1. Neuropsychological correlates in psychotic depression:Focus on attention A.M. Politis, Athens Medical School, Department of Psychiatry, Eginition Hospital

2. Impaired attention has been reported in several psychopathological groups such as : schizophrenia, schizophrenia, attention deficit hyperactivity disorder (ADHD), attention deficit hyperactivity disorder (ADHD), major depression major depression Ackerman et all 1986, Nuechterlein 1984, Veiel 1997, Zakzanis 1999.

3. 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 al 1998, Schatzberg et al 2000.

4. One avenue to better understanding of the neurocognitive dysfunction associated with psychotic depression involves comparison with clinically related conditions: One avenue to better understanding of the neurocognitive dysfunction associated with psychotic depression involves comparison with clinically related conditions: schizophrenia, with which psychotic depression shares psychotic features, and diffuse and severe neuropsychological dysfunction schizophrenia, with which psychotic depression shares psychotic features, and diffuse and severe neuropsychological dysfunction nonpsychotic depression, with which it shares affective symptoms. nonpsychotic depression, with which it shares affective symptoms. Prior studies of patients with nonpsychotic depression have reported executive and attention difficulties that are relatively benign,( effortful mental operations, namely, those tasks that require selective and sustained attention, or that necessitate larger amounts of cognitive capacity Prior studies of patients with nonpsychotic depression have reported executive and attention difficulties that are relatively benign,( effortful mental operations, namely, those tasks that require selective and sustained attention, or that necessitate larger amounts of cognitive capacity Hartlage 1993, Zakzanis 1999 P.P. Roy-Byrne 1986, M.E. Tancer, 1990

5. Global Neuropsychological Performance of Healthy Comparison Subjects and Patients With Nonpsychotic Depression, Psychotic Depression, and Schizophrenia a Healthy 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); patients with schizophrenia: mean=–0.95 (SD=0.86). Hill SK Am J Psychiatry. 2004 Jun;161(6):996-1003

6. Performance in Six Neuropsychological Domains of Healthy Comparison Subjects and Patients With Nonpsychotic Depression, Psychotic Depression, and Schizophrenia Hill SK Am J Psychiatry. 2004 Jun;161(6):996-1003

7. The study was designed to search for differences on attentional performance among: The study was designed to search for differences on attentional performance among: unmedicated inpatients with major depression with psychotic features, unmedicated inpatients with major depression with psychotic features, unmedicated inpatients with major depression without psychotic features, unmedicated inpatients with major depression without 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 the depressive symptomatology using, a visual search, attentional test not previously employed in psychotic depressed inpatients..

8. Ruff’s 2 and 7 selective attention test is a paper-and-pencil number cancellation, visual search test, assessing an individual’s attentional capacity to self-pacing targets for a 5-minute period in : Ruff’s 2 and 7 selective attention test is a paper-and-pencil number cancellation, visual search test, assessing an individual’s attentional capacity to self-pacing targets for a 5-minute period in : different distracting conditions known to influence selection speed in one, the two numbers are randomly dispersed among other digits; while selecting targets from the same stimulus category is described as "effortful mental operation." in one, the two numbers are randomly dispersed among other digits; while selecting targets from the same stimulus category is described as "effortful mental operation." in the second condition, the distractors are made of alphabetical letters. Selecting targets from different stimulus categories has been described as "effortless mental operation," in the second condition, the distractors are made of alphabetical letters. Selecting targets from different stimulus categories has been described as "effortless mental operation,"

9. Specific features of attention selective attention effortless (speed and accuracy) does not recruit cognitive capacity to any great extent. effortless (speed and accuracy) does not recruit cognitive capacity to any great extent. Δ Σ E 2 Φ Υ P 7 H Υ X H 7 Δ Γ 2 T A P Y 2 Δ Σ E 2 Φ Υ P 7 H Υ X H 7 Δ Γ 2 T A P Y 2 effortful (speed and accuracy) requires attention to a larger 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 attention (Total speed and total accuracy )

10. Furthermore, the two-number target is more easily codified in short-term memory and thus it is easily codified by patients with memory disturbances Furthermore, the two-number target is more easily codified in short-term memory and thus it is easily codified by patients with memory disturbances Finally, visual research of the target is categorical, and selection of the two-number target is performed by patients with a low educational profile Finally, visual research of the target is categorical, and selection of the two-number target is performed by patients with a low educational profile

11. Characteristic s N 16 N 16 Patients with psychotic major depressio n N 16 N 16 Patients with non psychotic major depressio n N20N20 Patients with schizophreni a N20N20 Healthy volunteers. FP Male8 8 1212 1212 Female8 8 8 8 Age 49±15 54±13 41±9 55±1 6.7 3 0.00 1 Education 10±4 11±3 12±3 1.4 3 0.24 Duration of illness (months) 67±83 149±133 3.5 9 0.07 Number of previous episodes patient 1.5±1 2±1 0.2 8 0.59

13. 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=0.004p=0.524p=0.041p=0.000 Automatic accuracy p=0.050p=0.127p=0.342p=0.001p=0.000 Controlled speed p=0.007p=0.431p=0.036p=0.000 Controlled accuracy p=0.156p=0.470p=0.269p=0.088p=0.001 Total speed p=0.003p=0.311p=0.064p=0.000 Total accuracy p=0.032p=0.091p=0.260p=0.022p=0.000

14. Psychological Tests in Psychotic or Nonpsychotic Depressed Patients, Patients With Schizophrenia, and Healthy Volunteers (MANOVA) Politis 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 schizophreniap=0.04 Patients with non-psychotic depression Vs Healthy volunteersp=0.000001 Patients with psychotic depression Vs Patients with schizophrenia0.52 Patients with psychotic depression Vs Healthy volunteers0.000 Patients with schizophreniaVs Healthy volunteers0.000

15. the present study indicates poor performance of psychotic depressed patients in speed on target selection in both effortful and effortless types of processing –selective attention-and poor performance on overall speed and accuracy-sustained attention- in the acute phase of the disease. the present study indicates poor performance of psychotic depressed patients in speed on target selection in both effortful and effortless types of processing –selective attention-and poor performance on overall speed and accuracy-sustained attention- in the acute phase of the disease. confirm other studies on attention impairment confirm other studies on attention impairment may underlie the specific mechanism that produces impairment on selective and sustained attention may underlie the specific mechanism that produces impairment on selective and sustained attention

16. . Our study evaluated subjects' attentional functioning not only during the acute psychotic episode, so it does provide data to clarify whether the attentional deficit in psychotic depression is: a state-dependent characteristic (which resolves with remission of the acute episode), a trait-dependent characteristic (and, thus, a possible marker for this subtype of depression which improves but does not fully resolve with remission of the acute episode )

17. The newer antidepressants (SSRIs) has a minor effect on cognitive functions because of a lack of anticholinergic side effects (Peretti et al 2000). The newer antidepressants (SSRIs) has a minor effect on cognitive functions because of a lack of anticholinergic side effects (Peretti et al 2000). The atypical neuroleptics improved cognition in schizophrenia such as verbal fluency, working memory, executive functions and attention (Meltzer 1999)(Keefe,1999) The atypical neuroleptics improved cognition in schizophrenia such as verbal fluency, working memory, executive functions and attention (Meltzer 1999)(Keefe,1999)

19. 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=0.007p=0.31*p=0.04 Automatic accuracy p=0.07p=0.15* p=0.61 Controlled speed p=0.007p=0.43* p=0.02 Controlled accuracy p=0.35p=0.84*p=0.41 Total speed p=0.006p=0.30*p=0.04 Total accuracy p=0.098p=0.39*p=0.351

20. Hamilton Depression Rating Scale comparison Psycotic vs non psychotic (F=3,52, P=0,07) Neuropsychological Differences between patients with psychotic major depression and patients with nonpsychotic major depression and patients with nonpsychotic major depression could not be attributed to differences in severity of depressive symptoms.

21. Psychotic depressed vs schizophrenic From a quantitative point of view psychotic depressed patients share the same pattern of attentional deficits in both acute and remission phase with patients with schizophreniasbut From a quantitative point of view psychotic depressed patients share the same pattern of attentional deficits in both acute and remission phase with patients with schizophreniasbut Psychotic depression vs non psychotic depression the present study indicates that patients with psychotic depression have qualitative and quantitative more impairment on both selective and sustained attention as compared to nonpsychotic depressed patients in both acute and remission phase the present study indicates that patients with psychotic depression have qualitative and quantitative more impairment on both selective and sustained attention as compared to nonpsychotic depressed patients in both acute and remission phase

22. In our study, psychotic depressed patients did more poorly than schizophrenic patients. As mentioned, distractibility (inability to direct attention away from irrelevant backround stimuli) was once thought to be the hallmark of the schizophrenic attentional deficit. It seems that this type of disturbances is not specific to schizophrenia. In our study, psychotic depressed patients did more poorly than schizophrenic patients. As mentioned, distractibility (inability to direct attention away from irrelevant backround stimuli) was once thought to be the hallmark of the schizophrenic attentional deficit. It seems that this type of disturbances is not specific to schizophrenia. Cornblatt suggested that distractibility is a correlate of psychosis in general and "probably vulnerability to distraction is not a trait with predictive potential but a state marker that is displayed by acutely disturbed patients with psychotic symptoms“ Cornblatt suggested that distractibility is a correlate of psychosis in general and "probably vulnerability to distraction is not a trait with predictive potential but a state marker that is displayed by acutely disturbed patients with psychotic symptoms“ Cornblatt B 1989

23. . 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

24. To summarize, The present study demonstrates that attention deficits exist in major depression, it is more prominent in psychotic depression. The present study demonstrates that attention deficits exist in major depression, it is more prominent in psychotic depression. It seems that these deficits may not be due to the severity of depression. It seems that these deficits may not be due to the severity of depression. The two depressive groups appear to differ both quantitatively and qualitatively The two depressive groups appear to differ both quantitatively and qualitatively Distractibility does not discriminate between depressed and schizophrenic patients but may discriminate psychotic from nonpsychotic depressed patients and it seems to be a trait marker Distractibility does not discriminate between depressed and schizophrenic patients but may discriminate psychotic from nonpsychotic depressed patients and it seems to be a trait marker

25. These data not only provide additional support for psychotic depression as a distinct mood disorder but also document the considerable neuropsychological morbidity associated with the disorder. These data not only provide additional support for psychotic depression as a distinct mood disorder but also document the considerable neuropsychological morbidity associated with the disorder. Psychotic major depression (or depression with significant cognitive impairment) may biologically separate from major depression Psychotic major depression (or depression with significant cognitive impairment) may biologically separate from major depression (Kopell BS 1970, Lyons DM, 2000 Schatzberg 2000) (Kopell BS 1970, Lyons DM, 2000 Schatzberg 2000) Furthermore, taking attention as a criterion, psychotic depression although of mood congruent subtype, is more close to schizophrenia than to non-psychotic depression. Furthermore, taking attention as a criterion, psychotic depression although of mood congruent subtype, is more close to schizophrenia than to non-psychotic depression. (Politis A, Lykouras L 2004)