Frontal lobe dysfunction and mental disorder: Commentator Call

Stevan Harnad harnad at phoenix.Princeton.EDU
Sun Feb 21 13:48:40 EST 1993

The following article on frontal lobe dysfunction and cognitive
disorder has just been published in PSYCOLOQUY, a refereed electronic
journal sponsored by the American Psychological Association and
publishing target articles reporting important new ideas and findings,
followed by open peer commentary.


    The qualified professional readership of PSYCOLOQUY is now invited
    to submit Open Peer Commentary on this target article, which
    appears below. Instructions follow the article.

most important topics in the current psychiatric literature is the
debate about the role played by the frontal lobes in mental disorder:
Dorsolateral prefrontal cortex has been widely proposed as an area
significantly involved in schizophrenia. Recent psychobiological
theories also suggest an important relationship between orbitofrontal
cortical dysfunction and obsessive-compulsive disorder (but so far the
evidence for this link is weaker).

The aim of the work reported here is to provide evidence that cognitive
impairment in schizophrenia and obsessive-compulsive disorder is indeed
related to the malfunctioning of these regions. With this target
article we hope to elicit the views and relevant findings of the
psychological, neuroscientific and psychiatric communities concerning
both the specific neuropsychological results reported here and the
topic of frontal dysfunction and cognitive disorder in general. We are
especially interested in complementing the psychiatric viewpoint with
feedback from cognitive scientists.

psycoloquy.93.4.9.frontal-cortex.1.abbruzzese         Sun, Feb 21 1993
ISSN 1055-0143      (24 paragraphs, 55 references, 3 tables, 660 lines)
PSYCOLOQUY is sponsored by the American Psychological Association (APA)
        Copyright 1993 M Abbruzzese, S Ferri, L Bellodi, S Scarone


        Massimo Abbruzzese, Stefano Ferri, Laura Bellodi & Silvio Scarone
        Psychiatric Branch
        Department of Biomedical and Technological Sciences
        University of Milan Medical School and IRCCS H S Raffaele
        Milano, 20127 Italy
        MACCIAF at IMIHSRA.bitnet

    0.0  ABSTRACT: Much converging evidence suggests that a specific
    role is played by the dorsolateral prefrontal cortex (DLPC) in
    schizophrenic disorders and by the orbitofrontal cortex (OFC) in
    obsessive-compulsive disorder (OCD). In this study, 25
    schizophrenic and 25 OCD patients were evaluated with the Wisconsin
    Card Sorting Test and the Object Alternation Test, tests that are
    sensitive to DLPC and OFC damage, respectively. The patients were
    also given the Weigl Sorting Test and Word Fluency Test to assess
    global frontal functioning. The results point to a DLPC deficit in
    schizophrenia and an OFC lability in OCD and confirm that
    functional disorders of the central nervous system can be
    investigated using neuropsychological methods.

    0.1  KEYWORDS: cognitive disorder, dorsolateral prefrontal cortex,
    mental disorder, neuropsychology, obsessive-compulsive disorder,
    orbitofrontal cortex, psychosis, schizophrenia.


1.1  Converging evidence indicates that abnormalities in the frontal
regions of the brain are involved in schizophrenia and obsessive-
compulsive disorder (OCD). This link between frontal lobe pathology and
schizophrenia and OCD has been proposed on the basis of several
structural and metabolic studies.

1.2  Structural abnormalities in schizophrenia associated with frontal
lobe areas have been reported from CT scan (Williamson et al., 1989)
and NMR (Andreasen et al., 1990) studies. Decreased metabolic activity
in the frontal cortex has been reported in schizophrenic patients using
PET (Buchsbaum et al., 1984; Wolkin et al., 1988); PET studies have
also reported increased metabolic activity in the basal ganglia in
schizophrenia (Gur et al., 1987; Berman and Weinberger, 1990).

1.3  Structural and metabolic abnormalities of subcortical frontal
regions in OCD patients have also been reported. Insofar as structural
abnormalities are concerned, CT scan and NMR have revealed reduced
(Luxemberg et al., 1988) or increased (Scarone et al., 1992) caudate
nuclear size in OCD patients. Metabolic data (Baxter et al., 1987;
Garber et al., 1989) have indicated higher levels of glucose metabolism
in the head of the caudate nucleus.

1.4  From a neuropsychological standpoint, cognitive dysfunctions
related to the frontal lobes have been noted in schizophrenia (Goldberg
et al., 1987; Butler et al., 1989; Levin et al., 1989; Seidman, 1990;
Bellini et al., 1991) and to a somewhat lesser extent in OCD (Malloy,
1987; Cattaneo et al., 1988). In schizophrenia, neuropsychological
abnormalities seem to be the expression of a malfunction in
dorsolateral prefrontal cortex (DLPC)-basal ganglia circuits
(Weinberger et al., 1986; Berman et al., 1988; Goldberg and
Weinberger, 1988).

1.5  A recent psychophysiological model of OCD (Alexander 1986; 1990;
Wise and Rapoport, 1989), supported by metabolic (Baxter et al., 1987)
and neuropsychological data (Malloy, 1987), suggests that a complex
dysfunction in the circuits which connect the basal ganglia with
orbitofrontal cortex (OFC) is at the basis of the thinking and motor
abnormalities of OCD patients. Unfortunately, as far as we know, no
supporting neuropsychological data are available.

1.6  In a series of recent neuropsychological experiments, Freedman
(1990) was able to demonstrate that the Object Alternation Test,
previously proposed as a neurofunctional probe both in primates and in
humans (Mishkin, 1964; Mishkin et al., 1969), is specifically sensitive
to orbitofrontal cortical malfunctioning,

1.7  This target article evaluates the neuropsychological
characteristics of frontal regions in a sample of OCD patients compared
with a sample of schizophrenics and a control group matched for age,
sex, educational level, and handedness. Our first objective was to test
further the hypothesis of global frontal lobe impairment, both in
schizophrenia and OCD; for this purpose, performance on the Weigl
Sorting Test (WST) and Word Fluency Test (WFT) was evaluated. Both
these neuropsychological tools have been described in the literature as
good indices of frontal functioning. Our second objective was to
confirm the involvement of DLPC in schizophrenia and of OFC in OCD
using the Wisconsin Card Sorting Test for DLPC and the Object
Alternation Test for OFC dysfunction.


2.1  Seventy-five subjects (25 OCD patients, 25 schizophrenic patients
and 25 controls matched for age, sex, educational level and handedness)
made up the three groups investigated. Table 1 shows the clinical and
demographic characteristics of the sample.

2.2  The 25 OCD patients were all recruited from the Anxiety In-patients
Unit and the 25 schizophrenics from the S. Raffaele Hospital
Rehabilitation In-Patients Service of the Psychiatric Branch in Milan,
Italy. All the schizophrenics were chronic and classified as paranoid
according to DSM III-R criteria. The diagnoses of OCD and schizophrenia
were made using the computerized version of DIS-R (Robins et al., 1989)
according to DSM III-R criteria (A.P.A. 1987) by two psychiatrists. In
addition, OCD symptomatology was assessed by means of the Yale-Brown
Obsessive-Compulsive Scale (Y-BOCS) (Goodman et al., 1989a, 1989b).

2.3  The 25 controls were recruited from among hospital employees and
the nursing staff; the inclusion criterion for recruitment was the
absence of a personal history of neurological, psychiatric illnesses or
alcohol abuse. Before being given the tests, all subjects were
submitted to a complete physical and neurological examination to
exclude any somatic illness. Furthermore, no subject had any history of
documented head injuries, loss of consciousness, neurosurgical
treatment or perinatal trauma.

2.4  At the time of their neuropsychological evaluation all the OCD
patients had been under treatment with Fluvoxamine Maleate at a mean
dosage of 234 + 35 mg/day for at least two months; the schizophrenic
patients were receiving neuroleptics at a mean chloropromazine dose
equivalent to 225 + 65 mg/day for at least six months. No patients had
taken benzodiazepines in the two weeks preceding the tests. All
subjects were right handed; handedness was evaluated using a
standardized questionnaire (Raczkowskj et al., 1974). Informed consent
concerning the purposes of the study was obtained from each subject
before starting the test.


3.1  The tests were administered by a trained neuropsychologist in a
quiet laboratory and in a single standard sequence: Weigl Sorting Test
(WST), Word Fluency Test (WFT), Wisconsin Card Sorting Test (WCST),
Object Alternation (OAT) Test. The complete task never took longer than
60 minutes. The examiner was not blind to the diagnosis. All the
subjects completed the neuropsychological battery with no problem of
fatigue or uncooperativeness.

3.2  WEIGL's SORTING TEST (WST) (Weigl, 1941; De Renzi et al., 1966).
This tool assesses the subject's ability to shift from one strategy to
another (patients with frontal lobe damage show impairment in sorting
or shifting: Kramer and Jarvik, 1979). The subject is presented 20 wood
blocks varying in shape (triangle, circle, square), colour, thickness,
symbol printed on the surface, and size. The subject is requested to
arrange them in homogeneous groups according to a common feature within
three minutes. The possible scores, based on the number of categories
the subject recognizes, range from 0 to 5.

3.3  WORD FLUENCY TEST (WFT). Many studies have confirmed that verbal
fluency is strongly connected with frontal lobe damage, particularly
the left frontal lobe anterior to Broca's area (Ramier and Hecaen,
1970). The controlled oral WFT (Benton and Hamsher, 1976) is a
neuropsychological task in which the subject is asked to say words
beginning with a particular letter of the alphabet. For each letter
there is one minute in which to produce as many words as possible.
The test consists of three word-naming trials; the letters F, A, and S
are usually used. The score consists of the total number of words
recalled, adjusted for age, sex and education, according to Benton's


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