Neuropsychological correlates in Neuropsychological correlates in psychotic depression:Focus on psychotic depression:Focus on
attentionattentionA.M. Politis, Athens Medical School, A.M. Politis, Athens Medical School, Department of Psychiatry, Eginition Department of Psychiatry, Eginition
HospitalHospital
Impaired attention has been reported in several Impaired attention has been reported in several psychopathological groups such as : psychopathological groups such as :
schizophrenia, schizophrenia, attention deficit hyperactivity disorder (ADHD), attention deficit hyperactivity disorder (ADHD), major depressionmajor depression
Ackerman et all 1986, Nuechterlein 1984, Veiel 1997, Zakzanis 1999Ackerman et all 1986, Nuechterlein 1984, Veiel 1997, Zakzanis 1999
. .
Evidence has recently suggested that psychotic depressed patients are more impaired, on neuropsychological testing measuring attention as compared to non-psychotic depressed patients
on the measures of psychomotor speed, motor skills, attention, and learning
had more unsatisfactory scores on the Continuous Performance Test
a significantly higher impairment in attention
Jeste et al.1998, Nelson et alJeste et al.1998, Nelson et al 1998, Schatzberg et al 20001998, Schatzberg et al 2000..
One avenue to better understanding of the neurocognitive dysfunctionOne avenue to better understanding of the neurocognitive dysfunction
associated with psychotic depression involves comparison withassociated with psychotic depression involves comparison with
clinically related conditionsclinically related conditions:: schizophreniaschizophrenia,, with with which psychotic depression shares psychotic which psychotic depression shares psychotic
features, features, and and diffuse and severe neuropsychologicaldiffuse and severe neuropsychological dysfunction dysfunction nonpsychoticnonpsychotic depressiondepression, with which it shares affective symptoms. , with which it shares affective symptoms.
Prior studiesPrior studies of patients with nonpsychotic depression have reported of patients with nonpsychotic depression have reported executiveexecutive and attention difficulties that are relativelyand attention difficulties that are relatively benign,benign,((effortful effortful mental operations, namely, those tasks that require selective and sustained attention, mental operations, namely, those tasks that require selective and sustained attention,
or that necessitate larger amounts of cognitive capacityor that necessitate larger amounts of cognitive capacity Hartlage 1993, Zakzanis 1999Hartlage 1993, Zakzanis 1999
P.P. Roy-ByrneP.P. Roy-Byrne 1986, M.E. Tancer, 19901986, M.E. Tancer, 1990
Global Neuropsychological Performance of Healthy Comparison Subjects and Patients Global Neuropsychological Performance of Healthy Comparison Subjects and Patients With Nonpsychotic Depression, Psychotic Depression, and SchizophreniaWith Nonpsychotic Depression, Psychotic Depression, and Schizophrenia aa Healthy Healthy comparison subjects: mean=<–0.01 (SD=0.52); patients with nonpsychotic depression: comparison subjects: mean=<–0.01 (SD=0.52); patients with nonpsychotic depression: mean=<0.01 (SD=0.47); patients with psychotic depression: mean=–0.59 (SD=0.91); mean=<0.01 (SD=0.47); patients with psychotic depression: mean=–0.59 (SD=0.91); patients with schizophrenia: mean=–0.95 (SD=0.86).patients with schizophrenia: mean=–0.95 (SD=0.86). Hill SK Hill SK Am J Psychiatry. 2004 Jun;161(6):996-1003Am J Psychiatry. 2004 Jun;161(6):996-1003
Performance in Six Neuropsychological Domains of Healthy Comparison Subjects and Performance in Six Neuropsychological Domains of Healthy Comparison Subjects and
Patients With Nonpsychotic Depression, Psychotic Depression, and SchizophreniaPatients With Nonpsychotic Depression, Psychotic Depression, and Schizophrenia Hill SK Hill SK Am J Psychiatry. 2004 Jun;161(6):996-1003Am J Psychiatry. 2004 Jun;161(6):996-1003
The study was designed to search for differences on attentional The study was designed to search for differences on attentional performance amongperformance among::
unmedicated inpatients with major depression with psychotic unmedicated inpatients with major depression with psychotic features,features,
unmedicated inpatients with major depression without unmedicated inpatients with major depression without psychotic features,psychotic features,
in a control group of unmedicated schizophrenic inpatients, in a control group of unmedicated schizophrenic inpatients, in a healthy control group in a healthy control group and to determine whether these attentional deficits correlate with and to determine whether these attentional deficits correlate with
the depressive symptomatology using, a visual search, the depressive symptomatology using, a visual search, attentional test not previously employed in psychotic depressed attentional test not previously employed in psychotic depressed inpatients. inpatients.
..
Ruff’s 2 and 7 selective attention testRuff’s 2 and 7 selective attention test is a paper-and-pencil is a paper-and-pencil number cancellation, visual search testnumber cancellation, visual search test, assessing an , assessing an individual’s attentional capacity to self-pacing targets for a individual’s attentional capacity to self-pacing targets for a 5-minute period in :5-minute period in :
different distracting conditions known to influence selection different distracting conditions known to influence selection speedspeed
in one, the two numbers are randomly dispersed among in one, the two numbers are randomly dispersed among other digits; while selecting targets from the same stimulus other digits; while selecting targets from the same stimulus category is described as category is described as "effortful mental operation"effortful mental operation."."
in the second condition, the distractors are made of in the second condition, the distractors are made of alphabetical letters. Selecting targets from different alphabetical letters. Selecting targets from different stimulus categories has been described as stimulus categories has been described as "effortless "effortless mental operation,"mental operation,"
Specific features of attentionSpecific features of attention
selective attentionselective attention
effortless (speed and accuracy)effortless (speed and accuracy) does not recruit does not recruit cognitive capacity to any great extent.cognitive capacity to any great extent.
ΔΔ ΣΣ E 2 E 2 ΦΦ ΥΥ P 7 H P 7 H ΥΥ X H 7 X H 7 ΔΔ ΓΓ 2 T A P Y 2 2 T A P Y 2
effortfuleffortful (speed and accuracy)(speed and accuracy) requires attention to a larger requires attention to a larger extent, extent,
3 2 7 9 3 2 6 4 3 7 5 6 1 3 4 5 9 8 7 0 2 1 5 2 6 5 3 2 7 9 3 2 6 4 3 7 5 6 1 3 4 5 9 8 7 0 2 1 5 2 6 5
sustained attentionsustained attention(Total speed and total accuracy )(Total speed and total accuracy )
Furthermore, Furthermore, the two-number targetthe two-number target is more easily codified is more easily codified in short-term memoryin short-term memory and thus it is easily codified by and thus it is easily codified by patients with memory disturbances patients with memory disturbances
Finally, Finally, visual research of the target is visual research of the target is categoricalcategorical,, and and selection of the two-number target is performed by patients selection of the two-number target is performed by patients with a low educational profilewith a low educational profile
Characteristics
N 16
Patients with psychotic major depression
N 16
Patients with non psychotic major depression
N20
Patients with schizophrenia
N20
Healthy volunteers. F P
Male 8 8 12
12
Female 8 8 8 8
Age 49±15 54±13 41±9 55±1 6.73
0.001
Education 10±4 11±3 11±3 12±3 1.43
0.24
Duration of illness (months)
67±83 149±133 3.59
0.07
Number of previous episodes patient
1.5±1 2±1 0.28
0.59
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scizophreniapsychotic depressiondepressionhealthy
Post hoc, comparison, LSD test
Patients with psychotic depression vs. Patients with non-psychotic depression
Patients with psychotic
depression vs. Patients with schizophrenia
Patients with non psychotic depression vs. Patients with schizophrenia
Healthy volunteers vs. Patients with
non-psychotic depression
Healthy volunteers vs.
Patients with non psychotic depression
Automatic speed
p=0.004 p=0.524 p=0.041 p=0.000 p=0.000
Automatic accuracy
p=0.050 p=0.127 p=0.342 p=0.001 p=0.000
Controlled speed
p=0.007 p=0.431 p=0.036 p=0.000 p=0.000
Controlled accuracy
p=0.156 p=0.470 p=0.269 p=0.088 p=0.001
Total speed p=0.003 p=0.311 p=0.064 p=0.000 p=0.000
Total accuracy
p=0.032 p=0.091 p=0.260 p=0.022 p=0.000
Psychological Tests in Psychotic or Nonpsychotic Depressed Psychological Tests in Psychotic or Nonpsychotic Depressed Patients, Patients With Schizophrenia, and Healthy Volunteers Patients, Patients With Schizophrenia, and Healthy Volunteers
(MANOVA) (MANOVA) Politis A, Lykouras L. et al 2004Politis A, Lykouras L. et al 2004
Patients with non-psychotic depression
Vs Patients with psychotic depression
P=0.011
Patients with non-psychotic depression
Vs Patients with schizophrenia p=0.04
Patients with non-psychotic depression
Vs Healthy volunteers p=0.000001
Patients with psychotic depression
Vs Patients with schizophrenia 0.52
Patients with psychotic depression
Vs Healthy volunteers 0.000
Patients with schizophrenia Vs Healthy volunteers 0.000
the present study indicates poor performance of psychotic the present study indicates poor performance of psychotic depressed patients in speed on target selection in both depressed patients in speed on target selection in both effortful and effortless types of processing –effortful and effortless types of processing –selective selective attentionattention-and poor performance on overall speed and -and poor performance on overall speed and accuracy-accuracy-sustained attentionsustained attention- - in the acute phase of the in the acute phase of the diseasedisease. .
confirm other studies on attention impairmentconfirm other studies on attention impairment may underlie the specific mechanism that produces may underlie the specific mechanism that produces
impairment on selective and sustained attentionimpairment on selective and sustained attention
. . Our study evaluated subjects' attentional functioning Our study evaluated subjects' attentional functioning not not only during the acute psychotic episodeonly during the acute psychotic episode, so it does provide , so it does provide data to clarify whether the attentional deficit in psychotic data to clarify whether the attentional deficit in psychotic depression is: depression is:
a state-dependent characteristica state-dependent characteristic (which resolves with (which resolves with remission of the acute episode), remission of the acute episode),
a trait-dependent characteristica trait-dependent characteristic (and, thus, a possible (and, thus, a possible marker for this subtype of depression which improves but marker for this subtype of depression which improves but
does not fully resolve with remission of the acute episode )does not fully resolve with remission of the acute episode )
The newer antidepressants (SSRIs) has a minor effect on The newer antidepressants (SSRIs) has a minor effect on cognitive functions because of a lack of anticholinergic cognitive functions because of a lack of anticholinergic side effects (Peretti et al 2000). side effects (Peretti et al 2000).
The The atypical neuroleptics improved cognition in atypical neuroleptics improved cognition in schizophrenia such as verbal fluency, working memory, schizophrenia such as verbal fluency, working memory, executive functions and attention (Meltzer 1999)executive functions and attention (Meltzer 1999)(Keefe,1999) (Keefe,1999)
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scizophrenia a
psychotic depression a
depression
healthy
Multiple Analysis of Variance (MANOVA) COMPARISONS BEFORE AND AFTER TREATMENT
Patients with psychotic depression vs. Patients with non-psychotic depression
Patients with psychotic
depression vs. Patients with schizophrenia
Patients with non psychotic depression vs. Patients with schizophrenia
Automatic speed
p=0.007 p=0.31* p=0.04
Automatic accuracy
p=0.07 p=0.15*p=0.61
Controlled speed
p=0.007 p=0.43*p=0.02
Controlled accuracy
p=0.35 p=0.84* p=0.41
Total speed p=0.006 p=0.30* p=0.04
Total accuracy
p=0.098 p=0.39* p=0.351
Hamilton Depression Rating Scale comparison Psycotic vs non psychotic Hamilton Depression Rating Scale comparison Psycotic vs non psychotic
(F=3,52, P=0,07)(F=3,52, P=0,07)
0
5
10
15
20
25
30
35
40
45
50
Neuropsychological DNeuropsychological Differences between ifferences between patients with psychotic majorpatients with psychotic major depressiondepression
and patients with nonpsychotic major depression and patients with nonpsychotic major depression couldcould not be attributed to differences in severity of depressive symptoms.not be attributed to differences in severity of depressive symptoms.
Psychotic depressed vs schizophrenicPsychotic depressed vs schizophrenic From a From a quantitativequantitative point of view point of view psychotic depressed psychotic depressed
patients sharepatients share the same pattern of attentional deficits the same pattern of attentional deficits in in both acute and remission phaseboth acute and remission phase with patients with with patients with schizophreniasbut schizophreniasbut
Psychotic depression vs non psychotic depressionPsychotic depression vs non psychotic depression the present study indicates that patients with psychotic the present study indicates that patients with psychotic
depression depression have have qualitative and quantitativequalitative and quantitative more more impairmentimpairment on both selective and sustained attention as on both selective and sustained attention as compared to nonpsychotic depressed patients compared to nonpsychotic depressed patients in both acute in both acute and remission phaseand remission phase
In our study, psychotic depressed patients did more poorly In our study, psychotic depressed patients did more poorly than schizophrenic patients. As mentioned, than schizophrenic patients. As mentioned, distractibilitydistractibility (inability to direct attention away from irrelevant (inability to direct attention away from irrelevant backround stimuli) backround stimuli) was once thought to be the hallmark of was once thought to be the hallmark of the schizophrenic attentional deficit.the schizophrenic attentional deficit. It seems that this type It seems that this type of disturbances is not specific to schizophrenia. of disturbances is not specific to schizophrenia.
Cornblatt Cornblatt suggested that distractibility is a correlate of suggested that distractibility is a correlate of psychosis in general and psychosis in general and "probably vulnerability to "probably vulnerability to distraction is not a trait with predictive potential but a state distraction is not a trait with predictive potential but a state marker that is displayed by acutely disturbed patients with marker that is displayed by acutely disturbed patients with psychotic symptomspsychotic symptoms“ “
Cornblatt B 1989Cornblatt B 1989
. Schatzberg propose that psychosis in depression may be caused by increased cortisol levels, which may be more pronounced in psychotic depression than in nonpsychotic depression, leading to the greater neuropsychological
deficits, including decreased attention. Increased cortisol levels may lead to less accurate
encoding of meaningful stimuli and may impair selective attention, thereby reducing an individual’s ability to discriminate relevant and important information from irrelevant and unimportant information
Schatzberg AF 1985
To summarize,To summarize, The present study demonstrates that The present study demonstrates that attention deficitsattention deficits exist exist
in major depression, in major depression, it is more prominent in psychotic it is more prominent in psychotic depression. depression.
It seems that these deficits It seems that these deficits may not be due to the severity may not be due to the severity of depression. of depression.
The two depressive groups appear to differ both The two depressive groups appear to differ both quantitatively and qualitatively quantitatively and qualitatively
DistractibilityDistractibility does not discriminate between depressed does not discriminate between depressed and schizophrenic patients and schizophrenic patients but may discriminate psychotic but may discriminate psychotic from nonpsychotic depressed patients and it seems to be a from nonpsychotic depressed patients and it seems to be a trait markertrait marker
These data not only provide additional support forThese data not only provide additional support for psychotic psychotic depression as a depression as a distinct mood disorderdistinct mood disorder but also document but also document the the considerable neuropsychological morbidity associated withconsiderable neuropsychological morbidity associated with the the disorder. disorder.
Psychotic major depressionPsychotic major depression (or (or depression with significant depression with significant cognitive impairmentcognitive impairment) ) maymay biologically separate from major biologically separate from major depression depression
((Kopell BS Kopell BS 1970, 1970, Lyons DM, 2000 Lyons DM, 2000 Schatzberg 2000Schatzberg 2000))
Furthermore, taking attention as a criterion, psychotic Furthermore, taking attention as a criterion, psychotic depression although of depression although of mood congruentmood congruent subtype, is more close subtype, is more close to schizophrenia than to non-psychotic depressionto schizophrenia than to non-psychotic depression..
(Politis A , Lykouras L 2004)(Politis A , Lykouras L 2004)
