their cooperation in the production of this program.
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