neuropsychology of bipolar disorder (bj of psychiatry 2001)

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N E U R O P S Y C H O L O G Y O F B I P O L A R D I S O R D E RN E U R O P S Y C H O L O G Y O F B I P O L A R D I S O R D E R

example, because knowing the stage ofexample, because knowing the stage of

illness is crucial to an understanding ofillness is crucial to an understanding of

potential links between mood and cognitivepotential links between mood and cognitive

function, this review considers only thosefunction, this review considers only those

studies that specify phase of illness.studies that specify phase of illness.

Although it is much more difficult toAlthough it is much more difficult to

resolve questions posed by medication andresolve questions posed by medication andmatching for severity of illness, caution ismatching for severity of illness, caution is

essential, and in what follows we haveessential, and in what follows we have

attempted to be particularly sensitive toattempted to be particularly sensitive to

the credibility of results compromised bythe credibility of results compromised by

uncertain methodologies.uncertain methodologies.

COGNITIVE FUNCTIONINGCOGNITIVE FUNCTIONING

IN THE AFFECTIVEIN THE AFFECTIVE

DISORDERSDISORDERS

The first step in our reconsideration ofThe first step in our reconsideration of

mood and cognitive functioning is a reviewmood and cognitive functioning is a review

of the evidence relevant to neuropsycholo-of the evidence relevant to neuropsycholo-

gical functioning in the depressed, manicgical functioning in the depressed, manic

and euthymic phases of bipolar disorder.and euthymic phases of bipolar disorder.

Distinguishing between unipolar and bi-Distinguishing between unipolar and bi-

polar forms of depressive illness representspolar forms of depressive illness represents

another contentious but essential problemanother contentious but essential problem

in this area of research. It should be notedin this area of research. It should be noted

that the DSMIV (American Psychiatric As-that the DSMIV (American Psychiatric As-

sociation, 1994) no longer uses the termssociation, 1994) no longer uses the terms

`unipolar' and `bipolar' depression. Instead,`unipolar' and `bipolar' depression. Instead,

the terms `major depressive disorder' andthe terms `major depressive disorder' and

`bipolar disorder' are used. However, the`bipolar disorder' are used. However, the

former terms are used here for the purposesformer terms are used here for the purposes

of clarity and consistency with past studies.of clarity and consistency with past studies.

We also consider whether differences existWe also consider whether differences exist

between patients with major (unipolar)between patients with major (unipolar)

depressive disorder and patients in thedepressive disorder and patients in the

depressed phase of bipolar illness. Finally,depressed phase of bipolar illness. Finally,

we address the extent to which cognitivewe address the extent to which cognitive

impairment remains in patients with bi-impairment remains in patients with bi-

polar disorder who are euthymic at the timepolar disorder who are euthymic at the time

of neuropsychological assessment.of neuropsychological assessment.

Cognitive impairment inCognitive impairment in

depressiondepression

Until fairly recently it was thought thatUntil fairly recently it was thought thateven severe forms of depression wereeven severe forms of depression were

associated with only minor impairments inassociated with only minor impairments in

cognitive function. An important and com-cognitive function. An important and com-

prehensive review by Miller (1975) chal-prehensive review by Miller (1975) chal-

lenged this belief by suggesting that bothlenged this belief by suggesting that both

mild and severe forms of depression are as-mild and severe forms of depression are as-

sociated with pronounced deficits on cogni-sociated with pronounced deficits on cogni-

tive, motor, perceptual and communicationtive, motor, perceptual and communication

tasks. Since then, many studies have de-tasks. Since then, many studies have de-

monstrated the presence of wide-rangingmonstrated the presence of wide-ranging

neuropsychological deficits in paneuropsychological deficits in patients withtients with

depression (Weingartnerdepression (Weingartner et alet al, 1981; Brown, 1981; Brown

et alet al,, 1994; Beats1994; Beats et alet al, 1996; Elliott, 1996; Elliott et alet al,,1996), with current investigation focusing1996), with current investigation focusing

on theon the relationship of these now establishedrelationship of these now established

deficits to clinical and neurobiological di-deficits to clinical and neurobiological di-

mensions of the disorder.mensions of the disorder.

Although patients with depression haveAlthough patients with depression have

been studied using a wide range of neuro-been studied using a wide range of neuro-

psychological tests, researchers have focusedpsychological tests, researchers have focused

on memory and executive function, as theon memory and executive function, as theneuroanatomical regions thought to sub-neuroanatomical regions thought to sub-

serveserve these cognitive domains are fairlythese cognitive domains are fairly

well specified (see Elliott, 1998). Given thatwell specified (see Elliott, 1998). Given that

patients with depression frequently com-patients with depression frequently com-

plain of memory difficulties, it is perhapsplain of memory difficulties, it is perhaps

not surprising that these subjects demon-not surprising that these subjects demon-

strate impairments on a range of memorystrate impairments on a range of memory

tasks (see Blaney, 1986; Johnson & Magaro,tasks (see Blaney, 1986; Johnson & Magaro,

1987; Burt1987; Burt et alet al, 1995, for reviews). Deficits, 1995, for reviews). Deficits

have been reported on tests of short-termhave been reported on tests of short-term

memory, verbal and visual recognitionmemory, verbal and visual recognition

memory, spatial working memory andmemory, spatial working memory and

immediate or delayed recall (Austinimmediate or delayed recall (Austin et alet al,,1992; Brown1992; Brown et alet al, 1994; Ilsley, 1994; Ilsley et alet al, 1995;, 1995;

BeatsBeats et alet al, 1996; Elliott, 1996; Elliott et alet al, 1996)., 1996). As suchAs such

a broad spectrum of findings may suggest,a broad spectrum of findings may suggest,

there has been much debate over the pre-there has been much debate over the pre-

cise nature of memory impairment, and acise nature of memory impairment, and a

number of distinct formulations have beennumber of distinct formulations have been

offered to explain the observed deficitsoffered to explain the observed deficits

(see Robbins(see Robbins et alet al, 1992, for discussion)., 1992, for discussion).

Executive abilities are also compro-Executive abilities are also compro-

mised in these patients, and it has been ar-mised in these patients, and it has been ar-

gued that of the neuropsychological tasksgued that of the neuropsychological tasks

showing impairment, tests of executiveshowing impairment, tests of executive

function may be the most sensitive. Thesefunction may be the most sensitive. Thesehigh-level tasks, of which the Wisconsinhigh-level tasks, of which the Wisconsin

Card Sorting Test (WCST) (Grant & Berg,Card Sorting Test (WCST) (Grant & Berg,

1948) and the Tower of London test of1948) and the Tower of London test of

planning ability (Shallice, 1982) are classicplanning ability (Shallice, 1982) are classic

examples, require the coordination of cog-examples, require the coordination of cog-

nitive processes for their successful comple-nitive processes for their successful comple-

tion, and are thought to depend on intacttion, and are thought to depend on intact

functioning of the prefrontal cortex. Indeed,functioning of the prefrontal cortex. Indeed,

patients with major depressive disorderpatients with major depressive disorder

have been shown to be impaired on bothhave been shown to be impaired on both

of these tests (Martinof these tests (Martin et alet al, 1991; Franke, 1991; Franke

et alet al, 1993; Elliott, 1993; Elliott et alet al, 1996), leading some, 1996), leading some

researchers to postulate the importance ofresearchers to postulate the importance ofprefrontal dysfunction in the pathogenesisprefrontal dysfunction in the pathogenesis

of clinical depression (e.g. Elliott, 1998).of clinical depression (e.g. Elliott, 1998).

UnipolarUnipolar v.v. bipolar depressionbipolar depression

Many studies are based on samples of pa-Many studies are based on samples of pa-

tients with depression that includes bothuni-tients with depression that includes both uni-

polar and bipolar disorders, presupposingpolar and bipolar disorders, presupposing

the essential similarity of these conditions.the essential similarity of these conditions.

Of the few studies that have directly com-Of the few studies that have directly com-

pared the two, the general findings suggestpared the two, the general findings suggest

that, at least on some neuropsychologicalthat, at least on some neuropsychological

tasks, deficits are more marked in bipolartasks, deficits are more marked in bipolarthan in unipolar depression. For example,than in unipolar depression. For example,

SavardSavard et al et al (1980) administered the(1980) administered the

HalsteadReitan Category Test to acutelyHalsteadReitan Category Test to acutely

depressed unipolar and bipolar groups ofdepressed unipolar and bipolar groups of

patients who were free of medication atpatients who were free of medication at

the time of testing, and found that patientsthe time of testing, and found that patients

in the bipolar group made significantlyin the bipolar group made significantly

more errors than either patients in the uni-more errors than either patients in the uni-polar group or control subjects. On tests ofpolar group or control subjects. On tests of

learning and verbal fluency, Wolfelearning and verbal fluency, Wolfe et alet al

(1987) similarly found more marked im-(1987) similarly found more marked im-

pairments in patients with bipolar disorderpairments in patients with bipolar disorder

than in patients with unipolar depressionthan in patients with unipolar depression

matched for age and education. It shouldmatched for age and education. It should

be noted that the conclusions drawn frombe noted that the conclusions drawn from

both of these studies may be compromisedboth of these studies may be compromised

by the presence of confounding variables.by the presence of confounding variables.

For example, patients in the bipolar groupFor example, patients in the bipolar group

of Savardof Savard et alet al (1980) were significantly(1980) were significantly

older than those in the unipolar group, sug-older than those in the unipolar group, sug-

gesting that age alone may have accountedgesting that age alone may have accountedfor their findings. Additionally, Wolfefor their findings. Additionally, Wolfe etet

alal (1987) cautioned that differences be-(1987) cautioned that differences be-

tween their unipolar and bipolar groupstween their unipolar and bipolar groups

might actually reflect subtle differences inmight actually reflect subtle differences in

severity: the rate of hospitalisation in bi-severity: the rate of hospitalisation in bi-

polar patients was twice that noted in thepolar patients was twice that noted in the

unipolar patients.unipolar patients.

Cognitive impairment in maniaCognitive impairment in mania

In contrast to the large amount of work de-In contrast to the large amount of work de-

voted to the cognitive changes accompany-voted to the cognitive changes accompany-

ing depression, only a few studies haveing depression, only a few studies haveaddressed the precise nature of impairmentaddressed the precise nature of impairment

in patients with mania. A possible explana-in patients with mania. A possible explana-

tion for this imbalance may be the practicaltion for this imbalance may be the practical

difficulties of using standard neuropsycho-difficulties of using standard neuropsycho-

logical procedures to assess mania; the nat-logical procedures to assess mania; the nat-

ure of the illness may prevent patients withure of the illness may prevent patients with

mania from being reliable subjects, espe-mania from being reliable subjects, espe-

cially in tests of cognitive functioning.cially in tests of cognitive functioning.

Nevertheless, it has long been recognisedNevertheless, it has long been recognised

that mania is associated with changes inthat mania is associated with changes in

cognition as well as in affect (Kraepelin,cognition as well as in affect (Kraepelin,

1921; Bunney & Hartmann, 1965), and1921; Bunney & Hartmann, 1965), and

more recent empirical studies confirm thismore recent empirical studies confirm thisview.view.

Patients with mania have been studiedPatients with mania have been studied

using tasks that sample aspects of learningusing tasks that sample aspects of learning

and memory, visuospatial ability and ex-and memory, visuospatial ability and ex-

ecutive function. In a study conducted byecutive function. In a study conducted by

Taylor & Abrams (1986), tests of attention,Taylor & Abrams (1986), tests of attention,

visuospatial function and memory were ad-visuospatial function and memory were ad-

ministered to patients with mania, approxi-ministered to patients with mania, approxi-

mately half of whom exhibited moderate ormately half of whom exhibited moderate or

severe global cognitive impairment. Withsevere global cognitive impairment. With

respect to memory processes, Bunney &respect to memory processes, Bunney &

Hartmann (1965) noted memory lossHartmann (1965) noted memory loss

during manic states in a patient with regu-during manic states in a patient with regu-lar manicdepressive cycles every 48 hours.lar manicdepressive cycles every 48 hours.

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M U R P HY & S A H A K I A NM U R P HY & S A H A K I A N

Furthermore, HenryFurthermore, Henry et alet al (1971) reported(1971) reported

impaired serial word list learning duringimpaired serial word list learning during

mania, with decrements in performance di-mania, with decrements in performance di-

rectly related to increasing severity of ill-rectly related to increasing severity of ill-

ness. More recent findings suggest thatness. More recent findings suggest that

patients with bipolar disorder in the manicpatients with bipolar disorder in the manic

phase of their illness are impaired on testsphase of their illness are impaired on testsof pattern and spatial recognition memoryof pattern and spatial recognition memory

and delayed visual recognition (Murphyand delayed visual recognition (Murphy

et alet al,, 1999). In an attempt to explain ob-1999). In an attempt to explain ob-

served memory deficits, Henryserved memory deficits, Henry et al et al

(1971) proposed that memory impairment(1971) proposed that memory impairment

may at least sometimes be owing to alteredmay at least sometimes be owing to altered

patterns of verbal association. Andreasenpatterns of verbal association. Andreasen

& Powers (1974) reached a similar conclu-& Powers (1974) reached a similar conclu-

sion with their finding that, relative to con-sion with their finding that, relative to con-

trol subjects, the memory structures oftrol subjects, the memory structures of

patients with mania were loose, overinclu-patients with mania were loose, overinclu-

sive and idiosyncratic, leading to difficultiessive and idiosyncratic, leading to difficulties

in filtering environmental stimuli and ain filtering environmental stimuli and atendency to overgeneralise.tendency to overgeneralise.

The notion that mania is associatedThe notion that mania is associated

with some form of `dysexecutive syndrome'with some form of `dysexecutive syndrome'

also seems reasonable, since patients typi-also seems reasonable, since patients typi-

cally exhibit disrupted social behaviourcally exhibit disrupted social behaviour

and decision-making reminiscent of thatand decision-making reminiscent of that

observed in patients with lesions to frontalobserved in patients with lesions to frontal

regions of the cortex (Bechararegions of the cortex (Bechara et alet al, 1994)., 1994).

It is thus surprising that so little researchIt is thus surprising that so little research

assesses executive functioning in theseassesses executive functioning in these

patients. To date, this type of functioningpatients. To date, this type of functioning

has been studied using tests of attentionalhas been studied using tests of attentional

set-shifting (Morice, 1990; Clarkset-shifting (Morice, 1990; Clark et al et al ,,2000), planning ability (Murphy2000), planning ability (Murphy et alet al, 1999), 1999)

and decision-making (Clarkand decision-making (Clark et alet al, 2000;, 2000;

MurphyMurphy et alet al, 2001). Although impairments, 2001). Although impairments

have been observed across the full range ofhave been observed across the full range of

tasks, it is not yet clear to what extent thesetasks, it is not yet clear to what extent these

deficits stand over and above those observeddeficits stand over andabove those observed

in other non-executive domains.in other non-executive domains.

Residual neuropsychologicalResidual neuropsychological

impairments in euthymiaimpairments in euthymia

Kraepelin (1921) distinguished manicdepres-Kraepelin (1921) distinguishedmanic depres-sion from schizophrenia on the basis of itssion from schizophrenia on the basis of its

relapsing and remitting course. Patients withrelapsing and remitting course. Patients with

affective illness, unlike those with dementiaaffective illness, unlike those with dementia

praecox, were thought to experience remis-praecox, were thought to experience remis-

sion without cognitive impairment. Recentsion without cognitive impairment. Recent

investigations of patients in the euthymicinvestigations of patients in the euthymic

phase of bipolar disorder, however, havephase of bipolar disorder, however, have

challenged this view. Many patients con-challenged this view. Many patients con-

tinue to experience psychological and socialtinue to experience psychological and social

difficulties, and while the extent to whichdifficulties, and while the extent to which

neuropsychological impairment remains isneuropsychological impairment remains is

less clear, most studies report at least someless clear, most studies report at least some

degree of residual cognitive dysfunction indegree of residual cognitive dysfunction inone or more tasks administered.one or more tasks administered.

Asarnow & MacCrimmon (1981) usedAsarnow & MacCrimmon (1981) used

a test of attention and visual informationa test of attention and visual information

processing to compare the performance ofprocessing to compare the performance of

out-patients with manic depression orout-patients with manic depression or

schizophrenia both groups judged by theirschizophrenia both groups judged by their

attending psychiatrists to be free from majorattending psychiatrists to be free from major

symptoms with that of healthy controls.symptoms with that of healthy controls.Performance of the manic depressionPerformance of the manic depression groupgroup

was midway between that of the schizo-was midway between that of the schizo-

phrenia and control groups, suggesting thatphrenia and control groups, suggesting that

people with bipolar disorder demonstratepeople with bipolar disorder demonstrate

cognitive impairments that are probablycognitive impairments that are probably

not entirely due to residual psychoticnot entirely due to residual psychotic

symptoms. Similarly, Thamsymptoms. Similarly, Tham et alet al (1997)(1997)

administered an extensive range of neuro-administered an extensive range of neuro-

psychological tasks to patients with recur-psychological tasks to patients with recur-

rent mood disorder (10 unipolar and 16rent mood disorder (10 unipolar and 16

bipolar) who were euthymic at the time ofbipolar) who were euthymic at the time of

neuropsychological assessment. Cognitiveneuropsychological assessment. Cognitive

functioning was markedly impaired in afunctioning was markedly impaired in asubstantial number of these patients. Moresubstantial number of these patients. More

recently, Ferrierrecently, Ferrier et alet al (1999) reported resi-(1999) reported resi-

dual impairment of executive function indual impairment of executive function in

people with euthymic bipolar disorder afterpeople with euthymic bipolar disorder after

controlling for age, premorbid intelligencecontrolling for age, premorbid intelligence

and depressive symptomatology. Rubinsz-and depressive symptomatology. Rubinsz-

teintein et alet al (2000) found asymptomatic pa-(2000) found asymptomatic pa-

tients with bipolar disorder (in remissiontients with bipolar disorder (in remission

for at least 4 months) to show deficits onfor at least 4 months) to show deficits on

tests of visuospatial recognition memory;tests of visuospatial recognition memory;

response latency, but not accuracy, on fourresponse latency, but not accuracy, on four

distinct tests of executive function, was alsodistinct tests of executive function, was also

impaired. Other investigators have reportedimpaired. Other investigators have reportedevidence of residual impairment as wellevidence of residual impairment as well

(Jones(Jones et alet al, 1994; McKay, 1994; McKay et alet al, 1995; Kes-, 1995; Kes-

sing, 1998 but see Kerrysing, 1998 but see Kerry et alet al, 1983)., 1983).

While the jury is still out on the preciseWhile the jury is still out on the precise

neuropsychological profile found in euthy-neuropsychological profile found in euthy-

mic bipolar disorder, the balance ofmic bipolar disorder, the balance of

evidence from such studies supports aevidence from such studies supports a

hypothesis of residual cognitive impair-hypothesis of residual cognitive impair-

ment. It is important to note that the bulkment. It is important to note that the bulk

of these studies employ cross-sectional,of these studies employ cross-sectional,

between-subject designs that compare eu-between-subject designs that compare eu-

thymic patients with bipolar disorder withthymic patients with bipolar disorder with

healthy controls. As mentioned above,healthy controls. As mentioned above,longitudinal, within-subject designs arelongitudinal, within-subject designs are

more effective in assessing how cognitivemore effective in assessing how cognitive

performance changes with symptomaticperformance changes with symptomatic

recovery. Clearly, both types of study arerecovery. Clearly, both types of study are

necessary if we are to address whethernecessary if we are to address whether

performance of euthymic patients with bi-performance of euthymic patients with bi-

polar disorder is inferior to that of healthypolar disorder is inferior to that of healthy

controls, and to demonstrate deteriorationcontrols, and to demonstrate deterioration

or improvement of cognitive functioningor improvement of cognitive functioning

within a single subject group. One final notewithin a single subject group. One final note

of caution is that some studies do not mea-of caution is that some studies do not mea-

sure manic or depressive symptomatologysure manic or depressive symptomatology

during the euthymic phase under studyduring the euthymic phase under study(see Rubinsztein(see Rubinsztein et alet al, 2000, for a notable, 2000, for a notable

exception). It is therefore possible thatexception). It is therefore possible that

subclinical psychopathology may at leastsubclinical psychopathology may at least

partially account for the residual deficitspartially account for the residual deficits

observed.observed.

Thus, while recent experiments have es-Thus, while recent experiments have es-

tablished the range and depth of cognitivetablished the range and depth of cognitive

impairments associated with depression,impairments associated with depression,mania is clearly suffering from a lack ofmania is clearly suffering from a lack of

attention. Preliminary results suggest wide-attention. Preliminary results suggest wide-

ranging deficits in patients with mania;ranging deficits in patients with mania;

but a comprehensive investigation of cogni-but a comprehensive investigation of cogni-

tive functioning across a full spectrum oftive functioning across a full spectrum of

tasks should still be undertaken. Compari-tasks should still be undertaken. Compari-

sons of unipolar and bipolar forms of de-sons of unipolar and bipolar forms of de-

pression have revealed interesting findings;pression have revealed interesting findings;

they suggest that studies presupposing thethey suggest that studies presupposing the

essential similarity of unipolar illness withessential similarity of unipolar illness with

bipolar illness may be too simplistic.bipolar illness may be too simplistic.

Likewise, the presumption that (bipolar)Likewise, the presumption that (bipolar)

mania and unipolar depression representmania and unipolar depression representopposite emotional pales in a cognitiveopposite emotional pales in a cognitive

affective continuum may also be an over-affective continuum may also be an over-

simplified model. It is also possible thatsimplified model. It is also possible that

the cognitive deficits observed in bipolarthe cognitive deficits observed in bipolar

disorder (depressed phase) could stemdisorder (depressed phase) could stem

from a source unrelated to that of similarfrom a source unrelated to that of similar

impairments in unipolar depression, andimpairments in unipolar depression, and

that the relationship of affect to all thesethat the relationship of affect to all these

impairments might be more complicated.impairments might be more complicated.

GENERALGENERAL V.V. SPECIFICSPECIFIC

DEFICITS : DISTINGUISHINGDEFICITS : DISTINGUISHINGMANIA FROMMANIA FROM

SCHIZOPHRENIA ANDSCHIZOPHRENIA AND

DEPRESSIONDEPRESSION

Some studies have adopted a comparativeSome studies have adopted a comparative

strategy for characterising possible cogni-strategy for characterising possible cogni-

tive deficits associated with mania. Thesetive deficits associated with mania. These

studies compare mania with other neuro-studies compare mania with other neuro-

psychiatric disorders, such as schizophreniapsychiatric disorders, such as schizophrenia

and depression, to determine whether man-and depression, to determine whether man-

ia is associated with qualitatively differentia is associated with qualitatively different

forms of cognitive impairment from thoseforms of cognitive impairment from those

found in seemingly related illnesses. Thisfound in seemingly related illnesses. Thismethod of establishing a specific psycholo-method of establishing a specific psycholo-

gical profile for mania could prove verygical profile for mania could prove very

fruitful for the more general investigationfruitful for the more general investigation

of mood and cognition, as it compares theof mood and cognition, as it compares the

cognitive performance of patients withcognitive performance of patients with

mania with that of those with depression,mania with that of those with depression,

and tests for deficits that might be identicaland tests for deficits that might be identical

in both illnesses. These studies determinein both illnesses. These studies determine

whether the impairments observed in maniawhether the impairments observed in mania

can be explained by factors specific to thecan be explained by factors specific to the

manic state or whether they are, alterna-manic state or whether they are, alterna-

tively, owing to global pathology and moretively, owing to global pathology and more

general problems such as psychosis orgeneral problems such as psychosis ordisordered thought.disordered thought.

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Comparing mania andComparing mania and

schizophreniaschizophrenia

Several studies have compared performanceSeveral studies have compared performance

in mania and schizophrenia (Andreasen &in mania and schizophrenia (Andreasen &

Powers, 1974; Oltmanns, 1978; StraussPowers, 1974; Oltmanns, 1978; Strauss

et alet al, 1984; Morice, 1990; Goldberg, 1984; Morice, 1990; Goldberg et alet al,,

1993). Findings from these studies indicate1993). Findings from these studies indicate

thaton tests of selective attention (Oltmanns,thaton tests of selective attention (Oltmanns,

1978), perceptual span (Strauss1978), perceptual span (Strauss et alet al, 1984), 1984)

and shifting attentional set (measures byand shifting attentional set (measures by

the WCST (Morice, 1990)), the deficits inthe WCST (Morice, 1990)), the deficits in

patients with mania are indistinguishablepatients with mania are indistinguishable

from those in patients with schizophrenia.from those in patients with schizophrenia.

Oltmanns (1978) found that although bothOltmanns (1978) found that although both

sets of patients were more distractable thansets of patients were more distractable than

normal controls, they did not differ fromnormal controls, they did not differ from

each other. Other investigators have alsoeach other. Other investigators have also

demonstrated the non-specific nature ofdemonstrated the non-specific nature of

mania-related deficits. Otteson & Holzmanmania-related deficits. Otteson & Holzman

(1976) studied patients with schizophrenia,(1976) studied patients with schizophrenia,

patients with psychosis but without schizo-patients with psychosis but without schizo-

phrenia and non-psychotic patients andphrenia and non-psychotic patients and

compared them to one another and tocompared them to one another and to

healthy controls on a variety of cognitivehealthy controls on a variety of cognitive

measures. While group differences emergedmeasures. While group differences emerged

between psychiatric patients and controlbetween psychiatric patients and control

subjects, and also between patients withsubjects, and also between patients with

and without psychosis, there were no differ-and without psychosis, there were no differ-

ences between the schizophrenia and maniaences between the schizophrenia and mania

groups. Any group differences appeared togroups. Any group differences appeared to

be related to degree, rather than type, ofbe related to degree, rather than type, of

disorganisation.disorganisation.

In contrast to the above, differencesIn contrast to the above, differences

between patients with mania and schizo-between patients with mania and schizo-

phrenia have also been reported. For ex-phrenia have also been reported. For ex-

ample, Andreasen & Powers (1974)ample, Andreasen & Powers (1974)

found overinclusive thinking to be morefound overinclusive thinking to be more

prominent in mania than in schizophrenia.prominent in mania than in schizophrenia.

Similarly, GoldbergSimilarly, Goldberg et alet al (1993) reported(1993) reported

that patients with schizophrenia consis-that patients with schizophrenia consis-

tently performed at lower levels than thosetently performed at lower levels than those

with affective disorder (unipolar depression,with affective disorder (unipolar depression,

bipolar depression and bipolar mania) onbipolar depression and bipolar mania) on

tests of psychomotor speed, attention,tests of psychomotor speed, attention,

memory and attentional set-shifting. It ismemory and attentional set-shifting. It is

perhaps noteworthy that generalised intel-perhaps noteworthy that generalised intel-

lectual deterioration was more marked inlectual deterioration was more marked in

schizophrenia than in the affective dis-schizophrenia than in the affective dis-

orders, and when intelligence was con-orders, and when intelligence was con-

trolled for, group differences emerged onlytrolled for, group differences emerged only

on a test of memory and the WCST. Thus,on a test of memory and the WCST. Thus,

the balance of evidence suggests marked si-the balance of evidence suggests marked si-

milarities between the neuropsychologicalmilarities between the neuropsychological

profiles in mania and schizophrenia.profiles in mania and schizophrenia.

Comparing mania and depressionComparing mania and depression

Similar findings have been reported fromSimilar findings have been reported from

work on comparative cognitive perfor-work on comparative cognitive perfor-mance in mania and depression. Bulbenamance in mania and depression. Bulbena

& Berrios (1993) assessed performance of& Berrios (1993) assessed performance of

patients during acute episodes of major de-patients during acute episodes of major de-

pression and mania using tests of attention,pression and mania using tests of attention,

memory, visuospatial function and choicememory, visuospatial function and choice

reaction time. Relative to controls, patientsreaction time. Relative to controls, patients

were impaired on most cognitive measures,were impaired on most cognitive measures,

but no differences between mania and de-but no differences between mania and de-pression were found. Moreover, Goldbergpression were found. Moreover, Goldberg

et alet al (1993) found that in bipolar disorder,(1993) found that in bipolar disorder,

patients in manic and depressed episodespatients in manic and depressed episodes

did not differ on the Wechsler Adult Intelli-did not differ on the Wechsler Adult Intelli-

gence Scale Revised (WAISR), WCST,gence Scale Revised (WAISR), WCST,

or on neuropsychological tests of reading,or on neuropsychological tests of reading,

line orientation and facial recognition.line orientation and facial recognition.

While direct statistical comparison be-While direct statistical comparison be-

tween patients with mania and depressiontween patients with mania and depression

is clearly the best approach in searchingis clearly the best approach in searching

for distinct neuropsychological profiles, in-for distinct neuropsychological profiles, in-

direct comparison between patient groupsdirect comparison between patient groups

who have been assessed using standardisedwho have been assessed using standardisedneuropsychological tasks can also be infor-neuropsychological tasks can also be infor-

mative. In a study by Murphymative. In a study by Murphy et alet al (1999),(1999),

patients in the manic phase of bipolar ill-patients in the manic phase of bipolar ill-

ness were given tests of memory and execu-ness were given tests of memory and execu-

tive function taken from the Cambridgetive function taken from the Cambridge

Neuropsychological Test Automated BatteryNeuropsychological Test Automated Battery

(CANTAB, CeNes Plc, Cambridge, UK).(CANTAB, CeNes Plc, Cambridge, UK).

These tests are reliable and valid (RobbinsThese tests are reliable and valid (Robbins

et alet al, 1994, 1998), and had been previously, 1994, 1998), and had been previously

administered as part of a much larger testadministered as part of a much larger test

battery to a sample of patients with majorbattery to a sample of patients with major

depressive disorder (Elliottdepressive disorder (Elliott et alet al , 1996)., 1996).

Patients with mania demonstrated sub-Patients with mania demonstrated sub-stantial impairments on tests of patternstantial impairments on tests of pattern

and spatial recognition memory, andand spatial recognition memory, and

delayed visual recognition. This pattern ofdelayed visual recognition. This pattern of

impairment was strikingly similar to thatimpairment was strikingly similar to that

previously observed in patients withpreviously observed in patients with

depression (Table 1). Executive function, asdepression (Table 1). Executive function, as

assessed by the computerised one-touchassessed by the computerised one-touch

Tower of London test of planning ability,Tower of London test of planning ability,

was also similarly impaired in the twowas also similarly impaired in the two

patient groups (Fig. 1).patient groups (Fig. 1).

The cognitive impairments observed inThe cognitive impairments observed in

both groups of patients in these studies wereboth groups of patients in these studies were

interpreted as evidence for relatively globalinterpreted as evidence for relatively globalneuropsychological dysfunction (Elliottneuropsychological dysfunction (Elliott et alet al,,

1996; Murphy1996; Murphy et alet al, 1999). The deficits ob-, 1999). The deficits ob-

served in patients with mania and depres-served in patients with mania and depres-

sion when tested on object recognitionsion when tested on object recognition

memory were comparable to those pre-memory were comparable to those pre-

viously reported in patients with posteriorviously reported in patients with posterior

dysfunction, such as temporal lobe lesionsdysfunction, such as temporal lobe lesions

(Owen(Owen et alet al, 1995, 1995aa) or mild Alzheimer's) or mild Alzheimer's

dementia (Sahakiandementia (Sahakian et al et al , 1988). The, 1988). The

deficits seen on tests of spatial recognitiondeficits seen on tests of spatial recognition

memory and planning ability, however,memory and planning ability, however,

were similar to those in patients with fron-were similar to those in patients with fron-

tal dysfunction (Owental dysfunction (Owen et alet al , 1995, 1995bb) or) orbasal ganglia disorders such as Parkinson'sbasal ganglia disorders such as Parkinson's

disease (Owendisease (Owen et alet al, 1995, 1995bb), in which there), in which there

is disrupted functioning of frontostriatalis disrupted functioning of frontostriatal

`loops' (Alexander`loops' (Alexander et alet al, 1986). At first, 1986). At first

glance, these findings suggest that patientsglance, these findings suggest that patients

with mania and depression are similarly im-with mania and depression are similarly im-

paired on a range of cognitive tasks sub-paired on a range of cognitive tasks sub-

served by different neural regions, andserved by different neural regions, andthat a single common underlying mechan-that a single common underlying mechan-

ism may account for the noted deficits inism may account for the noted deficits in

both groups. Investigators of depressionboth groups. Investigators of depression

have suggested that the pervasive deficitshave suggested that the pervasive deficits

observed could be due to reduced motiva-observed could be due to reduced motiva-

tion (Miller, 1975; Seligman, 1975; Ri-tion (Miller, 1975; Seligman, 1975; Ri-

chards & Ruff, 1989), a conservativechards & Ruff, 1989), a conservative

response style (Johnson & Magaro, 1987;response style (Johnson & Magaro, 1987;

WilliamsWilliams et alet al, 1997), diminished cognitive, 1997), diminished cognitive

capacity and processing resources (Hashercapacity and processing resources (Hasher

& Zacks, 1979), or a narrowing of atten-& Zacks, 1979), or a narrowing of atten-

tional focus to depression-relevant or task-tional focus to depression-relevant or task-

irrelevant thoughts (Ellis & Ashbrook,irrelevant thoughts (Ellis & Ashbrook,1988). To date, few investigators have con-1988). To date, few investigators have con-

sidered mania-related deficits within thesesidered mania-related deficits within these

or similar frameworks.or similar frameworks.

The bulk of research suggests that inThe bulk of research suggests that in

both mania and depression, patients are im-both mania and depression, patients are im-

paired on a range of cognitive tasks sub-paired on a range of cognitive tasks sub-

served by different neural regions. Inserved by different neural regions. In

addition, although the few studies thataddition, although the few studies that

actually compare mania and depressionactually compare mania and depression

employ a limited range of tasks, it appearsemploy a limited range of tasks, it appears

that conventional neuropsychological teststhat conventional neuropsychological tests

of attention, memory and executive func-of attention, memory and executive func-

tion are unable to discriminate between pa-tion are unable to discriminate between pa-tients with mania and depression. Together,tients with mania and depression. Together,

these findings suggest that global pathologi-these findings suggest that global pathologi-

cal change, rather than factors unique tocal change, rather than factors unique to

either disorder, may account for the ob-either disorder, may account for the ob-

served deficits, and that similar processesserved deficits, and that similar processes

may be involved despite markedly differentmay be involved despite markedly different

clinical presentations.clinical presentations.

New approaches to distinctNew approaches to distinct

profiles: biases in informationprofiles: biases in information

processingprocessing

So far, this review has focused on the perfor-So far, this review has focused on the perfor-mance of cognitive and neuropsychologicalmance of cognitive and neuropsychological

tasks employing neutral materials thosetasks employing neutral materials those

that are not emotionally relevant to the pa-that are not emotionally relevant to the pa-

tient's condition, i.e. materials not see-tient's condition, i.e. materials not see-

mingly positive or negative in affective ormingly positive or negative in affective or

emotional tone. This exclusion of affectiveemotional tone. This exclusion of affective

material effectively removes mood frommaterial effectively removes mood from

the experimental dynamic; in order to assessthe experimental dynamic; in order to assess

the possible relationship between mood andthe possible relationship between mood and

cognition in the affective disorders, we mustcognition in the affective disorders, we must

consider studies incorporating affective ma-consider studies incorporating affective ma-

terial in the experimental design. In patientsterial in the experimental design. In patients

with depression, empirical studies of mood-with depression, empirical studies of mood-congruent biases in information processingcongruent biases in information processing

s 1 2 3s 1 2 3


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are abundant, with biases reported in eva-are abundant, with biases reported in eva-

luative processes, social judgements, deci-luative processes, social judgements, deci-

sion-making, attention and memory (Clarksion-making, attention and memory (Clark

& Teasdale, 1982; Blaney, 1986; Gotlib && Teasdale, 1982; Blaney, 1986; Gotlib &

Cane, 1987; MoggCane, 1987; Mogg et alet al, 1995; Bradley, 1995; Bradley etet

alal, 1996).One of the earliest studies examin-, 1996).One of the earliest studies examin-

ed the recall of past experiences in patientsed the recall of past experiences in patients

who were clinically depressed and healthywho were clinically depressed and healthy

control participants (Lloyd & Lishman,control participants (Lloyd & Lishman,1975). The results indicated that when1975). The results indicated that when

patients with depression were required topatients with depression were required to

recall pleasant or unpleasant experiencesrecall pleasant or unpleasant experiencesfrom their past in response to various cuefrom their past in response to various cue

words (e.g. `house', `table'), patients recalledwords (e.g. `house', `table'), patients recalled

unpleasant memories more quickly thanunpleasant memories more quickly than

pleasant ones as the severity of depressionpleasant ones as the severity of depression

increased.increased.

In light of these findings, it seemed rea-In light of these findings, it seemed rea-

sonable to suppose that if differences insonable to suppose that if differences in

cognitive functioning in mania and depres-cognitive functioning in mania and depres-

sion do indeed exist, they will emerge onsion do indeed exist, they will emerge on

tasks involving the interaction between cog-tasks involving the interaction between cog-

nitive and affective (or emotional) proces-nitive and affective (or emotional) proces-

sing. We attempted to address thissing. We attempted to address this

hypothesis by administering a novel àffec-hypothesis by administering a novel àffec-tive go/no-go' task to patients with maniative go/no-go' task to patients with mania

and depression, and to healthy controlsand depression, and to healthy controls

matched for age and premorbid intelligencematched for age and premorbid intelligence

(Murphy(Murphy et alet al, 1999). This task required, 1999). This task required

both attentional and affective processesboth attentional and affective processes

for its successful completion. Specifically,for its successful completion. Specifically,

subjects were required to respond to targetsubjects were required to respond to target

words of either positive or negative affec-words of either positive or negative affec-

tive tone by tapping the space bar of a com-tive tone by tapping the space bar of a com-

puter keyboard as quickly as possible, andputer keyboard as quickly as possible, and

to inhibit this response to words of theto inhibit this response to words of the

competing affective category. As shown incompeting affective category. As shown in

Fig. 2,Fig. 2, both groups of patients exhibitedattention and response biases in maniaattention and response biases in mania

towards the positive stimuli and intowards the positive stimuli and in

depression towards the negative stimuli. Indepression towards the negative stimuli. In

addition, patients with mania but notaddition, patients with mania but not

those with depression were impaired inthose with depression were impaired in

their ability to inhibit behavioural re-their ability to inhibit behavioural re-

sponses and focus attention. These findingssponses and focus attention. These findings

were particularly interesting against a back-were particularly interesting against a back-

ground of similar impairments on conven-ground of similar impairments on conven-

tional neuropsychological tests of memorytional neuropsychological tests of memory

and executive function (see above).and executive function (see above).

Neuroimaging studies of the neural re-Neuroimaging studies of the neural re-

gions that underlie cognitive processing ofgions that underlie cognitive processing ofaffective meaning suggest that medial andaffective meaning suggest that medial and

orbitofrontal prefrontal cortex (PFC) areorbitofrontal prefrontal cortex (PFC) are

particularly involved (Beauregardparticularly involved (Beauregard et al et al ,,

1997; Teasdale1997; Teasdale et alet al, 1999). In line with, 1999). In line with

these findings, Murphythese findings, Murphy et alet al (1999) con-(1999) con-

cluded that performances in mania andcluded that performances in mania and

depression were most likely to differ on cog-depression were most likely to differ on cog-

nitive tasks subserved by functioning of thenitive tasks subserved by functioning of theorbital/ventromedial regions of PFC. In-orbital/ventromedial regions of PFC. In-

deed, Drevetsdeed, Drevets et alet al (1997) found that the(1997) found that the

subgenual PFC, which lies in the ventrome-subgenual PFC, which lies in the ventrome-

dial PFC, is differentially activated duringdial PFC, is differentially activated during

periods of mania and depression. The disin-periods of mania and depression. The disin-

hibited response often observed in mania,hibited response often observed in mania,

but not in depression, provides further evi-but not in depression, provides further evi-

dence for differential performance on tasksdence for differential performance on tasks

requiring ventromedial prefrontal function-requiring ventromedial prefrontal function-

ing, as patients with medial or ventral pre-ing, as patients with medial or ventral pre-

frontal damage are similarly impaired onfrontal damage are similarly impaired on

`go/no-go' tasks (Drewe, 1975; Malloy`go/no-go' tasks (Drewe, 1975; Malloy etet

alal, 1993)., 1993).At first glance it might seem puzzlingAt first glance it might seem puzzling

that patients with mania and depression inthat patients with mania and depression in

the study by Murphythe study by Murphy et alet al were differentlywere differently

impaired on the àffective go/no-go' taskimpaired on the àffective go/no-go' task

but not on the Tower of London test ofbut not on the Tower of London test of

planning, tasks both thought to be sub-planning, tasks both thought to be sub-

served by PFC. This apparent inconsistencyserved by PFC. This apparent inconsistency

may be explained by the functional andmay be explained by the functional and

anatomical distinctions between the dorso-anatomical distinctions between the dorso-

lateral and orbital/ventromedial regions oflateral and orbital/ventromedial regions of

PFC that have been postulated in recentPFC that have been postulated in recent

years. It is now known that tasks such asyears. It is now known that tasks such as

the WCST and the Tower of London testthe WCST and the Tower of London testactivate a neural network that includesactivate a neural network that includes

important areas such as dorsolateral regionsimportant areas such as dorsolateral regions

of PFC (Bermanof PFC (Berman et alet al, 1986; Baker, 1986; Baker et alet al,,

1996). These regions have numerous con-1996). These regions have numerous con-

nections with cortical systems involved innections with cortical systems involved in

information processing. In contrast, tasksinformation processing. In contrast, tasks

that assess ability to make decisions andthat assess ability to make decisions and

reverse associations between stimulus andreverse associations between stimulus and

reward are thought to be subserved byreward are thought to be subserved by

ventromedial regions (Rahmanventromedial regions (Rahman et alet al, 1999;, 1999;

RogersRogers et alet al, 1999), which are more exten-, 1999), which are more exten-

sively connected with limbic structuressively connected with limbic structures

(Pandya & Yeterian, 1996). As a result, it(Pandya & Yeterian, 1996). As a result, itis possible that this inconsistency is relatedis possible that this inconsistency is related

to the different neural pathways subservingto the different neural pathways subserving

cognitive function in these two tasks.cognitive function in these two tasks.

To the best of our knowledge, no otherTo the best of our knowledge, no other

studies have compared information proces-studies have compared information proces-

sing biases in mania and depression. Thesing biases in mania and depression. The

mood-congruent bias observed in depres-mood-congruent bias observed in depres-

sion is consistent with many depression stu-sion is consistent with many depression stu-

dies demonstrating biases of memory anddies demonstrating biases of memory and

attention (see above), but this may be theattention (see above), but this may be the

first demonstration of a positive attentionalfirst demonstration of a positive attentional

bias in mania. In this context, it is worthbias in mania. In this context, it is worth

noting that a recent study demonstrated anoting that a recent study demonstrated abias for processing negative information inbias for processing negative information in

s 1 2 4s 1 2 4

Fig. 1Fig. 1 Performance of patients with maniaPerformance of patients with mania

(triangles), depression (circles) and control subjects(triangles), depression (circles) and control subjects

(squares) as a function of difficulty level on the(squares) as a function of difficulty level on the

one-touchTower of London task. The dependentone-touchTower of London task. The dependent

measures shown are (a ) mean percentage ofmeasures shown are (a) mean percentage of

problems solved correctly by first response andproblems solved correctly by first response and(b) mean latency to first response.Data for patients(b) mean latency to first response.D ata for patients

with mania and depression are taken from Murphywith mania and depression are taken from Murphy

et alet al (1999) and Elliott(1999) and Elliott et alet al (1996), respectively.(1996), respectively.

Table 1Table 1 Neuropsychological performance of patients with major depression and bipolar disorder (manicNeuropsychological performance of patients with major depression and bipolar disorder (manic

phase) on memory tests taken from the Cambridge Neuropsychological Test Automated Battery (CANTAB)phase) on memory tests taken from the Cambridge Neuropsychological Test Automated Battery (CANTAB)

Manic phase of bipolar disorderManic phase of bipolar disorder DepressionDepression

Pattern recognition ^ proportion correctPattern recognition ^ proportion correct __ __

Pattern recognition ^ latencyPattern recognition ^ latency __ __

Spatial recognition ^ proportion correctSpatial recognition ^ proportion correct __ __

Spatial recognition ^ latencySpatial recognition ^ latency __ [[

Simultaneous MTS ^ proportion correctSimultaneous MTS ^ proportion correct [[ __

Simultaneous MTS ^ latencySimultaneous MTS ^ latency __ __

Delayed MTS ^ proportion correctDelayed MTS ^ proportion correct __ (i)(i) __ (i)(i)

Delayed MTS ^ latencyDelayed MTS ^ latency __ (i)(i) __ (i)(i)

Data for patients with bipolar disorder (manic phase) taken from MurphyData for patients with bipolardisorder (manic phase) taken from Murphy et alet al (1999 ); data for patients with depression(1999); data for patients with depressiontaken from Elliotttaken from Elliott et alet al (1996).(1996).__, impaired;, impaired; [[, unimpaired; (i) independent of delay or level of difficulty (i.e. equally impaired at all delays)., unimpaired; (i) independent of delay or level of difficulty (i.e. equally impaired at all delays).MTS, matching-to-sample.MTS, matching-to-sample.


6/8


bipolar mania (Lyonbipolar mania (Lyon et alet al, 1999). While, 1999). While

such results may seem directly contradic-such results may seem directly contradic-tory to the findings reported above, thetory to the findings reported above, the

authors suggested that negative bias mayauthors suggested that negative bias may

be limited to implicit tests of affectivebe limited to implicit tests of affective

orientation; the `go/no-go' task used byorientation; the `go/no-go' task used by

MurphyMurphy et alet al and described here surelyand described here surely

taps affective bias more explicitly.taps affective bias more explicitly.

Abnormal response toAbnormal response to

performance feedbackperformance feedback

Another concept related to cognitive proces-Another concept related to cognitive proces-

sing of emotional material and to mood-sing of emotional material and to mood-

congruent bias is that of reinforcement orcongruent bias is that of reinforcement orreward. It has been argued that the manifoldreward. It has been argued that the manifold

signs and symptoms of manic depressionsigns and symptoms of manic depression

may be viewed in terms of dysregulation ofmay be viewed in terms of dysregulation of

three major neurobiological systems: thosethree major neurobiological systems: those

that involve reinforcementreward func-that involve reinforcementreward func-

tions, central pain mechanisms and psycho-tions, central pain mechanisms and psycho-

motor activity (Carroll, 1994). Althoughmotor activity (Carroll, 1994). Although

research has yet to demonstrate a distur-research has yet to demonstrate a distur-

bance of reinforcementreward systems inbance of reinforcementreward systems in

bipolar disorder, a series of related studiesbipolar disorder, a series of related studies

has suggested that such systems may behas suggested that such systems may be

disrupted in patients with major depressiondisrupted in patients with major depression

(Beats(Beats et alet al, 1996; Elliott, 1996; Elliott et alet al, 1996, 1997, 1996, 1997aa).).Sahakian and colleagues have suggested thatSahakian and colleagues have suggested that

an abnormal response to negative feedbackan abnormal response to negative feedback

may contribute to the poor performancemay contribute to the poor performance

often observed in individuals with depres-often observed in individuals with depres-

sion. Specifically, Elliottsion. Specifically, Elliott et alet al (1996) found(1996) found

that on two CANTAB computerised neuro-that on two CANTAB computerised neuro-

psychological tasks, which tap differentpsychological tasks, which tap different

cognitive functions and involve differentcognitive functions and involve different

neural substrates, failure on one problemneural substrates, failure on one problem

appeared to elevate the probability of failureappeared to elevate the probability of failure

on the immediately subsequent problem,on the immediately subsequent problem,

suggesting that negative feedback may havesuggesting that negative feedback may have

a detrimental effect on subsequent perfor-a detrimental effect on subsequent perfor-mance.mance. This effect was specific to patientsThis effect was specific to patients

with depression and was not observed inwith depression and was not observed in

any of the other clinical groups examined,any of the other clinical groups examined,i.e. those with Parkinson's disease, schizo-i.e. those with Parkinson's disease, schizo-

phrenia or neurosurgical legions of thephrenia or neurosurgical legions of the

frontal or temporal lobes (Elliottfrontal or temporal lobes (Elliott et alet al ,,

19971997aa). The investigators suggested that). The investigators suggested that

this effect may represent an important linkthis effect may represent an important link

between negative affect and the cognitivebetween negative affect and the cognitive

impairments associated with depression.impairments associated with depression.

Whether this type of effect is specific toWhether this type of effect is specific to

depression or extends to patients who aredepression or extends to patients who are

manic at the time of testing, however,manic at the time of testing, however,

remains to be determined. In this regard,remains to be determined. In this regard,

itit is worth mentioning that in a study inves-is worth mentioning that in a study inves-

tigating the neural response to performancetigating the neural response to performancefeedback, the presence of feedback increasedfeedback, the presence of feedback increased

blood flow in the ventromedial/orbitofrontalblood flow in the ventromedial/orbitofrontal

cortex for a guessing but not for a planningcortex for a guessing but not for a planning

task (Elliotttask (Elliott et alet al, 1997, 1997bb, 1998)., 1998).

Also relevant is a study by CorwinAlso relevant is a study by Corwin et alet al

(1990) that investigated response bias (i.e.(1990) that investigated response bias (i.e.

the decision rule subjects adopt when un-the decision rule subjects adopt when un-

certain) on a task of recognition memory incertain) on a task of recognition memory in

patients with unipolar depression, bipolarpatients with unipolar depression, bipolar

mania and controls. An abnormally conser-mania and controls. An abnormally conser-

vative response bias was associated with de-vative response bias was associated with de-

pression whereas a liberal response biaspression whereas a liberal response bias

was associated with mania, regardless ofwas associated with mania, regardless ofseverity of illness. Consequently it seems thatseverity of illness. Consequently it seems that

cognitive performance in depression andcognitive performance in depression and

mania may be influenced by different emo-mania may be influenced by different emo-

tional or affective responses to task stimuli.tional or affective responses to task stimuli.

CONCLUSIONCONCLUSION

In this review we have considered researchIn this review we have considered research

on the neuropsychology of bipolar disorderon the neuropsychology of bipolar disorder

with special attention to the relationshipwith special attention to the relationship

between mood and cognitive functioning.between mood and cognitive functioning.

Unlike the more advanced research focus-Unlike the more advanced research focus-ing on major (unipolar) depression, working on major (unipolar) depression, work

to date on bipolar disorder has not achievedto date on bipolar disorder has not achieved

a satisfactorily comprehensive assessmenta satisfactorily comprehensive assessment

of cognitive functioning. Patients sufferingof cognitive functioning. Patients suffering

from depression have been shown to befrom depression have been shown to be

cognitively impaired on a wide range ofcognitively impaired on a wide range of

tasks, and euthymic patients have demon-tasks, and euthymic patients have demon-

strated residual impairments on some testsstrated residual impairments on some testsof attention and visual information pro-of attention and visual information pro-

cessing. Although studies of mania indicatecessing. Although studies of mania indicate

a wide range of possible cognitive deficits,a wide range of possible cognitive deficits,

the comprehensive review of cognition sug-the comprehensive review of cognition sug-

gested by these findings has not yet beengested by these findings has not yet been

undertaken. At the same time, comparativeundertaken. At the same time, comparative

studies of unipolar depression have broughtstudies of unipolar depression have brought

the essential similarity of these conditionsthe essential similarity of these conditions

into some doubt, with complicating conse-into some doubt, with complicating conse-

quences for a perhaps oversimple under-quences for a perhaps oversimple under-

standing of the relationship between moodstanding of the relationship between mood

and cognition in affective disorders. Inand cognition in affective disorders. In

particular, comparative studies have soughtparticular, comparative studies have soughtto establish distinct neuropsychologicalto establish distinct neuropsychological

profiles for mania, depression and schizo-profiles for mania, depression and schizo-

phrenia as a way of determining whetherphrenia as a way of determining whether

general or specific deficits obtain in thegeneral or specific deficits obtain in the

affective disorders.affective disorders.

The establishment of such distinct pro-The establishment of such distinct pro-

files is crucial to our understanding of thefiles is crucial to our understanding of the

neuropsychology of the affective disorders.neuropsychology of the affective disorders.

Until recently, most comparative studiesUntil recently, most comparative studies

noted striking similarities between schizo-noted striking similarities between schizo-

phrenia, mania and depression. However,phrenia, mania and depression. However,

these studies employed affectively neutralthese studies employed affectively neutral

designs, eliminating emotional processingdesigns, eliminating emotional processingfrom the experimental dynamic and thusfrom the experimental dynamic and thus

compromising their usefulness in the inves-compromising their usefulness in the inves-

tigation of mood and cognition. More re-tigation of mood and cognition. More re-

cent studies, based on the model of earliercent studies, based on the model of earlier

investigations of mood-congruent bias ininvestigations of mood-congruent bias in

depression, have attempted to differentiatedepression, have attempted to differentiate

mania and depression by employing tasksmania and depression by employing tasks

with affective components. These studieswith affective components. These studies

have noted biases in informational proces-have noted biases in informational proces-

sing and abnormal responses to feedbacksing and abnormal responses to feedback

that appear to be consistent with other datathat appear to be consistent with other data

obtained from neuroimaging work on man-obtained from neuroimaging work on man-

ia and depression.ia and depression.Historically, studies of mood disordersHistorically, studies of mood disorders

have made virtually no reference to basichave made virtually no reference to basic

research on emotion in healthy volunteers,research on emotion in healthy volunteers,

and conventional neuropsychologicaland conventional neuropsychological

testing has shied away from emphasisingtesting has shied away from emphasising

emotional components of cognition. Aemotional components of cognition. A

neuropsychological approach that incorpo-neuropsychological approach that incorpo-

rates both elements in experimental designsrates both elements in experimental designs

requiring both cognitive and emotionalrequiring both cognitive and emotional

processing could go a long way towards aprocessing could go a long way towards a

better characterisation of the deficits sobetter characterisation of the deficits so

far observed in depression and in maniafar observed in depression and in mania

(see, for example, Murphy(see, for example, Murphy et alet al, 1999)., 1999).Such an integrated approach could benefitSuch an integrated approach could benefit

s 1 2 5s 1 2 5

Fig. 2Fig. 2 Mean response times for`happy' and`sad' targetsin theaffective go/no-go task forpatients with maniaMean response times for`happy' and`sad' targetsin theaffective go/no-go task forpatients with mania

(black bars), depression (white bars) and control subjects (shadedbars). Bars represent one standard error of(blackbars), depression (white bars) and control subjects (shaded bars). Bars represent one standard error of

themean (s.e.m.). Data taken from Murphythemean (s.e.m.). Data taken from Murphy et alet al (1999).(1999).


7/8


greatly by incorporating ideas from emo-greatly by incorporating ideas from emo-

tion theories that emphasise cognitiontion theories that emphasise cognition

emotion interactions (e.g. Barnard & Teas-emotion interactions (e.g. Barnard & Teas-

dale, 1991; Teasdale & Barnard, 1993;dale, 1991; Teasdale & Barnard, 1993;

Williams, 1996) and from recent advancesWilliams, 1996) and from recent advances

in our understanding of the brain mechan-in our understanding of the brain mechan-

isms that underlie emotion (e.g. Damasio,isms that underlie emotion (e.g. Damasio,1994; LeDoux, 1995). Studies focusing on1994; LeDoux, 1995). Studies focusing on

the neural networks involved in such emo-the neural networks involved in such emo-

tional processes in the neuropsychiatric af-tional processes in the neuropsychiatric af-

fective disorders of depression and maniafective disorders of depression and mania

may provide the key to resolving thesemay provide the key to resolving these

important issues.important issues.

ACKNOWLEDGEMENTSACKNOWLEDGEMENTS

This research was funded by a Programme GrantThis research was funded by a Programme Grant

from the Wellcome Trust to Dr B. J. Sahakian, Pro-from the Wellcome Trust to Dr B. J. Sahakian, Pro-

fessor T.W. Robbins, Professor B. J. Everitt and Drfessor T.W. Robbins, Professor B. J. Everitt and Dr

A. C. Roberts, and was completed within the Medi-A. C. Roberts, and was completed within the Medi-

cal Research Council Co-operative Group in Brain,cal Research Council Co-operative Group in Brain,Behaviour and Neuropsychiatry. Dr F. C. Murphy isBehaviour and Neuropsychiatry. Dr F. C. Murphy is

supported by the Natural Sciences and Engineeringsupported by the Natural Sciences and Engineering

Research Council of Canada. We also thank theResearch Council of Canada. We also thank the

Searle Memorial Trust and the Charles and ElsieSearle Memorial Trust and the Charles and Elsie

Sykes Trust.SykesTrust.

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